Practical Radiation Oncology

The Value of Patient-Reported Outcomes to Predict Symptom Burden and Health-Related Quality of Life After Chemoradiation for Cervical Cancer: A Prospective Study

Patients with cervical cancer undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected data on patient-reported outcomes to determine characteristics predictive of poor treatment experience. Between 2021 and 2023, we prospectively collected data on patient-reported outcomes from patients with cervical cancer undergoing definitive chemoradiation. The European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Question-Core 30 and the EORTC-Quality of Life Question-Cervical Cancer module were completed at baseline (BL) and at the end of treatment (EOT). Poor treatment experience was defined as EOT poor health-related quality of life (HRQOL), low physical function, or significant overall symptom burden. Predictive factors analyzed included demographic, clinical, and disease-specific factors and BL financial toxicity, depression, social function, and emotional function. Receiver operating characteristic analysis provided appropriate predictive cutoff values. Univariable and multivariable (MVA) linear regression analyses were performed. Forty-nine patients completed BL and EOT questionnaires. Median age was 43 years (range, 18-85 years). Most patients (59%) had stage III disease. BL financial toxicity ≥66.7, depression ≥66.7, social function ≤50, and emotional function ≤58 on the EORTC linear transformed scale of 0 to 100 were significant predictors for poor treatment experience (p ≤ .04) based on receiver operating characteristic analysis. On MVA, poor BL social function was associated with reduced EOT HRQOL (β, -9.3; 95% CI, -16.1 to -2.6; p < .008), decreased physical function (β, -24.4; 95% CI, -36.3 to -12.6; p < .001), and high symptom burden (β, 26.9; 95% CI, 17.5-36.3; p < .001). Earlier disease stage predicted decreased symptom burden (β, -6.7; 95% CI, -13.1 to -0.3; p = .039). BL financial toxicity was a significant predictor in univariable analysis (p = .001-.044) and showed a significant interaction term on MVA (p = .024-.041) for all 3 domains of poor treatment experience. Demographic and treatment-related factors were not predictive. Patients with cervical cancer with poor BL social function or high financial toxicity were at risk for increased symptom burden and poor HRQOL. Screening for these factors provides an opportunity for early intervention to improve treatment experience.

Can Immunotherapy Replace Radiation in Locally Advanced Endometrial Cancer?

PROshot: Immunotherapy for Cervical Cancer, Epidermal Growth Factor Receptor-Mutated Stage III Lung Cancer, Perioperative Chemotherapy for Esophageal Cancer, Salvage Postprostatectomy Radiation and Androgen Deprivation Therapy, and Immunotherapy for Head and Neck Cancer

Spine Stereotactic Radiosurgery, Prostate Radiation Frequency, Adjuvant Chemotherapy for Cervical Cancer, Bacteria and Radiation Dermatitis, and Breast Conservation Therapy for Multifocal Disease

Longitudinal Changes in Bone Mineral Measurements Inside and Outside Radiation Fields Used for Cervical Cancer Treatment

We compared the magnitude of changes in bone mineral density (BMD), within and outside the radiation field, among women who received pelvic radiation therapy (RT) with or without chemotherapy for cervical cancer. In this secondary analysis of a prospective study, we analyzed serial computed tomography scans and dual-energy x-ray absorptiometry scans from 78 patients who received definitive RT or chemoradiation therapy (CRT) for cervical cancer at a single institution from 2008 to 2015. BMD values at L1, L2, L3, and L4 were measured. We compared changes in BMD within the radiation field (ie, at L4) with those outside the field (ie, at L1). Linear mixed models were also used to examine the effect of RT on changes in BMD over time and covariate adjustment. The median age of the 78 patients was 45.5 years (range, 23-88 years); all received RT and 76 (97%) received concurrent CRT. Treatment was associated with significant declines in BMD in all 4 lumbar vertebral bodies over time (P < .05), with nadir at 3 months for L4 and at 1 year for L1. Pairwise comparisons at 3 months and 2 years after treatment indicated that BMD in L4 (within the RT field) had improved (P = .037), but BMD in L1 (outside the RT field) was no different at 3 months and 2 years. Significant BMD declines were observed in all lumbar vertebral bodies immediately after RT. However, in-field vertebral bodies reached nadir BMD earlier than those located outside the RT field. Our results suggest that treatment and patient-related factors other than RT may contribute to declines in BMD after treatment for cervical cancer. Routine bone density screening and post-RT therapy with hormones may be beneficial for selected patients who receive CRT for cervical cancer.

