Brachytherapy

Definitive radiation for advanced cervix cancer is not associated with vaginal shortening—a prospective vaginal length and dose correlation

Prospectively measure change in vaginal length after definitive chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD). Twenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3-dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. The mean initial VL was 8.7 cm (6.5-12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5-12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6-252.2), 96.9 Gy (84.2-114.9), and 89.6 Gy (82.4-102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.

Early outcomes after definitive chemoradiation therapy with Vienna/Venezia hybrid high-dose rate brachytherapy applicators for cervical cancer: A single-institution experience

The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan-Meier method. Median follow-up was 16 months (IQR 9-32 mos). Median HRCTV volume was 31.6 cm Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers

To evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. Seventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. Median age at recurrence was 55 years (Range: 35-73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30-50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. The use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

To protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥85 Gy to high-risk clinical target volume D Twenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between 2017 and 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy treatment outcomes and incidence of adverse events were also examined. The median cumulative CTV The use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

The effect of one-room CT guided brachytherapy on procedure time and cost in the treatment of cervical cancer

Brachytherapy is associated with improved overall survival in cervical cancer patients, but the utilization seems hindered by high costs and relatively low reimbursement, particularly in the US. A one-room brachytherapy suite with CT (ORBT) could optimize the treatment workflow. By eliminating transport and waiting times, limiting applicator movement, and providing real-time applicator placement feedback, treatment time and costs could potentially be reduced. This study assesses the potential value of implementing ORBT in cervical cancer treatment. A variable cost model was developed to compare current (multi-room) brachytherapy workflows (MBRT) to ORBT, taking into account staff utilization, staff, equipment and consumables costs and room expenses. Two current care scenarios were simulated; applicator placement performed in the operating room (S1), and applicator placement performed in a brachytherapy suite (S2). For both scenarios literature reported fraction times of MBRT were compared to a range of ORBT times. Sensitivity analyses were performed to determine the influence of input parameters. In scenario one, the results showed yearly savings of $45,572 up to $339,439 (USD), assuming a 5% and 20% reduction in fraction duration, respectively, in ORBT compared to MRBT. In scenario two, ORBT does not result in costs savings at 5% to 15% improvement. Therefore, only when ORBT results in a >20% improvement of fraction time, cost will be saved. The results indicate that reducing procedure time (using ORBT) can lead to cost savings, depending on the current workflow. Savings seem to depend mostly on applicator placement location, number of patients per year, and involved personnel.

Upfront radiotherapy with brachytherapy for medically inoperable and unresectable patients with high-risk endometrial cancer

Comprehensive surgery with adjuvant therapy is standard of care for high-risk endometrial cancers, whereas upfront radiotherapy with brachytherapy is indicated for inoperable/unresectable patients, irrespective of risk. We evaluated outcomes for inoperable/unresectable patients with high-risk endometrial cancer (HREC: stage III and/or grade 3) and low-risk endometrial cancer (LREC: stage I/II and grade 1/2) treated with upfront radiotherapy. Twenty-nine patients with inoperable/unresectable endometrial cancer were treated with upfront radiotherapy at an academic medical center from 2012 to 2019. Cancer-specific survival (CSS), overall survival (OS), and recurrence rates between patients with HREC and LREC were compared. Median follow-up was 17.0 months (range 3.7-54.0). Twenty cancers were stage I + II and nine were stage III. Twenty-one cancers were grade 1 + 2 and eight were grade 3. Thirteen patients (45%) had HREC. Twenty-five patients received radiotherapy/chemoradiotherapy for primary treatment, while 4 patients received chemoradiotherapy before surgery. All patients underwent high dose rate brachytherapy (HDR) with 7 receiving HDR alone and 22 receiving external beam radiation and HDR. Two-year CSS was 100% for both HREC and LREC patients (log-rank p = 0.32). There was no OS difference between HREC and LREC patients (2-year: 73% vs. 77%; log-rank p = 0.33). Four HREC and 1 LREC patients recurred with one local recurrence in each group. There were no acute grade ≥3 and two late grade ≥3 gastrointestinal/genitourinary toxicities. Upfront radiotherapy for inoperable/unresectable HREC patients was well tolerated with high local control and CSS rates. Upfront radiotherapy with brachytherapy remains important even for high-risk inoperable and unresectable endometrial cancer patients.

The impact of rectal/bladder filling and applicator positioning on in vivo rectal dosimetry in vaginal cuff brachytherapy using an enhanced therapy setting

The impact of rectal filling and bladder volume on in vivo rectal dosimetry (IVD) in vaginal cuff brachytherapy (VCBT) is unknown. The purpose of this study was to compare rectal doses from IVD with those calculated from treatment planning and to identify influencing factors. We collected data of 80 VCBT sessions, four for each of 20 patients. Each was retrospectively compared with doses determined by the treatment planning system. Factors potentially predicting the IVD rectum dose were analyzed. For a series of 80 brachytherapy applications, the calculated mean dose to the rectum was 2.52 Gy. The mean difference between all calculated and measured doses for the 80 applications with five probe positions each was 0.09 Gy (p = 0.952) proving high overall accordance between IVD and calculated doses at the rectum. The mean volume of the rectum was 119 ± 57 cm³. The rectal volume was not statistically significantly associated with the IVD or the calculated rectum doses. At the third and fourth rectal probe position in craniocaudal ordering, increased filling of the urinary bladder resulted in decreased measured and calculated doses (p < 0.05 for both). A rectum pointing position of the applicator significantly increased the maximum rectum dose compared with a bladder-oriented position (p < 0.05). IVD provided valuable data for rectal exposure in VCBT. Increased bladder filling and vaginal applicator positioning off the rectum elicited related with less rectal radiation exposure, whereas rectal filling did not. Further confirmation including assessment of IVD in bladder is pending to define optimal dosimetric conditions in VCBT.

Economic impact of decreasing the fraction number in vaginal cuff brachytherapy: A direct cost analysis

The purpose of this study was to analyze the direct economic impact of two vaginal cuff brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) with similar vaginal control and toxicity results. From 2006 to 2015, 397 PEC patients (p) were treated with VBT: mean 40p/year, 67.5% received external beam radiotherapy (EBRT)+VBT and 32.5% exclusive VBT. Schedule 1: 3 fractions (Fr) after EBRT and 6Fr (4-6 Gy/Fr) in exclusive VBT. Schedule 2: 7Gy × 1Fr + EBRT and 6Gy × 3Fr in exclusive VBT. Differential cost analysis of the two schedules was retrospectively performed. The direct costs in each schedule were (1) Personnel: radiotherapy technicians, nurses, radiation oncologists, medical physicists, administrative personnel, orderlies; time dedicated by each professional during CT planning acquisitions and delineation of vagina/organs at risk, dosimetric study and evaluation, autoradiography, procedure reporting time during/after treatment, removal of bladder/rectal tubes and applicators, material cleaning and transportation for sterilization; (2) Health care material (gels, gauzes, gloves, etc); (3) Equipment (time equipment used). The differential between the two schedules was estimated. Indirect costs and evaluation of quality of life-adjusted costs were not considered. The overall reduction in the number of Fr per year in Schedule 2 was 93. Cost savings included treatment time per year: 4,185 min (70 h); personnel: 221€ ($246)/p in EBRT + VBT and 331€ ($368)/p in exclusive VBT; and health care material and equipment: 40€ ($44.5)/p in EBRT + VBT and 90€ ($100.2)/p in exclusive VBT. The overall savings per patient was 261€ ($295) in combined treatment and 421€ ($475.7) in exclusive VBT. The total savings per year with Schedule 2 in 40p was 12,503€ ($13,915.8). A 41% reduction in the fractions number in VBT for PEC allowed economic savings of 261€ ($290.5)/p in combined treatment and 421€ ($475.7)/p in exclusive VBT. Other benefits include patient comfort and fewer treatment visits.

Is single implant and multiple fractions radio-biologically iso-effective for cervical cancer high-dose-rate brachytherapy: Observation from patient cohorts during COVID pandemic

To report clinical outcomes of cervical cancer patients treated with single implant and multiple fractions of high-dose-rate brachytherapy (HDR BT). Patients treated with (chemo)radiation followed by single implant with all fractionated HDR BT delivered within 24-36 hours were included. Treatment protocol recommended >70 Gy equivalent doses in 2 Gy (EQD2 From 2020-2022, 116 patients were treated with single implant multiple fractions HDR-BT. The median dose to Point A, HRCTV D90, B2cc, R2cc and S2cc was 75.1 (72.4-77.8), 80.2 (76-84), 85.2 (83.1-90.1), 69.1 (65.0-73.9) and 67.9 (61-75.3) Gy for those treated with ICBT. The median dose to high risk clinical target volume D90, Bladder 2cc, Rectum 2cc and Sigmoid 2cc was 83.2 (78.2-88.4), 87.4 (84.2-91), 69.6 (64.1-75) and 68.1 (59.5-77.1) Gy in those with IC-ISBT respectively. The median follow-up was 36 months (2-60 months). The 5-year local control, loco-regional control, disease free survival and overall survival was 89%, 84%, 70.8% and 81.6% respectively. Grade ≥3 GI and GU toxicity were 11.3% and 1.7% respectively. The incidence Grade ≥3 GI was higher in those who received 8-9 Gy in three fractions than 5-7.5 Gy in 3-4 fractions. The abbreviated HDR BT schedule of single implant 3-4 fractions for LACC patients is radiobiological iso-effective for tumor control. There seems to be a fraction size dependence of abbreviated fractionation schedule for severe GI toxicity.

Applicator reconstruction in cervical cancer brachytherapy: A systematic review of current methods, challenges, and AI-driven future directions

Accurate applicator reconstruction is a critical step in 3D image-guided brachytherapy (3D-IGBT) for cervical cancer, directly influencing tumor control and organ-at-risk sparing. This systematic review evaluates the accuracy, efficiency, and clinical impact of applicator reconstruction methods, focusing on AI's potential to overcome existing limitations. Following PRISMA guidelines, 23 studies from MEDLINE, PubMed, Scopus, Embase, Lilacs and Web of Science (up to May 2025) were analyzed. Evaluation metrics included geometric accuracy (tip error, Hausdorff distance), reconstruction time, and dosimetric parameters (D90 HR-CTV, D2cc OARs). Methods assessed spanned manual (e.g., MPR, scout-based), semi-automatic (library method, clustering algorithms), and AI-driven approaches (e.g., U-Net, Dilated-Supervised Deep U-Net, Attention-Gated networks). Special focus was placed on deep learning (DL) architectures and their ability to overcome metallic artifacts, partial-volume effects, and inter-operator variability. Manual methods exhibited significant limitations, with tip errors reaching 4.1 mm. Semi-automated approaches reduced variability (library-based methods: 0.89) and dosimetric consistency (D2cc deviations <3%). Notably, DL models like DSD-UNet and Attention-Gated U-Net reduced reconstruction time to <30 s per case while maintaining robustness against CT artifacts. However, challenges persist, including limited clinical validation (60% of studies used phantoms), data heterogeneity (slice thickness: 0.6-5 mm), and generalizability to novel applicator designs. AI-driven reconstruction reduces human-dependent errors and enhances efficiency, but clinical validation remains a priority. Reducing CT slice thickness (≤1.5 mm) and combining scout images to mitigate metal artifacts are recommended. Future research should focus on generalizable AI models for nonlibrary applicators and large-scale clinical validation.

Clinical outcomes of abbreviated high dose-rate brachytherapy in locally advanced cervical cancer: lessons from the COVID pandemic for high dose-rate fractionation

To evaluate outcomes of cervical cancer patients treated with abbreviated high dose rate brachytherapy (HDR-BT) that used 2-implants and delivered 4-5 fractions over 7-12 days rather than 21-28 days. Patients with stage IB2-IVA cervical cancer, treated with external beam radiation (EBRT) ± chemotherapy followed by abbreviated MR/CT-based HDR-BT were included. The planning aim was to achieve > 70Gy equivalent doses in 2Gy (EQD2 From 2020 to 2022, 245 patients were treated with EBRT followed by MR/CT-based HDR-BT. Median OTT was 57 days. The median HRCTV volume was 35.5cc with higher HRCTV in MR than CT-based (42.3cc vs. 32.8cc). The median dose to Point-A, HRCTV-D90, B2cc, R2cc and S2cc for ICBT was 78.1, 86.2, 87, 70.2 and 70.4Gy respectively. For IC-ISBT cohort, the median dose to HRCTV-D90, B2cc, R2cc, and S2cc was 86.1, 88.6, 70 & 66.7Gy respectively. The 3-years local control, pelvic control, locoregional, disease free and overall survival was 90%, 88%, 83.7%, 75.5% and 85% respectively. Late ≥ grade III gastrointestinal and genitourinary toxicities were 7.3% and 1.6% respectively with marginally higher toxicity in CT based cohort. Accelerated HDR-BT schedule of 2-implants 4-5 fractions is radiobiological iso-effective and clinically safe with comparable oncological outcomes and adverse events.

Evaluation and improvement of the safety of 3D-printed template assisted intracavitary/interstitial brachytherapy for cervical cancer using repeat FMEA

3D-printed templates are used in intracavitary/interstitial brachytherapy (3DP-IC/IS) for locally advanced cervical cancer (LACC). We applied failure mode and effects analysis (FMEA) twice in one year to improve 3DP-IC/IS safety. A risk assessment group was established. We created a process map for 3DP-IC/IS procedures, identifying potential failure modes (FMs) and evaluating occurrence (O), detectability (D), severity (S), and risk priority number (RPN = O*D*S). High RPN values identified high-risk FMs, and quality control (QC) methods were determined by root cause analysis. A second FMEA was performed a year later. The 3DP-IC/IS process included 10 main steps, 48 subprocesses, and 54 FMs. Initial RPN values ranged from 4.50 to 171.00 (median 50.50; average 52.18). Ten high-risk FMs were identified: (1) unreasonable needle track design (171.00/85.50), (2) noncoplanar needle label identification failure (126.00/64.00), (3) template model reconstruction failure (121.50/62.50), (4) improper gauze filling (112.00/60.25), (5) poor needle position (112.00/52.50). QC interventions lowered all high-risk RPN values during the second assessment. A feasible 3DP-IC/IS process was proposed. Staff training, automatic needle path planning, insertion guidance diagrams, template checking, system commissioning, and template design improvements effectively enhanced process safety.

Complications of intracavitary brachytherapy for gynecologic cancers and their management: A comprehensive review

Intracavitary gynecologic brachytherapy in the form of tandem-based brachytherapy and vaginal cylinder-based brachytherapy represents a fundamental component of the treatment of women with cervical or uterine cancer due to the ability to deliver a therapeutic dose of radiation with sharp dose falloff. This results in highly effective treatment in terms of oncologic outcomes with an overall favorable toxicity profile. Still, complications and side effects of brachytherapy do exist. While advances in brachytherapy techniques have led to a significant decrease in the rates of toxicity, a thorough understanding of the potential complications is crucial to ensuring optimal outcomes for women with gynecologic cancer undergoing brachytherapy. Use of equivalent dose at 2 Gy per fraction (EQD2) models has allowed incorporation of external beam radiotherapy dose to the brachytherapy dose leading to development of consolidated dose constraints for organs-at-risk in the modern era. This manuscript offers a comprehensive review of potential complications associated with intracavitary brachytherapy for gynecologic cancer including predictive factors, mitigation tactics, and management strategies.

Learning curve and proficiency assessment for gynecological brachytherapy amongst radiation oncology trainees in India: Results from a prospective study

The quality of cervical cancer intracavitary brachytherapy (ICBT) depends on the training and experience of the radiation oncologist (RO). The present study was performed to establish primary learning curve for ICBT. Forty-three skill parameters were identified for performing ICBT and were included for Brachytherapy Proficiency Assessment and Scoring System (Brachy-PASS) questionnaire. Brachy-PASS score was first compared with blinded objective scoring of implant quality for 10 trainees by two ROs. Twenty eight consecutive trainees were scored with Brachy-PASS by two RO's. The impact of number of procedures and training years was ascertained using Mann Whitney-U test. Minimum number of intracavitary procedures to attain proficiency (score≥ 75%) were ascertained and learning curve plot of proficiency and procedures was generated. Between January, 2022 to September, 2023 38 trainees were evaluated (20: post graduate year (PGY) 1-3, and 18: PGY 4-5) after due consent for skill evaluation. Good congruence was reported of objective scoring and Brachy-PASS (83.4% vs 88%). Ten trainees had performed <15 ICBT, and 28 had performed ≥15 ICBT procedures. Overall 30/38 trainees (78.9%) achieved a Brachy-PASS score of ≥129 (75%). The average score for trainees with <15 procedures was 126.6 (73.6%) vs 148.8 (86.5%) in trainees who performed ≥15 procedures. PGY 4-5 trainees had higher score (153.8 (89.4%) vs 134 (77.9%)). Learning curve threshold of 15 ICBT was identified to attain 75% score (129/172) with no plateauing of learning curve even with ≥30 procedures. Competency is established for independently performing intracavitary brachytherapy at 15 procedures and further increase in competency scores continues with increasing procedures.

Comparison of vaginal stenosis following vault brachytherapy monotherapy between common fractionation schemes in the treatment of endometrial cancer

Vaginal stenosis is a well-documented toxicity of vaginal brachytherapy (VBT), which can lead to impaired quality of life and difficulty with surveillance pelvic exams. While multiple dosing and fractionation schemes have proven efficacy at preventing local recurrence, the comparative rates and severity of vaginal stenosis is not well-documented. This study aims to evaluate the rate of vaginal stenosis in patients with endometrial cancer treated with 2 common high-dose rate (HDR) adjuvant VBT without external beam radiation (EBRT) using vaginal cylinders. A retrospective review of patients treated at a single institution with adjuvant VBT following hysterectomy for uterine cancer was performed. The 2 regimens evaluated were 21 Gray (Gy) delivered in 3 fractions (fx) prescribed to a depth of 5 mm, delivered once weekly, and 30Gy/5fx prescribed to the vaginal surface, delivered every other day. Patient demographic and treatment information was collected from electronic medical records, including patient age at the time of treatment, BMI, cancer histology, chemotherapy status, common terminology criteria for adverse events (CTCAE) grade of vaginal stenosis, cylinder size, treatment length, sexual activity, and subsequent dilator use. Bivariate analysis was completed using Odds Ratios and χ2 tests with KNIME software version 5.4.0. Of the 150 patients treated with VBT between 2018 and 2024, 92 received cuff brachytherapy alone with a single-channel cylinder, utilizing either 30Gy/5fx or 21Gy/3fx. Of these patients, 88 were available for at least 3 months of follow-up with median follow-up of 23 months. Median patient age was 66 years. Seventy-two (82%) patients were white and 47 (53%) patients received chemotherapy. Thirty-three patients received 21Gy/3fx (38%) and 55 patients received 30Gy/5fx (62%). Vaginal stenosis was reported in 54% of patients who received 21Gy/3fx, compared to 22% of those who received 30Gy/5fx (OR 4.3 [95% CI: 1.7-11.0, p = 0.002]). Most patients in each group had common terminology criteria for adverse events (CTCAE) grade 1 stenosis (90% in 21Gy/3fx-group and 67% in 30Gy/5fx-group). The median cylinder size was 30 mm, and the mean treatment length was 5 cm, neither of which appeared to affect risk of developing vaginal stenosis (OR 1 [95% CI: 0.4-2.5, p = 1] and OR 1.4 [95% CI: 0.5-3.4, p = 0.6, respectively). Receipt of adjuvant systemic therapy had a numerical, but not statistically significant increase in risk of developing vaginal stenosis (OR 2.3 [95% CI: 0.9-5.7, p = 0.1]). The risk of developing vaginal stenosis in the absence of sexual activity following completion of therapy was not significant (OR 2 [95% CI: 0.6-7, p = 0.3]), and this was true also for vaginal dilator utilization (OR 1.2 [95% CI: 0.5-3, p = 0.8]). Diagnosis with a high-risk histology did not impact risk of stenosis (OR 1.5 [95% CI: 0.6-3.6, p = 0.5]). Finally, age and BMI did not appear to affect stenosis rates (OR 1.1[95% CI: 0.4-2.6, p = 1] and OR 1.4 [95% CI: 0.6-3.4, p = 0.5], respectively). Our findings suggest that treatment with 21Gy/3fx prescribed to 5 mm depth increased the risk of developing vaginal stenosis compared to 30Gy/5fx prescribed to surface. Patient age, BMI, cancer histology, receipt of systemic therapy, sexual activity, dilator use, treatment length, and dilator size did not appear to affect the odds of stenosis. Further prospective data would be beneficial.

The Kelowna template for combined intracavitary and interstitial brachytherapy for gynecologic malignancies: Design, application, treatment planning, dosimetric and treatment outcomes

We report the feasibility, experience, and early outcomes of the combined intracavitary and interstitial dedicated applicator using the Kelowna GYN template (Varian, Palo Alto, CA). The Kelowna GYN template is CT compatible and used for the treatment of gynecologic cancers. In cases with patients that have an intact uterus, a modified applicator system using the Kelowna GYN template and a 3D printed adapter piece allows for compatibility with an intrautaerine tandem. We reviewed the treatment course of 23 patients comprising of 86 fractions of HDR treatment. Median D90 for cervical tumors (n = 7) was 82.4 Gy (range 77.7-92.6); for postoperative cervical tumors (n = 2) was 73.9 Gy (range 72.0-5.8); for vaginal tumors (n = 4) was 85.8 Gy (range 79.8-88.1); for recurrent endometrial (n = 10) was 86.9 Gy (range 74.8-103.2). Median EQD2 D2cc for bladder was 72.4 Gy (range 47.7-99.4), for rectum was 61.2 Gy (range 52.4-80.6), and for sigmoid colon of 50.5 Gy (44.3-66.9). At a median follow-up of 12 months, 2 patients had a local recurrence. Two patients had distant recurrence: one with carcinomatosis at 6 months, and one with pulmonary metastases at 3 months. No patients had late grade three toxicities. Our single institutional experience supports the use of the Kelowna template as a robust system as a combined IC-IS applicator resulting in versatile and reproducible implants for a variety of gynecologic malignancies.

Dose distribution of brachytherapy for locally advanced (stage IIB) cervical cancer

The aim of the study was to compare the dose distributions of combined intracavitary and interstitial (IC/IS) brachytherapy with 3-catheter IC brachytherapy in treating locally advanced (stage IIB) cervical cancer. In total, 46 patients were included, each with stage IIB cervical cancer, local lesion sizes ≥5 cm, and tumors that had not regressed after 45 Gy/25 F external intensity-modulated radiotherapy. To identify the dosimetric advantage of delivering a local boost to high-risk (HR)-cervix in IC/IS, patients were divided into two groups: IC/IS and IC/IS + HR-cervix. The differences in dosimetric parameters were compared between the two groups. Comparisons were then made between the parameters of the four planning methods: IC (Point A), IC (three dimensional [3D]), IC/IS, and IC/IS + HR-cervix. In patients with IC/IS implants, the relative uterine tandem dwell time was significantly extended in the IC/IS + HR-cervix group, and the V150 and V200 volumes of HR-cervix were increased (all p < 0.001), whereas the D90 and D100 values of the IC/IS + HR-cervix group were lower than those in the IC/IS group. In pairwise comparisons, HR-cervix V150 and V200 values were lowest in the IC/IS group, followed by the IC (3D), IC/IS + HR-cervix, and IC (Point A) groups. All differences were statistically significant (p < 0.05), with the exception of IC/IS vs. IC (3D). When treating locally advanced cervical cancer (stage IIB, local residual volume ≥5 cm after external radiotherapy), the IC/IS + HR-cervix optimization method can meet the HR clinical target volume D90 dose requirement, normal tissue dose limits, and can escalate doses to local areas of the cervix.

Adjuvant electronic brachytherapy for endometrial carcinoma: A 4-year outcomes report

The purpose of the study was to report the outcomes of a single-center adjuvant electronic brachytherapy (e-BT) experience for patients with endometrial carcinoma. Patients were retrospectively assessed. Intracavitary e-BT was applied through a cylindrical applicator (diameters 2.5-3.5 cm). e-BT single doses ranged between 4 and 7 Gy (EQD2 ∼ 6-12, α/β of 10 Gy and an relative biological effectiveness of 1.3) at 5-mm depth. Adverse events are reported at first week, 1-3 months, 3-12 months, 12-24 months, and >24 months. The overall survival, disease-free survival, distant disease control rate, and local control rate were estimated using the Kaplan-Meier method. Twenty-nine patients were assessed. The median age was 68 [48-86] years. External beam radiotherapy was added in n = 8 (27.6%) patients. Staging was 13.8% for T1a, 51.7% for T1b, 24.1% for T2, 6.9% for T3a, and 3.4% for T3b. Grading was G3 in 51.7% (n = 15), G2 in 20.7% (n = 6), and G1 in 27.6% (n = 8). Median followup was 47 months [5-88]. Overall Grade 1, 2, and 3 toxicity was 89.7% (n = 26), 17.2% (n = 5), and 6.9% (n = 2), respectively. No Grade 3 cystitis or proctitis or any Grade 4 or 5 toxicity occurred during followup. No local recurrences were detected. Estimated distant disease control rate was 92.1% (n = 2, distant metastasis at 7 and 11 months). Estimated 4-year overall survival was 84.8% (n = 4 events, two unrelated to disease) and disease-free survival was 84.6%. Our data suggest that e-BT resembles a very-low-toxicity profile and a high local control rate in the adjuvant scenario for patients with endometrial carcinoma.

Brachytherapy-based radiotherapy is associated with improved survival for newly diagnosed metastatic cervical cancer

The purpose of this study was to explore the value of brachytherapy (BT) in metastatic cervical cancer, as it has not been well evaluated before. We analyzed 2391 patients with Stage IVB cervical cancer from 2004 to 2015 by using data from the Surveillance, Epidemiology, and End Results registry. The parameters were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate cancer-specific survival (CSS) and overall survival. In general, both univariate and multivariate analysis showed that age, histologic type, tumor size, and chemotherapy were associated with CSS and overall survival (p < 0.05). Further subgroup analysis showed BT alone or BT combined with external beam radiotherapy improved CSS despite the tumor size. In addition, chemotherapy and chemoradiotherapy prolonged CSS compared with external beam radiotherapy alone or no chemotherapy or radiotherapy independently of tumor size (p < 0.05). For newly diagnosed metastatic cervical cancers, BT with or without external beam radiotherapy is associated with improved survival. As an aggressive option, chemoradiotherapy is also a potential treatment strategy.

Clinical values of transrectal ultrasound in judging GTV of cervical cancer

To investigate the clinical value of transrectal ultrasound in judging the Gross Target Volume (GTV) of cervical cancer (CC). A total of 196 CC patients admitted to the Department of Radiotherapy, China-Japan Union Hospital, Jilin University, from January 2016 to June 2019 were selected as the study subjects. The GTVs before and after applicator insertion were determined by transrectal ultrasound and compared with those judged by MRI. All 196 patients were successfully undergoing applicator insertion according to the pretreatment plan. The GTV doses reached the clinical requirements during treatment. There was no significant difference between the GTVs judged by MRI and ultrasound before insertion in terms of upper/lower diameter (MRI Before 1 vs. Ultrasound Before 1) (MB1 vs. UB1), left/right diameter (MB2 vs. UB2), or ventral/dorsal diameter (MB3 vs. UB3), and the intragroup correlation coefficients (ICC) were 0.59, 0.77, and 0.66, respectively; moreover, there was no significant difference between the GTVs judged by MRI and ultrasound after insertion in terms of MRI After one vs. Ultrasound After one (MA1 vs. UA1), MA2 vs. UA2, and MA3 vs. UA3, and the ICC values were 0.62, 0.79, and 0.76, respectively. Transrectal ultrasound can satisfactorily determine the GTV of CC and has certain value in brachytherapy for CC.

Vaginal dose-surface maps in cervical cancer brachytherapy: Methodology and preliminary results on correlation with morbidity

The purpose of the study was to develop a methodology for vaginal dose-surface maps (DSMs) in patients with cervix cancer and to investigate dose-surface histogram metrics as predictors for vaginal stenosis (St) and mucositis (Muc). Thirty-one patients with locally advanced cervix cancer with no vaginal St/Muc (CTCAE-v3) G ≥ 2 at baseline were analyzed. Patients were divided in four morbidity groups: 15 with St/Muc G0/1, 6 with St G ≥ 2, 4 with St/Muc G ≥ 2, and 6 with Muc G ≥ 2. Patients received external beam radiotherapy and 4-fraction intracavitary/interstitial high-dose-rate brachytherapy using tandem and ovoids. DSMs were generated from inner/outer vaginal surfaces. DSMs of external beam radiotherapy and brachytherapy (Gy EQD2 Best predictors of stenosis were D A novel method was developed to generate vaginal DSMs and spatial-dose metrics. DSMs were found to correlate with vaginal stenosis. The findings of this study are promising and should be further validated on a larger patient cohort, treated with different applicators.

