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

OBJECTIVE:Neighborhood-level social determinants of health (N-SDoH) impact cancer survival. However, the relationship between N-SDoH and epithelial ovarian cancer (EOC) survival remains understudied. METHODS:We used data on all Pennsylvania residents diagnosed with EOC from 2000 to 2023 throughout the University of Pittsburgh Medical Center to assess the impact of N-SDoH on survival. We used the Social Vulnerability Index (SVI) to characterize four N-SDoH themes and overall N-SDoH vulnerability based on each case's census tract at diagnosis. High-SVI overall and by N-SDoH theme was defined as being in the 75th percentile in Pennsylvania for that metric. Cox proportional hazard models assessed the association between high-SVI and overall mortality. RESULTS:Among 4970 EOC cases, high-SVI overall was associated with later stage at diagnosis, greater residual disease, and a lower likelihood of receiving standard-of-care platinum-based therapy. High-SVI was also associated with a 13 % increased mortality hazard (adjusted-HR:1.13 95 %CI:1.02-1.25). The Household Characteristics, Racial and Ethnic Minority Status, and Housing Type and Transportation themes were also associated with increased mortality hazards (adjusted-HR[95 %CI]: 1.10[1.01-1.21], 1.23[1.08-1.39], 1.09[1.00-1.18], respectively). The Socioeconomic Status theme was associated with an increased mortality hazard of borderline significance (adjusted-HR 1.10, 95 %CI:0.99-1.23). The overall high-SVI association appeared similar when stratifying by race, although the number of Black cases was small (n = 168). CONCLUSION:Higher neighborhood social vulnerability is associated with worse EOC survival. Replicating study findings in more diverse populations can help illuminate the neighborhood factors most influencing survival and support the design and testing of programs to reduce poor EOC outcome, especially within marginalized communities.

Objective. Elevated allostatic load (AL), an integrated, cumulative marker of physiologic damage due to socioenvironmental stress, is associated with increased mortality in patients with breast, lung, and other cancers. The relationship between allostatic load and mortality in ovarian cancer patients remains unknown. We examined the relationship between allostatic load and overall survival in ovarian cancer patients. Methods. This cross-sectional study used data from 201 patients enrolled in a prospective observational ovarian cancer cohort study at a National Cancer Institute -designated Comprehensive Cancer Center from October 2012 through June 2022. All patients underwent debulking surgery and completed a full course of standardof -care platinum -based chemotherapy. Follow-up was completed through January 2024. Allostatic load was calculated as a summary score by assigning one point to the worst sample quartile for each of ten biomarkers measured within 45 days before the ovarian cancer diagnosis. High allostatic load was de fined as having an allostatic load in the top quartile of the summary score. A Cox proportional hazard model with robust variance tested the association between allostatic load and overall survival. Results. There were no associations between allostatic load and ovarian cancer clinical characteristics. After accounting for demographic, clinical, and treatment factors, high allostatic load was associated with a signi ficant increase in mortality (hazard ratio 2.17 [95%CI, 1.13 -4.15]; P = 0.02). Conclusion. Higher allostatic load is associated with worse survival among ovarian cancer patients. Allostatic load could help identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during treatment. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

OBJECTIVE:Social determinants of health (SDOH) impact cancer outcomes. The CDC Social Vulnerability Index (SVI) integrates scores for four neighborhood-based SDOH domains (socioeconomic status, household characteristics, minority status, and housing type/transportation) to assess neighborhood social vulnerability (NSV). While NSV has been associated with overall cancer mortality and lung, breast, colon, and endometrial cancer-specific mortality, the relationship between NSV as defined by the SVI and ovarian cancer outcomes remains unknown. METHODS:We used data from 177 patients enrolled in an observational ovarian cancer cohort study from October 2012 through September 2022. All patients underwent debulking surgery and completed an entire course of standard-of-care platinum-based chemotherapy. Follow-up was completed through May 2024. SVI was calculated using census tract at diagnosis. High NSV was defined as SVI in the top quartile of the cohort. Cox proportional hazard models assessed the association between NSV and progression-free (PFS) and overall (OS) survival. RESULTS:After accounting for demographic and clinical factors, high NSV was associated with significantly worse PFS (HR:2.31 [95% CI:1.48-3.61]; P < 0.001) and OS (HR:1.79 [95% CI:1.10-2.92]; P = 0.02), with neighborhood socioeconomic status associated with significantly worse PFS (HR:2.29 [95% CI:1.47-3.56]; P < 0.001) and OS (HR:1.71 [95% CI:1.04-2.80]; P = 0.03). Neighborhood housing type/transportation was also associated with significantly worse PFS (HR:1.65 [95% CI:1.07-2.55]; P = 0.02) and trended towards worse OS (HR:1.43 [95% CI: 0.80-2.33]). CONCLUSION AND RELEVANCE:Higher neighborhood social vulnerability is associated with worse outcomes among ovarian cancer patients. Validating these results in a population-based cohort and assessing programs to reduce neighborhood social vulnerability to improve ovarian cancer outcomes is warranted.