Consensus Guidelines for Delineation of Clinical Target Volumes for Intensity Modulated Radiation Therapy for Intact Cervical Cancer: An Update

Accurate target delineation is essential when using intensity modulated radiation therapy for intact cervical cancer. In 2011, the Radiation Therapy Oncology Group published a consensus guideline using magnetic resonance imaging (MRI). The current project expands on the previous atlas by including computed tomography (CT)-based contours, contours with MRI and positron emission tomography (PET) registrations, the addition of common and complex scenarios, and incorporating information on simulation and treatment planning techniques. Twenty-eight experts in gynecologic radiation oncology contoured 3 cases, first on a noncontrast CT simulation scan and then with registered diagnostic scans. The cases included (1) International Federation of Gynecology and Obstetrics (FIGO) IIIC1 with a bulky tumor and vaginal metastasis, (2) FIGO IIB with calcified uterine fibromas, and (3) FIGO IIIC2 with large lymph nodes. The contours on all 6 data sets (3 CT simulations without diagnostic images and 3 with registered images) were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement. The contours were reviewed, discussed, and edited in a group meeting prior to finalizing. Contours showed considerable agreement among experts in each of the cases, with kappa statistics from 0.67 to 0.72. For each case, diagnostic PET ± MRI was associated with an increase in volume. The largest increase was the clinical target volume (CTV) primary for case 2, with a 20% increase in volume and a 54% increase in simultaneous truth and performance level estimation volume, which may be due to variance in registration priorities. For the third case, 92.9% increased their CTVs based on the addition of the diagnostic PET scan. The main areas of variance were in determining the superior extent of CTV coverage, coverage of the mesorectum, and simulation and planning protocols. This study shows the value and the challenges of using coregistered diagnostic imaging, with an average increase in volumes when incorporating MRI and PET.

Navigating the Complexities of Lymph Node Management in Vulvar Cancer: Insights and Perspectives

Path to Precision: Refining Radiation Therapy Guidelines for Early Stage Endometrial Cancer Through Incorporation of Primary Tumor Size, Lower Uterine Segment Invasion, and Molecular Markers

Differences in Outcomes of Chemoradiation in Women With Invasive Cervical Cancer by Human Immunodeficiency Virus Status: A Systematic Review

Cervical cancer is one of the leading causes of cancer death among women worldwide, and women living with human immunodeficiency virus (HIV) carry the highest burden of disease. Chemoradiation (CRT) is the current standard treatment for locally advanced cervical cancer, without specific treatment modifications based on HIV status. This systematic review evaluates existing literature reporting differences in outcomes between HIV+ and HIV- women with invasive cervical cancer treated with CRT. Searches were conducted through Pubmed, Ovid MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library. Two researchers independently conducted article selection; articles were selected by title, then abstract, and then by full text content. Data were extracted using a structured form. Thirteen articles were included in the analysis, all of which were either retrospective or prospective cohort studies published between 2012 and 2018, and most of which were conducted in Sub-Saharan Africa. Treatment outcomes included treatment response, survival, toxicities, and quality of life. The majority of studies (8 of 13) reported no differences in treatment outcomes by HIV status. Out of 8 studies that assessed survival, 6 reported no significant difference based on HIV status. All 4 studies assessing treatment response found no significant differences based on HIV status. Among 6 studies primarily assessing treatment toxicity, 3 showed no differences based on HIV status. Factors affecting treatment outcomes, such as treatment selection bias, pretreatment hemoglobin levels, and antiretroviral therapy administration, were not systematically accounted for. The majority of studies analyzed showed no differences in treatment outcomes, including overall toxicity, treatment response, or mortality, on the basis of HIV infection status. These results suggest CRT should continue to be the treatment of choice for locally invasive cervical cancer regardless of HIV status. Further study is required to more precisely account for other variables that influence treatment outcome.

Identification and Management of Late Toxicities After Radiation Therapy for Vulvar Cancer

Vulvar cancer is a rare malignancy, with an estimated 6.900 cases diagnosed in 2024, though incidence has been rising in recent years. Radiation plays a critical role in definitive and adjuvant management, however late toxicities including pelvic insufficiency fractures (PIFs), anal/fecal incontinence, sexual dysfunction, cutaneous and sub-cutaneous fibrosis, and lymphedema may significantly impact quality of life in long-term survivors. This article will describe the most commonly encountered late radiation-induced toxicities seen in the management of vulvar cancers and provide practical guidance regarding work-up, and evidence-based management.

Use of Radiation Therapy in the Management of Vulvar Cancers—Identification and Management of Acute and Late Toxicities

Radiation therapy plays a critical role in the management of locally advanced vulvar cancers but can lead to a unique spectrum of side effects, with >25% of patients experiencing high-grade toxicities. The treatment phase requires meticulous perineal skincare and may require pharmacologic management of dysuria and cystitis, diarrhea, nausea, and dermatitis/mucositis. The addition of chemotherapy warrants close laboratory monitoring for hematologic and metabolic derangements.

Vulvar Cancer: Histopathologic Considerations and Nuances to Management

Vulvar cancer, although rare, poses significant challenges in diagnosis and treatment because of its histopathologic complexities and nuances. This paper reviewed key aspects of the management of vulvar cancer, focusing on histopathologic diagnosis, margin status interpretation, lymph node involvement assessment, and ongoing clinical trials.