Dose fusion and efficacy evaluation of different radical radiotherapy doses for cervical cancer

The recommended external beam radiotherapy (EBRT) dose for cervical cancer is 40-50 Gy, but there is no consensus. In this study, 45-Gy and 50.4-Gy treatment groups were compared for fused doses to target tumor areas and organs at risk (OARs), clinical efficacy, and quality of life. Seventy-nine cases receiving radical radiotherapy within the past 3 years were retrospectively analyzed. EBRT and three-dimensional brachytherapy dose fusion values were calculated for target areas and OARs using Elastix V5.0. Clinical efficacy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST), adverse events using Common Terminology Criteria for Adverse Events v4.03 (CTCAE4.03), and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Minimum fused dose delivered to 90% of the high-risk clinical target volume (HRCTV D90) did not differ significantly between 45-Gy and 50.4-Gy groups, whereas D2cc values of rectum and bladder (OARs) were significantly lower in the 45-Gy group (both p 0.05). However, quality of life was markedly higher in the 45-Gy group (p < 0.05). Appropriate EBRT dose reduction can reduce OAR irradiation without compromising total target area dose or clinical efficacy. Dose fusion can facilitate the judicious choice of EBRT to limit OAR exposure, reduce adverse events, and enhance the quality of life.

Rule-based AI automated adaptive treatment planning for image guided cervical cancer brachytherapy

A rule-based AI system for automated adaptive treatment planning for image guided adaptive brachytherapy (IGABT) of locally advanced cervical cancer (LACC) was developed at Erasmus MC, and internally and externally validated by Erasmus MC and Tata Memorial Centre (TMC), respectively. The BiCycle system generates automated plans with adapted requirements for each fraction, considering previously delivered external beam radiotherapy (EBRT) and BT doses, according EMBRACE-II protocol. It optimizes dosimetric parameters and loading patterns for available radioactive source positions. The system's effectiveness was validated by comparing automatically generated plans (AUTO) with manually generated, clinically delivered plans (MANUAL) of (1) dosimetry parameters and loading pattern visual inspection of 15 previously treated patients, for internal validation and (2) dosimetry and qualitative comparison by two TMC physicians of 20 previously treated patients, for external validation. With comparable target doses, AUTO plans had reduced D A novel AI-system for fully automated IGABT treatment planning for LACC allowed high-quality plan optimization in on average 1.6 min. AUTO plans were considered superior in quality compared to MANUAL plans in both internal and external validations, even without optimizing the system's configuration for the external center.

AI-assisted 3D-printed transvaginal template guidance for interstitial brachytherapy in patients with cervical cancer with parametrial invasion

Three-dimensional (3D) interstitial brachytherapy (BT) can improve bulky cervical cancer treatment efficacy. BT technology guided by 3D-printed templates can assist radiation oncologists in accurately inserting needles and ensuring optimal dose coverage. Artificial intelligence (AI) holds promise for enhancing the accuracy, precision, efficiency, and overall quality of radiotherapy (RT) for cancer patients. This retrospective study aimed to evaluate the safety and efficacy of using AI-assisted transvaginal 3D-printed (AI/3D-printed) templates for guiding interstitial BT as a part of definitive RT for patients with cervical cancer with parametrial invasion. Localization data from computed tomography scans of 17 patients were gathered and imported into the software. Using AI-assisted technology, individualized 3D-printed templates were automatically configured based on the specific anatomical morphology and volume of the target. To ensure the precision and consistency of the AI/3D-printed template, the patient's clitoris and anus were used as localization markers. Needle positions in the template were adjusted to maintain a designated distance from the insertion needles to the tip of the tailbone. The difference in the distance between the actual interstitial needle and the designed needle to the tailbone was aimed to be less than 2 mm. The target dose dosimetric parameters were evaluated and compared between AI/3D-printed applicator guidance and free-hand (FH) insertion methods, with one fraction of AI/3D-printed BT paired with one fraction of FH BT per patient for direct comparison. No instances of severe bleeding or infection associated with puncture were observed. Compared with FH BT, the AI/3D-printed approach required no intraoperative needle adjustment. The mean (with standard deviation) values of the dose-volume histogram (DVH) parameters of AI/3D-printed BT showed significantly higher high-risk clinical target volume (HR-CTV) V100 (90.19 ± 0.72% vs. 88.89 ± 0.11%, p = 0.011) and HR-CTV D98 (5.67 ± 0.14 Gy vs. 5.55 ± 0.13 Gy, p = 0.044), but no significant difference in D90 (6.80 ± 0.10 Gy vs. 6.79 ± 0.10 Gy, p = 0.163). For organs at risk (OARs), the AI/3D-printed approach resulted in lower doses to the bladder (4.92 ± 0.06 Gy vs. 5.10 ± 0.06 Gy, p = 0.004) and rectum (3.95 ± 0.10 Gy vs. 4.24 ± 0.05 Gy, p = 0.01), but no significant difference for the sigmoid (2.99 ± 0.13 Gy vs. 3.23 ± 0.14 Gy, p = 0.125). The AI/3D-printed approach exhibited significantly superior conformal index(CI), dose homogeneity index (HI), and overdose volume index (OI) compared with the FH approach. AI/3D-printed applicator-guided BT for cervical cancer with parametrial invasion demonstrated successful implementation, significant dosimetric benefits to organs at risk (OARs) and better plan quality indicators (CI, HI, and OI), and minimal treatment-related complications. This method represents a promising advancement in BT for cervical cancer treatment.

Role of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump

This study aimed to determine the effectiveness of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump, and to identify the candidates most likely to benefit. Newly diagnosed, non-metastatic cervical cancer patients treated in our hospital between January 2012 and November 2015 were retrospectively reviewed. Early stage patients receiving radical surgery and needing adjuvant external radiotherapy were included, but those with positive stump were excluded. All patients received external radiotherapy. They were divided into two groups: one group received vaginal brachytherapy and the other did not. The 5-year local-regional recurrence free survival (LRRFS) and overall survival (OS) rates in the two groups were compared. Two hundred and twenty-five patients were included in this study; while 99 received brachytherapy, 126 did not. The brachytherapy group had significantly superior 5-year LRRFS (87.7% vs. 72.5%, p = 0.004), but did not show a significant overall survival benefit (78.4% vs. 75.3%, p = 0.055). In multivariate analysis, brachytherapy, pathological type, high-risk factors, duration of radiotherapy, and transfusion were independent prognostic factors for 5-year LRRFS. In stratified analysis, the brachytherapy group showed superior LRRFS in those meeting Sedlis criteria (p = 0.017). The combination of external beam radiation therapy and brachytherapy can improve LRRFS in post-operative cervical cancer patients with risk factors other than positive stump. Therefore, brachytherapy should be considered for these patients.

Time-action and patient experience analyses of locally advanced cervical cancer brachytherapy

Although MRI-based image guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC) has resulted in favorable outcomes, it can be logistically complex and time consuming compared to 2D image-based brachytherapy, and both physically and emotionally intensive for patients. This prospective study aims to perform time-action and patient experience analyses during IGABT to guide further improvements. LACC patients treated with IGABT were included for the time-action (56 patients) and patient experience (29 patients) analyses. Times per treatment step were reported on a standardized form. For the patient experience analysis, a baseline health status was established with the EQ-5D-5L questionnaire and the perceived pain, anxiety and duration for each treatment step were assessed with the NRS-11. The median total procedure time from arrival until discharge was 530 (IQR: 480-565) minutes. Treatment planning (delineation, reconstruction, optimization) required the most time and took 175 (IQR: 145-195) minutes. Highest perceived pain was reported during applicator removal and treatment planning, anxiety during applicator removal, and duration during image acquisition and treatment planning. Perceived pain, anxiety and duration were correlated. Higher pre-treatment pain and anxiety scores were associated with higher perceived pain, anxiety and duration. This study highlights the complexity, duration and impact on patient experience of the current IGABT workflow. Patient reported pre-treatment pain and anxiety can help identify patients that may benefit from additional support. Research and implementation of measures aiming at shortening the overall procedure duration, which may include logistical, staffing and technological aspects, should be prioritized.

Brachytherapy outcome modeling in cervical cancer patients: A predictive machine learning study on patient-specific clinical, physical and dosimetric parameters

To predict clinical response in locally advanced cervical cancer (LACC) patients by a combination of measures, including clinical and brachytherapy parameters and several machine learning (ML) approaches. Brachytherapy features such as insertion approaches, source metrics, dosimetric, and clinical measures were used for modeling. Four different ML approaches, including LASSO, Ridge, support vector machine (SVM), and Random Forest (RF), were applied to extracted measures for model development alone or in combination. Model performance was evaluated using the area under the curve (AUC) of receiver operating characteristics curve, sensitivity, specificity, and accuracy. Our results were compared with a reference model developed by simple logistic regression applied to three distinct clinical features identified by previous papers. One hundred eleven LACC patients were included. Nine data sets were obtained based on the features, and 36 predictive models were built. In terms of AUC, the model developed using RF applied to dosimetric, physical, and total BT sessions features were found as the most predictive [AUC; 0.82 (0.95 confidence interval (CI); 0.79 -0.93), sensitivity; 0.79, specificity; 0.76, and accuracy; 0.77]. The AUC (0.95 CI), sensitivity, specificity, and accuracy for the reference model were found as 0.56 (0.52 ...0.68), 0.51, 0.51, and 0.48, respectively. Most RF models had significantly better performance than the reference model (Bonferroni corrected p-value < 0.0014). Brachytherapy response can be predicted using dosimetric and physical parameters extracted from treatment parameters. Machine learning algorithms, including Random Forest, could play a critical role in such predictive modeling.

Evaluation of variability in applicator position and organs at risk dose in fractionated intracavitary brachytherapy for cervical cancer

Cervical cancer remains a major cause of mortality in low- and middle-income countries (LMICs). Intracavitary brachytherapy (ICBT) is critical for curative radiotherapy; however, inter-fractional variability in applicator positioning may compromise treatment reproducibility and organ-at-risk (OAR) sparing. This study assessed inter-fractional applicator positional stability and its dosimetric impact on OARs during fractionated ICBT for cervical cancer. A prospective analysis of 60 treatment plans from 20 patients receiving three ICBT fractions was conducted. Applicator shifts along the X, Y, and Z axes and corresponding bladder and rectal doses were evaluated. Descriptive statistics and repeated measures ANOVA determined positional reproducibility and dose variability, while correlation analysis examined associations between applicator displacement and OAR dose changes. Applicator positioning was reproducible across fractions, with no significant differences in any axis p > 0.05). Bladder dose, however, demonstrated significant variation (p = 0.027), progressively increasing across fractions. Moderate correlations (r ≈ 0.39) were observed between bladder dose escalation and applicator shifts along the X and Y axes, especially in the Y-axis. Rectal dose remained stable (p = 0.776). Although applicator positioning was geometrically stable, significant bladder dose variability occurred. Adaptive replanning and real-time imaging are recommended to optimize treatment precision in fractionated ICBT.

Randomized trial comparing hypnosis versus standard management on patient anxiety and pain during pelvic brachytherapy applicator removal

Removal of brachytherapy applicator is routinely performed under premedication including Kalinox® gas inhalation without general anesthesia. The applicator removal is nevertheless associated with discomfort, anxiety or pain. We assessed the adjunction of formal hypnosis during this procedure. This prospective, randomized, single-center study focused on adult patients undergoing pelvic brachytherapy applicator removal. Patients were randomly assigned to (1:1): standard management including Kalinox® (control group) vs. standard management including Kalinox® accompanied by formal hypnosis (hypnosis group). The primary endpoint was anxiety using the State-Trait Anxiety Inventory (STAI) Y-A form (state anxiety). A secondary endpoint was pain after applicator removal (numerical scale). A total of 68 patients (mean age, 51.9 years) were included (cervical cancer, 86.6%). Before applicator removal, mean (SD) STAI Y-A anxiety score was 45.9 (5.6) in the control group vs. 47.5 (5.9) in the hypnosis group. After applicator removal, the scores were 48.1 (4.3) versus 47.7 (4.2), respectively (p = 0.76). Pain score was not significantly different after applicator removal (p = 0.055) in the hypnosis group compared to the control group: 1.29 (1.72) versus 0.71 (1.51), respectively. There were no significant differences between the 2 groups concerning caregiver satisfaction with patient management (p = 0.27), ease of realization (p = 0.17) and caregiver comfort (p = 0.42). This study failed to demonstrate a substantial benefit of formal hypnosis on anxiety in patients undergoing pelvic brachytherapy applicator removal. But this study suggests that the use of hypnotic communication techniques enables a positive attitude to patient care, thus reinforcing the patient-caregiver relationship.

The influence of time and implants in high-dose rate image-guided adaptive brachytherapy for locally advanced cervical cancer

To compare the clinical outcomes of two different schedules of modern image-guided adaptive brachytherapy (IGABT) in patients underwent chemoradiotherapy (CCRT) and high-dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer treated (LACC) METHODS AND MATERIALS: Data from medical records of all consecutive patients with histologically proven cervical cancer (FIGO 2018 stage IB-IVA) treated by HDR-BT after CCRT at our institution between 2016 and 2021 were reviewed. Two hundred and 8 patients with LACC FIGO 2018 stages (IB 20.7%; II 26.5%, III 51%, IVA 1.9%) underwent brachytherapy at our institution. Depending on initial clinical features of disease and the clinical response to CCRT, HDR-BT was delivered with one implant (BT1i) or two implants (BT2i) in 39% and 61% of patients respectively. FIGO stages (≥IIB) were 63% vs. 78% for BT1i and BT2i patient group respectively. Combined brachytherapy technique [endocavitary/interstitial (IC/IS)] was required in 14.8% vs. 68.5% for BT1i and BT2i respectively. With a median follow-up of 32.5 months (95% confidence interval, [29.7-35.8]), local relapse was observed in sixteen patients: 8 patients (3.8%) had local (exclusive) relapse and 8 patients (3.8%) had locally persistent and progressive disease, without significant difference for each BT modality group (p = 0.27), even if BT2i group had more aggressive initial disease. The estimated 3-year disease free survival and overall survival for the entire population was 69% (95% confidence interval, [62-75%]) and 88% (95% confidence interval, [82-92%]) respectively. There was a significant difference in the incidence of global toxicity grade G≥2 in favour to the BT2i group (p = 0.026). HDR brachytherapy delivered with a long time interval between fractions, two implants, and combined IC/IS brachytherapy is the best way to ensure local control and to perform IGABT with low toxicity, even in advanced stages of disease.

MRI-guided brachytherapy for vaginal recurrence of endometrial cancer

Vaginal recurrence of endometrial cancer can be salvaged by external beam radiotherapy and vaginal brachytherapy, but data on MRI-guided brachytherapy is limited. This study evaluated disease and toxicity outcomes of patients treated with MRI-guided brachytherapy for vaginal recurrence of endometrial cancer. Patients who received salvage MRI-guided interstitial/intracavitary brachytherapy for vaginal recurrence of endometrial cancer between 2015 and 2023 were retrospectively reviewed. Local failure (LF) was estimated using the cumulative incidence function. Disease-free (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria for Adverse Events (version 5). Of the 56 patients, 17 (30%) and 39 (70%) were treated with intracavitary (multichannel vaginal applicator) and interstitial (Syed-Neblett template) brachytherapy, respectively. Fifty-three (94%) had endometroid adenocarcinoma histology. The median high-risk clinical target volume D Patients with vaginal recurrence of endometrial cancer treated with MRI-guided interstitial/intracavitary brachytherapy had favorable local control, DFS, OS and toxicity rates.

Exploring access to brachytherapy for cervical cancer in Texas: Geographic availability and distribution

Cervical cancer remains a leading diagnosis among women in the state of Texas and manifests in a backdrop of health access and care inequities. In our study we aim to examine and highlight the geographic gaps in availability of brachytherapy across the state. Using data obtained from the Texas State Department of Health Services and industry records we identified a list of brachytherapy centers with active Ir-192 licenses. Using data obtained from the Texas Cancer Registry, we examined epidemiological rates of cervical cancer between 2010 and 2020, calculated the relative availability of centers across the state, and mapped our findings. There are currently 48 active HDR brachytherapy centers/providers for cervical cancer across 28 counties in Texas. The majority of counties across the state had no brachytherapy centers or providers. The highest number of brachytherapy centers were housed in Harris (n = 7) and Tarrant (n = 5) counties which are home to the Houston and Fort Worth metropolitan areas. Mismatches between high incidence and mortality rates and low brachytherapy availability were noted in public health regions and counties near the Texas-Mexico border regions and northern/northeastern regions of Texas. A mapping tool (tinyurl.com/BrachytherapyTX) was developed to visualize active brachytherapy centers offering definitive cervical cancer treatment. Our findings suggest that geographic discrepancies in brachytherapy availability for cervical cancer exist across the state of Texas. We hope to not only raise awareness for the inequity but also work towards implementing resources and sustainable solutions to help bridge the statewide gaps.

Automatic digitization of applicator and catheters for MRI-guided cervical cancer brachytherapy

MRI is the standard imaging modality for contouring organs-at-risk and clinical target volume in cervical cancer brachytherapy, and is widely used along with CT for treatment planning and image guidance. However, MRI-CT fusion-based approach is time-consuming and error-prone as it requires two imaging sessions and image registration. To realize more efficient and streamlined MRI-guided workflow, we propose an automatic method for digitizing the applicator and catheters using MRI alone. Applicator digitization consists of applicator mesh reconstruction, applicator ring identification, and alignment of the mesh model with MRIs. For catheter digitization, we employ an uncertainty-aware deep-learning model that simultaneously segments catheters and computes uncertainty on its prediction. These uncertainty facilitate initial localization of the catheters and subsequent refinement. This study was performed on 35 T2-weighted MRIs from 30 cervical cancer patients treated with the Venezia applicator. The dataset was divided into 80% for development and 20% for testing. The method successfully digitized all applicators, with mean translation and rotation errors of 1.13 ± 0.26 mm and 2.19 ± 2.09°, respectively. All catheters except one were successfully digitized with shaft and tip errors of 0.74 ± 0.32 mm and 2.52 ± 2.04 mm, respectively. Furthermore, plans derived from the automatic digitization showed no significant differences compared to clinical plans (p > 0.05). The proposed MRI-based applicator and catheters digitization simplifies the brachytherapy planning process by eliminating the need for CT and manual tasks. Our results demonstrate that this approach is feasible and can be integrated into clinical workflows, offering potential improvements in efficiency and accuracy.

Integration of single-click, AI-based brachytherapy auto-planning for cervical cancer within a treatment planning system

Previous work developed an automated cervical brachytherapy treatment planning pipeline consisting of a U-Net dose prediction model and dwell time optimizer. While this method can produce clinically acceptable plans, it relies on time-consuming, manual export and import of DICOM data. This study proposes to increase efficiency by combining scripts into an all-in-one tool that can be used directly within the BrachyVision treatment planning system, producing automated plans in a single click. We developed an AI-based planning tool through four main tasks; data retrieval, model inference, dwell time optimization, and auto-plan import. First, a C# plug-in interacts with the currently open patient in BrachyVision. Next, for data retrieval, model inference, and dwell time optimization, a Python executable operates on the data before the optimized dwell times are copied back into the open plan in BrachyVision. The script was tested on 28 brachytherapy plans spanning 7 applicator types, and auto-plans were compared to clinical plans using mean absolute error (MAE) in voxel-based 3D dose and dwell times. The average (± standard deviation) MAE in 3D dose and dwell times were 3.8 ± 0.7% (normalized to the prescribed dose) and 10.3 ± 7.4 s (2.1 ± 0.9% of the total plan dwell time), respectively. The average runtime of the script was 3.5 ± 1.2 minutes. We developed a script that enables efficient, streamlined auto-planning directly within BrachyVision. After contouring and digitization are performed, the script can be run to produce high-quality, customized plans with a single button-click in a few minutes.

Role of brachytherapy in stage III endometrial cancer treated with adjuvant chemotherapy: Identifying factors predictive of a survival benefit

To determine which patients with stage III endometrial cancer receiving adjuvant chemotherapy derive benefit from the addition of vaginal brachytherapy, as stage III is a highly heterogeneous population with substantial variations in practice. Patients with FIGO stage III endometrial carcinoma diagnosed 2004-2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of brachytherapy, stratified by histologic type, pathological features, and status of pelvic external beam radiotherapy (EBRT), and analyzed using the Kaplan-Meier method and Cox multivariable regression. In total, 9369 patients were identified (24% stage IIIA, 5% stage IIIB, 71% stage IIIC; 61% endometrioid, 39% nonendometrioid histology), and 28% received brachytherapy. In the endometrioid cohort, brachytherapy was associated with a 5% absolute increase in 3-year overall survival (87% vs. 82%, p < 0.0001), which persisted in multivariable analysis (adjusted hazard ratio 0.74, 95% confidence interval 0.64-0.84, p < 0.0001). The benefit of brachytherapy was greater in patients not also receiving EBRT, and in patients with vaginal/parametrial extension, grade 3 disease, lymphovascular invasion, and/or deep myometrial invasion. In the nonendometrioid cohort, brachytherapy was associated with a significant survival benefit in univariable but not multivariable analysis, regardless of EBRT status or pathological features. Factors predictive of brachytherapy benefit were endometrioid histology and pathological risk factors for local recurrence. Additionally, brachytherapy appeared more beneficial in patients not already receiving pelvic EBRT. Further research is warranted to determine which stage III patients may be best served by brachytherapy, EBRT, or both.

Image guided brachytherapy quality assurance on NRG GY017 investigating immunotherapy in addition to chemoradiation for locally advanced cervical cancer

Brachytherapy is a critical component of curative treatment in locally advanced cervical cancer. NRG GY-017 is a randomized Phase I trial of the anti-PD-L1 antibody atezolizumab administered neoadjuvantly and concurrently with chemoradiation (Arm A) or only concurrently with chemoradiation (Arm B) in patients with node positive locally advanced cervical cancer. Image guided brachytherapy (IGBT) was mandated in the protocol with a quality assurance (QA) workflow. Herein, we report the BT quality data on NRG GY-017 trial and practice patterns from the participating centers in this trial as a guide for future protocol brachytherapy QA. The participating sites were to submit brachytherapy plans online after BT was completed. IROC QA center compiled the BT fractions for each patient using the trial specific dosimetry evaluation template. An expert physician reviewer scored the contours and plans as per protocol, variation acceptable or major deviation as prespecified in the protocol dose metrics. The BT dosimetry results were available for 32 patients. Seventeen patients (53%) had intracavitary applicator, and 15 patients (47%) had hybrid or interstitial applicators. Point A directed planning was performed for 4 patients (12.5%) and 28 patients had volume directed plans (87.5%). For imaging use, 2 patients had MRI based plans, and 30 had CT based planning (94%). For the dose constraints compliance per protocol, 7 patients had 9 events scored as major deviations (22%). BT trial specific QA has the potential to enhance BT quality for clinical trials. This report will help guide future gynecologic BT trial data collection and QA process.

Iterative intraoperative 3T MRI (iMRI)-guided brachytherapy: A prospective study on enhancing implantation precision and dosimetric gains in advanced gynecologic cancers

To report on primary outcomes and dosimetric results of a prospective clinical trial and protocol for use of iterative intraoperative magnetic resonance imaging (iMRI) in gynecologic brachytherapy. Patients with locally advanced cervical or vaginal cancer (FIGO stages IB2 - IVA, and stage II-IVA, respectively) undergoing pulsed dose rate (PDR) brachytherapy were enrolled in a prospective clinical trial (NCT03634267) using iterative 3T iMRI during brachytherapy implant placement. Applicator and optional interstitial needles were placed under iMRI guidance in a 3T clinical MRI scanner. Imaging, dosimetry and clinical outcomes (local control (LC), recurrence-free survival (RFS), overall survival (OS)), and acute and long-term toxicity were evaluated prospectively and confirmed by chart review. To explore dosimetric gains, an EQD2 estimate comparing iMRI-guidance versus standard of care guidance, as well as a 3-patient analysis of dose changes with iMRI-guided optimization was included. Fourteen patients underwent iMRI-guided brachytherapy. Seventy percent (70%) of patients presented with FIGO stage III disease or higher. Median follow-up was 44 months. . Patients had 2-year median LC, RFS, and OS rates of 83.3%, 76%, and 84.6%, respectively. Acute toxicities were minimal with one (1) case of grade 3 nausea. No grade 3 or higher long-term toxicities were observed. Median operating room (OR) time was 283 minutes (range 174-380 mins). On exploratory analysis, implant placement performed with iMRI guidance demonstrated higher HR-CTV D90 doses (mean difference of +784.7 cGy, p = NS) were achieved compared to US and CT guided implantation in the same patients. iMRI-guidance for gynecologic brachytherapy is safe, associated with minimal high-grade toxicity and excellent clinical outcomes. Future studies to optimize resource use, image acquisition efficiency, and identifying predictive imaging features are warranted.

Interstitial cervical needle-guide ring-cap prototype for patient-specific ring-and-tandem brachytherapy

We have developed a unique cap that could be paired with our existing commercially-available MRI-compatible ring-and-tandem applicator (R&T) that can provide a patient-specific cervical needle guide for hybrid intracavitary-interstitial brachytherapy (IC/ISBT). Prototype guide caps with six channels for interstitial needles were rendered in SolidWorks (Dassault Systèmes SE, Vélizy-Villacoublay, France), coupled with Mick Radio-Nuclear Instruments (Mt Vernon, NY, USA) R&T. Prototypes were printed using Formlabs 3B printers and Gray Resin (Formlabs, Somerville, MA, USA). Achievable bend radii for interstitial needles were determined using custom jigs. A pilot cohort of previously-treated IC/ISBT patients was replanned with virtual needle paths reconstructed in EclipseBV (Varian Medical Systems, Palo Alto, CA, USA). Physical design constraints (bend radius, position) were used to determine the impact on EQD Software-rendered guide caps prototypes were 3D-printed and tested to all be physically compatible with our existing commercially-available R&T. The channels physically accommodated six interstitial needles with bending precision ±1°. Among the cohort, the HR-CTV D We have designed and produced a guide cap prototype that can be used to improve our existing commercially-available R&T with IC/ISBT capabilities for customizable angles and positions. The guide caps have been shown to enhance dosimetry and can be used for patient-specific treatment.

Understanding anxiety in patients receiving vaginal brachytherapy for low-grade early-stage endometrial cancer

Vaginal brachytherapy (VBT) is a standard treatment after hysterectomy for early-stage endometrial cancer. Despite only requiring a few treatments with minimal toxicity, many women have significant anxiety regarding VBT. This study was to assess and quantify anxiety in early-stage endometrial cancer patients receiving VBT and to evaluate correlations with clinicopathologic and demographic variables. A survey-based cohort study of patients ages 18-99 with stage I-II endometrioid endometrial cancer treated with adjuvant VBT after hysterectomy between 2014 and 2020 was performed to assess experience with VBT and related anxiety. Patients with recurrent disease were excluded. Assessments included: (1) qualitative questionnaire measuring anxiety and mood pre- and post-VBT, (2) clinical factors questionnaire measuring health status, (3) Hospital and Anxiety Depression Scale (HADS), and (4) demographics questionnaire. Pearson's chi-squared test was used to correlate demographics with anxiety. About 185 patients met inclusion criteria and of those, 75 completed all 4 surveys. Forty-nine patients (65%) reported anxiety or fear prior to receiving VBT, related to concerns of pain (40%), quality of life (27%), bladder/bowel function (24%). On univariate analysis, patients with a college degree or higher, income of ≥ $80,000, and HADS-Anxiety ≥ 8 were significantly more likely to experience anxiety with X A majority of patients experience anxiety prior to treatment with adjuvant VBT. It is important to increase the general knowledge surrounding VBT and to establish educational tools to reduce VBT related anxiety and fear.

