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Objective African American women are increasingly being diagnosed with advanced and type II histology endometrial cancers. Outcomes have been observed to be worse in African American women, but whether or not race itself is a factor is unclear. We sought to evaluate the rates of diagnosis and outcomes on a stage-by-stage basis with respect to race using a large national cancer registry database. Methods The National Cancer Data Base was searched for patients with surgically staged non-metastatic endometrial cancer between 2004 and 2015. Women were excluded if surgical stage/histology was unknown, there was no follow-up, or no information on subsequent treatment. Pairwise comparison was used to determine temporal trends and Cox hazards tests with Bonferroni correction were used to determine overall survival. Results A total of 286 920 women were diagnosed with endometrial cancer and met the criteria for analysis. Median follow-up was 51 months (IQR 25.7--85.3). In multivariable models, in women with stage I disease, African American women had a higher risk of death than Caucasian women (HR 1.262, 95% CI 1.191 to 1.338, p<0.001) and Asian/Pacific Islander women had a lower risk of death than Caucasian women (HR 0.742, 95% CI 0.689 to 0.801, p<0.001). This held for African American women with stage II type I and type II disease (HR 1.26, 95% CI 1.109 to 1.444, p<0.001 and HR 1.235, 95% CI 1.098 to 1.388, p<0.001) but not for Asian/Pacific Islander women. African American women with stage IIIA--B disease also had a higher risk of death for type I and type II disease versus Caucasian women (HR 1.221, 95% CI 1.045 to 1.422, p=0.010 and HR 1.295, 95% CI 1.155 to 1.452, p<0.001). Asian/Pacific Islander women had a lower risk of death than Caucasian women with type I disease (HR 0.783, 95% CI 0.638 to 0.960, p=0.019) and type II disease (HR 0.790, 95% CI 0.624 to 0.999, p=0.05). African American women with stage IIIC1--2 had a higher risk of death with type I disease (HR 1.343, 95% CI 1.207 to 1.494, p<0.001) and type II disease (HR 1.141, 95% CI 1.055 to 1.233, p=0.001) whereas there was no significant difference between Caucasian women and Asian/Pacific Islander women. Conclusion Race appears to play an independent role in survival from endometrial cancer in the USA, with African American women having worse survival on a stage-forstage basis compared with Caucasian women. [ABSTRACT FROM AUTHOR]

Background: Randomized trials describe differing sets of high–intermediate risk criteria. Objective: To use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different criteria, and define a classification of "unfavorable risk." Methods: Patients with stage I endometrial cancer between January 2010 and December 2014 were identified in the National Cancer Database and stratified into two cohorts: (1) patients meeting Gynecologic Oncology Group (GOG)-99 criteria only for high–intermediate risk, but not Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 criteria and (2) those meeting PORTEC-1 criteria only. High-risk stage I patients with both FIGO stage IB (under FIGO 2009 staging) and grade 3 disease were excluded. In each cohort, propensity score-matched survival analyses were performed. Based on these analyses, we propose a new classification of unfavorable risk. We then analyzed the association of adjuvant radiation with survival, stratified by this classification. Results: We identified 117,272 patients with stage I endometrial cancer. Of these, 11,207 patients met GOG-99 criteria only and 5,920 patients met PORTEC-1 criteria only. After propensity score matching, adjuvant radiation therapy improved survival (HR=0.73; 95% CI 0.60 to 0.89; p=0.002) in the GOG-99 only cohort. However, there was no benefit of adjuvant radiation (HR=0.89; 95% CI 0.69 to 1.14; p=0.355) in the PORTEC-1 only cohort. We, therefore, defined unfavorable risk stage I endometrial cancer as two or more of the following risk factors: lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB. Adjuvant radiation improved survival in stage I patients with adverse risk factors (HR=0.74; 95% CI 0.68 to 0.80; p<0.001), but not in other stage I patients (HR=1.02; 95% CI 0.91 to 1.15; p=0.710; p interaction <0.001). Conclusion: Our study showed that adjuvant radiation was associated with an overall survival benefit in patients meeting GOG-99 criteria only; however, no survival benefit was seen in patients meeting PORTEC-1 criteria only. We propose a definition of unfavorable risk stage I endometrial cancer: ≥2 risk factors from among lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB disease. [ABSTRACT FROM AUTHOR]