Changing Landscape of Radiation Therapy for Advanced Cervical Cancer With a Focus on Interstitial Brachytherapy: A Canadian Practice Patterns Survey

To document the evolution of radical radiation therapy and interstitial brachytherapy (ISBT) utilization practice patterns across Canada, including use of imaging, technical details, and usage of anesthesia/analgesia, and to compare advanced (AC) versus nonadvanced (nAC) brachytherapy (BT) center practices. All Canadian centers with BT services were identified. One gynecology radiation oncologist per center was sent a 64-item questionnaire regarding the center's practice for patients with cervical cancer. Centers were categorized based on availability of advanced BT expertise (AC) versus those referring patients to other centers for advanced BT techniques (nAC). Aggregate responses are reported and compared with practice patterns identified in our previous survey. Descriptive statistics were used to summarize data, and the Fisher exact test, Fisher-Freeman-Halton, or Mann-Whitney-Wilcox test was used for comparisons. Thirty-seven of 38 respondents completed the survey (response rate: 97.4%). Compared with 2015, there has been an increase in utilization of magnetic resonance imaging as the sole imaging modality for BT planning: 3 of 26 (11%) versus 12 of 37 (32%; P = .03). The number of centers with the ability to perform ISBT increased in 2020 compared with 2015 (26/37 [70%] vs 13/26 [50%], P = .710); this trend is likely due to an increase in use of hybrid (Vienna, Utrecht, Venezia) applicators (36% [2015] vs 84% [2020]; P = .175). Fifteen (40%) centers had the ability to perform perineal-ISBT (P-ISBT). Sixteen and 21 centers were identified as AC and nAC, respectively. All 16 AC centers had the ability to perform ISBT, compared with only 10 nAC centers (P < .001). A higher proportion of AC centers had fellowship-trained radiation oncologists performing brachytherapy, compared with nAC centers (94% vs 14%, P < .001). In terms of anesthesia, conscious sedation was the only available choice at low-patient-volume centers (8/37, 21%) performing intracavitary BT only. Those performing ISBT had choice of general, spinal, and epidural anesthesia. In Canada, high-quality, modern management radiation therapy practices are consistently offered to patients with cervical cancer. There is a trend toward increased utilization of ISBT. Accumulation of evidence toward the use of ISBT, increased utilization of high-quality imaging modalities such as magnetic resonance imaging, and availability of hybrid applicators are potential contributors for this upward trend.

Higher Dose to Organs at Risk: The Unintended Consequences of Intravenous Contrast Use in Computed Tomography Simulation for Cervical Cancer

To compare the volumes of interest and doses to the organs at risk on contrast and noncontrast scans in patients with cervical cancer who underwent prophylactic extended-field radiation therapy (EFRT). We reviewed twenty cervical cancer patients treated with prophylactic EFRT at Peking Union Medical College Hospital between March 2021 and April 2021. Each patient underwent noncontrast and contrast scans during simulation. All structures were contoured, and radiation therapy plans were created based on both scans. Student t test and Pearson correlation coefficient test were performed. Compared with the noncontrast scan, on the contrast scan, the mean volume of the inferior vena cava expanded by 44% (P ≤ .001), and the mean volume of the para-aortic nodal clinical target volume increased by 17% (P ≤ .001). For the second portion of the duodenum, the V30 (38.2% vs 43.8%, P = .038), V35 (27.6% vs 35.1%, P = .002), V40 (18.3% vs 26.3%, P = .014), V45 (11.2% vs 18.5%, P = .008), and V50 (4.2% vs 9.1%, P = .005) were significantly lower on the noncontrast scan than on the contrast scan. For the third portion of the duodenum, the V45 (78.4% vs 81.6%, P = .03) and V50 (59.7% vs 67%, P ≤ .001) were significantly lower on the noncontrast scan than on the contrast scan. For the right kidney, the V5, V10, V15, V20, and V25 on the contrast and noncontrast scans were 85.4% versus 79.8% (P = .013), 52.5% versus 45.6% (P = .021), 25.6% versus 20.1% (P = .003), 11.1% versus 7.5% (P = .001), and 3.8% versus 2.3% (P = .027), respectively. Compared with the noncontrast scan, expansion of the inferior vena cava on the contrast scan can lead to excessive contouring and an overdose to the duodenum and right kidney in cervical cancer patients treated with prophylactic EFRT.

Updating and Optimizing Anatomic Atlases for Elective Radiation of Para-Aortic Lymph Nodes in Cervical Cancer