Objectives. A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. Methods. A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). Results. In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 53) (p = .005), with a similar trend in the PORTEC-1 cohort Extent of LVSI correlated with disease burden in LN metastases. Conclusion. Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings. (C) 2020 Elsevier Inc. All rights reserved.

AIMS:There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. MATERIALS AND METHODS:Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm. RESULTS:Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). CONCLUSION:This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.

Purpose: Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus has been implicated as a causative factor for a subset of these patients. The purpose of this study was to evaluate whether p16-positivity (a human papillomavirus surrogate) predicts for better response rates in women who undergo surgery followed by adjuvant radiation therapy (RT). Methods and Materials: We retrospectively analyzed data from women with VSCC who were treated with adjuvant RT. p16-Positivity was defined as diffuse strong immunoreactivity within the tumor. Time to event outcomes was performed with Kaplan-Meier and cumulative incidence methodologies. Results: Thirty-nine women were identified. Ten had positive results for p16 (p16+), and 29 had negative results (p16-). The median follow-up was 25.7 months. The median age at diagnosis was 59 years for women with p16+ tumors and 74 years for women with p16- tumors (P = .022). The distribution of stage did not differ by p16 status. The indications for adjuvant RT were close/positive margins in 19 women, positive nodes in 9 women, and both in 11 women. There were 21 recurrences: 15 vulvar, 3 isolated nodal, 2 synchronous vulvar/nodal, and 1 distant metastasis. In-field relapse rates at 3 years were lower in p16+ patients (32.5%) than in p16- patients (59.1%, P = .072). This trend was also observed in progression-free survival (P = .062). A p16+ status and a lower International Federation of Gynecology and Obstetrics stage were associated with fewer in-field relapses and improved progression-free survival in multivariable analyses. The p16 status was not a predictor of overall survival. Conclusions: p16-Positivity appears to be a prognostic factor for in-field relapse rates in patients with VSCC appropriately treated with adjuvant RT. (C) 2018 Elsevier Inc. All rights reserved.

Endometrial cancers are primarily managed with surgery which includes lymph node staging or debulking of any involved lymph nodes. Currently, there is limited data for nodal control of involved nodes with (chemo) radiotherapy (CRT). The goal of the current study is to assess nodal control with CRT for locally-advanced endometrial cancers managed with preoperative CRT followed by hysterectomy. From July 1999-November 2018, 105 patients with ≥ clinical stage II endometrial cancer treated with pre-operative CRT followed by extrafascial hysterectomy were retrospectively reviewed. Patients not completing therapy (n=6) or receiving CRT at outside institutions were excluded (n=4). Limited nodal dissection after CRT was performed if nodal disease persisted on imaging or was seen intraoperatively. PET/CT was performed for initial nodal staging in 80 (84%). The CTV included pelvic nodes up to the common iliac for node-negative and para-aortic lymph nodes up to the renal vessel for node-positive patients. Involved nodes most commonly received a simultaneous integrated boost of 55Gy in 25 fractions ± 4-6Gy sequential boost for nodes >2cm. Of the included 95 patients, 55 (58%) had clinically positive lymph nodes: 17 (31%) pelvic only, 5 (9%) para-aortic only, and 33 (60%) pelvic + para-aortic. The median number of positive nodes was 4 [interquartile range (IQR): 2-7] with a total number of 300 positive nodes. Nineteen (20%) patients had limited nodal dissection with a median of 3 (IQR:2-5) nodes dissected. At a median follow-up of 25 months (IQR: 9-46), the 3-year regional control was 91% (95%CI: 85-98%). In clinically node-negative patients, 2 (5%) developed isolated recurrence out-of-field in the para-aortic region. In clinically node-positive patients, failure in involved nodes occurred in 4 (7%) and in prophylactic treated nodal regions in 4 (7%), 3 of which had synchronous nodal failure at both sites. Regional recurrence was higher in patients with lymph nodes ≥2cm (3-year regional control 100% <2cm vs. 72% ≥2cm, p=0.005) and nodal maximum SUV (100% <10.6 vs 76% ≥10.6, p=0.045). For the 300 clinically-involved lymph nodes, the median size was 1.2cm (IQR: 0.8-1.7). The 3-year involved nodal control rate was 96% (95%CI: 93-99%). Involved nodal failure was higher in type-II histology (3-year control 100% type-I vs 90% type-II, p=0.002), lymph nodes ≥2cm (98% <2cm vs 84% ≥2cm, p=0.007), and by radiation dose (75% for <55Gy, 98% 55Gy in 25 fractions, and 89% >55Gy, p=0.03). This is largest study looking at regional control rates of involved lymph nodes with CRT. Despite a high burden of clinical involvement and low rates of dissection, nodal failure is low following neoadjuvant CRT, suggesting efficacy of CRT. A dose of at least 55Gy in 25 fractions is suggested for clinically involved nodes, with consideration of higher dose or alternative strategies in non-endometrioid histologies and bulky nodes ≥2cm.