Objectives: To determine the impact of histological grade on overall survival in patients with clinical stage I endometrioid endometrial adenocarcinoma when radiation therapy is used as primary definitive treatment. Methods: Patients with stage I endometrioid endometrial adenocarcinomas who underwent definitive radiation therapy with brachytherapy ± external beam radiation therapy were identified from the National Cancer Database. Overall survival was estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine factors affecting overall survival. Inverse probability of treatment weights were also used in multivariable analysis to estimate casual effects of external beam radiation therapy. Results: A total of 947 patients were identified. Median overall survival for grade 1, grade 2, and grade 3 tumors was 62 months (95% CI 53.8 to 70.2), 48.5 months (95% CI 38.2 to 58.8), and 33.5 months (95% CI: 23.1 to 43.8), respectively. Grade, age, and insurance status were associated with overall survival in univariate analysis with only grade and age remaining significant in multivariate analysis. Brachytherapy with external beam radiation therapy was not associated with survival in comparison with brachytherapy alone. Compared with grade 1 tumors, patients with grade 3 (HR 1.4, 95% CI 1.15 to 1.89), but not grade 2 (HR 1.0, 95% CI 0.82 to 1.26), had an increased risk of death, which persisted in an inverse probability of treatment weights-adjusted model (HR 1.56, 95% CI 1.21 to 1.93). Conclusions: Patients with grade 3 stage I endometrioid endometrial adenocarcinoma treated with primary definitive radiation therapy have worse survival than those with lower grade tumors. Addition of external beam radiation therapy to brachytherapy did not affect survival. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this American Brachytherapy Society task force is to present a literature review and patterns of care by a panel of experts for the management of vaginal recurrence of endometrial cancer. Methods and materials In 2016, the American Brachytherapy Society Board selected a panel of experts in gynecologic brachytherapy to update our current state of knowledge for managing vaginal recurrence of endometrial cancer. Practice patterns were evaluated via an online survey and clinical updates occurred through a combination of literature review and clinical experience and/or expertise. Results There are various retrospective series of patients treated with radiation for vaginal recurrence of endometrial cancer, which include a varied group of patients, multiple treatment techniques, and a range of total doses and demonstrate a wide scope of local control and overall survival outcomes. In the era of image-guided brachytherapy, high local control rates with low significant late-term morbidities can be achieved. Lower rates of local control and higher late-term toxicity are reported in the retreatment setting. In patients with no previous history of radiation treatment, external beam radiation therapy followed by brachytherapy boost should be used. There are varying practices with regard to the definition and appropriate doses of both the high-risk clinical target volume and the intermediate-risk clinical target volume in the setting of vaginal recurrence of endometrial cancer. There are limited data to provide appropriate dose constraints for some organs at risk with the majority of guidance taken from the definitive cervical cancer literature. Conclusions A summary of literature and expert practice patterns for patient selection, dose recommendations, and constraints are provided as guidance for practitioners. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this consensus statement from the American Brachytherapy Society (ABS) is to summarize recent advances and to generate general guidelines for the management of medically inoperable endometrial cancer patients with radiation therapy. Methods Recent advances in the literature were summarized and reviewed by a panel of experts. Panel members participated in a series of conference calls and were surveyed to determine their current practices and patterns. This document was reviewed and approved by the full panel, the ABS Board of Directors and the ACR Commission on Radiation Oncology. Results A transition from two-dimensional (2D) to three-dimensional (3D) treatment planning for the definitive treatment of medically inoperable endometrial cancer is described. Magnetic resonance (MR) imaging can be used to define the gross tumor volume (GTV), clinical target volume (CTV), and the organs at risk (OARs). Brachytherapy alone can be used for medically inoperable endometrial cancer patients with clinical Stage I cancer with no lymph node involvement and no evidence of deep invasion of the myometrium on MR imaging. In the absence of MR imaging, a combined approach using external beam and brachytherapy may be considered. Conclusions Recent advances support the use of MR imaging and 3D planning for brachytherapy treatment for medically inoperable endometrial cancer. [ABSTRACT FROM AUTHOR]

Standard of care for adjuvant treatment of stage III endometrial cancer includes chemotherapy and radiation. In addition to stage, tumor molecular profiles may predict treatment outcomes, and prospective clinical trials are ongoing. However, tumor molecular testing is costly and time-consuming. Our objective was to evaluate the cost-effectiveness of tumor molecular testing in stage III endometrial cancer. A Markov decision model compared two strategies for stage III endometrial cancer: Tumor Molecular Testing (TMT) versus No TMT. TMT included sequential POLE next generation sequencing, mismatch repair immunohistochemistry (IHC), and p53 IHC. POLE -mutated patients were assigned to adjuvant radiation therapy; all others including controls were assigned to adjuvant chemoradiation. First recurrences were treated with 6 cycles of carboplatin and paclitaxel. Second recurrences were treated with pembrolizumab alone for mismatch repair deficient patients and both pembrolizumab and lenvatinib for other patients. Sensitivity analyses were performed to test model robustness. Compared to No TMT, TMT was cost saving with equivalent effectiveness. On one-way sensitivity analysis, TMT remained cost saving over all parameter ranges. TMT was also favored on probabilistic sensitivity analysis in 80% of iterations at a willingness-to-pay threshold of $100,000/quality adjusted life-year (QALY) gained. However, when TMT was compared to mismatch repair IHC alone, TMT cost $182,798/QALY gained. In this model of patients with stage III endometrial cancer, TMT was cost saving compared to No TMT. However, when compared to mismatch repair IHC alone, TMT was economically unfavorable. • Tumor molecular testing is an area of ongoing investigation in endometrial carcinoma. • A Markov decision model was created to compare two strategies: tumor molecular testing versus no tumor molecular testing. • For stage III endometrial cancer, TMT was cost saving with equivalent effectiveness compared to no TMT. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: With the increasing elderly population, more women with newly diagnosed endometrial cancer may not be surgical candidates due to medical comorbidities. Definitive radiation therapy with external beam radiation (EBRT) and/or brachytherapy is a reasonable primary treatment for endometrial cancer in patients who cannot undergo surgery. Methods: A retrospective review identified 26 women 75 years and older with endometrial cancer who were not operative candidates due to comorbidities and received definitive radiation. Results: The median age of the treated patients was 83, all of whom had significant medical comorbidities precluding surgical treatment. Seventy-three percent of the patients had stage T1 disease, 19% were stage T2, and 8% were stage T3. Seventy-three percent of patients received EBRT before brachytherapy (median dose: 45 Gy). The median brachytherapy dose was 20 Gy in 5 fractions. The types of brachytherapy used were Rotte Y applicator (42%), tandem and cylinder (42%), and ring and tandem (16%). Median followup was 12 months (1–60 months). No treatment breaks were required for the entire group and only 2 patients (8%) developed late toxicity. The overall survival for all patients was 89% and 28% at 1 and 2 years, respectively. Disease-specific survival for all patients was 93% at 1 year and 73% at 3 years. Conclusions: The results in this study indicate that definitive radiation with EBRT and/or brachytherapy for endometrial cancer is feasible and well tolerated in an elderly population. [Copyright &y& Elsevier]

