Search

Introduction: The optimal overall treatment time (OTT) from radical surgery to the end of adjuvant radiation therapy for some squamous cell carcinomas has been found to impact treatment outcomes. This study aims to identify the impact of OTT on overall survival (OS) for women with completely resected, node-positive squamous cell carcinomas of the vulva., Materials and Methods: The National Cancer Data Base was queried for women with surgically resected, node-positive vulvar squamous cell carcinomas between 2004 and 2016 who were treated with adjuvant radiation therapy. Kaplan-Meier analysis with log-rank test and Cox proportional hazards tests were utilized for OS calculations., Results: A total of 1500 women met inclusion criteria. The median OTT was 104 days. Shorter OTT was associated with age, facility volume, private insurance, and duration of post-operative hospitalization. Median OS with OTT ≤ 104 days was 56.1 months vs 45.4 months if ≥105 days (p = 0.015). On multivariable Cox analysis, OTT was independently associated with an increased risk of death of 0.4% per additional day (95%CI 1.001-1.007, p = 0.003), as were age at diagnosis (HR 1.031 [95%CI 1.024-1.037], p < 0.001), number of nodes positive (HR 1.031 [95%CI 1.024-1.037], p = 0.006), the use of concurrent chemotherapy (HR 0.815 [95%CI 0.693-0.960], p = 0.014) and increasing pT/pN stage. After propensity adjustment for factors predicting a shorter OTT, OTT continued to be associated with an increased risk of death per additional day (HR 1.004 [95%CI 1.001-1.007], p = 0.007)., Conclusion: Overall treatment time is an independent risk factor for death in women being treated with adjuvant radiation therapy following complete resection of node-positive squamous cell carcinoma of the vulva., Competing Interests: Declaration of Competing Interest The authors of this manuscript do not have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Vaginal necrosis is a late radiation tissue injury with serious morbidity complications. It is rare, and its incidence is not well assessed in prospective trials. Patient comorbidities and radiation dose can significantly increase the risk. As treatment of gynecologic malignancies often involve a multidisciplinary approach, timely diagnosis and appropriate management by physicians of the team are crucial. Untreated vaginal necrosis can lead to infection, hemorrhage, necrosis-related fistulation to the bladder or rectum, perforation, and death. In this review, we describe the pathophysiology of vaginal necrosis, its clinical course, and management options., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to disclose. Dr. Viswanathan is the principal investigator for NIH R01 CA237005., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest Christina Annunziata (American Society of Clinical Oncology representative): MaxCyte, Medivir, and Precision Biologics (research), Horizon Pharma and Merck (provided drugs for clinical trial); Sushil Beriwal: Eisai, Institute of Education, and Via Oncology (honoraria), Varian (consultant), XOFT (DSMB); Matthew Harkenrider: AstraZeneca (advisory board [ended]), Varian (advisory board [ended]); Christine Holschneider (Society of Gynecologic Oncology representative): UpToDate (honoraria); Mitchell Kamrava: Augmenix (speakers bureau); Lilie Lin: AstraZeneca (research); Jyoti Mayadev: AstraZeneca (consultant), Varian (advisory board); Marc Morcos: Elekta (travel); Daniel Petereit: (American Brachytherapy Society representative and president): BMS Foundation (research and salary support), Irving A Hansen Memorial Foundation (patient funding), Ralph Lauren Pink Pony Foundation (board member); Beth Erickson: Elekta (research and travel); and Junzo Chino, Akila Viswanathan, Emma Fields, Jane Fitch (patient representative), Eric Leung, and Chika Nwachukwu reported no disclosures.