Neoadjuvant chemoradiotherapy effectively downstages the majority of locally-advanced type II endometrial cancers, thereby increasing the likelihood of achieving complete resection with negative margins.

Objective: To report on fertility preservation outcomes utilizing ovarian tissue cryopreservation (OTC) in premenopausal women undergoing surgery for suspected gynecologic malignancy.

PURPOSE:Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC. METHODS AND MATERIALS:Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70-80 Gy. RESULTS:The median high-risk clinical target volume was 24.4 cm3 (interquartile range [IQR], 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11-78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%. CONCLUSIONS:Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

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. Ninetynine (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. (C) 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus (HPV) has been implicated as a causative factor for a subset of these patients. The purpose of this study is to evaluate if p16-positivity, which is surrogate for HPV infection, predicts for better response rates and survival. A retrospective chart review was undertaken of all women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000-2016 for VSCC at our institution. Available tissue blocks were stained for p16. Each tumor was assigned an H-score according to the College of American Pathologists criteria. P16-positivity was defined as strong immunoreactivity within invasive tumor with an H-score of 200+. P16 +/- groups were compared using Chi-squared and t-test. These were correlated with outcomes via Kaplan-Meier with log-rank technique. Factors which predicted for disease outcomes and overall survival were analyzed via Cox proportional hazards methods. Time to an event was defined as the time from completion of CRT or surgery following CRT if treated neoadjuvantly. A total of 74 women were identified who had follow-up and specimen available for staining. Median follow up was 14.1 months for all patients (range: 0.4-166.7 months) and 40.6 months for living patients. Thirty two (42.7%) women had p16+ tumors. Median age was 71.5 years (range: 37-91); for women with p16+ tumors, the average age was 67.8 years vs 70.0 years for women with p16- tumors (p=NS). The distribution of stage between p16-status did not differ. The median maximal vulvar dose was 50.4Gy (range: 33.6-70.2Gy). The complete clinical response (cCR) rate for p16+ tumors was 68.0% vs 34.2% for p16- tumors (p=0.009). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 56.5% vs 29.7% for p16+ vs p16-, respectively (p=0.037). The combined clinical or pathologic complete response (CR) rate was 63% for p16+ and 27.5% for p16- (p=0.004). Two-year vulvar control for women with p16+ tumors was 77.8% vs. 45% for p16- (p=0.010). In women with p16+ tumors who achieved clinical or pathologic complete response, 2-year vulvar control was 90.9% vs 66.7% if p16- and CR (p=0.071). If complete response was not achieved, 2-year control rates were 55.6% vs. 34.9% (p=0.230). No woman with a p16+ tumor developed distant metastases vs. 7 with p16- tumor (p=0.013). OS was not statistically different between p16+/- complete responders (67.3% vs. 71.6%, p=0.719) but non-responders with p16+ tumors had higher 2-year OS compared with p16- tumors (70.0% vs. 22.6%, p=0.161). This is first study evaluating response to chemoradiation therapy for VSCC based on p16 positivity. P16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes. Future clinical trials may need to focus on different treatment strategy for p16-negative tumors as they seem to have a worse outcome with lower response rates and higher risk of distant metastases.