Purpose: To determine the dosimetric and toxicity differences between prone and supine position intensity-modulate radiotherapy in endometrial cancer patients treated with adjuvant radiotherapy. Methods: Forty-seven consecutive endometrial cancer patients treated with adjuvant RT were analyzed. Of these, 21 were treated in prone position and 26 in the supine position. Dose–volume histograms for normal tissue structures and targets were compared between the two groups. Acute and chronic toxicity were also compared between the cohorts. Results: The percentage of volume receiving 10, 20, 30, 40, 45, and 50 Gy for small bowel was 89.5%, 69%, 33%, 12.2%, 5%, and 0% in the prone group and 87.5%, 62.7%, 26.4%, 8%, 4.3%, and 0% in the supine group, respectively. The difference was not statistically significant. The dose–volume histograms for bladder and rectum were also comparable, except for a slightly greater percentage of volume receiving 10 Gy (1.5%) and 20 Gy (5%) for the rectum in the prone group. Acute small bowel toxicities were Grade 1 in 7 patients and Grade 2 in 14 patients in the prone group vs. Grade 1 in 6 patients and Grade 2 in 19 patients in the supine group. Chronic toxicity was Grade 1 in 7 patients and Grade 3 in 1 patient in the prone group and Grade 1 in 5 patients in the supine group. Conclusion: These preliminary results suggest that no difference exists in the dose to the normal tissue and toxicity between prone and supine intensity-modulated radiotherapy for endometrial cancer. Longer follow-up and more outcome studies are needed to determine whether any differences exist between the two approaches. [Copyright &y& Elsevier]

Abstract: Objective. : To assess local control and chronic toxicity with IMRT for adjuvant treatment of endometrial carcinoma. Methods. : Forty-seven patients with endometrial cancer were treated with adjuvant IMRT and HDR brachytherapy (HDRB). The external beam dose was between 45 and 50.4 Gy, and all patients received 10 Gy in 2 fractions of HDRB to the vaginal cuff. Eight of these patients were treated with extended field to include the paraaortic region. Results. : IMRT dosimetry showed excellent coverage of the planning target volume (PTV) with mean PTV 95, PTV 110 and PTV 120 of 97.8%, 8.2% and 0.9% respectively. At a median follow-up of 20 months, four patients have recurred at extra pelvic sites. No patient had pelvic recurrence. The treatment was well tolerated with late toxicities as follows: small bowel grade 1: 25%, rectal grade 1: 2% and bladder grade 1: 13%. One patient had grade 3 small bowel toxicity. The 3-year actuarial rate of grade 2 or greater toxicity, disease-free survival and overall survival rate were 3.3%, 84% and 90%, respectively. Conclusions. : The preliminary analysis of IMRT for adjuvant treatment of endometrial carcinoma shows excellent local control and low toxicity. However, longer follow-up and more patients are needed to ascertain whether the benefits of IMRT treatment seen here translate into long-term reductions in toxicities and local recurrence. [Copyright &y& Elsevier]

The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy. This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27. In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P <.001). However, no difference in OS was seen (90.8% vs 93.2%, P =.5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P =.001) but not OS. MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted. [ABSTRACT FROM AUTHOR]