A dosimetric evaluation of ureteric doses with and without ureter as avoidance organ in patients treated with MR hybrid brachytherapy for cervical cancer

Ureteric stenosis is a known complication with radiotherapy with studies showing correlation of ureteric dose with stenosis. This study was done to assess the dose delivered to the ureters with and without ureter as avoidance organ in cervical cancer patients treated with hybrid brachytherapy. Cervical cancer patients treated with EBRT and MR hybrid brachytherapy were retrospectively analyzed. They were treated without ureter contoured as organ at risk. The right and left ureters were retrospectively contoured on T2 weighted MRI images. Dose to 0.1cc volume of ureter was documented. 26 patients treated with hybrid brachytherapy were analyzed. The median HRCTV volume was 23.9cc. The median HRCTV D90 & GTV D98 EQD2 were 91.09Gy (IQR 92.36-87.28) and 104.67Gy (IQR 113.90-95.04) respectively. The median D2cc for bladder, rectum and sigmoid were 75.46Gy, 58.10Gy and 61.3Gy EQD2 respectively. The mean minimum distance of the left ureter from HRCTV was 3.2mm (IQR 6.75-1) & right ureter was 2.3mm (IQR 8-0). The mean D The ureter is at risk of receiving high doses when we use hybrid applicator. MR planning to delineate the ureter and careful optimization of needles can result in significant reduction of ureter dose with similar target coverage.

Evaluation of dose distribution to the tumor and organs at risk for cervical cancer patients treated using HDR-ICBT without central tandem applicator: A single center based experience

Cervical cancer is the most prevalent type of cancer among women in numerous low and middle-income countries. Tandem-based applicator is a widely used technique in High Dose Rate Intercavitary Brachytherapy (HDR-ICBT) for treating cervical cancer. For cases where central tandem insertion is not feasible due to patient-specific conditions, a ring-only applicator is used as an alternative. This paper presents an assessment of the impacts of dose distribution on cervical cancer treatment using HDR-ICBT without a central tandem applicator. Total 30 patients with cervical cancer (stage IB to IVA) who received brachytherapy with a ring applicator alone were singled out and used in the study. Orthogonal radiographs were used during dose treatment planning. Results indicate that the dose normalized to the Equivalent dose in 2 Gy fractions (EQD2) at Manchester Dosimetry System (MDS) point A was 60.60 ± 1.08 Gy, which is significantly below the recommended curative dose of 80 Gy. This suggests that relying solely on a ring applicator may not provide enough radiation doses to the tumor. The results also show that the International Commission on Radiation Units (ICRU) dose point underestimated the radiation doses to the bladder and rectum, with the ratios of maximum dose (D The study underscores the importance of not exclusively depending on a ring applicator alone in HDR-ICBT treatment for cervical cancer, as it may lead to suboptimal tumor doses. The ICRU point's results show an underestimation of the rectum and bladder dose during HDR-ICBT.

Transition from point A to volume based image guided brachytherapy across a network of centers in India through workshop and mentoring

To demonstrate how workshop and mentoring across a network of radiotherapy centers helped in transitioning from point A to volume-based image guided brachytherapy in carcinoma cervix. Based on discussion with different centers across the network, the lapses in cervical cancer treatment were identified and a workshop was designed to change the practice pattern. The main focus of the workshop was to streamline EBRT dose prescription protocols and implement volume based image guided brachytherapy through mentoring and hands on training. Patient data was analyzed 1 year post workshop to assess the impact in changing practice pattern. A total of 246 cervical cancer patients treated with radical chemo radiotherapy and image guided brachytherapy were analyzed. 207 patients received CT based intracavitary brachytherapy whereas 39 patients received MR based hybrid brachytherapy. In patients who received EBRT and brachytherapy at the same center, the EBRT prescription dose was 45Gy in 25 fractions in 95% patients. The mean dose received by 90% of the HRCTV was 80.8Gy EQD2 in CT based intracavitary brachytherapy and 89.48Gy EQD2 in MR based hybrid brachytherapy. The mean bladder, rectum, sigmoid and small bowel D2cc doses were 63.87Gy, 62.18Gy, 61.2Gy and 55.1Gy EQD2 respectively. This report demonstrates successful implementation and change of carcinoma cervix treatment practice pattern through workshop and mentoring across a network of radiotherapy centers in India.

Are outcomes of locally advanced cervical cancer associated with prebrachytherapy hemoglobin values and transfusion practice? An observational study comparing two large academic centres with divergent clinical guidelines

Anemia is common in locally advanced cervical cancer. Clinical practice varies greatly for management of anemia during brachytherapy, with some centres providing red cell transfusion to increase hemoglobin levels above 100 g/L. This is a retrospective observational cohort study of adult patients with cervical cancer treated with brachytherapy at two academic hospitals. One hospital (H1) uses a liberal transfusion strategy with hemoglobin threshold of 100 g/L during brachytherapy and the other uses a restrictive target of 70 g/L (H2). Overall, 336 patients met inclusion criteria (H1: 150 patients, H2: 186 patients). 11 patients were excluded (2 at H1, 9 at H2). Demographics at both sites were comparable, except for cancer stage and smoking history. External beam radiation and chemotherapy provided was similar. Hemoglobin values were compared at baseline (within 4 weeks of oncology consult), and prior to the first and second brachytherapy treatments. In total, 101red blood cell (RBC) units were transfused to patients at H1 and 19 units to patients at H2. Patients were followed for a median of 37.0 months (0.6-80.5) at H1, and 33.3 months (1.6-82.0) at H2. There was no significant difference in progression-free or overall survival. Multivariable logistic regression analysis showed that FIGO stage was a predictor for both overall survival and cancer progression. Age, tumor size, chemotherapy, and hemoglobin levels were not predictors of disease progression or mortality. The practice of liberal transfusion should be re-evaluated in the absence of robust data to support its use.

Dosimetric and toxicity comparison between Syed-Neblett and Fletcher-Suit-Delclos Tandem and Ovoid applicators in high dose rate cervix cancer brachytherapy

To compare patient and tumor characteristics, dosimetry, and toxicities between interstitial Syed-Neblett and intracavitary Fletcher-Suit-Delclos Tandem and Ovoid (T&O) applicators in high dose rate (HDR) cervical cancer brachytherapy. A retrospective analysis was performed for cervical cancer patients treated with 3D-based HDR brachytherapy from 2011 to 2023 at a single institution. Dosimetric parameters for high-risk clinical target volume and organs at risk were obtained. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. A total of 115 and 58 patients underwent Syed and T&O brachytherapy, respectively. Patients treated with Syed brachytherapy were more likely to have larger tumors and FIGO stage III or IV disease. The median D2cc values to the bladder, small bowel, and sigmoid colon were significantly lower for Syed brachytherapy. Patients treated with Syed brachytherapy were significantly more likely to be free of acute gastrointestinal (44% vs. 21%, p = 0.003), genitourinary (58% vs. 36%, p = 0.01), and vaginal toxicities (60% vs. 33%, p = 0.001) within 6 months following treatment compared to patients treated with T&O applicators. In contrast, Syed brachytherapy patients were more likely to experience late gastrointestinal (68% vs. 49%, p = 0.082), genitourinary (51% vs. 35%, p = 0.196), and vaginal toxicities (70% vs. 57%, p = 0.264). Syed-Neblett and T&O applicators are suitable for HDR brachytherapy for cervical cancer in distinct patient populations. Acute toxicities are more prevalent with T&O applicators, while patients treated with Syed-Neblett applicators are more likely to develop late toxicities.

The impact of a positive COVID-19 test on timeliness of radiation in patients receiving brachytherapy

Delays in initiating and completing brachytherapy may have adverse oncologic outcomes for patients with cervical, uterine, and prostate cancer. The impact of the COVID-19 pandemic on brachytherapy in the United States has not been well-characterized. We aim to evaluate how a positive COVID-19 test affected timeliness of treatment for patients undergoing brachytherapy for cervical, uterine, and prostate cancer. We queried the National Cancer Database to identify patients diagnosed with cervical, uterine, and prostate cancer in 2019 and 2020 who received brachytherapy in their treatment. Patients who tested positive for COVID-19 between cancer diagnosis and start of radiation were compared to those who did not test positive for COVID-19. Time in days from cancer diagnosis to initiation of radiation was compared using two-sample t-tests with p < 0.05 signifying significant differences. We identified 38,341 patients with cervical (n = 6,925), uterine (n = 18,587), and prostate cancer (n = 12,829). Rates of COVID-19 positivity were cervical cancer (n = 135; 2%), uterine cancer (n = 236; 1.3%), and prostate cancer (n = 141; 1%). Of those, 35% of cervical, 49% of uterine, and 43% of prostate cancer patients tested positive between their cancer diagnosis and initiation of radiation. Median days to radiation was significantly longer in these patients: 78 versus 51 for cervical cancer (p < 0.01), 150 versus 104 for uterine cancer (p < 0.01), and 154 versus 124 for prostate cancer (p < 0.01). For patients with cervical, uterine, and prostate cancer diagnosed between 2019-2020, testing positive for COVID-19 after their cancer diagnosis was associated with a delay to initiation of radiation by 4-7 weeks.

Exploratory analysis of the cervix tumoral HPV antigen-specific T-cell repertoire during chemoradiation and after brachytherapy

Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-β/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy.

Redefining the role of pulsed-dose-rate brachytherapy in cervical cancer treatment using a preplanned approach

This study aims to determine predictive factors for cervical cancer patients who would benefit more from high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy. The sample included 50 patients treated with brachytherapy following external radiochemotherapy. PDR plans were compared to HDR preplans, with a focus on patients who may benefit from PDR using preplan metrics and clinical variables. The expected clinical effect was quantified using a tumor control probability model. Results showed PDR plans with 60 pulses to be optimal for achieving target clinical goals for D90CTVHR. A CTVHR volume of >67.5cc and/or D90CTVHR dose on the HDR preplan of 3% increase in TCP with PDR. The process showed 96% accuracy, 88% sensitivity, and 98% specificity. Only 16% of patients showed a relevant benefit from PDR over HDR, with a mean D90CTVHR of 7 Gy higher and a mean TCP at 3 years of 4.8% higher for PDR. The benefit of PDR is highly influenced by the choice of alpha/beta ratio and repair halftime. A small subset of cervical cancer patients may gain from PDR over HDR. CTVHR volume and preplan D90CTVHR doses may be useful in selecting patients for PDR brachytherapy.

Utilizing a novel hybrid brachytherapy technique FINITO (Freehand Interstitial Needles in addition to Tandem and Ovoid) for locally advanced cervical cancer

We aimed to assess the clinical feasibility and advantages of using a novel hybrid brachytherapy technique by placing Freehand Interstitial Needles in addition to the Tandem and Ovoid applicator (FINITO) for the treatment of locally advanced cervical cancer (LAC). A retrospective analysis was performed on two cohorts of patients with LACC treated at our institution: 29 patients in the FINITO group and 17 patients in the control group using T&O only approach. Clinical outcomes of interest included local control (LC), progression-free survival (PFS), overall survival (OS), and rates of acute and late toxicities. Kaplan-Meier methodology was used to estimate OS, PFS, and LC. Wilcoxon signed-rank test was used to compare the median values for dosimetry parameters. A p-value of ≤ 0.05 was considered statistically significant. All statistical analyses were performed using RStudio. At a median of 2 years there was no difference in rates of OS, PFS or LC between the FINITO and the control group of patients. The 2-year OS, PFS, and LC for the FINITO group were 59% (95% CI 34%-100%), 58% (95% CI 38%-89%), and 84% (95% CI 69%-100%), respectively. Late toxicities were significantly lower in the FINITO group for both gastrointestinal and genitourinary symptoms (p = 0.001 and 0.01, respectively) as compared to the T&O group. Based on the equivalent LC rate and lower toxicity profile, our FINITO technique appears to be an excellent alternative to the standard intracavitary brachytherapy in patients with advanced disease, especially in resource-limited settings.

Comparing long-term sexual dysfunction across different uterine cancer treatment modalities

The objective of this study was to assess differences in long-term sexual and menopausal side effects after uterine cancer treatment among treatment modalities. This is a cross-sectional study that examined women treated for uterine cancer from 2006-2018. Eligible women included those who underwent a hysterectomy/bilateral salpino-oophorectemy alone (HS), with brachytherapy (BT), or with external beam radiation therapy (EBRT). A noncancer cohort of women who underwent a hysterectomy/BSO for benign indications were also identified (non-CA). To compare outcomes, we utilized a shortened form of the female sexual function index (FSFI) and the menopause survey, which consists of 3 subscales: hot flashes, vaginal symptoms, and urinary symptoms. Demographic, comorbidity, and other treatment variables were collected. Survey totals were compared across cohorts using ANOVA tests and logistic regression. A total of 284 women completed the Menopause Survey (Non-CA 64, HS 60, BT 69, EBRT 91); 116 women reported sexual activity in the last 4 weeks and completed the FSFI (NC 32, HS 21, BT 31, EBRT 32). The mean FSFI score for the entire cohort was 11.4 (SD 4.16), which indicates poor sexual function. There was no significant difference between any cohort in the overall FSFI score (p = 0.708) or in any of the FSFI subscales (all p > 0.05). On univariate analysis, BT was associated with fewer menopausal hot flashes and vaginal symptoms compared to the non-CA cohort (p < 0.05), which did not persist on multivariable analysis. There was no significant difference in sexual dysfunction or menopausal symptoms in those treated for uterine cancer with or without adjuvant radiation. Most patients reported poor sexual function.

How do you do it?: Gynecologic brachytherapy best practices at high volume institutions within the United States and Canada

Definitive treatment including chemoradiation and brachytherapy for patients diagnosed with locally advanced cervical cancer requires significant multidisciplinary coordination. Our goal was to assess and share gynecologic brachytherapy best practices from high volume brachytherapy centers. A survey was sent to 42 centers within the United States and Canada that perform a high volume of complex gynecologic brachytherapy. Responses were collected from 32/42 (76%) institutions. 41% of responding institutions perform > 100 complex brachytherapy procedures per year. Most departments have >1 brachytherapist and 85% of respondents complete 1-2 complex brachytherapy procedures per day. 91% of surveyed departments have support staff specifically devoted to brachytherapy. Approximately 50% of intracavitary/hybrid procedures are performed in departmental brachytherapy suites. Institutions use MRI (35%), CT (24%) or a combination (24%) for treatment planning. 88% of respondents use sedation for tandem based procedures. Respondents cite high complexity of care, insufficient reimbursement, untimely referrals, shared operative and clinical duties, expensive applicator acquisition and complex scheduling as challenging aspects of providing brachytherapy services. Conversely, respondents cite a dedicated team, departmental brachytherapy suite, well organized coordination of procedures and personnel, anesthesia support, a full range of applicators, image-based planning near the department and supportive administration as integral components in providing brachytherapy. Most surveyed institutions have >1 brachytherapist who perform 1-2 procedures per day in a dedicated brachytherapy space with a team that assists with coordination and scheduling efforts. A well supported multidisciplinary team is vital to ensure state of the art brachytherapy which is essential in curing these challenging malignancies.

Development and clinical implementation of simple needle attachment post placement interstitial template (SNAPP-IT) enabling a shorter, more direct needle path while preserving tumor visualization

Historical gynecologic interstitial brachytherapy templates block direct tumor visualization during needle placement, presenting an opportunity for clinical innovation to develop a novel interstitial template allowing direct tumor visualization during needle insertion. We designed and implemented a novel interstitial template, simple needle attachment post placement interstitial template (SNAPP-IT), that allowed direct visualization of the target vaginal tumor during interstitial needle placement while maintaining the ability to individually secure needles to the template, allow a vaginal cylinder, suture holes for securing to the perineum, MRI compatibility and sterilizable for repeat use. Procedure outcomes including procedure time, needle path lengths, and plan dosimetry were prospectively captured in a patient database. Forty gynecologic interstitial brachytherapy cases were recorded (20 SNAPP-IT, 20 traditional templates). Needle insertion depth was reduced using the SNAPP-IT in comparison with traditional interstitial templates (11.8 cm vs. 3.6 cm, p < 0.0001). The average CTV volume was 25.6 cc for SNAPP-IT and 20.7 cc for traditional; both methods averaged a similar number of needles (15.8, 15.6). Dosimetric constraints were similarly met in both treatment groups. Procedures performed using the SNAPP-IT were shorter compared with those performed with traditional interstitial devices (83.4 minutes vs. 100.7 minutes) and there were no post-operative infections in the SNAPP-IT group. Implementation of a novel gynecologic interstitial brachytherapy template (SNAPP-IT) reduced procedure times, allowed direct tumor visualization, and decreased needle insertion depth. SNAPP-IT provides a useful alternative approach for vaginal interstitial brachytherapy, may increase brachytherapist efficiency with complex procedures and potentially expands access to interstitial brachytherapy.

Simulation-based graduate medical education in MR-guided brachytherapy for cervical cancer

Brachytherapy is critical for the curative treatment of locally advanced cervical cancer. Although brachytherapy use is declining in the United States (U.S.), novel interstitial or intracavitary applicators and advances in image guidance for applicator placement and treatment planning have allowed for tumor dose escalation while reducing normal tissue toxicity. Recent survey data have suggested insufficient brachytherapy training for radiation oncology trainees in the United States. This study aimed to address these gaps by developing and piloting a simulation-based education (SBE) workshop for MR-guided cervical cancer brachytherapy. An SBE workshop was developed for graduate medical education (GME) trainees focusing on MR-guided brachytherapy for cervical cancer. Four hands-on stations, simulating aspects of the procedure, were led by a team of gynecological brachytherapy experts. The learners were radiation oncology residents and fellows in a U.S. GME training program. The primary outcome was feasibility, assessed by completion of the workshop within the time constraints of the curriculum. Learners completed preworkshop and postworkshop surveys to provide information on efficacy. The workshop was successfully completed in a 1-h block of GME didactic time. Ten trainees completed all four stations, and all completed preworkshop and postworkshop surveys, which showed improvements in knowledge and technical proficiency. Feedback was positive, and trainees requested additional learning opportunities. This study showed that GME-focused SBE in MR-guided cervical cancer brachytherapy was feasible. SBE provided a nonclinical environment in which to practice aspects of MR-guided brachytherapy. Ongoing work includes collaboration with other U.S. institutions. Future studies should focus on international adaptation.

Hypnosedation for endocavitary uterovaginal applications: A pilot study

Implantations for uterovaginal brachytherapy are usually performed under general or spinal anesthesia, which are not without risk. As it is a rather short procedure and since postoperative pain is minimal, hypnosedation was proposed to selected patients requiring endocavitary applications as part of their routine treatment. Consecutive patients requiring intracavitary uterovaginal brachytherapy from January to October 2019 were included if they accepted the procedure. A premedication was systematically administered. Hypnosedation was based on an Ericksonian technique. The procedure was immediately interrupted if the patient requested it, in cases of extreme anxiety or pain. Procedure was in that case rescheduled with a "classical" anesthesia technique. A total of 20 patients were included. Four patients had to be converted toward a general anesthesia: one because of a fibroma on the probe's way and three young patients with a very anteverted/retroverted uterus that was painful at every mobilization. Mean and maximum pain scores during implant were 2.9/10 and 5.1/10, respectively. The most painful maneuver was cervical dilation for 45% of the patients, followed by mold insertion in 40% of cases. About 85% of the patients declared that hypnosis helped them relax; 90% of the patients would recommend the technique. No procedure-related complication occurred. With a 70% success rate (correct implant with mean pain and anxiety scores < 5), one can conclude that uterovaginal brachytherapy implantation under hypnosedation is feasible and received a high satisfaction rate from the patients. This technique may reduce overall treatment time in a context of difficult access to the OR and to anesthesiologists, while reducing anesthetic drugs resort and postoperative nausea.

Hyaluronic acid gel injection in rectovaginal septum reduced incidence of rectal bleeding in brachytherapy for gynecological malignancies

The purpose of this study was to report our initial clinical results of hyaluronic acid gel injection (HGI) in the rectovaginal septum (RVS) to reduce the incidence of rectal bleeding in vaginal brachytherapy for gynecologic malignancies. Since 2008, CT based image-guided adaptive brachytherapy (IGABT) was initiated, and since 2015, HGI in the RVS was introduced in our institution. Vaginal cylinder with or without tandem or additional interstitial needles were applied for patients with gynecologic malignancies. Rectum dosimetric parameters and incidence of late rectum bleeding were compared between patients with and without HGI in the RVS. Between May 2008 and October 2017, 83 patients with gynecologic malignancies were treated with IGABT involving vaginal cylinder. Eleven patients who were treated for palliative intention were excluded, and 72 patients were subjected to the analysis. Of the total 72 patients 46 were with uterine cervical cancer, 19 uterine corpus cancer, five vaginal cancer, one vulvar cancer, and one ovarian cancer. Fifteen and 57 patients were irradiated with and without HGI in the RVS, respectively. With a median follow-up period of 57.7 (4.7-123.1) months, 30 (41.7%) patients suffered from radiation-related rectal bleeding. Patients with HGI in the RVS had a statistically significant lower incidence of rectal bleeding compared with those without it (13.3% vs. 49.1%, p = 0.01). HGI in the RVS reduced the incidence of late rectal bleeding for patients with gynecologic malignancies treated by vaginal cylinder and was not associated with HGI-procedure-related adverse events.

Outcomes of 3D MRI based HDR brachytherapy with hybrid multichannel vaginal cylinder applicator and freehand needles for treatment of vaginal disease

Freehand needles can be used with multichannel vaginal cylinders (MCVC) to cover vaginal cancer >7 mm thick or with supra-vaginal extension. We report our institutional outcomes using this novel hybrid technique. Patients with vaginal malignancies treated with HDR BT using MCVC plus freehand needles from 2014-2021 at our institution were identified. Clinical characteristics, details of brachytherapy, initial response, and overall local control (LC) outcomes were recorded. LC was analyzed via Kaplan-Meier method. 34 patients were identified with median follow-up 1.9 years. 19 patients had primary endometrial cancer with vaginal recurrence/disease, and remaining had primary vaginal cancer or other primaries. 7 patients had recurrence after previous RT course. 25 patients received EBRT with median dose 45 Gy in 25 fractions, and rest received BT alone. Median HR-CTV D90 for patients treated with EBRT plus BT was 77.4 Gy. 30 patients had complete local response to BT on initial examination and/or follow-up imaging. 1 and 2-year LC rates in patients without prior RT treated with EBRT + BT were 94.1% and 94.1%, respectively. 1 and 2-year LC rates for those without prior RT were 88.1% and 76.4%, respectively. 1 and 2-year LC rates for those with prior RT were 68.6% and 34.3%, respectively. 1 patient had vaginal laceration requiring surgical repair, and 1 patient developed small bowel obstruction 1 month after BT, with no additional acute grade 3+ toxicities identified. Our approach with MCVC plus freehand needles with MRI-based planning was feasible and safe, with excellent initial local response and low rate of serious toxicities.

Development of a gynecologic brachytherapy curriculum and simulation modules to improve radiation oncology trainees’ skills and confidence

Brachytherapy in the management of cervical cancer is directly linked to improved survival. Unfortunately, we continue to see a decline in its utilization. A recent survey of U.S. residents demonstrated limited caseload as the greatest barrier to achieving independence in brachytherapy practice. To improve residents' brachytherapy skills and confidence in performing brachytherapy independently, a gynecologic brachytherapy simulation course was developed and tested. The gynecologic brachytherapy curriculum and simulation modules were developed using a combination of didactic education, self-study, practicums, and patient-centered cases. The simulation modules consisted of 2-h sessions. The first hour occurred within a simulated OR environment, where residents independently performed all aspects of applicator insertion in a cadaver model. The second hour consisted of contouring, dosimetric planning, and treatment evaluation. A brachytherapy training survey developed by the Association of Residents in Radiation Oncology was given before and after the course. The perceived ability to perform brachytherapy independently for a given disease site correlated directly with number of cases performed. Most residents believed that after performing five cases they would be capable of performing additional cases independently (10 of 18). All strongly agreed (8 of 18) or agreed (10 of 18) this to be true after 15 cases. Compared with survey data before the brachytherapy simulation course, trainees felt that their ability to independently perform brachytherapy (p < 0.001) improved. A brachytherapy simulation course can be used to gain further experience in a controlled environment. Our results demonstrate that gynecologic brachytherapy simulation increased trainees' confidence in performing the procedures independently.

Predicting which patients may benefit from the hybrid intracavitary+interstitial needle (IC/IS) applicator for advanced cervical cancer: A dosimetric comparison and toxicity benefit analysis

The purpose of this study is to compare the predicted rate of local control and bladder and rectum toxicity rates for image-guided adaptive brachytherapy plans using a tandem and ovoid (T/O) applicator versus using a simulated hybrid intracavitary/interstitial tandem and ring applicator with needles (T/R + N) for patients with locally advanced cervical cancer (LACC). Patients with ≥ FIGO Stage IIB locally advanced cervical cancer treated with T/O from a single institution were included. Simulated treatment plans were created with a T/R + N applicator for the best high-risk clinical target volume (CTV) coverage and minimal dose to organs at risk. Three-year local control rate was estimated using published dose-volume effect relationships. Next, the high-risk CTV EQD2 D90 of T/R + N plans were calculated, and bladder and rectum toxicity rates were estimated. Analysis was performed in subpatient groups defined based on tumor volume and ratio of maximal and minimal tumor radii (RR) that reflects tumor shape asymmetry. Improvements in predicted local control rate for the T/R + N were 0.8, 4.1, 1.6, and 3.9% for groups with tumor volume <35 cc, ≥35 cc, RR < 2.0, and ≥2.0, respectively, with the latter three being statistically significant. Predicted reductions in Grade 2-4 toxicity rates of bladder and rectum were significant in all groups except bladder toxicity in tumor volume <35 cc, when T/R + N plans were normalized to the same CTV coverage as the T/O plans. Comparing unnormalized T/R + N plans and T/O plans, predicted toxicity reductions were significant in all groups except rectum toxicity in RR ≥ 2.0. Predicted reduction of toxicity rate was larger for patients with large tumor or large tumor RR, although some reductions were relatively small. Cases with large tumor (volume ≥35 cc) or large tumor asymmetry (RR ≥ 2.0) would probably benefit more from the use of hybrid applicators.

Three-dimensional image-guided combined intracavitary and interstitial high-dose-rate brachytherapy in cervical cancer: A systematic review

To evaluate the local control and toxicities of three-dimensional image-guided combined intracavitary and interstitial (IC/IS) high-dose-rate brachytherapy (BT) in cervical cancer through a systematic review. A systematic review of relevant studies was performed through the PubMed, Web of Science, and Cochrane Library databases through May 10, 2020. Articles reporting on IC/IS technology, volumetric doses to high-risk clinical target volume (HR-CTV) and organs at risk (OARs), tumor control and/or treatment-related side effects were identified. The key information, including the type of applicator, implantation technology, characteristics of implantation, volumetric doses, tumor control, and/or treatment-related side effects, was extracted. A probit model analysis between HR-CTV D90 and tumor local control was performed. Twelve studies encompassing 520 patients were included in the probit model between HR-CTV D90 and the local control rate. The probit model showed a significant relationship between the HR-CTV D90 value and the local control probability, p = 0.003. The prescribed dose of 85 Gy IC/IS BT is an appropriate method to achieve a high therapeutic ratio for tumors with large volumes or poor responses after external irradiation in cervical cancer. The probit model showed that the dose escalation of HR-CTV D90 was helpful to improve the local tumor control rate.

Configuration analysis of the injection position and shape of the gel spacer in gynecologic brachytherapy

In this single-institution retrospective study, configuration analysis was performed to determine the optimal location and volume of hyaluronic acid gel spacer injection into the rectovaginal or vesicovaginal septum for effective dose reduction (DR) to the organs at risk (OARs), the rectum and bladder. 70 and 50 intracavitary brachytherapy treatment plans used only vaginal cylinders with gel spacers for the rectal and bladder sides, respectively, whereas 28 did not use spacers. Correlation analysis was performed between the geometrical parameters and injection position of the gel spacers and the 2-cm A higher DR was predicted for hyaluronic acid gel spacer injection within ±5 mm and ±2.5 mm in the lateral-medial direction from the midpoint on the rectal and bladder sides, and ±10 mm in the cranial-caudal direction from the midpoint on the rectal side. There were correlations between 2-cm A gel spacer volume of ∼10 cm

Letter to the editor on the research article “Total reference air kerma can accurately predict isodose surface volumes in cervix cancer brachytherapy. A multicenter study”

Brachytherapy in India: Learning from the past and looking into the future

India has a longstanding tradition in the practice of brachytherapy and has actively contributed to the scientific literature by conducting prospective studies, clinical audits, developing innovative techniques, and performing randomized studies. Indian investigators have also contributed to international collaborative research, education, training programs along with guideline development for brachytherapy in cervix and head and neck cancers. The present article summarizes the key contributions to scientific literature, current infrastructure, skill set for brachytherapy, existing challenges, and strategy to further strengthen brachytherapy practice in the next decade.