How an initiative designed to improve patient outcomes and satisfaction while containing costs led to sustainable change in surgical practice and physician behavior.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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. (C) 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Purpose: Recent Groupe Europeen de Curietherapie-European Society for Radiotherapy and Oncology guidelines recommend that the dose to 90% (D90) of the high-risk clinical target volume (HRCTV) in cervical cancer be at least 85 Gy, with higher doses for poor response to radiation therapy. Methods and Materials: A retrospective review of brachytherapy delivered at a single institution was evaluated for dosimetry and outcomes. Significance of tumor parameters on local control was evaluated with Kaplan-Meier and univariable and multivariable Cox regression analysis. Correlations were determined with a linear regression model. Results: A total of 239 women underwent high-dose-rate brachytherapy for cervical cancer between 2007 and 2018 with evaluable dosimetry. Median follow-up was 28.6 months. The median prescribed dose was 27.5 Gy in 5 fractions, with a median HRCTV D90 of 83.9 Gy (range, 81.9-85.7 Gy), HRCTV volume of 31 cm(3) (range, 14.9-121.9 cm(3), and treatment time of 51 days (range, 36-83 days). Local control for the entire cohort at 5 years was 90.8%. Local control was worse with adenocarcinomas, HRCTV >40 cm(3) at brachytherapy, requirement for a higher brachytherapy dose, and treatment >51 days. On multivariable analysis, local control was worse with adenocarcinoma (hazard ratio, 4.141; 95% confidence interval, 1.498-11.444; P = .006) and HRCTV >40 cm(3) (hazard ratio, 3.640; 95% confidence interval, 1.316-10.069; P = .013). HRCTV EQD2 D90 > 85 Gy did not statistically improve outcomes for any subset. The 2-year progression-free survival for HRCTV >40 cm(3) was 66.2% versus 84.1% if <= 40 cm(3) (P < .001). Overall survival was predicted by HRCTV and overall treatment time in multivariable analysis. For women with HRCTV <= 40 cm(3), overall survival at 2 years was 90.4% versus 68.5% if >40 cm(3) (P < .001). Conclusion: Local control was excellent with magnetic resonance imaging-based planning in the entire cohort of patients. A poor response to external beam radiation (larger HRCTV) and adenocarcinoma histology predicted for worse local control despite association with higher brachytherapy prescription. Women with these risk factors face higher rates of extrapelvic progression and poorer overall survival. (C) 2019 Elsevier Inc. All rights reserved.

Objective: The purpose of this study is to characterize the outcomes of patients who refuse initial treatment for endometrial cancer.

Objective: This study aims to determine the impact of histological grade on overall survival in patients with clinical stage I endometrioid endometrial adenocarcinoma who receive radiation therapy as primary definitive treatment.

Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus (HPV) has been implicated as a causative factor for a subset of these patients. The purpose of this study is to evaluate if p16-positivity, which is surrogate for HPV infection, predicts for better response rates and survival in women who undergo surgery followed by adjuvant radiation therapy (RT). A retrospective chart review was undertaken of all women treated with adjuvant radiation therapy from 2000-2016 for VSCC at our institution. Available tissue blocks were stained for p16. Each tumor was assigned an H-score according to the College of American Pathologists criteria. P16-positivity was defined as diffuse, strong immunoreactivity within invasive tumor with an H-score of 200+. P16 +/- groups were compared using Chi-squared and t-test. These were correlated with outcomes via Kaplan-Meier with log-rank technique. Time to an event was defined as the time from completion of RT. Thirty-nine women were identified. Median follow up was 25.6 months and 43.3 months for living patients. Ten women (25.6%) had p16+ pathology. The median age at diagnosis was 59.3 years for women with p16+ tumors and 70.2 years for women with p16- tumors (p=0.04). The distribution of stage did not differ by p16-status. The median maximal vulvar dose was 54.4Gy (range: 42.6-63.0Gy). The indication for adjuvant RT was close/positive margins in 19 women (48.7%), positive nodes in 8 (20.5%), and both in 12 (30.8%). The average pathologic tumor size was 2.1cm for p16+ tumors and 3.4cm for p16- tumors (p=0.028). Average margin size was not statistically different. There was a trend towards differences in the average number of pathologically involved lymph nodes, 0.5 vs 1.26 for p16+ vs p16-, p=0.077. Vulvar control rates differed by p16 status at 2 years: 88.9% vs 52.3% for p16+ vs p16-, p=0.041. This translated to a strong trend in differences in two-year locoregional control as well: 77.8% vs 47.4% for p16+ vs p16-, respectively, p=0.064. In women with only one indication for adjuvant RT, this benefit was more pronounced for women with p16+ tumors vs p16-: 2-year locoregional control 100% vs 48.5%, p=0.041. Two-year overall survival was not significantly different between p16+/- cohorts (88.9% vs 64.6%, p=0.405). Survival was impacted by risk factors necessitating adjuvant RT, however. Women with either close/positive margins or positive nodes had a 2-year survival of 80.4% vs 50.0% for women with both risk factors (p=0.044). p16+/- status did not statistically influence survival for women with one risk factor, but survival was numerically different at 2 years (100% vs 73.2%). The p16 positivity appears to be a prognostic factor for locoregional control rates in VSCC treated with vulvectomy and adjuvant radiation therapy for close/positive margins or positive lymph nodes. This benefit was pronounced especially in women with only close/positive margins or positive lymph nodes.

Brachytherapy is an essential component of the treatment of locally advanced cervical cancer; recent GEC-ESTRO guidelines recommend that the dose to 90% (D90) of the high-risk clinical target volume (HRCTV) be at least 85Gy with even higher doses for poor response to external beam radiation.