Lymphovascular space invasion (LVSI) predicts for higher rates of recurrence and increased mortality in endometrial cancer. Using 3-tier LVSI scoring, a PORTEC-1 and -2 trials analysis demonstrated that substantial LVSI was associated with worse locoregional (LR-DFS) and distant metastasis disease-free survival (DM-DFS), and these patients possibly benefited from external beam radiation therapy (EBRT). Furthermore, LVSI is a predictor for lymph node (LN) involvement, but the significance of substantial LVSI is unknown in patients with a pathologically negative LN assessment. We aimed to evaluate clinical outcomes of these patients in relation to the 3-tier LVSI scoring system. We performed a single-institutional retrospective review of patients with stage I endometrioid-type endometrial cancer who underwent surgical staging with pathologically negative LN evaluation from 2017 to 2019 with 3-tier LVSI scoring (none, focal, or substantial). Clinical outcomes (LR-DFS, DM-DFS, and overall survival) were analyzed using the Kaplan-Meier method. A total of 335 patients with pathologically LN-negative stage I endometrioid-type endometrial carcinoma were identified. Substantial LVSI was present in 17.6% of patients; 39.7% of patients received adjuvant vaginal brachytherapy and 6.9% of patients received EBRT. Adjuvant radiation treatment varied by LVSI status. In patients with focal LVSI, 81.0% received vaginal brachytherapy. Among patients with substantial LVSI, 57.9% received vaginal brachytherapy alone, and 31.6% of patients received EBRT. The 2-year LR-DFS rates were 92.5%, 98.0%, and 91.4% for no LVSI, focal LVSI, and substantial LVSI, respectively. The 2-year DM-DFS rates were 95.5%, 93.3%, and 93.8% for no LVSI, focal LVSI, and substantial LVSI, respectively. In our institutional study, patients with pathologically LN-negative stage I endometrial cancer with substantial LVSI had similar rates of LR-DFS and DM-DFS compared with patients with none or focal LVSI. These findings highlight the need for multi-institutional studies to validate the prognostic value of substantial LVSI in this patient population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes.Methods and Materials: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method.Results: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001.Conclusions: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the impact of air gaps at the cylinder surface on the rate of vaginal cuff failure (VCF) after image-guided adjuvant vaginal cuff brachytherapy (VCBT) in the treatment of high-intermediate risk (HIR) FIGO (Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics)) Stage I endometrial cancer. A retrospective review of patients treated with image-guided VCBT from 2009 to 2016 for HIR FIGO Stage I endometrial cancer was performed. Air gaps present at the applicator surface on the first postinsertion CT were contoured. Vaginal cuff failure–free survival (VCFFS) was measured from the first fraction of VCBT to VCF. A total of 234 patients were identified. Air gaps were present on the first postinsertion CT scan in 82% of patients. The median number of air gaps was 2 (interquartile range [IQR] 1–3), median depth of the largest air gap was 2.7 mm (IQR 2.1–3.4 mm), and the median cumulative volume of air gaps was less than 0.1 cm3 (range < 0.1–0.7 cm3). At a median followup of 56 months (IQR 41–69), 12 patients (5%) experienced VCF, of which 4 had isolated VCF and 8 had synchronous pelvic or distant failure. Five-year VCFFS and isolated VCFFS were 96% (95% confidence interval 93–98%) and 98% (95% confidence interval 96–100%), respectively. On univariate analysis, no factors, including the presence, number, maximum depth, or cumulative volume of air gaps, were predictive for VCFFS. In this population, VCFFS remained high despite most patients having air gaps present on postinsertion CT scan. [ABSTRACT FROM AUTHOR]

Purpose: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions.Methods and Materials: An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets 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 between observers.Results: Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus.Conclusions: Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes. [ABSTRACT FROM AUTHOR]

Many patients with endometrial cancer cannot undergo surgery and instead receive definitive radiation therapy (RT). We investigate the correlation between MRI response to RT and clinical outcomes. Women with inoperable, clinical Stage I endometrial cancer were treated with definitive brachytherapy (BT) with/without pelvic RT (PRT). Patients underwent MRI with functional diffusion-weighted imaging before and after RT. A radiologist retrospectively classified cases as complete, partial, or indeterminate response (CR, PR, or IR, respectively) vs. disease progression. Local control was clinicopathologically defined. From 2007 to 2017, 50 women underwent definitive RT. Thirty-five (70%) received BT alone (median dose 37.5 Gy). For combined therapy, the median PRT and BT doses were 45 and 25 Gy, respectively. Median gross tumor volume and high-risk clinical target volume were 7.1 cc and 90.0 cc, respectively. Median followup among living patients was 20 months. All patients underwent post-RT MRI with T1/T2 sequencing at a median of 3.2 months after RT; 40 patients (80%) underwent functional diffusion-weighted imaging sequences. On initial post-RT MRI, CR was documented in 42 patients (84%), IR in 1 patient (2%), and PR in seven patients (14%). At median followup of 16.3 months, no CR patients had uterine failure. Among eight patients with initial PR/IR, all were found to be clinicopathologically no evidence of disease at the uterus on further evaluation. Definitive RT with BT or BT + PRT is associated with high response rates on MRI. Overall, initial CR predicted for excellent outcome with no infield failure. [ABSTRACT FROM AUTHOR]