Paracervical blocks facilitate timely brachytherapy amidst COVID-19

The COVID-19 pandemic presents serious challenges for brachytherapists, and in the time-sensitive case of locally advanced cervical cancer, the need for curative brachytherapy (BT) is critical for survival. Given the high-volume of locally advanced cervical cancer in our safety-net hospital, we developed a strategy in close collaboration with our gynecology oncology and anesthesia colleagues to allow for completely clinic-based intracavitary brachytherapy (ICBT). This technical report will highlight our experience with the use of paracervical blocks (PCBs) and oral multimodal analgesia (MMA) for appropriately selected cervical ICBT cases, allowing for completely clinic-based treatment. 18 of 19 (95%) screened patients were eligible for in-clinic ICBT. The excluded patient had significant vaginal fibrosis. 38 of 39 intracavitary implants were successfully transitioned for entirely in-clinic treatment utilizing PCBs and oral MMA (97% success rate). One case was aborted due to inadequate analgesia secondary to a significantly delayed case start time (PO medication effect diminished). 95% of patients reported no pain at the conclusion of the procedure. The median (IQR) D In a multidisciplinary effort, we have successfully transitioned many ICBT cases to the clinic with the use of PCB local anesthesia and oral multimodality therapy in direct response to the current pandemic, thereby mitigating exposure risk to patients and staff as well as reducing overall health care burden.

A comparison between revised Manchester Point A and ICRU-89–recommended Point A definition absorbed-dose reporting using CT images in intracavitary brachytherapy for patients with cervical carcinoma

This study is a comparison between revised Manchester Point A and International Commission on Radiation Units and measurements (ICRU) 89 report-recommended Point A absorbed-dose reporting in intracavitary brachytherapy for patients with cervical carcinoma. The retrospective dosimetric study is based on the data of 32 patients with cervical carcinoma treated with high-dose-rate brachytherapy. Patients received 21 Gy in three fractions (7.0 Gy X three fractions) to Point A (A When using the A It has been found that the position of revised Manchester (A

Techniques for and uncertainties of MRI-based reconstruction of titanium tandem and ring brachytherapy applicators

Eliminating patient computed tomography (CT) scans for tandem and ring (T&R) brachytherapy can reduce overall procedure time and eliminates imaging dose. However, reconstructing titanium applicators in magnetic resonance imaging (MRI) is challenging. We evaluated the uncertainty of different applicator reconstruction workflows in MR-guided brachytherapy, and assessed the clinical impact of reconstruction uncertainties. Titanium MRI-compatible T&Rs with aqueous gel in the buildup cap were reconstructed on CTs and MRIs to assess the uncertainties of four different workflows. Reconstruction was performed using (1) proton density-weighted MRIs with solid applicator from a library, (2) applicator-only reference CT fused with MRIs, (3) T2-weighted (T2W) MRIs following GEC-ESTRO guidelines, and (4) patient CTs fused with patient MRIs with in situ applicators. We evaluated dwell positions and plan quality differences using high-risk clinical target volume coverage, and EQD2 D The 2σ uncertainty for dwell positions for each workflow were (1) 2.7 mm for both ring and tandem, (2) 1.4 mm ring and 0.8 mm tandem, (3) 0.2 mm ring and 0.8 mm tandem, and (4) 1.9 mm ring and 0.4 mm tandem. Reconstruction uncertainties resulted in dose variations within acceptable levels (below 10%) except for (1) which resulted in larger dose to the rectum (20%). Dose uncertainties were similar between reference CT and patient CT. Reconstruction with a reference CT results in similar uncertainty to a patient CT. T2W MRI plans have acceptable uncertainty levels for the applicator reconstruction and resulting dose distributions.

A knowledge-based organ dose prediction tool for brachytherapy treatment planning of patients with cervical cancer

The purpose of this study is to explore knowledge-based organ-at-risk dose estimation for intracavitary brachytherapy planning for cervical cancer. Using established external-beam knowledge-based dose-volume histogram (DVH) estimation methods, we sought to predict bladder, rectum, and sigmoid D A total of 136 patients with loco-regionally advanced cervical cancer treated with 456 (356:100 training:validation ratio) CT-based tandem and ovoid brachytherapy fractions were analyzed. Single fraction prescription doses were 5.5-8 Gy with dose criteria for the high-risk clinical target volume, bladder, rectum, and sigmoid. DVH estimations were obtained by subdividing training set organs-at-risk into high-risk clinical target volume boundary distance subvolumes and computing cohort-averaged differential DVHs. Full DVH estimation was then performed on the training and validation sets. Model performance was quantified by ΔD Training set deviations were bladder ΔD

Clinical feasibility of MR-assisted CT-based cervical brachytherapy using MR-to-CT deformable image registration

The purpose of this study is to evaluate the feasibility of using deformable image registration algorithms to improve high-dose-rate high-risk clinical target volume (HR-CTV) delineation between preapplicator implantation MRI (pre-MRI) and postapplicator implantation CT (post-CT) in the treatment of locally advanced cervical cancer (LACC). Twenty-six patients were identified for the study. Regions of interest were segmented on MRI and CT. A HR-CTV was delineated on pre-MRI and compared with the previously contoured HR-CTV on the post-CT. Two commercially available algorithms, ANACONDA (anatomically constrained) and MORFEUS (biomechanical model based) with various controlling structure settings, including the cervix, uterus, etc., were used to deform pre-MRI to post-CT. MRI-to-CT deformed targets are denoted as HR-CTV'. Quantitative deformation metrics include Dice index, distance to agreement, and center of mass displacement. Qualitative clinical usefulness of deformations was scored based on HR-CTV identification on CT images. For ANACONDA and MORFEUS deformations, using a cervix controlling region of interest resulted in the highest Dice, lowest distance to agreement, and lowest center of mass displacement for HR-CTV'. With MORFEUS deformations, the deformed HR-CTV' proved clinically useful in 23 patients. Prebrachytherapy implantation MRI can aid target contours for CT-based brachytherapy through ANACONDA or MORFEUS algorithms with appropriate parameter selection for LACC patients.

Dose–effect response in image-guided adaptive brachytherapy for cervical cancer: A systematic review and meta-regression analysis

This study aimed to integrate and update the dose-effect relationship between volumetric dose and local control for cervical cancer brachytherapy. We identified studies that reported high-risk clinical target volume (HR-CTV) D Thirty-three studies encompassing 2893 patients were included. The probit model showed a significant relationship between the HR-CTV D A significant dependence of local control on HR-CTV D

The addition of interstitial needles to intracavitary applicators in the treatment of locally advanced cervical cancer: Why is this important and how to implement in low- and middle-income countries?

Cervical cancer is the leading cause of cancer mortality of women in low-/middle-income countries. Interstitial needles improve outcomes but require resources beyond those available in endemic regions. We conducted a retrospective review of the use of interstitial needles in locally advanced cervical cancer and simulated both 3D planning without needles and 2D planning to explore the benefit of interstitial needles. 57 brachytherapy plans of 17 patients who had intracavitary tandem and ring plus interstitial brachytherapy were reviewed. Prescribed dose was 7 Gy × four fractions. 2D plans prescribed to point A were generated to represent a standard Manchester loading. Dosimetric outcomes to clinical target volume and organs at risk (OARs) were compared with those of 3D-based plans. High-risk clinical target volume coverage was excellent: 93.2% for 2D plans, 93.9% for 3D plans without needles, and 96.2% for 3D with needles. The mean dose to 90% of target was 8.5 Gy/fraction for 2D plans, 7.5 for 3D without needles, and 7.9 Gy/fraction for 3D with needles. However, the 2D plans delivered 12% above recommended dose constraints for OARs (except rectum). Dosimetric differences were found between 3D planning and 3D with needles for target coverage (p = 0.002). Dose to OARs was significantly lower when 3D plans with needles were compared with 2D plans. Interstitial needles provide an optimal therapeutic ratio for patients with high-volume disease or/and unfavorable topography. This justifies additional capital investment in resources for implementation to provide optimal treatment for locally advanced cervical cancer globally.

Characterization of combined intracavitary/interstitial brachytherapy including oblique needles in locally advanced cervix cancer

To characterize and report on dosimetric outcomes of image guided adaptive brachytherapy (IGABT) using intracavitary and interstitial (IC/IS) applicators including oblique needles (O-needles) in locally advanced cervical cancer (LACC). Twenty LACC patients treated with radio-chemotherapy and offered IC/IS-IGABT including O-needles were analyzed. An in-house 3D-printed vaginal template was used to steer the needles parallel and obliquely in relation to the tandem, supplemented with free-hand needles if needed. Implant characteristics and loading patterns were analyzed. Using the equivalent dose in 2Gy-fractions (EQD2) concept, cumulative (EBRT+BT) V85, V75, V60Gy, targets/OARs doses and high dose volumes (150%, 200% and 300% (100% = 85 Gy EQD2 Median(range) tumor width at diagnosis was 5.5(3.6; 7.5)cm; CTV The use of O-needles in patients with large and/or unfavorable tumors resulted in excellent target coverage and OARs sparing. Intrauterine and vaginal loadings were reduced compared to standard loading and almost half of the loading was shifted into IS needles. This was achieved with gentle loading in the majority of dwell positions.

Dose planning variations related to delineation variations in MRI-guided brachytherapy for locally advanced cervical cancer

To examine the variability in prescribed dose due to contouring variations in intracavitary image-guided adaptive brachytherapy for cervical cancer. To identify correlations between dosimetric outcomes and delineation uncertainty metrics. A data set from an EMBRACE sub-study on contouring uncertainties was used, consisting of magnetic resonance images of six patients with cervical cancer delineated by 10 experienced observers (target volumes and organs at risk). Two gold standard contours were generated, an expert consensus and the simultaneous truth and performance level estimation. Plans were individually optimised to all of the contour sets (12 in total). Plans were applied to the gold standard contour sets, and dose volume histogram parameters including D There is a dosimetric variability between observers, patients and the gold standard contour used for analysis. Approximately 3 Gy D This study highlights the dosimetric differences interobserver uncertainty in contouring can have for cervical cancer brachytherapy. The importance of carefully choosing a gold standard from which to benchmark is reiterated.

Long-term effectiveness and safety of image-based, transperineal combined intracavitary and interstitial brachytherapy in treatment of locally advanced cervical cancer

The aim of the study was to evaluate the impact of image-based combined intracavitary-interstitial brachytherapy (IC-ISBT) using a transperineal template in locally advanced cervical cancer treatment. A total of 94 patients of cervical cancer stage IIB-IVA underwent image-based transperineal interstitial brachytherapy without tandem (ISBT) or with tandem (IC-ISBT) between June 2008 and June 2018 at our institution. After pelvic chemoradiation, 42 patients underwent ISBT and 52 IC-ISBT. Dosimetric data, clinical response, and toxicity records of these patients were reviewed. Clinical stage distribution was as follows: IIB: 22.4% (21), IIIA: 10.6% (10), IIIB: 56.4% (53), and IVA: 10.6% (10). Mean high-risk clinical target volume was 75.72 cc, and mean cumulative equivalent of 2 Gy per fraction for high-risk clinical target volume was 81 Gy. The median followup was 35.5 months. Overall 3- and 5-year local control, disease-free survival (DFS), and overall survival (OS) were 84% and 84%, 69.1% and 62.9%, and 80.9% and 71.5%, respectively. Local control (90.4% vs. 76.2%; p = 0.048) and DFS (78.8% vs. 57.1%; p = 0.04) were significantly better in the patients of IC-ISBT arm. IC-ISBT (hazard ratio: 0.763; 95% confidence interval 0.217, 1.38; p = 0.046) and D90 dose >85 Gy (hazard ratio: 0.957; 95% confidence interval 0.927, 1.07; p = 0.037) were predictors of better DFS on univariate analysis. Overall survival was not affected significantly by any of the factors. Grade 3 and 4 late complications were recorded in 3.2% (3) of patients and were similar in both arms (p = 0.86). However, the mean rectum 2 cc dose was significantly lower in the IC-ISBT arm (p = 0.038). Combined IC-ISBT is a safe and effective approach to treat ICBT unsuitable cases. It integrates the benefits of ICBT to the adaptability of ISBT around various targets and should be practiced whenever feasible to provide superior outcomes in locally advanced cervical cancer.

Analysis of dose-effect relationship between DVH parameters and clinical prognosis of definitive radio(chemo)therapy combined with intracavitary/interstitial brachytherapy in patients with locally advanced cervical cancer: A single-center retrospective study

The purpose of the study was to explore the dose-effect relationship between dose-volume histogram parameters and clinical prognosis of definitive radio(chemo)therapy followed by intracavitary/interstitial brachytherapy in locally advanced cervical cancer. A retrospective analysis was performed on 110 patients with locally advanced cervical cancer who underwent external beam radiotherapy combined with intracavitary/interstitial brachytherapy with or without chemotherapy from July 2010 to September 2018. We reported D The median followup time was 72.33 months. Multivariate Cox regression analysis showed that HR-CTV D A significant dependence of OS, CSS, and LC on D

Feasibility of ureter delineation and dose recording in the assessment of ureteric stenosis during brachytherapy for cervical cancer

Ureteric stenosis is the commonest complication to affect the ureter after radiotherapy for cervical cancer; despite this ureters are not contoured as organs at risk and limited dosimetric data exist for them. Bilateral ureters were retrospectively delineated on brachytherapy planning imaging for patients treated for cervical cancer between 2014 and 2019. Ureteric stenosis toxicity data and D2cc, D1cc, D0.1cc of the right and left ureter were collated. Ureter V80, V100, V120, and V150 were also analyzed. Univariate analysis was performed to identify predictors of high ureter dose and ureteric stenosis. 95 patients were identified and 190 ureters contoured on brachytherapy planning imaging, with a median follow-up duration of 24 months (IQR23.7). 4.2% (4) of patients had grade 3/4 ureteric stenosis. Mean ureter D0.1cc, D1.0cc and D2.0cc on the right were 80.4Gy (±28.9), 56.2Gy (±7.2) and 52.8Gy (±7.6), and on the left were 75.6Gy (±14.6), 54.3Gy (±5.5) and 52.7Gy (±5.5) respectively. Significantly higher ureter doses were present in patients with baseline hydronephrosis (p < 0.002) and interstitial needle use (p = 0.047). Ureters affected by ureteric stenosis received D0.1cc doses between 60-98Gy. 10-14% received point doses in excess of 150% of the prescribed dose (7Gy) with no resulting ureteric stenosis. No significant difference in D0.1cc was found in patients with or without ureteric stenosis. It is feasible to accurately contour ureters on brachytherapy planning imaging. Baseline hydronephrosis and interstitial needle use contribute to higher ureter doses. No association between dose and ureteric stenosis was found.

Reducing dose to rectum by placement of a rectum-emptying tube in cervical cancer patients treated with brachytherapy

Only scarce data are available on the possibility to reduce rectal dose by controlling rectum filling before HDR (high dose rate) IGABT (image-guided adaptive brachytherapy) in LACC (locally advanced cervical carcinoma) patients. We compared dosimetric outcomes before and after the evacuation of gasses using a rectum emptying tube. Sixty CT (computed tomography) scans from 30 consecutive patients with cancer of the cervix undergoing HDR IGABT after EBRT were reviewed. Patients who underwent at least one gas evacuation were included in the analysis. The three-dimensional dosimetric data of the dosimetric plan performed before and after gas evacuation were compared. Primary endpoint was the difference between D2cc of the rectum before and after the procedure. Expected probability of grade 2-4 overall rectum morbidity was assessed using a probit model from the prospective multicenter EMBRACE study. Thirty five (58.3%) CT scans from 23 patients (76.7%) requiring gas evacuation were analysed. The mean rectum volume, before and after gas evacuation, was 123.1 cc (sd, ± 60.4) and 66.4 cc (sd, ± 34.8), respectively. For each patient, the volume of the rectum after gas evacuation was lower than before. No major complication occurred during and after the procedure. After gas evacuation, a significant reduction in rectal dose per fraction was observed, on average -4.3 Gy (-38.4%, p < 0.001) for D0.1cc and -1.9 Gy (-30.6%, p < 0.001) for D2cc. Estimated mean probability to develop a grade 2-4 rectum morbidity was significantly lower after gas evacuation, 6.9% (sd,± 1.94) versus 9.5% (sd,± 3.17), p < 0.001. Gas evacuation using a rectal emptying tube in selected LACC patients treated with HDR BT after chemoradiotherapy, allowed a substantial reduction in the dose to the rectum. Such procedure could be of particular interest when a dose escalation strategy is being considered.

Effects of 3D image-guided brachytherapy compared to 2D conventional brachytherapy on clinical outcomes in patients with cervical cancer: A systematic review and meta-analyses

To assess the effects of three-dimensional image-guided brachytherapy (3D BT) compared to bi-dimensional BT (2D BT) on clinical outcomes in patients with cervical cancer. We searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL, Web of Science, and LILACS for studies assessing the effects of 3D BT versus 2D BT on clinical outcomes. Two reviewers independently screened retrieved citations, extracted data and assessed risk of bias from eligible studies. Hazard ratios (HR) were calculated from Kaplan-Meier curves considering the number of events, their timing and the followup of censored patients. We conducted meta-analyses of HR using the inverse-variance random-effects method. Risk Difference (RD) for toxicities were pooled using the Mantel-Haenszel random-effects method. We used the GRADE system to rate the certainty of evidence. Twenty observational studies involving 4287 patients were included. The meta-analyses assessing the effect of 3D BT versus 2D BT on overall survival resulted in a HR of 0.78 (95%CI 0.62-0.98), HR of 0.75 (95%CI 0.62-0.90) for pelvic disease-free survival, HR of 0.93 (95%CI 0.81-1.06) for metastatic disease-free survival, and HR of 0.77 (95%CI 0.59-0.99) for local control. Grade 3-4 global and gastrointestinal toxicities were, respectively, 9% lower (95%CI 6% to 11%) and 5% lower (95%CI 2% to 8%) in patients receiving 3D BT versus 2D BT. Certainty of evidence was very low for all assessed outcomes. Our study may suggest a benefit of 3D BT over conventional 2D BT on important clinical outcomes.

Can we reduce dose to ureters as avoidance organs for MRI based brachytherapy for cervical cancer? A dosimetric feasibility study

Ureteral stenosis (US) is an underreported complication of brachytherapy (BT) for cervical cancer (CC), with limited data on toxicity risk reduction. A previous study demonstrated ureter EQD2 D0.1cc > 77 Gy correlated with US development. We sought to assess feasibility of this constraint while maintaining similar HR-CTV coverage. Patients with locally advanced CC treated with EBRT plus HDR MRI-based brachytherapy boost without hydronephrosis at diagnosis and with ureter dose EQD2 D0.1cc > 77 Gy were included. Replan was attempted to achieve HR-CTV D90 ≥ 80-85 Gy and ureter dose reduction. Ureter distance from lateral margin of HR-CTV and tandem was recorded. t-test was performed to compare ureteral dose and HR-CTV D90. Of 25 patients were identified. Hundred percent received 45 Gy in 25 fractions to the pelvis ± paraaortic lymph nodes and 80% receiving median additional parametrial dose of 5.4 Gy. Replan meeting ureteral dose of ≤77 Gy was feasible in 18 of 25 patients, with a reduction in median ureter D0.1cc from 82.3 to 76.8 Gy (p < 0.001). Median HR-CTV D90 was similar (84.7 vs. 85.0 Gy). Replan achieved D0.1cc ≤77 Gy in 56% of patients who experienced US. All unilateral US cases occurred in the ureter closest to HR-CTV. Optimization to reduce ureter dose to ≤77 Gy is feasible when ureters are visible and contoured. Ureters may be considered as potential OAR during MRI-based brachytherapy treatment. Reduced ring to tandem total reference air kerma (TRAK) ratio may provide an additional metric by which to lower US risk.

US-guided versus US-assisted tandem insertion for cervical cancer: A nomenclature proposal

Dosimetric predictors of local control and complications in gynecologic transperineal implant patients: The medical college of wisconsin experience

Investigate the relationship between dosimetric parameters with local control (LC) and complications following transperineal high-dose rate (HDR) interstitial brachytherapy (ISBT) for gynecologic (GYN) malignancies. Between 2001 and 2016, 59 patients were treated for primary or recurrent GYN malignancies. Most patients received external beam irradiation, followed by transperineal ISBT via the Syed-Neblett applicator set with CT-based planning. Treatment plans were retrospectively reviewed to evaluate for an association among LC or toxicity with the equivalent dose at 2 Gy per fraction (EQD2) for the clinical target volume (CTV), 0.1 cc (D0.1cc), and 2 cc (D2cc) volumes of the organs at risk (OAR), low/high dose volumes for the OAR and CTV, and ratio of dose at the core vs. the implant periphery. The median follow-up among survivors was 24 months. 34% of patients had a component of local failure and in 12%, this was isolated. Late grade 3 (G3) toxicity occurred in 15% of patients. There were no G4-5 toxicities. Rectal D0.1cc > 75 Gy trended toward significance in predicting the development of non-fistula late G2-3 rectal complications. Bladder D0.1cc > 94 Gy significantly predicted for the development of late G2-3 vesicovaginal fistula formation. The ratio of the total dose at the vaginal surface to the needle periphery above 121% trended in predicting for any complication or fistula formation. HDR ISBT combined with EBRT achieved LC in 66% of patients with advanced or recurrent GYN cancers. Rectal and bladder D0.1cc doses may be predictive of complications as may the ratio of the implant dose at the core vs. periphery.

Laminaria tent insertion in preplanning MRI for CT-based cervical cancer brachytherapy

Preplanning magnetic resonance imaging (MRI) is routinely used in image-guided adaptive brachytherapy (IGABT) for cervical cancer. However, a preplanning MRI performed without an applicator does not have good accuracy of image fusion with a planning computed tomography (CT) performed with an applicator. This study aimed to evaluate the efficacy of laminaria tent insertion during pre-planning MRI for cervical cancer brachytherapy (BT). Sixteen patients with cervical cancer were enrolled in the study. Images obtained from a single preplanning MRI performed with a laminaria tent inserted into the cervix were fused with images from the planning CT performed with an applicator during each BT session. The alignment between the high-risk clinical target volume on MRI (HR-CTV Fifty-nine BT sessions were analyzed. Fusion images for 39 (66%) sessions were categorized as excellent, and those for the remaining 12 (20%) sessions were available, and 8 (14%) were not available. Complications reported after laminaria tent insertion were grade-1 fever for 5 (8%) BT sessions in 5 patients and grade-1 pain for 8 (13%) sessions in 5 patients. Laminaria tent insertion during pre-planning MRI may improve the accuracy of image fusion with planning CT and may help delineate the HR-CTV in CT-based IGABT for cervical cancer.

Comparison of dose delivered to vagina using two different intracavitary brachytherapy applicators for carcinoma cervix

The aim of the study was to compare the dose to vaginal points between two intracavitary applicators used for HDR brachytherapy in Carcinoma Cervix METHODS AND MATERIALS: Patients reporting to our center for Carcinoma cervix intracavitary brachytherapy were randomly allocated to treatment with either Manchester or Fletcher Suit Delclos (FSD) applicator. All patients received an EBRT dose of 50 Gy in 25 fractions along with weekly Cisplatin (40 mg/m Manchester applicator gives higher dose to the vagina as compared to FSD applicator for intracavitary brachytherapy in Carcinoma Cervix. The choice of using a particular applicator depends on the residual disease at the time of brachytherapy and patient anatomy.

Dose to pelvic lymph nodes during brachytherapy of locally advanced cervical cancer with 60Co HDR source

This study investigated the correlation between the prescription dose and dose to the Manchester and International Commission on Radiation Units and Measurements-report 38 (ICRU-38) lymphatic trapezoid points during high-dose-rate (HDR) brachytherapy of locally advanced cervical cancer with (Cobalt-60) 60Co . A retrospective study was designed for; patients with locally advanced cervical cancer, treated by external beam radiotherapy and concurrent weekly Cisplatin-based chemotherapy, had no extended parametrial invasion and was treated by tandem-ovoid set, from 2017 to 2020. Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) based target's volume, ICRU-89 revised version of Manchester points A and B, and ICRU-38 lymph node surrogate points were determined, and their dose was recorded. Paired sample t-test, linear regression analysis, and Pearson correlation analyses were done considering a statistical significance level of 0.05 and using IBM SPSS statistics (Version 23, IBM Crop.). Seventy-four brachytherapy cases were included. A positive and strong correlation was observed between D Strong correlations were obtained between dose to the pelvic lymphatic chains and their historical ICRU-38 surrogate points during HDR brachytherapy of locally advanced cervical cancer patients with 60Co tandem-ovoid applicator sets. The correlation strength between point A and prescription dose highly depends on the CTV

Demographic and clinical factors associated with variations in opioid administration using conscious sedation during HDR brachytherapy for cervical cancer

PURPOSE/OBJECTIVES To examine patient characteristics that predispose to higher opioid administration during tandem and ovoid (T&O) high-dose rate (HDR) brachytherapy. METHODS A single-institution retrospective review was performed on patients who underwent brachytherapy for cervical cancer. Patients were included if they received at least one fraction of HDR T&O brachytherapy with analgesia administration recorded in the Medication Administration Record. Fentanyl dose was dichotomized as "low" (mean <125 μg per fraction), or "high" (mean ≥ 125 μg per fraction). Descriptive statistics and multiple logistic regression analysis were performed comparing mean opioid dose per fraction with demographic and clinical information. RESULTS From July 2014 through May 2020, 113 patients underwent 531 T&O HDR brachytherapy fractions with oral benzodiazepine and intravenous opioid fentanyl for conscious sedation. The median opioid dose per fraction was 100 μg fentanyl (range 0-250 μg). Using multiple logistic regression analysis, younger age (OR 1.071, p = 0.002) and higher BMI (OR 1.091, p = 0.019) were associated with increased opioid administration during brachytherapy. Black women received less opioid during brachytherapy when compared to White women (OR 0.296, p = 0.047). FIGO stage, ECOG score, smoking status, prior narcotic use, prior illicit drug use, parity, prior cervical procedure, Smit sleeve placement, and distance to treatment center were not associated with high opioid dose. CONCLUSION Cervical cancer patients who are younger or have higher BMI receive more narcotic analgesia during HDR brachytherapy whereas Black women received less narcotic analgesia, irrespective of age and BMI. This underscores the immediate need to address how pain is assessed and managed during brachytherapy.

MRI-guided brachytherapy for locally advanced cervical cancer: Program initiation, learning curve and dose delivery results in Kuopio University Hospital

Image guided adaptive brachytherapy, the standard treatment for locally advanced cervical cancer (LACC), is a complex medical procedure that requires an experienced multidisciplinary team. The aims of this analysis were to assess (1) the learning curve of brachytherapy team, (2) dose-volume parameters, (3) the use of an interstitial component, and (4) the overall treatment time (OTT). Our study cohort comprised 117 LACC patients treated in Kuopio University Hospital with magnetic resonance imaging guided intracavitary (IC) or combined intracavitary/interstitial (IC/IS) high dose rate brachytherapy during 2009-2018. Target volumes and organs at risk (OAR) were contoured according to ICRU/GEC-ESTRO recommendations. Treatment plans were optimized individually without using standard loading patterns. Mean dose to 90% of the high-risk clinical target volume (HR-CTV D90) improved after the first 15 patients, however the team's learning curve to reliably fulfill the main planning aim (PA) of 85 Gy required a total 43 patients and more than 10 patients annually. Significant difference was detected between IC and IC/IS brachytherapy in achieving the PA of HR-CTV D90. Especially, HR-CTV volumes >30 cm Brachytherapy requires good experience of multidisciplinary team and the continuous development of the program to fulfill PA and to avoid OTT prolongation. The use of IS needles is safe and improves the fulfillment of PA to target volume.

Utilization of brachytherapy in Quebec, Canada

Despite the excellent clinical outcomes from brachytherapy treatments compared with other modalities and the low associated costs, there have been reports of a decline in utilization of brachytherapy. The aim of this study was to investigate in detail the trend in utilization of brachytherapy in the province of Québec, Canada, from 2011 to 2019. All radiotherapy clinics in the province of Quebec, and among these the clinics that provide brachytherapy treatments, were identified. This observational retrospective cohort study involved analysis of data compiled by the Ministère de la Santé et des Services Sociaux du Québec for the period of 2011 to end of 2019 on all brachytherapy procedures performed in the province of Quebec. Time series graphs were used to describe the number of high dose rate (HDR) and low dose rate (LDR) brachytherapy treatments during the studied time period. Statistical analysis was conducted using R statistical software. Between 2011 and 2019, 12 hospitals in the province of Québec provided radiotherapy treatments, and all of them offered brachytherapy services. The median annual number of brachytherapy sessions was 4413 (range 3930-4829). HDR brachytherapy represented over 90% of all brachytherapy treatments throughout the study period. Significant changes over time were observed in the number of treatments: at least 5% change was seen only for the two most common subtypes of brachytherapy, HDR interstitial and HDR intracavitary, with an increase of 9.6% and a decrease of 9.2%, respectively. The use of other subtypes of brachytherapy (HDR-plesiotherapy, LDR-interstitial, LDR-intracavitary, LDR-eye plaque) was stable between 2011 and 2019, with ≤ 2.5% variation. This study demonstrates an overall steady use of brachytherapy between 2011 and 2019 in Quebec. Brachytherapy offers numerous advantages for the treatment of diverse cancer sites. Although more sophisticated external beam radiotherapy treatments have emerged in the last decades, the precision and cost-effectiveness of brachytherapy remain unbeaten. To ensure the continued use and availability of brachytherapy, governments must put in place policies and regulations to that effect. Training and exposure of future health care professionals to brachytherapy within Quebec and Canada is essential to provide all patients the same access to this life saving modality.

