Elizabeth Kidd

Recurrence risk factors in stage IA grade 1 endometrial cancer

Patients with early-stage endometrial cancers (EC) with disease recurrences have worse survival outcomes. The purpose of this study was to identify clinical and pathologic factors that predict for all recurrences in stage IA grade 1 (IAG1) EC. Records from patients diagnosed with EC were retrospectively reviewed. Baseline characteristics of 222 patients with IAG1 EC who underwent surgical resection were analyzed. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors that predict for recurrence. Seventeen (7.65%) patients had recurrences. The 3-year cumulative incidence of recurrence were significantly higher for patients with time from biopsy to surgery ≥6 months (54% vs. 8%, p=0.003), simple hysterectomy with ovarian preservation vs. total hysterectomy and bilateral salpingo-oophorectomy (31% vs. 9%, p=0.032), any myometrial invasion vs. no invasion (18% vs. 2%, p=0.004), and tumor size ≥2 cm (15% vs. 2%, p=0.021). On, multivariate analysis, any myometrial invasion, increasing time from biopsy to surgery, and larger tumor size were independent predictors of any recurrence. Patients with recurrences had worse outcomes than those without (5-year overall survival [OS]=60%; 95% confidence interval [CI]=16%-86% vs. 5-year OS=95%; 95% CI=87%-99%, respectively, p=0.003). Time from biopsy to surgery, larger tumors, and myometrial invasion are the most important predictors of recurrence. Though the recurrence rates are generally low in IAG1 EC, the survival rate for the patients with recurrences was worse than those without. Identification of additional recurrence risk factors can help select patients who may benefit from adjuvant treatment.

Endometrioid Endometrial RNA Index Predicts Recurrence in Stage I Patients

Abstract Purpose: Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing. Experimental Design: We collected a 105-patient case-control cohort of stage I EEC comprising 45 patients who experienced recurrence less than 6 years after excision, and 60 Fédération Internationale de Gynécologie et d'Obstétrique grade-matched controls without recurrence. We first utilized two RNA-based, previously validated machine learning approaches, namely, EcoTyper and Complexity Index in Sarcoma (CINSARC). We developed Endometrioid Endometrial RNA Index (EERI), which uses RNA expression data from 46 genes to generate a personalized risk score for each patient. EERI was trained on our 105-patient cohort and tested on a publicly available cohort of 263 patients with stage I EEC. Results: EERI was able to predict recurrences with 94% accuracy in the training set and 81% accuracy in the test set. In the test set, patients assigned as EERI high-risk were significantly more likely to experience recurrence (30%) than the EERI low-risk group (1%) with a hazard ratio of 9.9 (95% CI, 4.1–23.8; P < 0.001). Conclusions: Tumors with high-risk genetic features may require additional treatment or closer monitoring and are not readily identified using traditional clinicopathologic and molecular features. EERI performs with high sensitivity and modest specificity, which may benefit from further optimization and validation in larger independent cohorts.

Survival benefit of radiation in high-risk, early-stage endometrioid carcinoma

To better delineate optimal management of high-risk, early-stage endometrial cancer, as national guidelines permit substantial practice variations. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB grade 3 and stage II endometrioid carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant treatments were brachytherapy (BT), external beam radiation therapy (EBRT), and chemotherapy. Death from endometrial cancer (cancer-specific mortality [CSM]) and local recurrence were analyzed using Gray's test and Fine-Gray regression. In total, 1,095 patients were identified: 52% received BT, 56% received EBRT, 16% received chemotherapy, and 29% received no adjuvant treatment. Survival outcomes were significantly worse for stage IB grade 3 and stage II grade 3 relative to stage II grades 1-2 (5-year CSM: 18% and 23% vs. 10%; p<0.001 and p=0.003, respectively), while there was no difference between stage IB grade 3 and stage II grade 3 (p=0.618). BT had a local control benefit across all patients (p<0.001) that translated into a survival benefit in stage IB grade 3 (adjusted hazard ratio [HR] for CSM=0.47, p=0.003). EBRT had a survival benefit in stage II grade 3 (adjusted HR for CSM=0.36; p=0.031), as did lymph node dissection (p=0.015). Chemotherapy was not significantly correlated with CSM. High-risk, early-stage endometrioid carcinoma is a heterogeneous population. BT was associated with a survival benefit in stage IB grade 3, whereas regional treatment with EBRT and lymphadenectomy was associated with a survival benefit in stage II grade 3.

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.

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-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.

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.

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.

Comparison of survival, acute toxicities, and dose–volume parameters between intensity‐modulated radiotherapy with or without internal target volume delineation method and three‐dimensional conformal radiotherapy in cervical cancer patients: A retrospective and propensity score‐matched analysis

AbstractBackgroundTo evaluate whether the use of the internal target volume (ITV) delineation method improves the performance of intensity‐modulated radiotherapy (IMRT) and three‐dimensional conformal radiotherapy (3DCRT) in terms of survival, acute toxicities, and dose–volume parameters.MethodsA total number of 477 cervical cancer patients who received concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016 were retrospectively analyzed. They were divided into four groups: the non‐ITV (N‐ITV) + IMRT, ITV + IMRT, N‐ITV + 3DCRT, and ITV + 3DCRT groups, with 76, 41, 327, and 33 patients, respectively. Survival analysis was performed with the Kaplan–Meier and the log‐rank tests, and acute toxicity analysis was performed with the chi‐squared test and the binary logistic regression test. Using the propensity score matching (PSM) method, 92 patients were matched among the four groups, and their dose–volume parameters were assessed with the Kruskal–Wallis method.ResultsThe median follow‐up time was 49 months (1–119) for overall survival (OS). The 5‐year OS rate was 66.4%. The ITV delineation method was an independent prognostic factor for OS (HR [95% CI]: 0.52 [0.27, 0.98], p = 0.044) and progression‐free survival (PFS) (HR [95% CI]: 0.59 [0.36, 0.99], p = 0.045). The ITV + IMRT group had the lowest incidence rate (22%) and the N‐ITV + IMRT group had the highest incidence rate of grade ≥3 hematological toxicity (HT) (46.1%) among the four groups. The pelvic bone marrow relative V10, V20, and V30 in the N‐ITV + IMRT group was higher than those in the ITV + IMRT and N‐ITV + 3DCRT groups (p &lt; 0.05).ConclusionsThe use of ITV for IMRT treatment planning was associated with improved overall survival and progression‐free survival, with lower HT rate.