Previous studies have proposed 2 different contouring guidelines for the prophylactic radiation of para-aortic lymph nodes (PANs) for locally advanced cervical cancer. Because PAN-mapping atlases in current literature are limited to small patient samples and nodal populations, we updated the PAN atlas with a large data set of positron emission tomography (PET)-positive PANs on PET/computed tomography (CT) from patients with cervical cancer. We identified 176 PET-positive PANs on pretreatment PET/CT of 47 patients with diagnosed International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer. PANs were classified as left-lateral para-aortic (LPA), aortocaval (AC), or right paracaval (RPC). PAN clinical target volume (CTV) contours were drawn for all patients based on previously published guidelines by Takiar (CTV-T) and Keenan (CTV-K) and nodal volumetric coverage was assessed. We identified 94 LPA nodes (54%), 71 AC nodes (40%), and 11 (6%) RPC nodes. CTV-T had improved nodal center coverage of 97.6% compared with 85.0% for CTV-K (P < .001). Nodal center coverage for CTV-K and CTV-T (with corresponding PAN) were 79 (84.0%) and 93 (99.0%) LPA nodes (P = .001), 64 (90.1%) and 68 (95.8%) AC nodes (P = .221), and 5 (45.5%) and 9 (81.8%) RPC nodes (P = .134), respectively. Additionally, our updated PAN atlas identified nodal centers anterior to the aorta and inferior vena cava that are not covered by CTV-T but covered by CTV-K due to the 10 mm anterior aortic expansion of CTV-K. We have updated the PAN anatomic map of 176 PET-positive nodes from 47 patients and demonstrated that CTV-T has significantly better PAN coverage over CTV-K for posterior LPA and retrocaval regions for our data set. Additionally, we suggest a modification that includes a blend of CTV-T and CTV-K to provide optimal coverage for the mapped nodes anterior to the great vessels in our data set.

Carpe Diem: Making the Most of Plan-of-the-Day for Cervical Cancer Radiation Therapy

Radiation therapy is the key treatment for locally advanced cervical cancer. Organ motion presents a challenge to accurate targeting of external beam radiation therapy. The plan-of-the-day (PotD) adaptive approach is therefore an attractive option. We present our experience and the procedural steps required to implement PotD for cervix cancer. We reviewed relevant studies on organ motion and adaptive radiation therapy identified through a literature search and cross referencing. These included 10 dosimetric and 3 quality of life studies directly assessing the PotD approach to radiation therapy in cervix cancer. Studies show improvements in target coverage and reduction of dose received by normal tissues and suggest improved toxicity. Clinical implementation of PotD has been slow because of a number of difficulties and uncertainties, which we discuss with the aim of helping teams to implement PotD at their center. The PotD approach improves dosimetry and may improve toxicity. We describe a framework to assist with practical implementation.

Does Prophylactic Paraortic Lymph Node Irradiation Improve Outcomes in Women With Stage IIIC1 Endometrial Carcinoma?

To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC). A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes. A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79). Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.

Stereotactic Body Radiation Therapy for Gynecologic Malignancies: A Case-Based Radiosurgery Society Practice Review

International Federation of Gynecology and Obstetrics Endometrial 2023 Is Better For Radiation Oncology Patients

The International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system for endometrial cancer has marked changes from the previous staging system instituted 14 years prior in 2009. The new staging system includes nonanatomic factors for the first time (lymphovascular space invasion and histology) and molecular classification, which impacts the stage in early-stage disease (IAm

Financial Improvements From Short Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared With Standard of Care, “SAVE” Trial

Early-stage endometrial cancer is often treated with hysterectomy followed by adjuvant vaginal cuff brachytherapy (VCB). Financial toxicity from cancer treatment can impact treatment completion. The Short Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared to Standard of Care trial is a multicenter, prospective randomized trial of standard of care (SoC) VCB doses delivered in 3 to 5 fractions per the physician's discretion compared with a 2-fraction course. We report on secondary cost endpoints, quantifying the financial impacts of shorter treatment courses on institutions and participating patients. Technical (TechCs), professional, and total charges (TotCs) were collected prospectively and are reported as raw and Medicare-adjusted charges per patient. Distance to the treatment center and the median income for each patient's zip code were estimated. The Mann-Whitney U statistic, t test, and X One hundred eight patients were analyzed. SoC VCB was delivered in 3, 4, and 5 fractions for 27 of 54 patients (50%), 11 of 54 (20%), and 16 of 54 (30%), respectively. The median total distance traveled per patient for SoC versus experimental arms was 213 versus 137 miles (p = .12), and the median cost of commute for patients was $36.3 versus $18.0 (p = .11). Compared with 2-fraction treatment, 5-fraction treatment resulted in longer travel distances (median, 462 vs 137 miles; p < .01) and increased travel costs (median, $59.3 vs $18.0; p ≤ .01). Unadjusted raw professional charges in USD per patient did not differ between SoC versus experimental arms ($9159 vs $7532; p = .19). TechCs were significantly higher in the SoC arm ($35,734 vs $24,696; p ≤ .01), as were TotCs ($44,892 vs $32,228; p < .01;). Medicare-adjusted TechCs and TotCs were higher for the SoC arm. Two-fraction VCB resulted in fewer treatments per patient, reduced cost of travel compared with longer courses, and an adjusted reduction in health care expenditures compared with SoC.

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline

With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy. These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.