Abstract Background Limited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT. Methods A retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to <75 Gy and <90 Gy, respectively. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities, defined according to CTCAE v4, were recorded. Results Prior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6–75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3–81.8), 70.6 Gy (range: 32.0–80.5), and 52.7 Gy (range: 29.6–75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities. Conclusion Re-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation. Highlights • 22 patients treated with definitive re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. • No ≥G3 rectosigmoid or bladder toxicities when cumulative rectosigmoid and bladder D2cc (EQD2) limited to <75 Gy and <90 Gy. • 3-year local control, disease-free survival, and overall survival rates were 65.8%, 40.8%, and 68.1%, respectively. • Re-irradiation with 3D conformal brachytherapy is feasible and safe when cumulative dose to organs-at-risk is limited. [ABSTRACT FROM AUTHOR]

Abstract Purpose We evaluated the utilization of vaginal brachytherapy (BT) and the resulting impact on survival in stage IA endometrial cancer of clear cell (CC), papillary serous (PS), and carcinosarcoma (CS) histology. Methods Patients with uterine cancer diagnosed from 2004 to 2015 were identified from the National Cancer Database. Patients underwent hysterectomy, showing FIGO stage IA disease with CC, PS, or CS histology. Logistic regression was used to evaluate predictors of BT utilization and to generate propensity scores. Survival was compared using log-rank test and Cox proportional hazards modeling, with propensity score adjustment. Results We identified 5711 patients who underwent hysterectomy showing FIGO pT1a, N0 or NX endometrial cancer with CC, PS, or CS histology, of which 29.5% received BT. Multivariate predictors of increased receipt of BT were identified. With a median follow-up of 3.3 years, 3-year overall survival (OS) was 87% for those receiving BT versus 78% for those without (p < 0.001). A survival benefit to BT was maintained across histologies. Similar results were seen whether tumor was confined to endometrium or had <50% myometrial invasion. On multivariate analysis, receipt of BT was associated with increased survival (hazard ratio [HR] 0.75, 95% confidence interval 0.65–0.87, p < 0.001). The benefit of BT persisted after propensity score adjustment (HR 0.76, p < 0.001). Conclusions In this cohort of women with stage IA endometrial cancer of unfavorable histology, the use of BT was associated with improved survival. In this study, 29.5% of patients in our cohort received BT. Highlights • Adjuvant brachytherapy is associated with improved survival in stage IA endometrial cancer of unfavorable histology. • Utilization of brachytherapy in this clinical scenario is rare currently, at 29.5% of patients from a national cohort. • Adjuvant chemotherapy improves survival in most situations, but may not be beneficial in clear cell patients. • Adjuvant external beam radiation is not routinely beneficial. It may help in those with additional risk factors. [ABSTRACT FROM AUTHOR]

Purpose Vaginal brachytherapy (VBT) alone has been shown to be a viable adjuvant treatment strategy for most patients with Stage I endometrioid endometrial cancer. We sought to examine our institutional data following practice pattern changes resulting from the publications of GOG-99 and PORTEC-2. Methods and Materials We retrospectively analyzed women who underwent adjuvant VBT after surgical staging for Stage 1 endometrioid endometrial cancer at our institution from 2007 to 2014. Results We identified 297 women. Median time to last followup or death was 52.3 months (interquartile range: 32.3–72.3 months). By International Federation of Gynecology and Obstetrics 2009 staging, 162 patients (54.5%) had Stage IA and 128 (43.1%) had Stage IB disease. Ninety-nine (33.3%) patients had Grade 1, 153 (51.5%) had Grade 2, and 45 (15.2%) had Grade 3 disease. According to GOG-249 and PORTEC-2 criteria, 167 (56.2%) and 127 (42.7%) patients were with high–intermediate–risk disease. Two women had Stage IB Grade 3 disease. The most common high-dose-rate–VBT regimen was 2100 cGy/three fractions to a depth of 5 mm. Four (two acute and two late) (1.3%) Grade 3 genitourinary toxicities were reported: three episodes of vaginal dehiscence (after second course of VBT, 2 months after completion of VBT, and 1 year after completion of VBT) and one episode of radiation necrosis. Twenty-one (7%) women recurred: three recurred in the vagina, two recurred in the pelvic lymph nodes, and 16 recurred distantly. Conclusions Outcomes appear consistent with published randomized data in women with high–intermediate–risk endometrial cancer who are treated with brachytherapy alone. Recurrence and complication rates were minimal. [ABSTRACT FROM AUTHOR]

Purpose Previous studies of stage II endometrial cancer have included cancers with cervical glandular involvement, a factor no longer associated with risk of recurrence. In order to better assess relapse patterns and the impact of adjuvant therapy, a retrospective analysis was conducted for patients with modern stage II endometrial cancer, defined as cervical stromal invasion. Materials and methods Patients diagnosed with surgically staged FIGO stage II endometrial cancer at the UPMC Hillman Cancer Center from 1990–2013 were reviewed. Factors associated with rates of locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were analyzed using the log rank test. Results 110 patients with FIGO stage II disease were identified. Most (84.5%) received EBRT ± BT, with 13.6% receiving BT alone. With a median follow-up of 64.6 months, the 5-year actuarial rates of LRC, DM, DFS, and OS were 94.9%, 85.1%, 67.9%, and 75.0%, respectively. With 5 locoregional failures, the only factor predictive of LRC was pelvic lymph node dissection. Characteristics associated with DM included age, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Factors predictive of both DFS and OS were age, grade, adverse histology, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Conclusions This represents the largest single-institution study for modern stage II endometrial cancer, confirming high rates of pelvic disease control after surgery and adjuvant therapy. With most patients receiving adjuvant radiotherapy, the predominant mode of failure, albeit low in absolute number, remains distant metastases. [ABSTRACT FROM AUTHOR]