Morbidity following image-guided brachytherapy for cervical cancer: Patient and treatment related factors

This retrospective study aims to assess factors associated with the occurrence of toxicity after brachytherapy (BT), as boost after external beam radiotherapy (EBRT) for treatment of invasive cervix carcinoma. All consecutive patients diagnosed with cervical carcinoma, and treated with concurrent radiochemotherapy from August 2017 to January 2020 were retrospectively included. An isodose conformation index (ICI) was developed to assess the percentage of the prescription isodose contained within the intermediate risk clinical target volume (IR-CTV). Eighty-one patients with invasive cervix carcinoma from stage IB to stage IVa were included. Thirty-two (40%) and 49 (60%) patients were treated with Pulsed Dose Rate (PDR) and High Dose Rate (HDR) BT, respectively. Median follow-up was 19.6 months (5.6-41.2). The main factors associated with development of gastrointestinal toxicity were: the median volume of the prescription isodose (67.9cm[3] [37.6-92.9] vs. 49.1cm[3] [34.5-53.5], p = 0.05), the value of ICI (59% [51%-83%] vs. 86% [65%-96%], p = 0.01), the median equivalent dose delivered to the sigmoid (D2cc= 58.4 GyEQD2 [53.9-61.1] vs. 55.2 GyEQD2 [52.8-57.5], p = 0.06) and the median equivalent dose delivered to the IR-CTV (D90= 63.9 GyEQD2 [60.6-66.4] vs. 61.2 GyEQD2 [59.4-64.5], p = 0.03). The proportion of patients who received EBRT lymph node boost was higher in patients who developed urinary toxicity than in patients who did not (57.1% vs. 28.6%, p = 0.08). Anticoagulant (p = 0.02) and antiaggregant therapy (p = 0.01) were associated with occurrence of both urinary and gastrointestinal toxicity. Our study confirms the predictive value of irradiated volume in the occurrence of gastrointestinal toxicity, as well as the need for a better conformation to the target volume. Precautions should be considered in patients with vascular comorbidities.

Uterine perforation during brachytherapy for cervical cancer: Complications, outcomes, and best practices for forward treatment planning and management

The purpose of the study was to determine the incidence of uterine perforations, review the associated complications, and propose guidelines for management of perforations after brachytherapy. A retrospective chart review was conducted for all patients with cervical cancer who received single or multiple high-dose-rate brachytherapy implants between April 2006 and May 2017 at a single academic institution. CT and MRI images were retrospectively evaluated to record incidences of uterine perforation of tandem during brachytherapy. Acute and long-term complications during and after treatment were scored using the Common Terminology Criteria for Adverse Events, Version 4.0, of the National Cancer Institute. A total of 123 patients were included in the study. Perforations were observed in 22 patients (17.9%) with 31 (6.4%) of the 482 total implants. Of the different categories of adverse events, only the rate of acute infectious complications among those with perforations (n = 3, 13.6%) versus those without perforations (n = 3, 3.0%) was significant (p = 0.040). Two of the three perforated patients with acute infections had mild urinary tract infections, and all resolved without complications or treatment delays. The remaining one patient had a frank perforation of the anterior uterine wall with a subsequent Grade 3 pyometra infection despite administration of prophylactic antibiotics and 1-week treatment delay. This case was eventually resolved with cervical dilation and evacuation of fluid. Long-term complications were not different between the two arms. Patients with cervical cancer with uterine perforations may be able to safely proceed with brachytherapy treatment without delay or need for prophylactic antibiotics in the acute setting. Further validating data would be able to assist in establishing a new standard of care and help prevent unnecessary and harmful breaks during treatment.

Reporting of dose–volume specifications for “Martinez Universal Perineal Interstitial Template–based interstitial high-dose-rate brachytherapy for gynecological cancers” according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes

The study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy. Forty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017-2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed. High-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm Our study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.

Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies

Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs. ≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstrated to be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

Brachytherapy impacts on sexual function: An integrative review of the literature focusing on cervical cancer

There is growing awareness of the importance of sexual health in the quality of life of cancer patients and survivors. Brachytherapy, a vital component for the curative treatment of cervical cancer, leads to both direct and indirect sequelae that result in vaginal and sexual morbidity. The emergence of 3D image-guided adaptive brachytherapy has led to a better understanding of dose-and-effect relationships for critical organs-at-risk and there are new recommendations for vaginal dose reporting in the ongoing EMBRACE II study. An understanding of the vagina as an organ-at-risk and its dose-and-effect relationships can help brachytherapists limit dose to the vagina and improve sexual morbidity. Brachytherapists play a critical role in the primary and secondary prevention of vaginal and sexual sequelae resulting from treatment. Through close surveillance and recognition of common symptoms, brachytherapists can intervene with effective strategies to prevent and treat vaginal and sexual symptoms. This review summarizes the current literature on dosimetric factors that may predict for vaginal morbidity. It will focus on quantitative and qualitative reports of brachytherapy-related vaginal toxicity and sexual dysfunction. Lastly, it will review the available evidence supporting clinical interventions to mitigate the development and progression of vaginal and sexual sequelae to improve functional quality post-treatment.

Evaluating the accumulated dose distribution of organs at risk in combined radiotherapy for cervical carcinoma based on deformable image registration

To evaluate the feasibility and value of deformable image registration (DIR) in calculating the cumulative doses of organs at risk (OARs) in the combined radiotherapy of cervical cancer. Thirty cervical cancer patients treated with external beam radiotherapy (EBRT) combined with intracavitary brachytherapy (ICBT) were reviewed. The simulation CT images of EBRT and ICBT were imported into Varian Velocity 4.1 for the DIR-based dose accumulation. Cumulative dose-volume parameters of D2cc for rectum and bladder were compared between the direct addition (DA) and DIR methods. The quantitative parameters were measured to evaluate the accuracy of DIR. The three-dimensional cumulative dose distribution of the tumor and OARs were graphically well illustrated by composite isodose lines. In combined EBRT and ICBT, the mean cumulative bladder D2cc calculated by DIR and DA was 86.13 Gy and 86.27 Gy, respectively. The mean cumulative rectal D2cc calculated by DIR and DA was 72.97 Gy and 73.90 Gy, respectively. No significant differences were noted between these two methods (p > 0.05). As to the parameters used to evaluate the DIR accuracy, the mean DSC, Jacobian, MDA (mm) and Hausdorff distance (mm) were 0.79, 1.0, 3.84, and 22.01 respectively for the bladder and 0.53, 1.2, 7.31, and 29.58 respectively for the rectum. In this study, the DSC seemed to be slightly lower compared with previous studies. Dose accumulation based on DIR might be an alternative method to illustrate and evaluate the cumulative doses of the OARs in combined radiotherapy for cervical cancer. However, DIR should be used with caution before overcoming the relevant limitations.

Letter to the editor regarding “Reducing dose to rectum by placement of a rectum-emptying tube in cervical cancer patients treated with brachytherapy”

Results of computer tomography-based adaptive brachytherapy in combination with whole-pelvic- and central-shielding-external beam radiotherapy for cervical cancer

To evaluate treatment results and investigate predictors of local control. In this retrospective study of 236 patients with cervical cancer, we administered CT-based adaptive brachytherapy (BT) in combination with whole- pelvic (WP)- and central shielding (CS)- external beam radiotherapy (EBRT) with or without chemotherapy. The study cohort comprised patients with cervical cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy between June 2013 and March 2019. Local control (LC), overall survival (OS), and late toxicity were evaluated. Predictive factors for LC were analyzed by univariate and multivariate analyses. Median doses of WP- and CS-EBRT and BT were 30.6 Gy The combination of WP- and CS-EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC outcomes with low rates of late toxicities for patients with small or medium-sized tumors. However, LC was less favorable for patients who had large T3 disease, and the use of CS requires caution in these patients.

Change in image-guided planning strategies over time impacts oncologic and survival outcomes for intracavitary cervical cancer brachytherapy

Intracavitary cervical brachytherapy (BT) has transitioned from a two-dimensional nonvolumetric (NV) dosimetry system to three-dimensional computed tomography (CT) and/or magnetic resonance imaging (MRI)-based planning techniques. The purpose of this study is to retrospectively evaluate the relative improvements in image-guided planning strategies over time with regards to dosimetry, survival, and toxicity. A single site retrospective review of 95 locally advanced cervical cancer patients treated with concurrent chemoradiation and high dose rate BT from 2009 to 2016 were divided into three BT planning groups: point-A based NV dosimetry using CT imaging (n = 37), CT-based volumetric dosimetry (n = 33), and MRI-based volumetric dosimetry (n = 25). Overall survival (OS), progression free survival (PFS), and pelvic control (PC) at 5 years were plotted using Kaplan-Meier curves. Univariate and multivariate (MVA) cox proportional-hazards models calculated hazard-ratios (HZ). Finally, acute and late grade 3-4 toxicities were compared between the cohorts. Both MRI and CT had significantly less D2cc to bowel (p < 0.001) and sigmoid (p < 0.001) compared to NV-based planning. On MVA, age (<60 vs. ≥60 years) was significant for worse 5-year OS (HZ: 2.48) and PC (HZ: 5.25). MRI, with NV as the reference, had significantly improved 5-year OS (HZ: 0.26), PFS (HZ: 0.34) and PC (HZ: 0.16). There was no significant difference in grade ≥3 toxicities between the cohorts. CT and MRI-based 3D planning had significantly less D2cc to bowel and sigmoid. MRI-based planning had significant improvement in 5-year OS, PFS, and LC compared to NV on MVA.

The association of vagina equivalent dose in 2Gy fraction (EQD2) to late vagina toxicity in patients of cervical cancer treated with WPRT plus IGABT

To evaluate the associations of vaginal dose parameters and incidence of vaginal stenosis in patients with cervical cancer treated with image-guided brachytherapy (IGBT). Fifty-four patients with cervical cancer treated with IGBT were included. The vagina contouring was done on previously treated CT images and the vaginal dose points were marked. The cumulative dose in EQD2 from EBRT and IGBT was calculated for both aspects and the vaginal toxicity was evaluated. At median follow-up time of 18.5 months, grade 2 or higher vaginal stenosis was observed in 24% of patients. On univariate analysis, parameters that were associated with ≥ grade 2 vaginal stenosis were age, mean dose of lateral 5 mm vagina, dose at PIBS-2 cm, mid vaginal D0 .03cc, mid vagina D1cc, lower vagina D0.03cc, lower vagina D0.1cc, lower vagina D1cc and lower vagina D2cc. On multivariate analysis, the significant parameters were age > 68.5 years old (P = 0.038), mean dose of lateral 5-mm (P = 0.034), and dose at PIBS-2 cm (P = 0.042). Age > 68.5 years old, mean dose of lateral 5 mm vagina and dose at PIBS-2 cm were associated with grade 2 or higher vaginal stenosis.

Knowledge-based three-dimensional dose prediction for tandem-and-ovoid brachytherapy

The purpose of this work was to develop a knowledge-based dose prediction system using a convolution neural network (CNN) for cervical brachytherapy treatments with a tandem-and-ovoid applicator. A 3D U-NET CNN was utilized to make voxel-wise dose predictions based on organ-at-risk (OAR), high-risk clinical target volume (HRCTV), and possible source location geometry. The model comprised 395 previously treated cases: training (273), validation (61), test (61). To assess voxel prediction accuracy, we evaluated dose differences in all cohorts across the dose range of 20-130% of prescription, mean (SD) and standard deviation (σ), as well as isodose dice similarity coefficients for clinical and/or predicted dose distributions. We examined discrete Dose-Volume Histogram (DVH) metrics utilized for brachytherapy plan quality assessment (HRCTV D90%; bladder, rectum, and sigmoid D2cc) with ΔD Ranges of voxel-wise dose difference accuracy (δD¯±σ) for 20-130% dose interval in training (test) sets ranged from [-0.5% ± 2.0% to +2.0% ± 14.0%] ([-0.1% ± 4.0% to +4.0% ± 26.0%]) in all voxels, [-1.7% ± 5.1% to -3.5% ± 12.8%] ([-2.9% ± 4.8% to -2.6% ± 18.9%]) in HRCTV, [-0.02% ± 2.40% to +3.2% ± 12.0%] ([-2.5% ± 3.6% to +0.8% ± 12.7%]) in bladder, [-0.7% ± 2.4% to +15.5% ± 11.0%] ([-0.9% ± 3.2% to +27.8% ± 11.6%]) in rectum, and [-0.7% ± 2.3% to +10.7% ± 15.0%] ([-0.4% ± 3.0% to +18.4% ± 11.4%]) in sigmoid. Isodose dice similarity coefficients ranged from [0.96,0.91] for training and [0.94,0.87] for test cohorts. Relative DVH metric prediction in the training (test) set were HRCTV ΔD¯ A 3D knowledge-based dose predictions provide voxel-level and DVH metric estimates that could be used for treatment plan quality control and data-driven plan guidance.

Brachytherapy workflow for locally advanced cervical cancer: A survey of Canadian Medical Physicists

To report on brachytherapy (BT) workflows for image-based treatments of locally advanced cervical cancer (CC) in Canada. Medical Physicists in every Canadian cancer center were contacted and those with a CC-BT program were emailed a 44-item electronic questionnaire surveying workflow patterns including: fractionation schedules, prescription, equipment, imaging, and treatment delivery. Of 47 centers contacted, all 34 who performed CC-BT participated in the survey. Brachytherapy boost, following external beam treatments, was delivered using high-dose-rate (HDR); one center also used pulsed-dose-rate. Intracavitary and/or interstitial treatments were done in 47% centers for 25-80% of their patients. All centers used image-based planning: CT (32%), CT planned with MRI for contouring (47%), MRI (18%), or cone beam CT (3%). For those performing volume-based planning (74%), the contours commonly included Clinical Target Volume (CTV)-High Risk (HR), CTV-Intermediate Risk, rectum, sigmoid, and bladder. The most common HDR dose-fractionation schedule was 7 [4.6 - 10] Gy in 4 [3 - 6] fractions with radiobiological dose prescriptions performed in 62% centers. Medical physics contribution was significant during most activities along the BT treatment pathway in all centers, especially in planning (88%), second checks (68%), and during treatment delivery (88%). Compared to previous surveys, there is an increasing trend in the use of image-based volumetric planning, interstitial procedures, and radiobiological dose prescription. Cervical cancer brachytherapy in Canada is becoming more streamlined with the use of international practice guidelines. Involvement of medical physicists is vital to all stages of CC-BT, including program implementation, routine quality control, dosimetry, and treatment delivery.

Ureter dose optimization during image guided brachytherapy for cervical cancer

In the era of image guided radiotherapy and interstitial needle use, radiation dose to ureters can cause toxicity. A retrospective analysis of 106 patients with cervical cancer was performed to investigate ureter dose in brachytherapy patients. Re-optimization of brachytherapy treatment plans in 20 MRI planned patients was performed to reduce ureter dose whilst maintaining HRCTV D90 and OAR dose constraints. A total of 212 ureters were contoured and dose recorded. The crude incidence of ureteric stenosis was 6.6%. Ureter dose for all patients was 75.8 Gy and 74.4 Gy on the right and left respectively. A cohort of 20 MRI planned patients were reoptimized to reduce dose to ureters. Ureter dose was reduced from 91.1 Gy to 84.4 Gy and 73.9 Gy to 67.8 Gy on the right and left side respectively. A subgroup of patients with HRCTV D90 ≥84.3 Gy prior to reoptimisation saw a greater reduction in ureter dose of 13.3%. These were smaller tumours with better HRCTV coverage at the outset. Larger tumours with poorer HRCTV coverage (<84.3 Gy) saw a smaller reduction in ureter dose of 6.4%. Organ at risk dose to rectum, sigmoid and bladder were also significantly reduced. Patients treated with MRI guided brachytherapy and interstitial needles are at risk of ureteric stenosis. Contouring ureters and setting dose constraints should be considered to reduce ureteric dose while tracking HRCTV coverage.

Preoperative high-dose-rate brachytherapy for high-risk early-stage cervical cancer: Long-term clinical outcome analysis

To report long-term oncological and toxicity outcomes after high-dose-rate brachytherapy (HDB) followed by oncologic surgery for patients with early-stage cervical cancer. From 2005 to 2019, all patients treated with preoperative HDB at Antoine Lacassagne Cancer Center for early-stage (IB1-IB2-IIA - FIGO 2018) cervical cancer with local relapse risk factors were included. HDB was performed followed by hysterectomy. Oncological and toxicity outcomes were evaluated prospectively. We identified 61 patients, with a median follow-up of 84 months. Posthysterectomy complete pathological response was observed in 46 patients (75.4%). Six patients (9.8%) experienced recurrence, including 4 local relapses (6.6%), and 2 deaths (3.3%) due to cervical cancer. Five-year local, nodal and metastatic relapse-free survivals were 94% (95% CI 87-100%), 96% (95% CI 90-100%) and 93% (95% CI 86-100%) respectively. Five-year overall survival was 98% (95% CI 95-100%). No grade ≥ 3 acute toxicity was observed, and 3 patients (4.9%) experienced grade 2 acute toxicity. One patient presented grade 4 late digestive toxicity, and 6 patients had grade 2 late toxicity. Only 1 patient still had grade 2 toxicity, after 9 years follow-up. To our knowledge, we are reporting the longest follow-up of a preoperative HDB cohort. With similar oncological outcomes and less morbidity compared to primary surgery treatment followed more or less by adjuvant radiotherapy, HDB followed by hysterectomy could be a promising therapeutic option for early-stage cervical cancers with poor prognostic factors.

Image guided cervical brachytherapy practice patterns: 2023/2024 survey of the American brachytherapy society

An update of the 2007 and 2014 surveys of the American Brachytherapy Society (ABS) will elucidate current practice patterns of cervical cancer brachytherapy. A 40-question survey was sent to all ABS members in June-July 2023 and February 2024; 167 responses were received, with 140 used for analysis. Results were compared to the 2014 survey using chi-squared testing. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) with 95% confidence intervals (CI) for outcomes of interest. Compared to 2014, MRI use for treatment planning of the first brachytherapy fraction increased from 34% to 63% (p 80%) (29% vs. 4%, p < 0.001). MRI availability around the time of procedure was the largest challenge to incorporating MRI into brachytherapy treatment planning. Compared to those with MRI access reserved specifically for Radiation Oncology, respondents with shared-access or out-of-department MRI were less likely to obtain treatment planning MRIs for each brachytherapy fraction (22% vs. 75%; aOR 0.10 [95% CI, 0.03-0.30], p < 0.001). For cervix cancer brachytherapy there has been significant increase in the use of MRI-based volumetric brachytherapy treatment planning, ultrasound guidance during procedures and the addition of interstitial needles. These advancements in practice patterns are congruent with published consensus guidelines and ongoing training initiatives. However, MRI access and lack of easy availability continue to be significant challenges for optimizing cervix brachytherapy.

Towards robust deep learning-based autosegmentation in MRI-planned gynecological brachytherapy: Importance of scalable development and comprehensive evaluation

To present comprehensive development and evaluation methodologies for a generalizable deep learning (DL)-driven autocontouring model of standard pelvic organs-at-risk (OARs) in MRI-planned cervical brachytherapy. A curated dataset of 200 3D-MRIs (85% training/validation, 15% testing) including multiple applicator types, varying treated anatomies, and manual contours of OARs (bladder, rectum, sigmoid, small bowel) by 3 physicians was utilized to develop an nnU-Net-based autocontouring model. Iterative tuning was conducted to determine the optimal hyperparameters and enhance evaluation metrics. Model performance was assessed using quantitative metrics, like geometric (e.g., Dice Coefficient (DC) and Hausdorff Distance 95th Percentile (HD95)) and dosimetric (dose-volume histograms (DVHs), dose differences (ΔD2cc)), and then correlated with qualitative physician-review (modified Turing and Likert tests). Geometric metrics were best for bladder (e.g., mean ± SD DC|HD95(mm) 0.93 ± 0.02|2.26 ± 1.07) with greater variability exhibited for small bowel (0.62 ± 0.16|24.90 ± 14.36). Dosimetric comparisons of manual vs predicted contours showed high agreement in DVHs, with mean ΔD2cc <0.60 Gy EQD2 The DL-based autocontouring model, trained on a heterogeneous in-house dataset, demonstrates clinical acceptability for OARs as determined by comprehensive evaluation. It also shows promise for translatability to target contouring, and adaptability to other gynecological (noncervix) brachytherapy applications. Differences in qualitative and quantitative results exist; directionality and magnitude should be considered in clinical usability assessments of brachytherapy autocontouring models.

Gastrointestinal and genitourinary toxicity following high dose rate vaginal cuff brachytherapy for endometrial cancer

There are currently no organs at risk dose constraints for adjuvant HDR vaginal cuff brachytherapy (VBT). This study evaluates OAR dosimetry and the association with acute and chronic gastrointestinal (GI) or genitourinary (GU) toxicity. Patients treated at a single institution with VBT of 21 Gray (Gy) in 3 fractions (Fx) prescribed to 5 mm depth twice weekly and CT-based 3D planning were reviewed. OAR doses (D2cc, D1cc, and D0.1cc) were recorded. Acute and chronic toxicities were graded by Common Terminology Criteria for Adverse Events v5.0. Boxplot and Wilcoxon-Mann-Whitney tests compared dose thresholds. 177 patients with stage I-IV endometrial cancer received a mean D2cc to rectum, sigmoid, small bowel, and bladder of 5.7 Gy (range: 2.8-8.7), 3.3 Gy (0.6-9.3), 3.8 Gy (0.0-9.1), and 5.4 Gy (2.0-8.2). Overall, 6.2% (n = 11) and 7.3% (n = 13) of patients experienced acute GI and GU toxicity of any grade. 14.7% (n = 26) and 14.7% (n = 26) of patients experienced chronic GI and GU toxicity of any grade, respectively. There were two grade 3 toxicities include one chronic GI and one acute GU. No dosimetric factors were identified that correlated with a higher likelihood of acute or chronic toxicity. The overall rate of GI and GU toxicity following VBT of 21 Gy in 3 Fx is low, and there are no dosimetric parameters that correlate with toxicity. The optimal dose fractionation schedule that balances high local control with minimal toxicity is yet to be determined.

Salvage interstitial brachytherapy for treatment of recurrent endometrial cancers in the vagina: Seven-year single institution experience and review of second recurrence patterns

Interstitial brachytherapy (ISBT) is a known treatment for vaginal recurrence of endometrial cancer. This study reviews a large tertiary institution's ISBT experience and outcomes for vaginal recurrences. Patients who underwent salvage ISBT for vaginal recurrence of endometrial cancer from January 1, 2014 to August 31, 2021, were identified. Initial and salvage disease factors and treatments were recorded. Outcomes were calculated including overall survival, local, and distant failure. Thirty-nine patients were included; thirty received external beam radiotherapy and interstitial brachytherapy (EBRT + ISBT) while 9 received ISBT alone. At initial diagnosis, the ISBT alone group had an older median age, with stage IA-IV disease, frequently receiving adjuvant treatment, compared to the EBRT with ISBT group with mainly stage IA disease who did not. Median follow up was 22 months and median time to recurrence 14 months (16.5 months in EBRT + ISBT group and 14 in the ISBT alone group). Two-year overall survival was 85% for all patients, 85.6% and 83.3%in the EBRT + ISBT and ISBT alone groups, respectively. Local failure was 22.7% for all patients, 16.7% in the EBRT + ISBT group and 11.1% in the ISBT alone group. Median HRCTV D90 (EQD2) was 76.8 Gy in the EBRT + ISBT group, and 57.9 Gy in the ISBT alone group. Late grade 3 or higher toxicity occurred in only 3 patients. EBRT + ISBT is an effective treatment for endometrial cancer vaginal recurrence, with acceptable toxicity. ISBT alone is an option for patients with contraindications to or with previous treatment of pelvic radiation.

Image-guided brachytherapy following external-beam radiation therapy for patients with inoperable endometrial cancer

To investigate the outcomes of definitive external-beam radiation therapy (EBRT) plus image-guided brachytherapy (IGBT) in patients with endometrial cancer (EC) unsuitable for surgery. A total of 50 patients with inoperable EC were included. The patients received EBRT in a median dose of 45 Gy to the pelvis over 5 weeks. Thereafter, the patients received brachytherapy using tandem and ovoid applicators. High-risk clinical target volume (HR-CTV) and gross tumor volume in brachytherapy (GTVp) were defined by the assistance of patients' pre-IGBT magnetic resonance imaging. The medical records of the 50 patients were analyzed. The main causes of inoperability were anesthesia contraindications, namely medical comorbidities and obesity. The median cumulative D90s (the minimum dose delivered to 90% of the volume) in EQD2 (equivalent dose in 2-Gy fractions) to the HR-CTV and GTVp were 72.9 Gy10 (range, 64.9 to 80.3) and 166.2 Gy10 (range, 123.0 to 189.8), respectively. Over a median follow-up period of 27 months, 8 of the patients died of cancer. The 2-year overall and cancer-specific survival rates were 75% and 83%, respectively. The cumulative incidences of pelvic and distant failure were 4% (n = 2) and 16% (n = 8), respectively. Gastrointestinal complications of grade 2 or above were noted in 2 patients (4%), and a grade 2 genitourinary complication was noted in one. For patients with inoperable EC, EBRT followed by IGBT is an effective approach for achieving high local control without a high risk of complications.

Change in vaginal length and sexual function in women who undergo surgery ± radiation therapy for endometrial cancer

Endometrial Cancer (EC) is the most common gynecologic malignancy in the United States. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk. Treatment can cause significant vaginal changes, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These are not life threatening, but affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are inconsistent recommendations on use. This prospective study compared vaginal length changes and sexual function in women compliant with dilation versus not after surgery and RT. Enrolled patients underwent surgery for Stage I-IIIC EC ±RT. Vaginal dilator use was recommended for women receiving RT (external beam or brachytherapy). Vaginal length was measured with a vaginal sound and the Female Sexual Function Index (FSFI) was used to assess sexual function. Forty-one enrolled patients had sufficient data for analysis. Dilation significantly increased FSFI scores (p = 0.02) while RT without dilation showed a significant decrease (p = 0.04). Dilation helped maintain vaginal length for all patients (0 cm vs. 1.8 cm loss (p = 0.03)). Individual arms did not show statistically significant changes in length with dilation, though the trend showed RT without dilation had an average loss of 2.3 cm as compared to only 0.2 cm for regular dilation. Notably, there was no difference in length change with dilation for surgery alone versus surgery and RT (p = 0.14). This data provides novel, prospective evidence of the benefit of vaginal dilation for maintaining vaginal length and improving sexual health after any pelvic treatment for EC. This evidence also supports that the addition of RT after surgery does not appear to significantly worsen vaginal shortening. This study has important implications for providing a strong foundation for future studies and helping to establish solid clinical management criteria for the prevention of vaginal stenosis and promotion of female sexual health.

The role for vaginal cuff brachytherapy boost after external beam radiation therapy in endometrial cancer

To evaluate the role and technique of a vaginal cuff brachytherapy (VB) boost to adjuvant external beam (EB) radiation for endometrial cancer through a systematic review. Relevant trials were identified through a systematic search of the literature. A total of 21 prospective and retrospective studies which had a patient cohort undergoing EB + VB was identified to evaluate for rates of vaginal and pelvic recurrences, overall survival, and toxicity. Additional database studies were utilized to demonstrate differences in local control and overall survival between EB and EB + VB. While there is limited prospective evidence to guide the use of a VB boost after EB, the evidence suggests that patients with a higher risk of a vaginal recurrence such as those with cervical stromal involvement in select Stage III patients may derive local control and survival benefits from a VB boost. Additional individual risk factors such as grade, histology, extent of invasion, margin status, age, and the use of lower doses of EB should be considered when deciding when to add a VB boost.