Indications for Adjuvant Radiation Therapy in Patients With pN0(i +) Adenocarcinoma of the Endometrium

Sentinel lymph node biopsy has led to an increase in the detection of isolated tumor cells (ITCs) in up to 10% of early stage endometrioid endometrial cancer patients. In addition, the risk of nonsentinel lymph node involvement is approximately 10% or lower in patients with ITCs. In most studies, approximately 60% to 70% of patients with ITCs either underwent completion lymphadenectomy or received adjuvant therapy. Therefore, although multiple studies have shown that the effect of ITCs on disease outcomes is favorable, the true effect of ITCs without additional treatment is not known. In this report we describe our philosophy of relying on extent of surgical nodal staging and presence or absence of adverse intrauterine pathologic factors at the time of adjuvant therapy decision making for endometrioid endometrial carcinoma patients with ITCs.

Adjuvant Radiation Field Extent and Sites of Failure in Node Positive Endometrioid Endometrial Cancer

In patients with node-positive endometrial cancer, adjuvant radiation therapy with chemotherapy decreases local-regional recurrence compared with chemotherapy alone. However, the optimal radiation field borders and extent of nodal coverage have not been well studied. In a multi-institutional cohort, survival outcomes and sites of failure were analyzed for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrioid endometrial cancer treated with pelvic radiation therapy (PRT) versus extended-field radiation therapy (EFRT), which encompassed high para-aortic lymph nodes. In a multi-institutional retrospective study, 143 patients with FIGO stage IIIC1 or IIIC2 endometrioid endometrial cancer treated with adjuvant radiation therapy from 2000 to 2016 were identified. Patient subgroups were classified by substage and radiation field extent: stage IIIC1 received EFRT, stage IIIC1 received PRT, and stage IIIC2 received EFRT. Recurrence-free survival (RFS), overall survival (OS), and out-of-field recurrence were calculated by the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model. Sites of failure were categorized as within or outside the radiation field. The median follow-up was 59 months; 87% of patients received chemotherapy. The 5-year RFS and OS rates were 73% and 87%, respectively. By subgroup, 5-year RFS rates were 79% for stage IIIC1 EFRT, 73% for stage IIIC1 PRT, and 69% for stage IIIC2 EFRT (P = .4). On multivariate analysis, the recurrence risk was highest for stage IIIC2 EFRT, although this result was not statistically significant (adjusted hazard ratio, 2.0; P = .4). In-field vaginal and nodal recurrences were observed in 2 patients (1%) and 4 patients (3%), respectively. Of 78 patients with stage IIIC1 cancer treated with PRT, 5 (6%) had isolated para-aortic nodal relapse outside the radiation field; 3 were long-term survivors (more than 6 years after salvage therapy). For patients with para-aortic recurrence, 86% had lymphovascular invasion, 71% had myometrial invasion of ≥50%, and 57% had grade 3 disease. Adjuvant chemoradiation therapy resulted in excellent survival outcomes for patients with FIGO stage IIIC endometrioid endometrial cancer. For patients with positive pelvic nodes, isolated para-aortic relapse outside the PRT field was uncommon and amenable to salvage therapy.

Low-Dose Adjuvant Cylinder Brachytherapy for Endometrioid Endometrial Cancer

Our purpose was to evaluate outcomes and sites of failure for women with early stage endometrial adenocarcinoma treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) with a low dose scheme. Retrospective review identified 318 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrioid endometrial cancer who received adjuvant HDR VB to a dose of 24 Gray (Gy) in 6 fractions from 2005 to 2017. Patients with <6 months follow-up were excluded. Dose was prescribed to cylinder surface and computerized tomography (CT) imaging was performed before each fraction to assess cylinder placement. Rates of vaginal relapse (VR), pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were calculated by Kaplan-Meier method. Univariate analysis was performed by log rank test or Cox proportional hazards. Pretreatment CT images were analyzed for patients with VR. Median follow-up was 42 months for 243 patients. The 3-year rates of VR, pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were 1.9%, 1.5%, 4.3%, 94.1%, and 98.9%, respectively. The 3-year VR rates by Gynecologic Oncology (GOG)-99 risk groups were 0%, 1.4%, and 3.2% for low risk, low-intermediate risk, and high-intermediate risk (HIR) disease (P = .5). By Post-operative Radiation Therapy in Endometrial Carcinoma (PORTEC) risk stratification, 3-year VR rate was 1.3% for HIR disease. On review of pretreatment CT images of the 6 patients with VR, 3 patients had relapse at the introitus outside of the treated vaginal length, and 3 had in-field recurrence at the vaginal apex. Higher body mass index (BMI) was associated with VR, with a 14% increase in risk per BMI unit (kg/m Adjuvant HDR VB with a low-dose regimen results in excellent clinical outcomes for patients with early stage endometrioid endometrial cancer. Patients with higher BMI may be at increased risk of VR, and additional study is needed to optimize brachytherapy treatment parameters.

Retained Surgical Sponge in the Pelvis From Magnetic Resonance Imaging–Guided Cervix Brachytherapy

Magnetic resonance imaging-guided brachytherapy is an essential component of curative treatment in locally advanced cervical cancer. The use of interstitial needles improves local control rate for locally advanced cervical cancer compared to intracavitary brachytherapy alone. Bleeding is one of the most common complications from cervix interstitial brachytherapy, typically managed by pressure with surgical sponge/packing with or without a hemostatic agent. Herein, we present a case of stage IVA cervical cancer with retained surgical sponge in the pelvis from magnetic resonance imaging-guided intracavitary/interstitial brachytherapy, and recommendations for future brachytherapy procedures.