Objectives Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. Methods Patients with grade 1–2, clinical stage I endometrial adenocarcinoma, < 50% myometrial invasion, and tumor ≤ 2 cm were reviewed. Definitive treatment consisted of 5–6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. Results From 2007 to 2016, 45 patients were treated to a median dose of 37.5 Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9 cm 3 (range, 0.7–18.7) and 80.9 cm 3 (17.2–159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8 Gy (76.5–295.6) equivalent 2 Gy dose, and the median CTV D90 was 49.7 Gy (34.5–57.2). Median follow-up among living patients was 18.6 months (3.0–64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3 + acute or late toxicity was observed. Conclusions HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series. [ABSTRACT FROM AUTHOR]

The Venezia gynecological applicator (Elekta) is a hybrid interstitial/intracavitary brachytherapy applicator used to treat cervical cancers. Previous data supporting the use of hybrid brachytherapy comes mainly from the EMBRACE cohort showing increased coverage of the high-risk CTV (HR-CTV) with decreased toxicity. Single-institution data, further supports this technique. We undertook this study to report our initial experience with the Venezia applicator for treatment of locally advanced cervical and endometrial cancers. We retrospectively reviewed 21 patients who received brachytherapy using the Venezia applicator for definitive treatment of cervical or endometrial cancer, treated from June, 2021 to March, 2022. All patients completed chemoradiotherapy followed by brachytherapy boost. For each brachytherapy fraction, patients received sedation and the Venezia applicator was placed. Radiation treatment planning was performed on CT imaging fused to daily MRI, using the Oncentra® treatment planning system. If needles were required for hybrid interstitial brachytherapy, the plan was optimized first without utilizing the needles, to meet constraint to organs at risk (OARs). Subsequently, planning was performed considering the interstitial needles with a focus on optimizing the balance of target coverage and dose to organs at risk. Radiation dose to target volumes and organs at risk were recorded as equivalent dose in 2Gy fractions (EQD2). Median age was 54 years. Ninety percent of patients were treated for a primary cervical cancer and 10% for primary endometrial cancer. Twenty-nine percent of patients had T1 primary tumor, 48% had a primary T2 tumor and 24% had a primary T3 tumor. The most common histology was squamous cell carcinoma (SCC) in 76% of patients, with adenocarcinoma in 10% and the remaining being undifferentiated or endometrioid. Median follow up was 4.3 months. Thirty-three percent of patients experienced acute toxicity with brachytherapy, all of which were grade 1-2. Twenty-nine percent experienced acute GI toxicity, 10% experienced acute GU toxicity and 10% experienced bleeding. Median brachytherapy dose and fractionation was 28Gy delivered over 4 fractions. Sixty-two percent of patients required hybrid interstitial brachytherapy and the median number of interstitial needles placed was 4. Median volume of the Gross Tumor Volume (GTV) and HR-CTV at first fraction were respectively 5.22cm3(IQR 4.26cm3-10.28cm3) and 27.84cm3(IQR 24.71cm3-40.36cm3). Median HR-CTV D90 and D98 were respectively 85.3Gy(IQR 83.1Gy-88.8Gy) and 76.8Gy (IQR 74.2Gy-79.6Gy). Median GTV D98 was 98.4Gy (IQR 94.3Gy-116.3Gy). Regarding OARs, median D2cc dose to the rectum, sigmoid and bladder were respectively 56.9Gy (IQR 53.7Gy-59.1Gy), 60Gy (IQR 55.9Gy-63.7Gy) and 75.3Gy (IQR 72.3Gy-77.6Gy). Median D1cc dose to the bowel was 50Gy (IQR 46.6Gy-56.8Gy). Median D0.1cc dose to the left and right ureter were respectively 71.8Gy (IQR 62.6Gy-85Gy) and 67.5Gy (IQR 61.6Gy-89.1Gy). Brachytherapy using the Venezia hybrid applicator was implemented with good dosimetry and sparing of organs at risk. Procedure related complications were mild. [ABSTRACT FROM AUTHOR]