A semiautomatic segmentation method for interstitial needles in intraoperative 3D transvaginal ultrasound images for high-dose-rate gynecologic brachytherapy of vaginal tumors

The purpose of this study was to evaluate the use of a semiautomatic algorithm to simultaneously segment multiple high-dose-rate (HDR) gynecologic interstitial brachytherapy (ISBT) needles in three-dimensional (3D) transvaginal ultrasound (TVUS) images, with the aim of providing a clinically useful tool for intraoperative implant assessment. A needle segmentation algorithm previously developed for HDR prostate brachytherapy was adapted and extended to 3D TVUS images from gynecologic ISBT patients with vaginal tumors. Two patients were used for refining/validating the modified algorithm and five patients (8-12 needles/patient) were reserved as an unseen test data set. The images were filtered to enhance needle edges, using intensity peaks to generate feature points, and leveraged the randomized 3D Hough transform to identify candidate needle trajectories. Algorithmic segmentations were compared against manual segmentations and calculated dwell positions were evaluated. All 50 test data set needles were successfully segmented with 96% of algorithmically segmented needles having angular differences <3° compared with manually segmented needles and the maximum Euclidean distance was <2.1 mm. The median distance between corresponding dwell positions was 0.77 mm with 86% of needles having maximum differences <3 mm. The mean segmentation time using the algorithm was <30 s/patient. We successfully segmented multiple needles simultaneously in intraoperative 3D TVUS images from gynecologic HDR-ISBT patients with vaginal tumors and demonstrated the robustness of the algorithmic approach to image artifacts. This method provided accurate segmentations within a clinically efficient timeframe, providing the potential to be translated into intraoperative clinical use for implant assessment.

Evaluation of an MR-only interstitial gynecologic brachytherapy workflow using MR-line marker for catheter reconstruction

Magnetic resonance imaging (MRI) offers excellent soft-tissue contrast enabling the contouring of targets and organs at risk (OARs) during gynecological interstitial brachytherapy procedure. Despite its benefit, one of the main challenges toward MRI-only workflows is that the implanted catheters are not reliably visualized on MR images. This study aims to evaluate the feasibility of MR-only workflow using an in-house MR line marker during interstitial gynecological high-dose-rate (HDR) brachytherapy. Ten patients diagnosed with locally advanced cervical cancer treated with HDR brachytherapy were included in this study. The hybrid CT/MR-treated plan was used as the study reference plan. Five users manually reconstructed the catheter's path on MR images (3D T1- and T2-weighted). Subsequently, the dwell positions from the users' plans were superimposed on the reference plans to evaluate the dosimetric impact of the using MR-only for catheter reconstruction in comparison with hybrid CT/MR approach. Variability of dwell positions between users and reconstruction time was also evaluated. More than 96.90% of catheter reconstruction variations were < 2 mm. No statistical differences were reported between MR-only and hybrid CT/MR in gross tumor volume D The feasibility of MR-only workflow using MR line marker during interstitial gynecological HDR brachytherapy has been validated in this study. The results show that the MR-only workflow is equivalent to the conventional hybrid CT/MR approach in terms of gross tumor volume and high-risk clinical target volume coverage and respecting of OARs dose limits.

Time-driven activity-based costing of adjuvant vaginal cuff brachytherapy for uterine cancer in an integrated brachytherapy suite

Adjuvant vaginal cuff brachytherapy is well tolerated and reduces the risk of local recurrence in endometrial cancer. However, there is provider variation in the number of radiation treatments, which ranges from three to six fractions. Using time-driven activity-based costing, we calculated the cost to deliver three vs six fractions to determine the value of each regimen at our brachytherapy suite with CT-on-rails. Process maps were created to represent each step from initial consult to completion of therapy. Components of care included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource and calculated for each regimen. The total direct costs to deliver three- and six-fraction treatment courses were $1,415 and $2,227, respectively. Personnel cost accounted for 63% of overall expenditures. Computed tomography simulation and planning, required for the first fraction, cost $232 for both regimens. Duties of the procedural nurse (scheduling, patient setup, and turnover) consumed the most time at 35% of total personnel minutes. Time-driven activity-based cost analysis revealed a 57% relative increase, but modest absolute increase, in delivery costs for six vs three fractions of brachytherapy at our institution. This current analysis may influence considerations of the relative value between the two treatment schedules, but this methodology should not be interpreted as informative for reimbursement policy evaluation.

Choosing between the best, the easiest and the most usual: Three different dose prescription methods for HDR vaginal-cuff brachytherapy planning in postoperative endometrial cancer

To evaluate and compare dosimetry parameters of three planning methods in high-dose-rate vaginal cuff brachytherapy (VCB) using cylinders for postoperative endometrial cancer (PEC). Two hundred seventeen patients were treated with 3D-based VCB for PEC, with the dose prescribed at 5 mm from the applicator surface. Three planning methods were retrospectively compared: T1-arm: point-based optimization at 5 mm from the applicator surface; T2-arm: volume-based optimization; T3-arm: graphical optimization. We evaluated the coverage index (CI), conformity index (COIN), D90 to clinical target volume (CTV) and dose to the organs at risk (OAR). Descriptive analysis, Chi-square test, Student`s t-test, GEE model, linear regression model. The mean CI was greater than 0.9 in all treatment arms. The T2-arm provided the highest COIN value while T1-arm provided the highest CI value. The T3-arm delivered the lowest doses to the vaginal CTV, rectum and bladder. The linear regression model suggested that in the T3-arm, COIN showed improvement at the expense of CI and achieving a balance between CI and COIN may be more feasible when administering the T2-arm. The T2-arm may be considered a general optimization method since it provides a better COIN within an acceptable D90 to the CTV. However, the T3-arm is easier in daily practice and could be more beneficial for patients who are more likely to develop late complications in OAR. More studies are needed to clarify the correlation of late complications with planning methods and dosimetry variables.

Radiomics-based machine-learning approach to predict response at brachytherapy using pretreatment magnetic resonance imaging in locally advanced cervical cancer

We investigated baseline magnetic resonance imaging (MRI) radiomic features for predicting tumor response in patients with locally advanced cervical cancer (LACC) at brachytherapy (BT). Seventy-four patients underwent baseline T2W MRI. Gross tumor volume at diagnosis (GTV-T initial) was delineated. Tumor radiomic features were extracted using TexRAD software. Feature enrichment using parameters indicative of response was done using least absolute shrinkage and selection operator (LASSO) regression. The support vector machine (SVM) algorithm was used to generate the model. Response to chemo-radiotherapy was based on the criteria GTV-BT/GTV-T initial ratio 0.20 was used for classifying good versus poor responders. Fifty-six radiomic features were extracted. LASSO enriched the number of features to 11 for the GTV-BT/GTV-T initial ratio. The SVM classifier with a 10-fold internal cross-validation demonstrated an AUC of 0.82 and 76.8% accuracy when the response was assessed using the GTV-BT/GTV-T initial ratio for response evaluation. When SVM was modeled using clinical features, the AUC was 0.55, and the accuracy was 62.6% for the GTV-BT/GTV-T initial ratio, CONCLUSION: Machine learning model employing radiomic features extracted from pre-treatment MRI reliably predicted treatment response in patients with LACC.

Understanding the value of paracervical block during gynecologic brachytherapy: A systematic review of the literature

Paracervical block is a technique to provide local anesthesia with evidence supporting its use for various gynecologic procedures; however, the literature on its use for gynecologic brachytherapy is limited. This systematic review seeks to understand the efficacy and safety of paracervical block in cervical cancer brachytherapy. PubMed and EMBASE/Cochrane Library databases were searched from inception to June 2023. Articles were included if they described or mentioned the use of paracervical block in the context of HDR brachytherapy for cervix cancer. Non-English language or abstract-only articles were excluded. Citations were reviewed for relevant papers. Pain control and toxicity outcomes were abstracted along with technical details of anesthesia and brachytherapy procedure. Of the 396 articles identified, eight were included. Two gave general recommendations around the role of paracervical block. The rest described its use during brachytherapy at their respective institutions. There was heterogeneity in paracervical block technique across different publications. The majority of included articles describe use of paracervical block for procedural pain control, while only one describe its use for postprocedure pain control. Pain was well controlled with <10% of patients experiencing moderate or higher pain. However, there were no studies specifically assessing pain management with versus without use of paracervical block. The rate of grade 3+ toxicity associated with its use was <5%. Paracervical block is safe and can be part of effective pain management for patients receiving cervical brachytherapy. However, the incremental benefit of adding paracervical block is not well assessed in the current literature.

Gel spacer-assisted salvage brachytherapy for pelvic recurrence after definitive chemoradiotherapy in cervical cancer: A single-institution retrospective study

To evaluate the safety and efficacy of gel spacer-assisted high-dose-rate (HDR) salvage brachytherapy for pelvic recurrence after definitive chemoradiotherapy (CRT) for cervical cancer. We retrospectively analyzed 15 consecutive patients who underwent salvage HDR interstitial brachytherapy for pelvic recurrence following definitive CRT for cervical cancer between 2016 and 2024. Gel spacers were injected between the recurrent tumors and adjacent organs at risk (OARs), mainly the rectum and bladder, under transrectal ultrasound guidance at each brachytherapy session. The spacer's effectiveness was evaluated by comparing the hypothetical dose delivered to the gel spacer volume (assuming no spacer was used) with the actual dose to the OARs. The median biological equivalent dose in 2-Gy fractions (EQD2, α/β = 10) delivered during reirradiation was 64.0 Gy (range: 44.5-72.0 Gy). After a median follow-up of 22 months (range: 0-93 months), the complete response rate was 66.7% (10/15). Gel spacer injection significantly reduced the rectal D2cc by a median of 29% (interquartile range [IQR]: 14%-55%) and the bladder D2cc by 16% (IQR: 10%-34%) compared with the hypothetical dose estimates assuming no spacer use (Wilcoxon signed-rank test, p < 0.001). Grade ≥3 late toxicities occurred in only one patient (10.0%) among complete responders, and no spacer-related adverse events were observed. Gel spacer-assisted salvage brachytherapy significantly reduced radiation exposure to critical OARs, particularly the rectum, while achieving effective tumor control in patients with pelvic recurrence of cervical cancer after definitive CRT. These promising results support this approach as a feasible and safe strategy, warranting further validation in larger prospective studies.

The American Brachytherapy Society (ABS) consensus guidance for hybrid intracavitary interstitial brachytherapy for locally advanced cervical cancer

The purpose of this consensus statement from the American Brachytherapy Society (ABS) is to summarize important considerations for adding interstitial needles to intracavitary implants for cervix cancer brachytherapy. A panel of experts in Gynecologic Brachytherapy, including both physicians and physicists completed surveys and met virtually on multiple occasions to discuss and define current practices and approaches in order to summarize these for the ABS community. This document was drafted, reviewed and approved by the full panel and the ABS Board of Directors. Hybrid brachytherapy is increasingly being utilized in cervix brachytherapy. In incorporating supplementary interstitial needles there are numerous key considerations including resources for an emergency, planning considerations, applicator selection, and pre-, intra- and postprocedural imaging. Additionally, approaches to challenging cases that would often benefit from a hybrid approach are discussed. While hybrid brachytherapy offers dosimetric advantages for cervix brachytherapy, it increases procedure complexity. Being aware of the necessary resources and defining considerations can help mitigate some of the challenges and improve procedural success.

3D HDR brachytherapy for cervical cancer in LMIC: Audit of a single institution experience in Lagos, Nigeria

The first 3D high-dose-rate brachytherapy (3D-HDR-BT) program for gynecological cancers in Lagos, Nigeria, was launched in August 2021. A retrospective audit of the pilot program was conducted to report the institution's initial experience in treating cervical cancer within the framework of the American Brachytherapy Society (ABS) guidelines. 24 patients were audited and divided into 2 groups: Group A, which included the first twelve (who had been treated within 3 months of the program launch), and Group B, which included the next twelve (who received treatment over a subsequent period of 5 months). The average age was 58.04 years, with the most common stage at presentation being FIGO Stage IIB (50%). Squamous cell carcinoma was the prevalent histologic type (87.5% of cases). The predominant EBRT regimen was 1.8Gy x 25 fractions in 66.67% of patients. For brachytherapy, 62.5% received the 8Gy x 3 fractions regimen. All patients received weekly concurrent chemotherapy with external beam radiation, with the majority getting cisplatin monotherapy during external beam radiotherapy (EBRT). The mean dose to D90 of the HR-CTV was 77.48 ± 6.95Gy and 88.93 ± 4.20Gy in Group A and B patients, respectively. A comparative assessment revealed significant improvement in HRCTV D90 doses for Group B patients. We report evident improvement in HRCTV D90 doses with increasing numbers and duration of practice, indicating that team proficiency improves with an increasing number of patients treated. Future studies will focus on overall survival and local control rates among patients treated on the program.

Patterns of practice survey for cervical cancer brachytherapy in Morocco

This study surveyed radiation oncologists in Morocco to explore current practices and perspectives on brachytherapy for cervix cancer. A 37-question survey was conducted in April 2023 among 165 Moroccan radiation oncologists using Google Forms. Of the 93 respondents, 39% treated over 20 patients in 2022 using 3D image-guided brachytherapy (BT) through the HDR technique; 2D techniques were not reported in the last five years. Intracavitary BT is uniformly applied with a tandem and ovoid applicator. Only 14% utilized interstitial needles for hybrid BT. Iridium-192 was the primary radioactive source (63%), followed by cobalt (37%). Ultrasound-guided 47% of applicator insertions. All used CT scans for planning, but only 6% used MRI fusion due to limited availability. Guidelines for target volume and dose prescription were mostly based on GEC-ESTRO recommendations (74%), followed by Manchester Point A (30.4%) and ABS (11%). Over 90% delineated CTV-HR and CTV-IR; 30% delineated GTV. All marked the bladder and rectum, while 52% marked the sigmoid, 5% the small bowel, and 3% the recto-vaginal point. For dosimetry, 12% used ICRU 89 points, 54% used dose-volume histograms (DVH), and 36% used both. Most reported EQD2cc for OARs for the rectum and bladder, with nine still using ICRU point doses. The most common fractionation schema was 7 Gy in four fractions (60%) and 7 Gy in three fractions (55%). Brachytherapy remains essential for treating cervical cancer in Morocco. Key areas for improvement include MRI fusion-guided brachytherapy, access to advanced applicators, expanding interstitial techniques, and professional training and national referential.

3D-printed needle guides for cervical cancer brachytherapy: Optimized dosimetry and improved local control outcomes

We previously designed three-dimensionally-printed needle guides (3D-NG) for cervical cancer brachytherapy, which improved procedure efficiency and tumor coverage while achieving similar organs at risk (OAR) sparing compared to non-3D-printed techniques (non-3D). The subject of this study was whether 3D-NG can help improve local control and other brachytherapy outcomes. This single institution cohort study includes 130 patients who underwent definitive external-beam radiotherapy and high-dose-rate intracavitary +/- interstitial brachytherapy from February 2017 to July 2023. 3D-NG were implemented for all cases after December 2019 (N = 77). Non-3D included applicator-only/no-needles (N = 28) or freehand-placed needles (N = 25). Median follow-up was 24 months. 3D-NG, versus non-3D, achieved higher mean D90 (+5.2 Gy, p < 0.001), D98 (+4.3 Gy, p < 0.001), and V100 3D-NG for cervix brachytherapy were associated with improved 2-year LF compared to non-3D/freehand-needles, with higher achievement of EMBRACE II goals for D90 and D98, with similar OAR doses. This study highlights the potential for 3D-NG to simplify needle insertion while simultaneously improving needle position, dosimetry, and disease control outcomes.

Quality control study of cervical cancer interstitial brachytherapy treatment plans using statistical process control

This study explored using statistical process control for quality control of cervical cancer interstitial brachytherapy treatment plans. For retrospective analysis, interstitial brachytherapy treatment plans were divided into first (n = 300) and second phases (n = 200). The first phase was chronologically divided 2:1 into training and validation sets. The Dn2cm The Dn2cm For all organs at risk, the Dn2cm

Impact of MRI-based planning in transperineal interstitial brachytherapy for locally advanced cervix tumors: Clinical, dosimetric and toxicity outcomes

To compare dosimetric characteristics, clinical outcomes, and toxicity in patients with locally advanced cervical cancer(LACC) treated with transperineal interstitial brachytherapy(P-ISBT), using CT-based planning or MRI-based planning with a monoinstitutional MRI-compatible applicator, Template Benidorm(TB). We retrospectively analyzed 106 women treated with P-ISBT for LACC from 2006 to 2022. P-ISBT was CT-based, with Martinez Universal Perineal Interstitial Template(MUPIT) between 2006 and 2012, or MRI-based planning (TB) since 2013. Volumetric, clinical, and dosimetric parameters were compared between applicators. Forty-six (43.4%) patients were treated with MUPIT, and 60 (56.6%) with TB. Median follow-up was 42 months (4-188). No significant difference was observed in 5-year local control (LC), regional control (RC), distant failure (DF), overall survival (OS), and disease-specific survival (DSS) between applicators. The TB cohort had fewer needles (p = 0.001), halved median CTV volume (p < 0.001), increased median D MRI's superior CTV-volume definition results in smaller treatment volumes, lower D

To whom and by whom: Discussions of sexual health, fertility, and premature menopause with women with locally advanced cervical cancer

To investigate whether gynecologic and radiation oncologists document discussions of chemoradiation treatment's gonadotoxicity for patients with cervical cancer and what patient and physician factors make discussions more likely. Women with LACC treated with definitive CRT between 2009 and 2022 were included. Visit notes with gynecologic and radiation oncologists were reviewed for sexual health discussions. Fertility and premature menopause discussions were only evaluated among premenopausal patients. Variables of interest including demographics and staging were collected. Univariate and multivariate analyses were conducted using Rv4.2.1. A total of 93 women were included (22-91 years old). Most were Stage IIB (32%) or IIIB (34%). Sexual health discussions occurred among 74.2% of patients and did not have a significant relationship with any patient factors. Fertility discussions occurred with 17.5% of the 57 premenopausal patients and were more likely among younger patients (≤31.9, p < 0.001) with fewer children (≤1, p < 0.001). Premature menopause discussions occurred among 73.7% of premenopausal patients and were more likely among younger patients (≤39.0, p = 0.015). It is promising to see that oncologists are discussing sexual health and premature menopause with most patients. The limited fertility discussions suggest that oncologists are less likely to discuss fertility as women approach the age of menopause or already have children. Involvement of reproductive endocrinologists and psychologists may provide patients with a more comprehensive understanding of long-term quality of life.

Radiotherapy induced ureteric stenosis in locally advanced cervical cancer: A review of current evidence

Concurrent chemo-radiation followed by high dose rate brachytherapy is the standard of care for locally advanced cervical cancer. The proximity of the ureters to the tumor volume risks ureteric stenosis. Here we outline the current understanding of radiotherapy induced ureteric stenosis in patients treated for cervical cancer, focusing on the incidence, risk factors, clinical consequences, and management. Searches on EMBASE, PubMed, Science Direct, and Google Scholar were performed for publications reporting on radiotherapy, cervix cancer and ureteric stenosis. Multi and single center, prospective/retrospective, cohort, and cross-sectional studies were included. This narrative review identified key issues relevant to radiation induced ureteric stenosis in cervical cancer in the literature. Thirteen studies were evaluated, identifying crude and actuarial rates of ureteric stenosis of 0.3-13.5% and 1.5-4.4% (at 5 years) respectively. The risk of ureteric stenosis is highest in the first 5 years after radiotherapy but continues to occur at a rate of 0.15% per year. Risk factors including advanced FIGO stage, tumor size >5 cm and baseline hydronephrosis increase the incidence of ureteric stenosis. EQD2 doses of ≥ 77Gy were significantly associated with ≥grade 3 ureteric morbidity. The majority of patients were managed with nephrostomy +/- ureteric stent insertion, with some requiring ureteral reimplantation, urinary diversion or nephrectomy. This review has identified multiple considerations, highlighting the need to identify patients highest at risk of ureteric stenosis. There is also a need to recognize ureters as organs at risk, record dose exposure, and apply dose constraints, all of which set the landscape for allowing dose optimization.

Clinical outcomes of adaptive intracavitary and interstitial brachytherapy technique in locally advanced cervical cancer: A real-world data

To evaluate clinical outcomes of CT-based adaptive intracavitary and interstitial brachytherapy (IC followed by IC-ISBT) in locally advanced cervical cancer (LACC) in resource-constrained settings. LACC patients treated with adaptive brachytherapy techniques were analyzed to evaluate treatment characteristics and clinical outcomes. The Kaplan-Meier method was used for survival analysis, and the log-rank test for univariate analysis. Out of 141 eligible patients with LACC, 87 (61.7%) patients received external beam radiotherapy (EBRT) in referral hospitals, while 54 (38.3%) were treated at our center. We divided our cohort into two groups: poor EBRT responder group (n = 70 [49.6%]) where IC-ISBT was adapted to achieve optimum tumor doses and OAR optimization group 71 (50.4%) where IC-ISBT was performed to reduce OAR doses. Median HRCTV-D90 dose was 88 Gy (range 70-109 Gy) with median HRCTV volume 33cc (range 15-96). Median D2cc doses to OARs were 90 Gy (range 70-107), 71 Gy (range 55-105) and 70 Gy (range 47-90) to bladder, rectum and sigmoid, respectively. At median follow-up of 32 months, 3-year local control (LC), locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) were 83%, 75%, 64% and 72%, respectively. Subgroup analysis revealed significantly better outcomes for OAR optimization compared to poor EBRT responders, with 3-year LC (95% vs. 70.1%, p < 0.001), LRC (87.3% vs. 62.7%, p < 0.001), DFS (79.2% vs. 49.4%, p < 0.001), and OS (86.2% vs. 57.4%, p < 0.001) CONCLUSION: In resource-constrained settings, implementation of Adaptive IC-ISBT is a viable alternative for optimizing OAR doses in LACC. However proactive approach employing IC-ISBT for tumor dose-escalation from first fraction of BT is warranted for improving LC in poor EBRT responders.

Explainable artificial intelligence analysis of brachytherapy boost receipt in cervical cancer during the COVID-19 era

Brachytherapy is a critical component of the standard-of-care curative radiotherapy regimen for women with locally advanced cervical cancer (LACC). However, existing literature suggests that many patients will not receive the brachytherapy boost. We used machine learning (ML) and explainable artificial intelligence to characterize this disparity. Patients with LACC diagnosed from 2004 to 2020 who received definitive radiation were identified in the National Cancer Database. Five ML models were trained to predict if a patient received a brachytherapy boost. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To identify trends that may be attributable to the coronavirus disease 2019 (COVID-19) pandemic, the previous analysis was repeated and limited to 2019 to 2020. A total of 37,564 patients with LACC were identified; 5799 were diagnosed from 2019 to 2020 (COVID cohort). Of these patients, 59.3% received a brachytherapy boost, with 76.4% of patients diagnosed in 2019 to 2020 receiving a boost. The random forest model achieved the best performance for both the overall and COVID cohorts. In the overall cohort, the most important predictive features were the year of diagnosis, stage, age, and insurance status. In the COVID cohort, the most important predictive features were FIGO stage, age, insurance status, and hospital type. Of the 26 patients who tested positive for COVID-19 during their course of radiotherapy, 19 (73.1%) received a brachytherapy boost. A gradual increase in brachytherapy boost utilization has been noted, which did not seem to be significantly impacted by the onset of the COVID-19 pandemic. ML could be considered to identify patient populations where brachytherapy is underutilized, which can provide actionable feedback for improving access.

Prospective validation of a machine learning model for applicator and hybrid interstitial needle selection in high-dose-rate (HDR) cervical brachytherapy

To Demonstrate the clinical validation of a machine learning (ML) model for applicator and interstitial needle prediction in gynecologic brachytherapy through a prospective clinical study in a single institution. The study included cervical cancer patients receiving high-dose-rate brachytherapy using intracavitary (IC) or hybrid interstitial (IC/IS) applicators. For each patient, the primary radiation oncologist contoured the high-risk clinical target volume on a pre-brachytherapy MRI, indicated the approximate applicator location, and made a clinical determination of the first fraction applicator. A pre-trained ML model predicted the applicator and IC/IS needle arrangement using tumor geometry. Following the first fraction, ML and radiation oncologist predictions were compared and a replanning study determined the applicator providing optimal organ-at-risk (OAR) dosimetry. The ML-predicted applicator and needle arrangement and the clinical determination were compared to this dosimetric ground truth. Ten patients were accrued from December 2020 to October 2022. Compared to the dosimetrically optimal applicator, both the radiation oncologist and ML had an accuracy of 70%. ML demonstrated better identification of patients requiring IC/IS applicators and provided balanced IC and IC/IS predictions. The needle selection model achieved an average accuracy of 82.5%. ML-predicted needle arrangements matched or improved plan quality when compared to clinically selected arrangements. Overall, ML predictions led to an average total improvement of 2.0 Gy to OAR doses over three treatment fractions when compared to clinical predictions. In the context of a single institution study, the presented ML model demonstrates valuable decision-support for the applicator and needle selection process with the potential to provide improved dosimetry. Future work will include a multi-center study to assess generalizability.

A randomized trial evaluating a novel hydrogel packing system compared to standard packing during image-guided high-dose rate brachytherapy boost for cervical cancer

The purpose of this prospective randomized trial was to compare the use of a novel vaginal hydrogel packing system (BrachyGel) to standard vaginal packing (VP) during high dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer (LACC). This cross-over study included LACC patients receiving HDR BT boost (intracavitary +/- interstitial). All patients received alternating gauze or BrachyGel VP on Arms A and B. Patients, physicians, and physicists evaluated BT characteristics via a 4-point Likert scale. Adverse events (AEs) were prospectively collected and scored per CTCAE. The 20 patients enrolled. The mean bladder D2cc difference between gauze and BrachyGel in Arm A was 0.117 Gray (Gy) and in Arm B 0.013 Gy. The mean difference in rectum D2cc in Arm A and Arm B was -0.189 Gy and -0.191 Gy, respectively. The mean dose to 90% of the high-risk clinical target volume (HR-CTV) for gauze compared to BrachyGel was -0.032 Gy (95% CI: 0.472, 0.409). Patient-reported discomfort was similar with BrachyGel and gauze ("mild/moderate" 70.0% vs 74.0%, respectively). The clarity of VP was similar between BrachyGel and gauze (86.8% vs 89.7%, respectively). The completeness of VP was more frequently "excellent/good" with BrachyGel (79.0%) compared to gauze (56.4%). The ease of packing was more frequently "extremely easy" with BrachyGel (21.2% vs 0%). No serious AEs were reported. This randomized trial found no clinically significant difference in OAR or HR-CTV dosimetry between BrachyGel and standard VP. BrachyGel performed well compared to gauze for the patient and physician use experience.

Effects of pain management using nonsteroidal anti-inflammatory drug suppositories during brachytherapy for cervical cancer: A single-center prospective observational study

No standardized pain management protocol exists for intracavitary brachytherapy, and various methods of analgesia have been used in different countries and institutions. This study aimed to investigate the effects of pain management during intracavitary brachytherapy using nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen suppositories. In this single-center, prospective, observational study, patients undergoing intracavitary brachytherapy for cervical cancer completed a questionnaire survey after each brachytherapy session, which comprised questions regarding pain intensity, satisfaction with analgesia, and desire for effective anesthesia. Data analysis was performed using data from 100 brachytherapy sessions of 27 patients. The median numerical rating scale (NRS; 0-10) score for each intracavitary brachytherapy session was 3-4. The median satisfaction scale score for analgesia (5-point scale, 1-5) for each session was approximately 4. Eight patients (29.6%) answered that they desired anesthesia more effective than suppositories at any session of brachytherapy. A comparison of the high (NRS ≥4) and low (NRS ≤3) NRS groups during the first session revealed that the high NRS group tended to have higher NRS scores and lower satisfaction with analgesia during all sessions. A positive correlation was observed between tumor size and the NRS score during the first brachytherapy session. The NRS score was approximately 3-4, and satisfaction with analgesia was approximately 4 out of 5 when NSAIDs or acetaminophen suppositories were used as analgesics during intracavitary brachytherapy for cervical cancer. Although the current pain management protocol is clinically acceptable, inadequate analgesia is indicated in approximately 30% of patients.