Computed Tomography–Guided Optimization of Needle Insertion for Combined Intracavitary/Interstitial Brachytherapy With Utrecht Applicator in Locally Advanced Cervical Cancer

There are no international guidelines for optimal needle insertion during interstitial intracavitary brachytherapy (IS-ICBT) for cervical cancer. We aimed to investigate the clinical feasibility and added value of computed tomography (CT) guidance to optimize needle insertion in IS-ICBT using the Utrecht applicator and to evaluate needle shifts. We enrolled 24 patients who were treated with interstitial-brachytherapy. Two CT scans each were performed for every patient: (1) after applicator insertion without needles (CT A total of 266 interstitial needles were inserted in 76 of 93 BT fractions with high intra- and interpatient variations in the number of inserted needles. Based on CT The adaptive CT-guided IS-ICBT application was feasible and resulted in fewer unloaded needle insertions or complications and more efficient use with higher needle contribution to the treatment. Needle shift was frequent but did not require needle reinsertion with the proposed method.

Computed Tomography Guided Brachytherapy With Hybrid Applicators: An Effective Curative Treatment for Vaginal Cuff Recurrences

This study evaluated the clinical feasibility of hybrid brachytherapy and the benefits of computed tomography (CT) guidance for optimizing applicator position and needle placement via Utrecht or Venezia applicators in the curative treatment of vaginal cuff recurrence. Sixteen previously operated patients with gynecological cancer treated with hybrid brachytherapy for vaginal cuff recurrence from 2018 to 2022 were included. The applicators were selected according to vaginal diameter and tumor location. CT scans were conducted before and after needle insertion. The high-risk clinical target volume (CTV-HR), including residual disease and suspicious regions, as well as normal tissues, was contoured. The dosimetry goal was to ensure that the reference isodose (100%) adequately covered the CTV-HR while minimizing overlap with organs at risk. The needle shifts were assessed according to their locations. Outcome measures, including disease-free survival and overall survival, were analyzed. A total of 64 fractions were administered, with Utrecht applicators used for 62.5% (n = 40). The median equivalent doses in 2 Gy fractions (EQD2 D90) for 90% of the CTV-HR and intermediate-risk CTV were 87.64 Gy (57.45-97.78 Gy) and 69 Gy (31.33-76.73 Gy), respectively. Among the 696 possible needle positions, 419 interstitial needles (60%) were successfully inserted. The median number of needles per fraction was 6 (range, 1-12). Needle shifts occurred in 93% of the patients, predominantly in the anteromedial direction, with a mean magnitude of 0.21 ± 0.14 cm. The median follow-up was 14 months, with a 90% local tumor control rate and an 85% overall survival rate over 2 years, without severe side effects. Despite challenges in treating vaginal cuff recurrence in patients with gynecological cancers, hybrid brachytherapy provides an effective and personalized approach. Although needle shifts are common, they do not significantly impact dosimetric outcomes, highlighting the method's adaptability and reliability.

Automatic Verification of Beam Apertures for Cervical Cancer Radiation Therapy

Automated tools can help identify radiation treatment plans of unacceptable quality. To this end, we developed a quality verification technique to automatically verify the clinical acceptability of beam apertures for 4-field box treatments of patients with cervical cancer. By comparing the beam apertures to be used for treatment with a secondary set of beam apertures developed automatically, this quality verification technique can flag beam apertures that may need to be edited to be acceptable for treatment. The automated methodology for creating verification beam apertures uses a deep learning model trained on beam apertures and digitally reconstructed radiographs from 255 clinically acceptable planned treatments (as rated by physicians). These verification apertures were then compared with the treatment apertures using spatial comparison metrics to detect unacceptable treatment apertures. We tested the quality verification technique on beam apertures from 80 treatment plans. Each plan was rated by physicians, where 57 were rated clinically acceptable and 23 were rated clinically unacceptable. Using various comparison metrics (the mean surface distance, Hausdorff distance, and Dice similarity coefficient) for the 2 sets of beam apertures, we found that treatment beam apertures rated acceptable had significantly better agreement with the verification beam apertures than those rated unacceptable (P < .01). Upon receiver operating characteristic analysis, we found the area under the curve for all metrics to be 0.89 to 0.95, which demonstrated the high sensitivity and specificity of our quality verification technique. We found that our technique of automatically verifying the beam aperture is an effective tool for flagging potentially unacceptable beam apertures during the treatment plan review process. Accordingly, we will clinically deploy this quality verification technique as part of a fully automated treatment planning tool and automated plan quality assurance program.