Objectives: Uterine clear cell carcinoma (UCCC) is a rare histologic subtype of endometrial carcinoma (EC) that is associated with early metastasis, chemoresistance, and poor survival. Due to the aggressive behavior of UCCC and the inability to perform prospective clinical trials for this rare tumor type, adjuvant treatment choices for stage I and II UCCC are often made at the provider's discretion. Our objectives were to determine if adjuvant chemotherapy (CT), radiation therapy (RT), or both were associated with differences in recurrence-free survival (RFS) and overall survival (OS) in stage I and II UCCC confirmed by gynecologic pathology review. Methods: All patients with stage I and II UCCC between 2006 and 2019 were identified via a single institution pathology database. Electronic medical records were used for demographic and clinical- pathologic data. All cases were reviewed by a gynecologic pathologist. Cases of both pure UCCC and mixed non-serous UCCC were included due to prior evidence that mixed UCCC outcomes are driven by the clear cell (CC) component. RFS and OS were analyzed using Kaplan-Meier (KM) failure functions and a Cox proportional hazards (PH) model. Results: A cohort of 71 patients was identified, including 39 (55%) pure UCCC and 32 (45%) mixed UCCC. Most patients were FIGO stage IA (77.5%). Mixed UCCC tumors ranged from 2-90% CC. Among 32 patients with mixed UCCC, 30 (94%) had endometrioid/CC, and two (6%) had endometrioid, CC, and mucinous histology. Of 58 (82%) patients receiving adjuvant therapy, 43 (61%) received CT, 50 (70%) received RT, and 35 (49%) received both. Recurrences were rare, with one local, three regional, and three distant recurrences in the cohort. Deaths were also rare (n =9) and most likely to be cancer-related (n =4). The Median follow-up time was 1078 days. The 5-year RFS was 85% (95% CI: 70-93%) and 5-year OS was 88% (95% CI: 74-94%). 5-year RFS and OS among patients with and without RT were 88% (95% CI: 39-98%) versus 85% (95% CI: 71-93%) and 88% (95% CI: 62-97%) versus 87% (95% CI: 68-95%). 5-year RFS and OS among patients with and without CT were 82% (95% CI: 0.64-0.92) versus 94% (95% CI: 65-99%) and 90% (95% CI: 75-96%) versus 79% (95% CI: 32-95%). There was no difference in RFS among patients receiving no or less than six cycles of CT (n =38) versus patients who received six cycles (n =32) (HR: 0.5, 95% CI: 0.1-2.4). OS was significantly improved for patients who received six cycles of CT versus patients who received no or less than six cycles of CT (HR: 0.1, 95% CI: 0.01-0.7). On univariate analysis, receiving six cycles of CT was predictive of OS. No other variables were statistically significant; however, lymphovascular space invasion and >2 medical comorbid conditions were included in the Cox PH multivariable analysis given their clinical significance. Adjuvant CT remained a significant predictor of improved OS (HR: 0.1, 95% CI: 0.01-0.8) when controlling for these clinically significant factors. Conclusions: In this cohort, OS was significantly improved with six cycles of CT, and CT remained a significant predictor of OS on multivariable analysis. While additional studies are needed, our findings support a full course of adjuvant CT in patients with early-stage UCCC. [ABSTRACT FROM AUTHOR]

Objectives: Treatment of advanced and recurrent endometrial cancer (EC) has traditionally been based on factors, such as histology and stage. Recent studies suggest that tumor molecular profiles may predict treatment outcomes and guide treatment choice. For example, pembrolizumab (PMB) use in patients with mismatch repair deficient (MMRd) tumors versus combined pembrolizumab and lenvatinib (PL) in patients with mismatch repair proficient tumors (MMRp). Furthermore, POLE mutated (POLE mut) tumors demonstrate a favorable prognosis even with minimal treatment. Prospective trials using molecular profiling for treatment assignment are ongoing, but tumor molecular testing (TMT) is costly and time-consuming. We, therefore, sought to evaluate the cost-effectiveness of TMT in stage III EC. Methods: A Markov decision model was created to compare two testing strategies in patients with stage III EC: TMT versus no testing (NT). TMT patients had sequential POLE next-generation sequencing (NGS), mismatch repair (MMR) immunohistochemistry (IHC), and p53 IHC. Adjuvant therapies included radiation (RT) alone for POLE mut and chemoradiation (CTRT) for NT, MMRd, p53 mutated (p53mut), and no specific molecular profile (NSMP) using PORTEC-3 data. All patients received six cycles of carboplatin and paclitaxel (CP) for first recurrence using GOG 209 outcomes. MMRd patients received PMB alone for the second recurrence, whereas all other patients received PL. National database and registry values, literature review, and expert input were used for cost and utility values. A healthcare payer perspective, willingness-to-pay (WTP) threshold of $100,000, and 5-year time horizon were used. Data analysis was done with TreeAge Pro Software 2021. Outcomes were reported in quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses tested model robustness, and a structural sensitivity analysis was performed in which controls underwent MMR IHC alone. Results: Compared to NT, TMT was less costly and more effective. While the model was most sensitive to median overall survival with PL, probability of MMRd status, and cost of lenvatinib, TMT remained cost-saving over all parameters tested. On Monte Carlo analysis, TMT was favored in 79% and 80% of iterations with a WTP of $50,000 and $100,000, respectively. When controls had MMR IHC alone, TMT was no longer cost-effective with an incremental cost of $3100 and incremental effectiveness of 0.017 QALYs, or $184,942/QALY gained. Conclusions: For patients with stage III EC, this model suggests TMT is associated with cost savings compared to NT. However, when compared to MMR IHC alone, a common clinical approach, TMT was no longer a cost-effective strategy at a WTP threshold of $100,000. Further prospective studies are needed to determine the prognostic value of molecular profiles in endometrial cancer. It will be essential to continue assessing the cost-effectiveness of these molecular tests as new data becomes available. [ABSTRACT FROM AUTHOR]