A general framework to develop a radiomic fingerprint for progression-free survival in cervical cancer

Treatment of locally advanced cervical cancer patients includes chemoradiation followed by brachytherapy. Our aim is to develop a delta radiomics (DRF) model from MRI-based brachytherapy treatment and assess its association with progression free survival (PFS). A retrospective analysis of FIGO stage IB- IV cervical cancer patients between 2012 and 2018 who were treated with definitive chemoradiation followed by MRI-based intracavitary brachytherapy was performed. Clinical factors together with 18 radiomic features extracted from different radiomics matrices were analyzed. The delta radiomic features (DRFs) were extracted from MRI on the first and last brachytherapy fractions. Support Vector Machine (SVM) models were fitted to combinations of 2-3 DRFs found significant after Spearman correlation and Wilcoxon rank sum test statistics. Additional models were tested that included clinical factors together with DRFs. A total of 39 patients were included in the analysis with a median patient age of 52 years. Progression occurred in 20% of patients (8/39). The significant DRFs using two DRF feature combinations was a model using auto correlation (AC) and sum variance (SV). The best performing three feature model combined mean, AC & SV. Additionally, the inclusion of FIGO stages with the 2- and 3 DRF combination model(s) improved performance compared to models with only DRFs. However, all the clinical factor + DRF models were not significantly different from one another (all AUCs were 0.77). Our study shows promising evidence that radiomics metrics are associated with progression free survival in cervical cancer.

Development and implementation of a 3d-HDR brachytherapy program for cervical cancer in a sub-Saharan African centre

Cervical cancer is the second most common cancer among women in Nigeria where, the gap between need for, and access to, radiation therapy including brachytherapy is significant. This report documents the implementation of the first three-dimensional high-dose-rate (3D-HDR) brachytherapy service for cervical cancer in Nigeria. This report details the steps taken to implement the 3D-HDR brachytherapy program, the challenges faced, and the adaptive strategies employed to overcome them. Our objective is to provide a guide for teams and centers in similar resource-restricted settings to implement 3D-HDR brachytherapy services, by leveraging our shared experience and lessons learned. The implementation process required investment in infrastructure: creating a dedicated brachytherapy suite equipped with modern technology; and human capital: conducting both virtual and hands-on training for staff; and involving international experts during the initial treatment phases. Quality assurance protocols were established to ensure the accuracy and safety of treatments. Key adaptations included extensive remote training, international experts flying in for the initiation phase, and preemptively re-ordering the radioisotope to prevent delays. The 3D-HDR brachytherapy program was successfully implemented, with five cases treated in the first 2 months despite challenges such as high equipment costs, expertise and proficiency needs, and source replacement delays. Continuous training and quality assurance measures ensured the program's sustainability and effectiveness. Implementing a 3D-HDR brachytherapy program in a system with restricted resources is possible with thorough planning, flexible strategies, and adaptive measures. We document our experience to provide insights for other institutions aiming to establish similar programs. Collaboration and innovative financial strategies are essential for ensuring sustainable access to cancer treatment in the region. Strategies such as remote training and proactive resource management, are critical for overcoming implementation barriers.

Comparison of 3D-printed multichannel non–co-planar vaginal applicators and single-channel vaginal applicators for brachytherapy with positive or close surgical margins in cervical cancer

This study was conducted to compare the differences between 3D-printed multichannel non-co-planar vaginal applicators and single-channel vaginal applicators in cervical cancer patients with positive or close surgical margins. Between January 2015 and June 2023, 104 cervical cancer patients who underwent radical surgery with positive or close surgical margins were enrolled to receive concurrent intensity-modulated chemoradiotherapy combined with 3D-printed multichannel non-co-planar vaginal applicators (3D-printed group, 41 patients) or single-channel vaginal applicators (single-channel group, 63 patients) guided brachytherapy. The dosimetric parameters, 5-year local control (LC), progression-free survival (PFS), overall survival (OS) of two groups were retrospectively analyzed. The high-risk clinical target volume (D90, D100) and high-dose volume fraction (V150) in 3D-printed group were significantly higher than those in single-channel group (p < 0.05), and the homogeneity index (HI) and conformal index (COIN) were equally better in 3D-printed group. In 3D-printed group, the D2cc, D1cc, and D0.1cc of the bladder and rectum were significantly lower than those of the single-channel group (p < 0.05). The 3D-printed group had significantly superior 5-year LC (70.0% vs. 51.3%, p = 0.041) and PFS (63.0% vs. 44.2%, p = 0.045), but OS were not significantly different between treatment groups (75.4% vs. 59.7%, p = 0.112). The incidence of radiation enteritis and cystitis was lower in the 3D-printed group than in the single-channel group, but no statistical difference was noted. The 3D-printed multichannel non-co-planar vaginal insertion applicators show the advantage of target dose, improve the LC and PFS in patients with positive or close surgical margins after cervical cancer surgery. Thus, the popularization of this method and its application may be of value.

Good safety of oblique needle insertion using the Venezia applicator for cervical cancer: A single-center cohort study

To evaluate procedural complications associated with the use of the Venezia applicator with oblique needles for treating locally advanced cervical cancer (LACC). We conducted a retrospective analysis of 30 patients treated at our center between November 2019 and August 2024 using the Venezia applicator. All patients underwent combined intracavitary and interstitial brachytherapy with oblique needle implantation. Procedural complications were classified using the Clavien-Dindo classification, focusing on organ perforations and bleeding events. The median age was 54.5 years. Most patients (90%) had squamous cell carcinoma, and the predominant stage FIGO was T3b (46.7%). The median HR-CTV volume was 32.8cc [24.5-39.3] and the median HR-CTV D90 was 86.0 Gy [82.7-90.5]. All organ at risk dose constraints were respected. Oblique needle perforation occurred in 7/30 patients (23.3%) and in 16/130 needles (12.3%), most often in the bladder. The majority (96.7%) experienced no or mild complications (grade 0-1). The most common complication was minor bleeding during applicator removal, controlled with manual compression. One patient experienced grade 2 bleeding requiring transfusion. No grade 3-5 complications were observed. The use of the Venezia applicator with oblique needles for locally advanced cervical cancer (LACC) appears safe and feasible, with a low rate of significant complications. Oblique needle insertion facilitates distal parametrial coverage, making it a valuable tool for challenging tumor extensions.

A machine learning-based decision support tool for standardizing intracavitary versus interstitial brachytherapy technique selection in high-dose-rate cervical cancer

To develop and evaluate a machine-learning (ML) decision-support tool that standardizes selection of intracavitary brachytherapy (ICBT) versus hybrid intracavitary/interstitial brachytherapy (IC/ISBT) in high-dose-rate (HDR) cervical cancer. We retrospectively analyzed 159 HDR brachytherapy plans from 50 consecutive patients treated between April 2022 and June 2024. Brachytherapy techniques (ICBT or IC/ISBT) were determined by an experienced radiation oncologist using CT/MRI-based 3-D image-guided brachytherapy. For each plan, 144 shape- and distance-based geometric features describing the high-risk clinical target volume (HR-CTV), bladder, rectum, and applicator were extracted. Nested five-fold cross-validation combined minimum-redundancy-maximum-relevance feature selection with five classifiers (k-nearest neighbors, logistic regression, naïve Bayes, random forest, support-vector classifier) and two voting ensembles (hard and soft voting). Model performance was benchmarked against single-factor rules (HR-CTV > 30 cm³; maximum lateral HR-CTV-tandem distance > 25 mm). Logistic regression achieved the highest test accuracy 0.849 ± 0.023 and a mean area-under-the-curve (AUC) 0.903 ± 0.033, outperforming the volume rule and matching the distance rule's AUC 0.907 ± 0.057 while providing greater accuracy 0.805 ± 0.114. These differences were not statistically significant. Feature-importance analysis showed that the maximum HR-CTV-tandem lateral distance and the bladder's minimal short-axis length consistently dominated model decisions.​ CONCLUSIONS: A compact ML tool using two readily measurable geometric features can reliably assist clinicians in choosing between ICBT and IC/ISBT, thereby reducing inter-physician variability and promoting standardized HDR cervical brachytherapy technique selection.

Design approach and benefits of the 3D-printed vaginal individualized applicator (VIA)

Interstitial gynecologic brachytherapy necessitates precise needle placement, requiring time and expertise. We aimed to simplify interstitial procedures and facilitate optimal needle distribution with individualized vaginal templates to guide interstitial needles. We developed the 3D-printed vaginal individualized applicator (VIA), a cylindrical template containing individualized internal channels that guide interstitial needles to cover the tumor extent. Eight patients underwent VIA only interstitial implants (VIA only), and five intact cervical cases were treated using tandem and customized VIA (VIA + T). Procedure length, number of needles utilized and dosimetric measures were evaluated. VIA was successfully designed and used clinically for 24 procedures (8 VIA only, 16 VIA + T). Average procedure needle insertion time reduced from 80.9 min for traditional interstitial to 42.9 min for VIA only, approximately 47% shorter with a similar mean high risk CTV volume (28.3 cc VIA only vs. 32.4 cc) and excellent dosimetry with average CTV V100% (94.3% and 94.4%). VIA + T was particularly useful in patients with small vaginal canals and large tumor size. For the five VIA + T patients average tumor size was 68.0cc (range 26.6-143.5 cc). VIA + T procedures were approximately 20% shorter than hybrid procedures with other applicators with mean length of 20.1 min and an average of 6.8 needles (range 3-12). Our novel 3D-printed VIA facilitates gynecologic interstitial brachytherapy by simplifying needle placement, reducing procedure time, and maintaining excellent dosimetry. VIA can be customized for various clinical scenarios, particularly beneficial for large tumors or small vaginal canals.

Impact of the COVID-19 pandemic on brachytherapy and cancer patient outcomes: A systematic review

To assess the impact of the COVID-19 pandemic on the use of brachytherapy in patients with gynecologic and prostate cancers including treatment delays, increased burden of mortality, and associated clinical outcomes. A comprehensive search of PubMed, Cochrane Library, CINAHL, Scopus, and Web of Science was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies published through September 2023 using MeSH terms and keywords related to "COVID and brachytherapy." Inclusion criteria included all studies reporting on the impact of COVID-19 on treatment delay, treatment omission, recurrence rates, and clinical outcomes in patients requiring brachytherapy for prostate or gynecologic cancers from December 2019 to September 2023. Data were extracted by two independent reviewers (LH, IV). Of the 292 screened records, 10 studies (9 retrospective, 1 prospective single-arm exploratory noninferiority) were included. Hypofractioned regimens were the preferred approach in radiation treatment (RT) centers, with 6 of 10 studies noting shift towards hypofractionation. For cervical cancer, intracavitary brachytherapy was limited to 3-4 fractions, reducing personnel and patient exposure. Treatment delays influenced by COVID-19 ranged between 19% and 53% and treatment omissions ranged between 2% and 28%. These disruptions arose from factors such as patient fear of contracting COVID-19, COVID-19 infection, barriers to accessing care, and operating room closures. Three studies reported on a single-application (SA) rather than a multiple application (MA) approach for cervical cancer. They reported excellent local control, shorter overall treatment time at the expense of higher grade ≥2 vaginal, genitourinary, and gastrointestinal events. For cervical cancer patients, overall treatment time (OTT) was significantly impacted by COVID-19 as reported by 2 studies from India. OTT > 60 days occurred in 40-53% of patients. This is the first systematic review to assess the impact of the COVID-19 pandemic on brachytherapy in patients with gynecologic and prostate cancers. Although many expert consensus recommendations have been published during the pandemic regarding radiation therapy, few studies evaluated its clinical impact on brachytherapy delivery and patient outcomes. The COVID-19 pandemic resulted in treatment delays, omissions in brachytherapy, and further adoption of hypofractionated regimens. Early results demonstrate that despite increased toxicities, local control rates with hypofractionated treatment are similar to standard fractionation. The impact of the pandemic on gynecologic and prostate cancers is yet to be determined as well as the long-term outcomes on patients treated during the lockdown period.

Safe dose escalation and reduction of the fraction number of uterine cervical brachytherapy using a gel spacer in the rectovaginal and vesicouterine septum: A planning study

To evaluate the possibility of dose escalation and reduction of fraction number in cervical brachytherapy using a gel spacer. Twenty patients with uterine cervical cancer treated with image-guided adaptive brachytherapy (IGABT) were selected. Hyaluronic acid gel injection (HGI) was performed in the rectovaginal and vesicouterine septum for 10 patients. The other ten patients were not with HGI. Both groups were treated with IGABT involving tandem/ovoid or cylindrical applicators along with additional interstitial needles. Dose distributions approved by radiation oncologists were retrospectively analyzed, and a dose summation of 45 Gy/25 of external beam radiation therapy and IGABT was performed. Dose constraints for D The median CTV In the HGI group, adequate dose delivery to CTV

Outcomes and comparison of dosimetric parameters between intracavitary (Fletcher) and combined intracavitary/interstitial (Utrecht) brachytherapy in locally advanced cervical cancer

To report outcomes of combined intracavitary/interstitial (IC/IS) image-guided brachytherapy (IGBT) in locally advanced cervical cancer, and to compare its dosimetric parameters with intracavitary-only (IC) brachytherapy in a first-in-country experience. Between January 2021 and September 2022, a total of 160 insertions were done in 40 patients with FIGO IB3-IVA cervical cancer undergoing IGBT using a hybrid (Utrecht) applicator. Corresponding treatment plans for IC brachytherapy were generated during treatment, and optimized. A preplanned comparison of dosimetric parameters, defined in GEC-ESTRO was conducted. The clinical use of a hybrid IC/IS applicator was feasible in all insertions. An average of 14 needles were inserted in each patient over four fractions. Mean HR-CTV D90 and D98 was 86 (SD 1.9) Gy and 75.7 (SD 2.3) Gy using hybrid applicator, and 80 (SD 5.4) Gy and 69.8 (SD 5.2) Gy using IC applicator, with a mean dose gain of 6.0 (SD 5.0) Gy and 5.9 (SD 4.7) Gy (p <0.001), respectively. Likewise, mean D2cc for bladder and sigmoid were significantly lower in the hybrid technique. Mean contribution of brachytherapy to total HR-CTV D90 (in absolute EQD2 Gy) was 41.7 Gy using IC/IS applicator while 35.7 Gy for IC-only applicator (p = 0.027). Clinical response at 12 weeks showed an overall response rate (ORR) and complete response (CR) rates of 92.5% and 77.5%, respectively. IGBT using a hybrid IC/IS applicator showed excellent tolerability and yielded favorable results, resulting in significant dosimetric improvement in terms of primary target dose, and sparing OARs.

Percutaneous interstitial brachytherapy ablation for targeting oligometastatic gynecologic cancers

Treatment of recurrent oligometastatic gynecologic malignancy may involve targeted surgery, thermal ablation, or CT-guided high-dose-rate interstitial brachytherapy ablation (CT-HDR-IBTA). The purpose of this study was to describe the safety and efficacy of CT-HDR-IBTA for oligometastatic gynecologic malignancies. With institutional review board approval (IRB) approval and compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliance, we searched our database to assemble a single-arm study cohort of all patients with oligometastatic gynecologic cancers who underwent CT-HDR-IBTA from 2012-2022 with follow-up. The electronic record was reviewed to determine relevant clinicopathological variables including patient demographics, prior treatments, clinical course, local control, and local and distant recurrence with follow-up imaging. The study cohort comprised 37 lesions in 34 patients treated with CT-HDR-IBTA for recurrent oligometastatic uterine (n = 17), cervix (n = 1), or ovarian cancer (n = 16) with an average lesion size of 2.5 cm with an average patient age of 61.4 years. Each lesion was treated with an average radiation dose of 23.8 Gy in 1.8 fractions and a median follow-up time of 24.0 months. The primary efficacy of CT HDR ITBA was 73% with a median progression-free survival of 8.0 months (95% CI 3.6-12.8 months) and with 58% of patients still alive at 43 months with median overall survival not reached. The rate of Grade 1 adverse events was 22% without any Grade 2, 3 or 4 events. CT HDR IBTA was safe and effective for treating oligometastatic gynecologic cancers in a heavily pretreated cohort.

Improving plan quality in cervical cancer brachytherapy using knowledge-based planning for direction modulated brachytherapy tandem applicator

The bladder and rectal toxicities in cervical cancer brachytherapy are positively correlated with the DVH parameter: D2cc. This study evaluates the feasibility of knowledge-based planning to predict the D2cc, identify suboptimal plans, and improve the plan quality with Direction Modulated Brachytherapy (DMBT) applicators using knowledge-based planning based on linear relationship between overlap distances and D2cc. The overlap volume histogram (OVH) method was used to determine the distances for 2 cm The mean bladder D2cc decreased by 4.3% and 10.3% for conventional applicators, and 4.4% and 3.6% for DMBT applicators for Models 1 and 2, respectively. The rectum D2cc decreased by 3.4% and 10.7% for conventional and 3.0% and 5.0% for DMBT applicators, respectively. The sigmoid D2cc decreased by 3.1% and 6.9% for conventional and 3.2% and 5.9% for DMBT applicators, respectively. There were also significant reductions for the recto-vaginal (RV-RP) point and posterior-inferior border of symphysis (PIBS) reference points: PIBS+2cm, PIBS+1cm, PIBS-1cm, and PIBS-2cm, for both models as well. A knowledge-based planning method successfully predicted D2cc and optimized brachytherapy plans for cervical cancer. The proposed model demonstrates the feasibility of predicting D2cc, detecting suboptimal plans, and improving the plan quality especially for DMBT where cumulative clinical experience is limited.

Efficacy and safety of a 3D-printed applicator for vaginal brachytherapy in patients with central pelvic-recurrent cervical cancer after primary hysterectomy

Intracavitary and/or interstitial brachytherapy is an integral component of the management of patients with central pelvic-recurrent cervical cancer after primary hysterectomy, and is typically delivered using conventional applicators. We investigated the efficacy and safety of three-dimensional (3D)-printed, customizable applicators for those patients. Twenty-six patients were treated with combination external beam radiotherapy and brachytherapy. Patients with lesions ≤1 and >1 cm before brachytherapy were treated with intracavitary and interstitial brachytherapy, respectively. Dosimetric plans were compared between the vaginal cylinder and 3D-printed applicator for the first 9 patients. Outcomes and treatment-related complications were also investigated. The median tumor size before brachytherapy was 0.81 cm. Intracavitary, interstitial, and combined interstitial-intracavitary brachytherapy were performed in 22 (85%), 3 (11%), and 1 (4%) of the patients, respectively. The clinical target volume (CTV) coverage goal was achieved with all 3D-printed plans but failed with three single-channel cylinder plans (33.3%). Owing to 3D-printed transvaginal applicator guidance, there was no need to adjust the needle position after implantation. The mean CTV dose for all patients was 71 ± 8.2 Gy; all met the dose constraints to the organs at risk, but 1 (4%) had a rectal D High-quality intracavitary and/or interstitial brachytherapy can be achieved using a 3D-printed applicator and yields favorable outcomes with acceptable toxicity.

Early outcomes of abbreviated multi-fractionated brachytherapy schedule for cervix cancer during COVID-19 pandemic

Brachytherapy (BT) for cervix cancer was listed as a level I priority and reduced number of implants and multiple fractions were recommended during COVID-19 pandemic. We present early clinical outcome of this approach. Patients treated with (chemo)radiotherapy and BT with single implant and multiple fractions BT were included. Treatment protocol included 3-5 fractions of 5-8.5 Gy with an aim to achieve point A dose of 70 Gy EQD2 From April 2020 to March, 2021, 64 patients with stage IB2-IV received single implant and multi-fraction BT after external radiation of 45 Gy/25 fractions/5 weeks. Only 76.7% (n = 49) received concurrent chemotherapy. Median overall treatment time (OTT) was 56 days (38-131 days). Overall, 62.5% (n = 40) patients received IC and 37.5% (n = 24) received IC+IS. The median HRCTV was 34.7 cc (IQR 25-41). Median (IQR) point A dose, HRCTV D90, B2cc, R2cc, and S2cc for those undergoing IC was 74 Gy (71-78), 80 Gy (73-84), 86 Gy (82-89), 70 Gy (65-74), 65 Gy (59-73) respectively. For the IC+IS cohort, HRCTV D90, B2cc, R2cc, and S2cc was 84 Gy (78-89 Gy), 89 Gy (86-92), 70 Gy (67-74), 68 Gy (59-76). At a median follow-up of 16 months (5-27) the 2-year local control, pelvic control, cause specific and overall survival was 88%, 85.3%, 92.2%, and 81.3% respectively. Late gastrointestinal and genitourinary grade ≥III toxicities were 14% and 1.5% each. Abbreviated BT outcomes are encouraging for oncological outcomes despite delays in overall treatment time and omission of chemotherapy. Further mature follow up is needed.

Dosimetric comparison of stereotactic MR-guided radiation therapy (SMART) and HDR brachytherapy boost in cervical cancer

The standard of care in locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy followed by high-dose-rate brachytherapy (HDR-BT). Although previous studies compared HDR-BT with stereotactic body radiotherapy (SBRT), there is scarce data regarding the dosimetric outcomes of stereotactic MR-guided adaptive radiation therapy (SMART) boost in lieu of HDR-BT. In this single-institutional in-silico comparative study, LACC patients who were definitively treated with external beam radiotherapy followed by HDR-BT were selected. Target volumes and organs at risk (OARs) were delineated in MRI and HDR-planning CT. An HDR-BT and a SMART boost plan were generated with a prescribed dose of 28 Gy in four fractions for all patients. The HDR-BT and SMART boost plans were compared in regard to target coverage as well OARs doses. Mean EQD2 D90 to HR-CTV and IR-CTV for HDR-BT plans were 89.7 and 70.5 Gy, respectively. For SMART, the mean EQD2 D90 to HR-PTV, HR-CTV, and IR-CTV were 82.9, 95.4, and 70.2 Gy, respectively. The mean D This dosimetric study demonstrates that SMART can be applied in cases where HDR-BT is not available or ineligible with acceptable target coverage and OAR sparing. However, prospective clinical studies are needed to validate these results.

Efficacy of high-dose-rate brachytherapy with different radiation source activities among cervical cancer patients and risk factors for long-term outcomes: A 6-year retrospective study

This study aimed to assess the impact of dose rates due to natural decay of Iridium-192 sources and the risk factors of clinical outcomes for cervical cancer patients treated with high-dose-rate (HDR) brachytherapy. Four ninety-four patients were divided into relatively-high-radioactive (rHR), relatively-medium-radioactive (rMR), and relatively-low-radioactive (rLR) groups for retrospective treatment response comparison. The short-term outcomes were evaluated using the 1-month /3-month follow-up results based on RECIST 1.1. Local recurrence-free survival (LRFS) and metastatic recurrence-free survival (MRFS) were selected as long-term outcomes. A class of transformation models with adaptive lasso was applied to assess the risk factors of long-term outcomes. No significant difference was identified in short- or long-term outcomes of different radioactive groups. Subgroup analyses demonstrated similar findings. In multivariate factor analysis, advanced stage was significantly associated with higher risk of local recurrence and metastatic recurrence (HR = 1.66, 95%confidence interval [CI] = 1.14-2.43, p = 0.008; HR = 1.57, 95%CI = 1.23-2.00, p < 0.001). Significant associations were observed between local recurrence and pathology, and between metastatic recurrence and pre-treatment serum indices, respectively (HR = 8.62, 95%CI = 2.28-32.60, p = 0.002; HR = 1.98, 95%CI=1.20-2.26, p = 0.008). Overall, there was no significant difference in long- or short-term efficacy of the HDR brachytherapy among the groups with different levels of activity of radiation sources. Stage, pathology, and pretreatment serum indices were crucial factors that affected the long-term outcomes.

A practical guide to hybrid interstitial/intracavitary brachytherapy for locally-advanced cervical cancer

In select cases of locally advanced cervical cancer, a hybrid brachytherapy (HBT) approach consisting of a combined intracavitary (IC)/insterstitial (IS) implant can yield improved target coverage and/or decreased organ at risk dose compared to IC techniques while limiting invasiveness compared to IS techniques. The technique involves placement of transvaginal and/or perineal needles in addition to the tandem and ring/ovoids using either a specialized applicator or free-hand placement. Following applicator and needle placement, brachytherapy may then be planned using principles similar to IC or IS techniques. During treatment planning, it can be helpful to obtain both MRI and CT imaging, as plastic MRI-compatible needles do not show up well on MRI. In patients where acceptable target coverage cannot be achieved using IC alone or doses to nearby OAR are too high, HBT should be evaluated. HBT can improve both dose to target and OAR while sparing patients the morbidity of perineal template-based interstitial brachytherapy. Specific scenarios where HBT may be preferred include bulky residual primary tumor especially with poor response to EBRT, extension into the lateral parametrium, vaginal extension of tumor, and an asymmetric target. Use of HBT can typically permit extension of dose coverage by an additional 1-2 cm beyond what can be achieved with an IC alone technique. HBT allows for improved therapeutic ratio by improving target volume coverage and/or lowering doses to OARs. Brachytherapists should be trained on the practical aspects of administering HBT to be able to offer a less invasive and impactful treatment option when appropriate.

Improving plan quality in cervical brachytherapy using a simple knowledge-based prediction tool for OAR dose (D2cm3)

Toxicity from cervical brachytherapy has been demonstrated to correlate with the D2cm The overlap volume histogram (OVH) method was used to determine the distance for 2cm Mean bladder D2cm A simplified knowledge-based planning method was used to predict D2cm

Retrospective analysis of local recurrence pattern by computed tomography image-guided intracavitary and interstitial brachytherapy for locally advanced cervical cancer in a single Japanese institution

The purpose of this study was to investigate the treatment results with focus on local control (LC) by computed tomography (CT)-guided intracavity brachytherapy and interstitial brachytherapy (ICBT/ISBT) for locally advanced cervical cancer (LACC). Patients with LACC undergoing ICBT/ISBT at least once in our institution between January 2017 and June 2019 were analyzed retrospectively. The primary endpoint was local control (LC), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and late toxicities. Differences between patient subgroups for prognostic factors in LC, PFS, and OS were analyzed using the log-rank test. The recurrence patterns of LC were also investigated. Forty-four patients were included in the present study. The median high-risk clinical target volume (HR-CTV) at the initial brachytherapy was 48.2 cc. The median total dose of HR-CTV D90 (EQD2) was 70.7 Gy. The median followup period was 39.4 months. The 3-year LC, PFS and OS rates in all patients were 88.2%, 56.6%, and 65.4% (95% CI 50.3-78.0%), respectively. Corpus invasion and large HR-CTV (70 cc or more) were significant prognostic factors in LC, PFS, and OS. Marginal recurrences at the fundus of the uterus were detected in 3 of 5 patients in whom local recurrence was observed. Late toxicities of Grade 3 or higher were detected in 3 patients (6.8%). Favorable LC was achieved by performing CT-guided ICBT/ISBT for LACC. The brachytherapy strategy for patients with corpus invasion or large HR-CTV may need to be reconsidered.

3D-printed individual template brachytherapy for the treatment of intractable central pelvic recurrent cervical cancer: A single institution experience

The prognosis of recurrent cervical cancer tends to be poor and there are limited effective treatments currently available for these patients. This study was developed to find a safe and effective treatment for patients with central pelvic recurrent cervical cancer. This retrospective study analyzed patients with central pelvic recurrent cervical cancer who received 3D-printed individual template (3D-PIT) brachytherapy between February 2019 and June 2023. Analyses of dosimetric parameters, toxicity-related complications, and survival were conducted based on the data of these patients. Twenty-one patients with central pelvic recurrent cervical cancer patients were enrolled. All of them received 3D-printed individual template (3D-PIT) brachytherapy. The mean respective adjusted cumulative HRCTV-D90 and HRCTV-D98 values for these patients were 86.9 Gy and 75.4 Gy. And the local control (LC) rate of these patients was 57.1%. In these 21 patients, only 2 (9.5%) of them experienced grade 3-4 rectal adverse reactions, while 7 (33.3%) patients experienced grade 3-4 bladder adverse reactions. 5(23.8%) patients had fistula, while 3 of these 5 patients had undergone prior anti-VEGF targeted drug treatment which is a risk factor of fistula. The respective 2-year rates of overall and progression-free survival (OS and PFS) for these patients were 72.9% and 57.4%, with a 26-month median PFS. These single-institution data highlight the potential viability of 3D-PIT brachytherapy as an approach to managing intractable central pelvic recurrent cervical cancer following first-line treatment.