Radiation Therapy for Cervical Cancer: Executive Summary of an ASTRO Clinical Practice Guideline

This guideline reviews the evidence and provides recommendations for the indications and appropriate techniques of radiation therapy (RT) in the treatment of nonmetastatic cervical cancer. The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT in definitive and postoperative management of cervical cancer. These questions included the indications for postoperative and definitive RT, the use of chemotherapy in sequence or concurrent with RT, the use of intensity modulated radiation therapy (IMRT), and the indications and techniques of brachytherapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. The guideline recommends postoperative RT for those with intermediate risk factors, and chemoradiation for those with high-risk factors. In the definitive setting, chemoradiation is recommended for stages IB3-IVA, and RT or chemoradiation is conditionally recommended for stages IA1-IB2 if medically inoperable. IMRT is recommended for postoperative RT and conditionally recommended for definitive RT, for the purposes of reducing acute and late toxicity. Brachytherapy is strongly recommended for all women receiving definitive RT, and several recommendations are made for target dose and fractionation, the use of intraoperative imaging, volume-based planning, and recommendations for doses limits for organs at risk. There is strong evidence supporting the use of RT with or without chemotherapy in both definitive and postoperative settings. Brachytherapy is an essential part of definitive management and volumetric planning is recommended. IMRT may be used for the reduction of acute and late toxicity. The use of radiation remains an essential component for women with cervical cancer to achieve cure.

Spare the Bowel, Don't Spoil the Target: Optimal Margin Assessment for Online Cone Beam Adaptive Radiation Therapy (OnC-ART) of the Cervix

The standard treatment for locally advanced cervical cancer involves pelvic chemoradiation. Intensity modulated radiation therapy planning requires expansion of the cervix and uterus clinical target volume (CTV) by 1.5 to 2 cm to account for motion. With online cone beam adaptive radiation therapy (OnC-ART), interfractional movement is accounted for, which can potentially lead to smaller CTV to planned target volume (PTV) margins. In this study, we attempted to determine the optimal CTV-to-PTV margin for adequate coverage with OnC-ART and factors that can affect CTV coverage. A retrospective cohort of 21 patients with cervical cancer treated with definitive chemoradiation was included. Nine patients treated with nonadaptive radiation had the uterocervix contoured on pretreatment cone beam computed tomography (CBCT) and end-treatment CBCTs. Anterior-posterior, lateral, and superior-inferior shifts and the average shift in all directions were calculated. A CTV-to-PTV expansion was determined and verified on a validation cohort of 12 patients treated with OnC-ART. The average anterior-posterior, lateral, and superior-inferior shifts with standard deviation were 0.32 ± 1.55 cm, 0.12 ± 2.31 cm, and 1.67 ± 3.41 cm, respectively. A uniform 5-mm expansion around the pretreatment CTV covered 98.85% ± 1.23% of the end-treatment CTV. This 5-mm expansion was applied to our validation cohort treated with OnC-ART, and 98.39% ± 3.0% of the end-treatment CTV was covered. Time between CBCTs >30 minutes and change in bladder volume were significantly correlated to CTV coverage. Based on our analysis, a CTV-to-PTV margin of 5 mm is adequate to encompass 98% of the CTV. A significantly reduced margin could potentially decrease the toxicities associated with radiation for patients with cervical cancer and lead to improved patient reported toxicity outcomes. We recommend physicians begin with a 5-mm margin and assess adequate coverage with image guidance during daily adaptation.

Optimizing Online Adaptation Timing in the Treatment of Locally Advanced Cervical Cancer

Online adaptive radiation therapy (ART) has emerged as a new treatment modality for cervical cancer. Daily online adapting improves target coverage and organ-at-risk (OAR) sparing compared with traditional image guided radiation therapy (IGRT); however, the required resources may not be feasible in a busy clinical setting. Less frequent adapting may still benefit cervical cancer patients due to large volume changes of the uterocervix of the treatment course. In this study, the dosimetry from different online adapt-on-demand schedules was compared. A retrospective cohort of 10 patients with cervical cancer treated with 260 fractions of definitive daily online ART was included. Plans with different adaptation schedules were simulated with adaptations weekly, every other week, once during treatment, and no adaptations (IGRT). These plans were applied to the synthetic computed tomography (CT) images and contours generated during the patient's delivered daily adaptive workflow. The dosimetry of the weekly replan, every-other-week replan, once replan, and IGRT plans were compared using a paired t test. Compared with traditional IGRT plans, weekly and every-other-week ART plans had similar clinical target volume (CTV) coverage, but statistically significant improved sparing of OARs. Weekly and every-other-week ART had reduced bowel bag V40 by 1.57% and 1.41%, bladder V40 by 3.82% and 1.64%, rectum V40 by 8.49% and 7.50%, and bone marrow Dmean by 0.81% and 0.61%, respectively. Plans with a single adaptation had statistically significantly worse target coverage, and moderate improvements in OAR sparing. Of the 18-dose metrics evaluated, improvements were seen in 15 for weekly ART, 14 for every-other-week ART, and 10 for single ART plans compared with IGRT. When every-other-week ART was compared with weekly ART, both plans had similar CTV coverage and OAR sparing with only small improvements in bone marrow dosimetry with weekly ART. This retrospective work compares different adapt-on-demand treatment schedules using data collected from patients treated with daily online adaptive radiation therapy. Results suggest weekly or every-other-week online ART is beneficial for reduced OAR dose compared with IGRT by exploiting the gradual changes in the uterocervix target volume.