Purpose The National Cancer Data Base (NCDB) was analyzed to evaluate practice patterns and the impact of radiotherapy modalities for endometrial cancer treated with primary radiotherapy. Methods and Materials The NCDB was queried for Stage I endometrioid adenocarcinoma patients treated with primary radiotherapy without surgery from 1998 to 2006. Brachytherapy (BT) utilization factors were established using multivariable logistic regression. Log-rank and Cox proportional hazards modeling were used to assess variables impacting survival. Results A total of 853 patients were analyzed: 23.7%, 31.3%, and 45.0% received BT alone, external beam radiotherapy (EBRT) and BT, or EBRT alone. The BT utilization ranged from 40.5% to 51.9% over time ( p = 0.70). Lower utilization was associated with advanced age (≥80 years: odds ratio [OR] 0.43, 95% confidence interval [CI] 0.28–0.65, p < 0.01) and facilities with volume in the bottom quartile (OR 0.44, 95% CI 0.30–0.66, p < 0.01). Utilization was higher among patients living more than 30 miles from the facilities (OR 2.14, 95% CI 1.35–3.42, p < 0.01). With 36-month median followup, unadjusted median survivals for EBRT dose of 30 Gy or lower, EBRT dose higher than 30 Gy, BT, and EBRT + BT were 12.6, 31.1, 44.6, and 57.1 months ( p < 0.01). After correcting for other factors, higher risk of mortality was seen with EBRT dose of 30 Gy or lower (hazard ratio [HR] 2.75, 95% CI 1.66–4.55, p < 0.01) and EBRT dose higher than 30 Gy (HR 1.43, 95% CI 1.07–1.91, p = 0.02) compared with EBRT + BT. No difference was seen using BT alone (HR 1.29, 95% CI 0.92–1.79, p = 0.14). Conclusion BT utilization for nonsurgically managed endometrial cancer remains low with most patients receiving EBRT alone. Despite concerns of overtreatment in a population with competing causes of death, BT appears to improve survival. [ABSTRACT FROM AUTHOR]

Purpose Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). Methods and Materials Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1–2 cm of vagina. Equivalent 2 Gy doses (EQD 2 ) were calculated. Results Thirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2–5 late toxicities were observed. Mean CTV D 90 EQD 2 for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D 90 EQD 2 was 172.3 ± 59.6 and 138.0 ± 64.6 Gy. Conclusions Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery. [ABSTRACT FROM AUTHOR]

Purpose For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Materials and methods Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix ± parametria treated with neoadjuvant external beam radiotherapy (45-50.4 Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5 Gy times 3-4 fractions) ± chemotherapy followed by extrafascial hysterectomy performed at a median of 6 weeks after radiotherapy. Results All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20 months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4 + toxicity. Conclusions Neoadjuvant radiation therapy ± chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5 Gy times 3-4 fractions, for a cumulative EQD2 of 60-70 Gy, is well tolerated with high rates of clinical and pathological response. [ABSTRACT FROM AUTHOR]

Purpose Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control. Materials and methods Forty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4. Results At a median follow-up of 18 months (range: 3–78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%. Conclusions Salvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate whether the three-dimensional (3D) CT-based high-dose rate planning for vaginal cuff brachytherapy offers any advantage over the 2D orthogonal film-based library plans for adjuvant treatment of endometrial cancers. Methods and Materials: Eighty-four consecutive postoperative patients with endometrial cancers treated with vaginal brachytherapy as an adjuvant treatment were analyzed. Patients had CT imaging-based plans. Clinical target volume (CTV) was defined by expanding the upper 2.5cm of the cylinder by 5mm in all directions and editing to exclude any bladder and rectum. The dose prescribed was 7Gy with three fractions at 5mm depth with a goal of D 90 ≥100% for CTV. All dosimetric parameters were compared with library-based plans. Results: Both the 2D- and 3D-based plans allowed sufficient dosage to the CTV (D 90 for CTV ≥95%). The doses of 0.1, 1, and 2cc to rectum and bladder were significantly higher for 2D-based plans (p ≤0.001 in each parameter). D 2 cc with 2D plan for rectum and bladder was >100% (range: 103–116%) in 7 (8%) and 6 (7%) patients, respectively. In contrast, no patients had D 2 cc >100% with 3D planning for both organs. Conclusion: Three-dimensional CT-based planning for high-dose rate vaginal cuff brachytherapy helps to decrease dose to critical organs without compromising coverage of CTV by customizing the dosimetry according to individual patient anatomy. [Copyright &y& Elsevier]