Primary vaginal cancer treated with high-dose rate brachytherapy and intraprocedural magnetic resonance imaging

To report outcomes among primary vaginal cancer patients treated definitively with either external beam radiation therapy plus high-dose rate (HDR) brachytherapy (EBRT-BT) or BT (BT) alone with placement of interstitial catheters under magnetic resonance imaging (MRI) guidance. Retrospective review of 41 patients treated for primary vaginal cancer from 2016 to 2022. Kaplan-Meier (KM) estimates were generated for disease-free survival (DFS), local control (LC), and overall survival (OS). Median follow-up was 28 months (range 2-82 months). A total of 36 patients had EBRT-BT, 5 had BT alone. Forty patients had template interstitial and 1 had a multichannel cylinder. Among patients who received EBRT-BT, median total D90 EQD2 was 68.3 Gray (Gy) (range 56.6-91.5 Gy); BT only, median 40.3 Gy (range 38.1-86.3 Gy). No patient experienced local only failure. Relapse occurred in 12 patients treated with EBRT-BT versus 1 with BT alone group. For the EBRT-BT cohort versus BT only cohort, 2-year OS was 81% versus 60%, DFS 61% versus 40%, and LC was 94% versus 80%, respectively. For the entire cohort, 2-year OS was 67%, and median OS was 5 years. The 2-year DFS was 57% and 2-year LC was 93%. The most common any grade acute treatment-related toxicity were grade 1 vaginal pain and stenosis. Grade 3 acute and late toxicities were minimal. MRI-guided HDR BT for primary vaginal cancer yields high rates of local control with limited toxicities. Lower rates of distant control indicate the need for newer options such as immunotherapy or other systemic agents.

A novel dose-based intra-preplan method for high-dose-rate brachytherapy in cervical cancer using modeling and optimization algorithms

This study presents the dose-based intra-preplan (DIP) method for intracavitary/interstitial brachytherapy (IC/ISBT) in cervical cancer, optimizing catheter configurations based on dose distribution. This study aimed to assess the DIP method's clinical feasibility and efficacy. The DIP method incorporates the implant modeling function and the hybrid inverse planning optimization algorithm in Oncentra Brachy. Virtual applicator and catheter models were created and merged with patient-specific computed tomography images. Subsequently, an optimization algorithm was used to automatically determine the optimal catheter configuration-including the number, positions, and insertion depths. The workflow was retrospectively validated in 14 IC/ISBT patients treated with the Geneva applicators. Catheter configurations from the DIP and conventional intra-preplan (IP) methods were compared in terms of catheter number and dose-volume histogram (DVH) parameters for high-risk clinical target volume (CTV The DIP workflow was successfully established. Compared to the IP method, the DIP method achieved similar DVH parameters for both CTV The DIP method enables patient-specific optimization of minimal catheter configurations and supports the broader implementation of high-quality IC/ISBT.

Quality of life of patients submitted to radical radiochemotherapy for cervical cancer: Comparison of outcomes between 2D and 3D image guided brachytherapy

To assess QoL in patients with locally advanced cervical cancer treated with radical radiochemotherapy combined with either 2D or 3D brachytherapy, and to compare outcomes between both techniques. A cross-sectional analytical study was conducted from January 2019 to March 2020. EORTC QLQ-C30 and QLQ-CX24 questionnaires were applied at five time points: before treatment, and 1, 3, 6 and 12 months after treatment. Descriptive statistics, Pearson's chi-square, Fisher's exact test and Bonferroni test were used (p ≤ 0.05). Seventy six out of 82 patients completed all the assessments. The overall mean global health status significantly improved from 63.7 to 72.0 (p = 0.019), with no significant difference between the 2D and 3D brachytherapy groups (69.8 vs. 67.8; p = 0.672). All functional domains of the QLQ-C30 improved over time, including financial difficulties, regardless of the brachytherapy technique. Sexual activity increased significantly (2.5-32.4, p < 0.0001), but also did sexual worry, menopausal symptoms, reduced sexual enjoyment, and vaginal dysfunction. Overall improvement in global health and functioning were observed in patients with locally advanced cervical cancer, regardless of the brachytherapy technique used. Despite improved sexual activity, aspects of sexual dysfunction increased, highlighting the need for comprehensive, multidisciplinary care that includes sexual and psychological support, emphasizing the need for individualized care.

Feasibility of deploying a U.S. simulation-based gynecological brachytherapy educational workshop to an international setting

A decline in brachytherapy (BT) use for cervical cancer has negatively affected cure rates in the United States and abroad. To improve trainee exposure to BT, a simulation-based educational curriculum incorporating a pelvic mannequin was developed and implemented at several U.S. residency programs. We sought to describe an initial experience with deployment of this curriculum to an international setting. The setting was in Israel, a middle eastern country with cervical cancer incidence of 5-8 cases per 100,000 women. Israel was selected for this pilot because of its desire to increase exposure to trainees, lack of mandatory BT case requirements, and few residencies nationally. In determining the feasibility of deployment to this setting, a partnership was formed between a U.S. and Israeli brachytherapist to understand cultural context and institutional and logistical needs. Feasibility was defined as successful completion of the workshop. Trainee comfort and knowledge with BT was assessed with preworkshop and postworkshop surveys, with changes compared. The curriculum was incorporated into a 1-day course on gynecologic malignancies, with adaptation to local setting and routine. Among 15 attendees, eight were residents, from four programs. All completed the workshop. All domains assessed by the surveys improved and all respondents found the program to be helpful. International deployment of the simulation-based educational BT curriculum was feasible and well-received. Further collaboration is needed to deploy and adapt the curriculum to countries of high cervical cancer incidence that could benefit from increased education.

Education and training for image-guided adaptive brachytherapy for cervix cancer—The (GEC)-ESTRO/EMBRACE perspective

Image-guided adaptive brachytherapy (IGABT) has been shown to improve local/regional control and survival for cervix cancer patients while reducing morbidity. However, the technique is complex involving several conceptual, methodological, and technical innovations compared to conventional brachytherapy. The delivery of high-quality IGABT which will translate into improved outcomes is therefore critically dependent on effective education and training of all health professionals involved in the brachytherapy treatment process. This paper reviews the (GEC)-ESTRO/EMBRACE initiatives for education and training to promote the dissemination and implementation of IGABT for cervix cancer worldwide. The new skills required in different health professionals for successful implementation of IGABT are described. The achievements and challenges of current educational strategies for disseminating IGABT are discussed. Innovations to improve the effectiveness of current and future educational strategies are explored.

Combined operative and radiotherapeutic treatment for locally recurrent gynaecologic cancer with pelvic wall invasion: A monocentric retrospective study

Managing locally recurrent gynecologic cancer with pelvic wall invasion, particularly after prior pelvic radiotherapy, presents a significant clinical challenge. Combined operative and radiotherapeutic treatment (CORT) is a potential curative approach. This study aims to evaluate the effectiveness and morbidity of this technique in this patient population as implemented within a single institution. A comprehensive, retrospective analysis was conducted on patients treated with CORT for recurrent gynecologic cancer with pelvic wall invasion after prior pelvic radiotherapy at the University Hospitals of Leuven between January 2000 and December 2023. A total of 21 patients were eligible for analysis. All patients underwent open surgical macroscopic tumor resection with intraoperative implantation of brachytherapy guiding tubes. The average radiation dose to 90% of the treatment volume (D90) was 45.6 Gy EQD2 (range 16.0 to 66.2 Gy). The median follow-up period was 37.8 months (range 3-230 months). Local control at 2 and 5 years was 87,4% and 77,8%; overall-survival at 2 and 5 years was 57,1% and 52,4%, respectively. Seventeen of the 21 patients experienced some form of adverse event, with 15 patients needing surgical re-intervention. Our retrospective analysis demonstrates high local control and favorable overall-survival outcomes in patients with recurrent gynecologic cancer involving the pelvic wall. However, the treatment is associated with a substantial risk of severe adverse events. Given the complexity and potential morbidity of this approach, CORT should be performed in specialized centers with experience in managing such cases.

A new development in ultrasound-compatible gynecologic brachytherapy simulators

Gynecologic brachytherapy is an essential component in the curative treatment of cervical cancer. With the decline in brachytherapy utilization, gynecologic brachytherapy simulators are being used to provide a mechanism to enhance proficiency-based resident training. However, most models that have been used lack procedural fidelity as they are either repurposed from OB/GYN basic models or from physics phantoms. Therefore, we set out to develop a high-fidelity, ultrasound- and CT-compatible gynecologic brachytherapy training simulator. Based on prior experience with gynecologic training simulators on the market, we developed a wish list for an ultrasound-compatible brachytherapy training model. A custom simulator was developed based on an existing pelvic ultrasound trainer. Features included a cervical os and endometrial canal as well as a palpable and hypoechoic cervical tumor. The model took about 3 months from the initial meeting with the developer to completion. The properties of the material were equivalent to water for ultrasound, CT, and also MRI and the model did not show signs of degradation after multiple tandem insertions. A high-fidelity ultrasound-compatible simulator was effectively developed and utilized to improve resident training to perform brachytherapy implants with a derivative benefit in the long term of improving survival for women with advanced gynecologic malignancies through having access to more proficient brachytherapists. Future directions include enhancing the model to allow for repetitive needle insertion and suturing for interstitial training as well as creating variations in anatomy (e.g., retroverted uterus, bulky tumors, etc.) for more advanced technical training.

Multimaterial three-dimensional printing in brachytherapy: Prototyping teaching tools for interstitial and intracavitary procedures in cervical cancers

As the utilization of brachytherapy procedures continues to decline in clinics, a need for accessible training tools is required to help bridge the gap between resident comfort in brachytherapy training and clinical practice. To improve the quality of intracavitary and interstitial high-dose-rate brachytherapy education, a multimaterial, modular, three-dimensionally printed pelvic phantom prototype simulating normal and cervical pathological conditions has been developed. Patient anatomy was derived from pelvic CT and MRI scans from 50 representative patients diagnosed with localized cervical cancer. Dimensions measured from patients' uterine body and uterine canal sizes were used to construct a variety of uteri based off of the averages and standard deviations of the subjects in our study. Soft-tissue anatomy was three-dimensionally printed using Agilus blends (shore 30 and 70) and modular components using Vero (shore 85). The kit consists of four uteri, a standard bladder, a standard rectum, two embedded gross tumor volumes, and four clip-on gross tumor volume attachments. The three anteverted uteri in the kit are based on the smallest, the average, and the largest dimensions from our patient set, whereas the retroverted uterus assumes average dimensions. This educational high-dose-rate gynecological pelvic phantom is an accessible and cost-effective way to improve radiation oncology resident training in intracavitary/interstitial brachytherapy cases. Implementation of this phantom in resident education will allow for more thorough and comprehensive physician training through its ability to transform the patient scenario. It is expected that this tool will help improve confidence and efficiency when performing brachytherapy procedures in patients.

Outcomes of freehand interstitial brachytherapy in advanced gynecologic malignancies

The purpose of the study is to present the first results of freehand interstitial brachytherapy (ISBT) used to treat patients with carcinoma of the cervix and the vagina. Patients diagnosed with carcinoma of the cervix or carcinoma of the vagina who were not suitable for intracavitary brachytherapy were treated with freehand ISBT. The implant was performed transperineally using C arm or transrectal ultrasound guidance. Patients received an external beam radiotherapy dose of 50 Gy in 25 fractions. The dose delivered by high-dose-rate ISBT was 18 Gy in three fractions, 6 Gy per fraction, 6 h apart. The brachytherapy dose volume parameters were analyzed after CT-based planning using GEC ESTRO image-guided brachytherapy-based guidelines. From June 2018 till November 2018, 14 patients were treated with freehand ISBT. The mean dose received by 90% of the high-risk clinical target volume (D A freehand interstitial implant is feasible in resource limited settings and provides acceptable local control with minimal acute toxicity.

Development of an indigenous low-cost multichannel cylinder applicator for vaginal tumors

The purpose of this study was to report our experience regarding the development of a low-cost multichannel vaginal cylinder applicator for superficial and recurrent vaginal tumors. The applicator mold was created by applying heated wax sheets in layers around a plastic tube. Interstitial stainless-steel needles were placed at equal distance around the mold surface to create multiple channels for treatment. Two plans were created using CT images for a patient with a recurrent tumor over the posterior vaginal wall for comparing single-channel and multichannel cylinder dosimetry. The doses received by the target (high risk clinical target volume) and organs at risk (OARs) were computed using dose-volume histograms. There was no significant difference in terms of the prescribed dose delivered to high risk clinical target volume between the two plans. The volume of the target receiving 150 and 200 percent (V Multichannel vaginal cylinders reduce doses to the OARs as compared with the single-channel vaginal cylinder in superficial vaginal lesions limited to the wall of the vagina. Their use is limited by the cost of the applicator. Our low-cost multichannel vaginal cylinder can be used as a reliable alternative in such situations.

Initiatives for education, training, and dissemination of morbidity assessment and reporting in a multiinstitutional international context: Insights from the EMBRACE studies on cervical cancer

In 2008, the GEC ESTRO Gyn network launched the first multiinstitutional, observational, and prospective international study on MRI-guided brachytherapy in locally advanced cervical cancer patients (EMBRACE-I). EMBRACE-I was followed by EMBRACE-II from 2016 and ongoing. Among the aims of the EMBRACE studies are to benchmark morbidity outcomes and develop dose-volume effects and predictive models for morbidity. The EMBRACE studies collect both physician (CTCAE v.3) and patient (EORTC QLQ-C30/CX24) reported outcomes, including baseline information, in a regular follow-up schedule. The EMBRACE studies feature high numbers of patients (EMBRACE-I N = 1416, EMBRACE-II N = 1500 expected) enrolled from many institutions worldwide (EMBRACE-I n = 23, EMBRACE-II n = 45). This large-scale multiinstitutional approach offers a unique opportunity to investigate and develop new strategies for improving the quality of assessment and reporting of morbidity. This report presents an overview of the challenges and pitfalls regarding the assessment and reporting of morbidity encountered during more than a decade of development and research activities within the EMBRACE consortium. This includes the recognition and evaluation of inconsistencies in the morbidity assessment, and consequently, the provision of assistance and training in the scoring procedure to reduce systematic assessment bias. In parallel, a variety of methodological approaches were tested to comprehensively summarize morbidity outcomes, and a novel approach was developed to refine dose-effect models and risk factor analyses. The purpose of this report is to present an overview of these findings, describe the learning process, and the strategies that have consequently been implemented regarding educational activities, training, and dissemination.

Addressing the burden of cervical cancer through IAEA global brachytherapy initiatives

Brachytherapy (BT) is an essential component of definitive therapy for locally advanced cervical cancer. Despite the advantages of the dose distribution with BT in cervical cancer, there is paucity of specific skills required for good-quality BT applications. Furthermore, replacing BT with other modern external beam techniques as a boost can lead to suboptimal results in cervix cancer. Review of available IAEA resources, research and cooperation programs available from the IAEA was completed. These opportunities can be used to address challenges in Brachytherapy. The International Atomic Energy Agency (IAEA) provides support for BT through various means that includes education and training, both long term, short term and continuing medical education of professionals, providing expert visits to support implementation, development of curricula for professionals, e-learning through the human health campus, contouring workshops, 2D to 3D BT training, and virtual tumor boards. In addition, the IAEA provides support for implementing quality assurance in radiotherapy to its member states and provides guidelines for comprehensive audits in radiation therapy (QUATRO), and produces safety standards and training in radiation safety. In addition, mapping BT resources, making the case for investment and support for setting up BT services and radiotherapy centers are also available. The IAEA Dosimetry Laboratory provides calibration services to Secondary Standards Dosimetry Laboratories for well chambers used to confirm the reference air kerma rate of Co60 and Ir192 high-dose-rate BT sources, as well as for Cs137 low-dose-rate sources. Furthermore, the IAEA supports research and development in radiotherapy (and BT) through coordinated research activities that include controlled randomized clinical trials, Patterns of Care studies among others. Partnerships with professional organizations and funding bodies, as well as through the United Nations Joint Global Programme on Cervical Cancer Prevention and Control support radiotherapy activities, including BT in countries worldwide. The IAEA supports brachytherapy implementation, training and research and provides resources to professionals in the area.

Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer

Image-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy. Thirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge. The measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10 MRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.

Evaluation of the dosimetric impact and safety of MucoUp as a spacer in gynecologic brachytherapy

Gynecologic brachytherapy (BT) is an essential component of definitive radiation therapy, but excessive radiation exposure to organs at risk (OARs) remains a major concern. MucoUp, a hyaluronic acid-based spacer, has been introduced to physically separate the high-risk clinical target volume (HR-CTV) from adjacent OARs. However, its clinical feasibility and dosimetric impact remain underexplored. This study aimed to evaluate the dosimetric impact and clinical feasibility of MucoUp in high-dose-rate (HDR) gynecologic BT. A retrospective analysis was conducted on 5 patients with gynecologic malignancies who underwent HDR BT with and without MucoUp injection. Dosimetric parameters, including HR-CTV D90 and OAR D2cc (bladder, rectum), were compared between sessions with and without MucoUp. Spacer volume retention was assessed using pre- and post-treatment CT scans. MucoUp injection resulted in a significant reduction in rectal D2cc (7.19 Gy vs. 6.73 Gy, p = 0.043), while maintaining HR-CTV dose coverage (D90: 8.82 Gy vs. 9.15 Gy, p = 0.043). A nonsignificant reduction in bladder D2cc was observed (7.51 Gy vs. 7.16 Gy, p = 0.34). Spacer volume retention remained stable throughout treatment. No procedural complications or acute toxicity were observed. This study suggests that MucoUp is a promising spacer for gynecologic BT, effectively reducing rectal dose while preserving HR-CTV coverage. Given its high stability and safety, MucoUp may serve as an alternative to existing spacer materials. Further large-scale and long-term studies are warranted to evaluate its impact on late toxicities.

Twice daily template-based interstitial brachytherapy for gynecologic cancers: What is the optimal dose?

Several factors of template-based interstitial brachytherapy in gynecologic cancers, including large tumor size, invasion into adjacent organs or fistula, dose heterogeneity, and twice daily fractionation cause inherent dose-escalation effects, potentially increasing toxicity. This study reports a single-institutional dose escalation experience in twice daily template-based interstitial brachytherapy treatments to demonstrate tumor control and toxicity outcomes, with the hypothesis that with image-based planning dose-escalation with interstitial brachytherapy is safe and efficacious. Patients treated with template-based interstitial brachytherapy at our institution from 2006 to 2022 were identified. Over time, HDR brachytherapy boost dose at our institution has been dose-escalated from 18.75 Gy in 5 fractions to 27.5 Gy in 5 fractions. Local control and survival outcomes were analyzed using the Kaplan-Meier method and log-rank test to compare between groups. Formal tumor control probability (TCP) analysis was performed using logistic dose-response modeling. 214 patients were identified with median follow-up of 28.1 months (IQR 8.2-58.7). Total HDR dose correlated significantly with local and locoregional control when analyzed as a continuous variable, and when dichotomized around median dose of 25 Gy (p = 0.024). TCP analysis showed a dose-response effect between HR CTV D90 and local control in the entire cohort, and separately in cervical and vaginal cancer subsets. The actuarial 5-year incidence of grade 3 or worse toxicity was 6.1%, and there was no significant association between toxicity and total HDR dose or HR CTV D90. In patient treated with twice-daily template-based interstitial brachytherapy for gynecologic cancers brachytherapy dose correlates with local control with no significant association between brachytherapy dose and toxicity, thus suggesting room for dose-escalation.

The 100 most cited articles in cervical cancer brachytherapy

This study aimed to identify the 100 most cited research articles on cervical cancer brachytherapy. The Institute for Scientific Information Web of Science was used to identify the 100 most cited articles in cervical cancer brachytherapy as of July 5, 2019. The following important information was extracted: journal, year and month, country of region, author, type of article, type of dose rate, type of radionuclide, and image modality for brachytherapy planning. The 100 most cited articles in cervical cancer brachytherapy were published between 1981 and 2016, and the citations ranged from 858 to 49, which collectively had been cited 11,372 times at the time of searching. The index of citations per year ranged from 63.56 to 1.43. These articles were from 16 countries or regions, with most publications being from the United States (n = 27), followed by Austria (n = 26), Japan (n = 10), France (n = 7), and the Netherlands (n = 7). The International Journal of Radiation Oncology, Biology, Physics produced the most articles (n = 46), followed by Radiotherapy and Oncology (n = 39) and Gynecologic Oncology (n = 5). These articles were categorized as original studies (n = 75), reviews (n = 2), editorials (n = 2), surveys (n = 2), guidelines (n = 3), and recommendations (n = 6). A high dose rate (n = 69) was the most widely used, dose rate followed by a low dose rate (n = 20) and pulsed dose rate (n = 16). The bibliometric analysis presents a detailed list of the 100 most cited articles in cervical cancer brachytherapy. This analysis provides an insight into historical developments and enables the important advances in this field to be recognized.

Clinical outcome of high-dose-rate interstitial brachytherapy in vulvar cancer: A single institutional experience

The aim was to evaluate the toxicities and survival of patients with inoperable vulvar cancer treated using brachytherapy (BT). Patients treated at Kuopio University Hospital, Finland, during years 2007-2022 were retrospectively analyzed. Twenty-seven patients with vulvar cancer received high-dose-rate (HDR) interstitial brachytherapy (BT), most of them after external beam radiotherapy (EBRT). Nineteen had primary locally advanced vulvar cancer, and 8 had recurrent cancer. The mean EBRT prescription dose was 48.5 Gy (39-60 Gy) in 13-33 fractions. Eighteen patients (67%) had cisplatin as a radiosensitizer. EBRT was followed by BT (16-36 Gy in 3-8 fractions). The mean HR-CTV (high-risk clinical target volume) D90 EBRT + BT dose was 71.2 Gy (EQD₂). The mean follow-up time was 30 months. The 2-year progression-free survival (PFS) was 41% in the primary cancer group and 38% in the recurrence group. The 2-year overall survival (OS) was 56% and 63%, respectively. There were 12/19 (63%) recurrences in the primary cancer group. In the recurrent cancer group, 4 out of 8 (50%) patients had a subsequent recurrence. 7/27 (26%) patients suffered from grade 3-4 late toxicities. Before EBRT, the median size of the tumors was 3.8 cm. Patients with a tumor ≥ 3.8 cm had significantly worse OS than patients with tumors <3.8 cm, 45 months and 54 months, respectively (p = 0.022). The use of radiosensitizing chemotherapy also predicted better overall survival (p = 0.037). Definitive radiation therapy, including EBRT and BT, is a potential option in the management of inoperable vulvar cancer. To avoid toxicities, the proper radiation doses are to be found.

Changes of CD68, CD163, and PD-L1 tumor expression during high-dose-rate and pulsed-dose-rate brachytherapy for cervical cancer

We hypothesized that radiation doses delivered with high-dose-rate (HDR) and pulsed-dose-rate (PDR) brachytherapy in patients with cervical cancer could trigger immune stimulation by modulating immune cells in the tumor microenvironment. The objective was to determine CD68, CD163, and PD-L1 expression in biopsies from patients with cervical cancer and to compare the effects of HDR vs. PDR brachytherapy on the expression of these proteins. Nineteen consecutive women (mean age, 55.9 years) with histologically proven cervical cancer scheduled for brachytherapy after standard external beam irradiation therapy combined with platinum-based chemotherapy were included in a prospective study. Core tissue biopsies were obtained before radiochemotherapy (biopsy #1), after completion of radiochemotherapy and before brachytherapy (biopsy #2), and 2 weeks after completion of brachytherapy (biopsy #3). HDR or PDR brachytherapy was delivered according to availability of equipment. CD68, CD163, and PD-L1 immunohistochemical expression was estimated using a quantitative method. Conditional logistic regression models were used to assess the relationship between gene expression and time of biopsy for each brachytherapy technique. In relation to CD68 and CD163, statistically significant relationships between gene expression and biopsy tissue samples were not found in any of the brachytherapy techniques, although there was trend toward downexpression of CD68 and CD163 in biopsies #2 and #3 in the HDR brachytherapy cohort only. There was a significant increase in PD-L1 expression in biopsy #3 also in the HDR cohort as compared with the PDR cohort. Decreased CD68 and CD163 expression did not reach statistical significance, but this trend may have clinical translational potential. Overexpression of PD-L1 in tissue biopsies taken at 14 days in the HDR brachytherapy cohort may tentatively suggest that this time period would be an adequate interval for blockade of the PD-1/PD-L1 axis.

Automated applicator digitization for high-dose-rate cervix brachytherapy using image thresholding and density-based clustering

The purpose of the study was to develop and evaluate an automated digitization algorithm for high-dose-rate cervix brachytherapy, with the goal of reducing the duration of treatment planning, staff resources, variability, and potential for human error. An automated digitization algorithm was developed and retrospectively evaluated using treatment planning data from 10 patients with cervix cancer who were treated with a titanium tandem and ovoids applicator set. Applicators were segmented, without human interaction, by thresholding CT images to isolate high-density voxels and assigning the voxels to applicator and nonapplicator structures using HDBSCAN, a density-based linkage clustering algorithm. The applicator contours were determined from the centroid of the clustered voxels on each image slice and written to a treatment plan file. Automated contours were evaluated against manual digitization using distance and dosimetric metrics. A close agreement between automatic and manual digitization was observed. The mean magnitude of contour disagreement for 10 patients equaled 0.3 mm. Hausdorff distances were ≤1.0 mm. The applicator tip coordinates had submillimeter agreement. The median and mean dose volume histogram parameter differences were less than or equal to 1% for high-risk clinical target volume D The digitization of titanium tandem and ovoids applicators for high-dose-rate brachytherapy treatment planning can be automated using straightforward thresholding and clustering algorithms. The adoption of automated digitization is expected to improve the consistency of treatment plans and reduce the duration of treatment planning.

Toward 3D-TRUS image-guided interstitial brachytherapy for cervical cancer

To qualitatively and quantitatively analyze needle visibility in combined intracavitary and interstitial cervical cancer brachytherapy on 3D transrectal ultrasound (TRUS) in comparison to gold standard MRI. Image acquisition was done with a customized TRUS stepper unit and software (Medcom, Germany; Elekta, Sweden; ACMIT, Austria) followed by an MRI on the same day with the applicator in place. Qualitative assessment was done with following scoring system: 0 = no visibility 1 (= poor), 2 (= fair), 3 (= excellent) discrimination, quantitative assessment was done by measuring the distance between each needle and the tandem two centimeters (cm) above the ring and comparing to the respective measurement on MRI. Twenty-nine implants and a total of 188 needles (132 straight, 35 oblique, 21 free-hand) were available. Overall, 79% were visible (87% straight, 51% oblique, 76% free-hand). Mean visibility score was 1.4 ± 0.5 for all visible needles. Distance of the visible needles to tandem was mean ± standard deviation (SD) 21.3 millimeters (mm) ± 6.5 mm on MRI and 21.0 mm ± 6.4 mm on TRUS, respectively. Difference between MRI and TRUS was max 14 mm, mean ± SD -0.3 mm ± 2.6 mm. 11% differed more than 3 mm. Straight needles were better detectable than oblique needles (87% vs. 51%). Detectability was impaired by insufficient rotation of the TRUS probe, poor image quality or anatomic variation. As needles show a rather indistinct signal on TRUS, online detection with a standardized imaging protocol in combination with tracking should be investigated, aiming at the development of real time image guidance and online treatment planning.

Toxicity and outcomes associated with high-dose rate brachytherapy for medically inoperable endometrial cancer

To evaluate toxicity in inoperable endometrial cancer (EC) treated with definitive radiation therapy (RT). Patients treated with definitive RT for EC were retrospectively reviewed. EQD2 values were calculated for bladder, rectum, and sigmoid. Acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. Fifty-one patients were included. The majority of patients had endometrioid histology (N = 46, 90.2%) and Grade 1 disease (N = 32, 62.75%). Thirty-seven patients (72.5%) were treated with image-guided BT (IGBT) and 14 (27.5%) with two-dimensional BT. Forty patients (78.4%) received EBRT + BT and 11 (21.57%) received BT alone. No grade 2 (G2) or higher toxicities were reported with BT alone. G2 or higher acute toxicities with EBRT + BT were G2 proctitis (N = 2, 5.0%) and G3 proctitis (N = 1, 2.5%). Late toxicities included G3 vaginal stenosis (N = 1, 2.5%), proctitis (N = 1, 2.5%), enteritis (N = 1, 2.5%), and one G4 gastrointestinal bleed. One- and 2-year local control were 100% with BT alone and 93% and 89%, respectively, with EBRT + BT. One- and 2-year locoregional control were 100% with BT and 97% and 93%, respectively, with EBRT + BT. Recurrence-free survival was 89% at 1 and 2 years with BT alone compared to 87% and 80% with EBRT + BT. One- and 2-year overall survival were 88% and 72% with BT alone compared to 94% and 84% with EBRT + BT. There were no statistically significant differences in cancer control between the two groups. Women with inoperable EC treated with definitive RT have low toxicity rates and durable local control.