Use of Specific Duodenal Dose Constraints During Treatment Planning Reduces Toxicity After Definitive Paraaortic Radiation Therapy for Cervical Cancer

This study aimed to validate the safety of paraaortic nodal (PAN) radiation therapy (RT) for patients with cervical cancer when the duodenal dose is limited to V A total of 97 patients who were treated with RT for cervical cancer between 2010 and 2018 received at least 56 Gy to grossly involved PANs. Patients were treated with concurrent chemoradiation (n = 88; 91%), with 93% of patients (n = 90) receiving intensity modulated RT to the initial PAN field and 98% (n = 95) receiving intensity modulated RT to a sequential PAN boost. The V The median duodenal V Limiting the duodenal dose to V

Neoadjuvant Chemotherapy and Surgery for Cervical Cancer, Timing of Surgery for Esophageal Cancer, Endometrial Cancer Molecular Classification, Vestibular Schwannoma, and Breast Boost Techniques

Partial-Length Treatment With Brachytherapy in Patients With Endometrial Cancer With High-Risk Features Is as Effective as Full-Length Vaginal Brachytherapy but With Reduced Toxicity

Full-length vaginal (FLV) brachytherapy for patients with endometrial cancer and high-risk features should be considered as per the American Brachytherapy Society to reduce distal vaginal recurrence in patients with endometrial cancers with papillary serous/clear cell histologies, grade 3 status, or extensive lymphovascular invasion. We sought to investigate this patient population and report outcomes of treatment with high-dose-rate (HDR) brachytherapy in women treated with FLV brachytherapy versus partial-length vaginal (PLV) brachytherapy. With institutional review board approval, we identified patients with endometrial cancer meeting American Brachytherapy Society criteria of high-risk features treated with adjuvant HDR between 2004 and 2010. HDR doses were 21Gy in 3 fractions delivered to either the full-length or partial-length vagina. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group scale and Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer grading, respectfully. Vaginal recurrences were assessed by physical examination and pap smears. Statistical analyses were performed using SPSS version 23 software. Of 240 patients treated with HDR brachytherapy, 121 were treated with FLV brachytherapy, and 119, with PLV brachytherapy. The median follow-up was 9.5 years (range, 8-11 years) for FLV patients and 8.5 years (range, 7-10 years) for PLV patients; 0% of patients had vaginal recurrences, and 1.4% and 0.9% had proximal vaginal recurrences, respectively (P = .54). All patients treated with FLV brachytherapy developed grade 3 mucositis of the lower vagina/introitus (P < .0001) and had increased analgesics use compared with those treated with PLV brachytherapy (P < .0001). In total, 23% of patients treated with FLV brachytherapy developed grade 3 stenosis of the lower vagina/introitus, in contrast to 0% of patients treated with PLV brachytherapy (P < .0001). PLV brachytherapy is as effective as FLV brachytherapy in reducing local recurrence and causes a significantly lower incidence of acute and late toxicities. The results of this study caution radiation oncologists regarding the careful use of FLV brachytherapy in patients with endometrial cancer and high-risk features.

(Potential) Mishaps of High-Dose-Rate Vaginal Cuff Brachytherapy

Considering how commonly vaginal cuff brachytherapy is used, there is relatively little literature regarding the potential, albeit low, risk for complications. We present 3 potentially serious mishaps involving cylinder misplacement, dehiscence, and excessive normal tissue irradiation due to unique anatomy. Three patients with potentially serious treatment errors were encountered in the authors' usual clinical practice. Each patient's records were reviewed for this report. For patient 1, computed tomography (CT) simulation revealed grossly inadequate cylinder insertion, which was most obvious on the sagittal view. For patient 2, CT simulation revealed that the cylinder extended beyond the perforated vaginal cuff and was surrounded by bowel. For patient 3, CT images were used only to verify cylinder depth. A standard library plan based on cylinder diameter and active length was used. In retrospect, the images revealed an unusually thin rectovaginal septum, with the lateral and posterior vaginal wall thickness estimated to be <2 mm. This patient's fractional normal tissue doses were calculated for this report, revealing a rectal maximum dose (per fraction) of 10.8 Gy, maximum dose that 2 cc of the organ receives of 7.4 Gy, and volume of the organ that receives the prescription dose or higher of 2.8 cc. All doses were far in excess of those anticipated for a minimal 0.5-cm vaginal wall depth. Vaginal cuff high-dose-rate brachytherapy is a high-volume, routine procedure. Even in experienced hands, however, it carries a risk of improper cylinder placement, cuff dehiscence, and excessive normal tissue dose, all of which could seriously affect outcomes. These potential mishaps would be better appreciated and avoided with more extensive use of CT-based quality assurance measures.