Objective: To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic., Methods: An international committee of ten experts in gynecologic radiation oncology convened to provide consensus recommendations for patients with gynecologic malignancies referred for radiation therapy. Treatment priority groups were established. A review of the relevant literature was performed and different clinical scenarios were categorized into three priority groups. For each stage and clinical scenario in cervical, endometrial, vulvar, vaginal and ovarian cancer, specific recommendations regarding dose, technique, and timing were provided by the panel., Results: Expert review and discussion generated consensus recommendations to guide radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Priority scales for cervical, endometrial, vulvar, vaginal, and ovarian cancers are presented. Both radical and palliative treatments are discussed. Management of COVID-19 positive patients is considered. Hypofractionated radiation therapy should be used when feasible and recommendations regarding radiation dose, timing, and technique have been provided for external beam and brachytherapy treatments. Concurrent chemotherapy may be limited in some countries, and consideration of radiation alone is recommended., Conclusions: The expert consensus recommendations provide guidance for delivering radiation therapy during the COVID-19 pandemic. Specific recommendations have been provided for common clinical scenarios encountered in gynecologic radiation oncology with a focus on strategies to reduce patient and staff exposure to COVID-19., Competing Interests: Declaration of Competing Interest Christen Elledge, Supriya Chopra, Beth Erikson, David Gaffney, Anuja Jhingran, Ann Klopp, and Catherine Yashar have nothing to disclose. Akila Viswanathan is the principal investigator of NIH R01 CA237005. Sushil Beriwal is a consultant for Varian and Medical Director of Via Oncology, outside the submitted work. Cyrus Chargari receives grant funding from Roche, personal fees from Merck Sharp & Dohme Corp., Elekta, and GlaxoSmithKline, as well as non-financial support from TherAguiX and GlaxoSmithKline, all outside the submitted work. William Small is the co-chair of the NRG Gyn Committee, has served on an advisory board for Merck, and has received honoraria for invited talks from Carl Zeiss Meditech, outside the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/-RAD., Methods: This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/-lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/-RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models., Results: In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/-RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/-RAD (HR = 0.18, 95% CI: 0.09-0.39) and RAD (HR = 0.31, 95% CI: 0.18-0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/-RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12-0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03-0.32). Overall survival did not differ by treatment., Conclusions: In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone., Competing Interests: Declaration of competing interest All authors reported their potential conflicts of interest, and there were not relevant conflicts of interest disclosed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To determine if readily obtainable markers of frailty predict disease-free survival (DFS) in elderly women with endometrial cancer treated with curative intent., Methods: 88 consecutive women≥age 60 treated with surgery, chemotherapy and radiation for stage I-IV endometrial cancer were included. We considered the following health deficits as markers of "frailty": albumin <3.5mg/dL, hemoglobin <10mg/dL, BMI<20kg/m, 2 unintentional weight loss, ECOG performance status ≥2, history of osteopenia or osteoporosis and Charlson comorbidity score. Kaplan-Meier estimates and Cox proportional hazards models of DFS were calculated., Results: The median age was 68.5 (range 60-88years). The majority of women (65/88) had at least one frailty factor at baseline and 23/88 had two or more. All women received radiation and chemotherapy. Treatment was delayed, modified or truncated in 46% (40/88) of women due to treatment-related toxicity. Age (< 70 vs. ≥70 y) did not independently predict toxicity or recurrence risk. Women with at least one baseline frailty factor had twice the risk of disease recurrence (HR=2.21;95% CI:1.02-4.80) when adjusted for age, stage, grade and Charlson score. The 3-year DFS was 77% in those with no frailty markers and 48% in those with at least one (p=0.02). The presence of a frailty marker also predicted shortened overall survival (HR=2.34;95% CI:1.08-5.03) irrespective of treatment administered and stage of disease., Conclusions: A combined frailty measure was a more robust predictor of DFS and OS than patient age, tumor characteristics and comorbidities in this cohort of older women with very good functional status., (Published by Elsevier Inc.)

Objective: The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT)., Methods: 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005-2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®., Results: Median follow-up time was 19.7months (MR group) and 18.4months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07-0.72) in a model with MR BT (HR 0.35, 95% CI 0.08-1.18). There was no difference in toxicities between CT and MR BT., Conclusion: In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent survival and toxicity rates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine prognostic factors for progression-free survival (PFS) and overall survival (OS) for stage I-II cervical-cancer patients treated using computed-tomography (CT)-planned high-dose-rate (HDR) intracavitary brachytherapy (BT)., Methods: A total of 150 patients were treated for Stage I-II cervical cancer using CT-planned BT between 4/2004 and 10/2014. Of these, 128 were eligible for inclusion. Kaplan-Meier local control (LC), pelvic control (PC), overall survival (OS), and PFS estimates were calculated., Results: After a median follow-up of 30months, the 2-year LC rate was 96%, PFS was 88%, and OS was 88%. Overall, 18 patients (14%) experienced any recurrence (AR), 8 had distant recurrence only and 10 had a combination of local, pelvic, regional, and distant recurrence. No patients had LR only. A prognostic factor for AR was tumor size >4cm (p=0.01). Patients with tumors >4cm were 3.3 times more likely to have AR than those with tumors ≤4cm (hazard ratio [HR]=3.3; 95% confidence interval [CI] 1.28-9.47). Point A was 85% of prescription for tumors < 4 cm and decreased approximately 3% over 5 fractions compared to 90% of prescription for tumors > 4 cm that decreased approximately 4% over 5 fractions. Two patients (2%) experienced grade≥2 late toxicity. There were no acute or late grade≥3 toxicities., Conclusion: CT-planned BT resulted in excellent local control and survival. Large tumor size was associated with an increased risk of recurrence outside the radiation field and worse PFS and OS. A volume-optimized plan treated a smaller area than a point A standard plan for patients with Stage I-II cervical cancer that have received chemoradiation. Given the outstanding LC achieved with modern therapy including chemoradiation, HDR, and image-based BT, further efforts to combat spread outside the radiation field with novel therapies are warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC)., Methods: Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58months among the 57 patients with an available tumor specimen., Results: HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (κ=0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65% vs. 16%, p<0.01) and OS (65% vs. 22%, p=0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p<0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2-0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06-0.6). Results were similar when analyzed by HPV DNA status., Conclusion: In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A large number of studies have looked at the role of radiation therapy in the treatment of endometrial cancer. One particular radiation strategy in common practice is the use of adjuvant external beam (EB) radiotherapy followed by vaginal brachytherapy (VB). While the addition of VB to EB provides a theoretical benefit of a localized boost with higher focused dose to an area of potentially high recurrence risk, a randomized clinical trial to compare outcomes and toxicities of EB+VB vs. EB alone is lacking. The goal of this review is to present the current data for and against the use of this combined radiation modality and to provide some preliminary evidence regarding which patient populations may be most likely to benefit., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Despite a concerning decline in the use of brachytherapy over the past decade, no other therapy is able to deliver a very high dose of radiation into or near a tumor, with a rapid fall-off of dose to adjacent structures. Compared to traditional X-ray-based brachytherapy that relies on points, the use of CT and MR for 3D planning of gynecologic brachytherapy provides a much more accurate volume-based calculation of dose to an image-defined tumor and to the bladder, rectum, sigmoid, and other pelvic organs at risk (OAR) for radiation complications. The publication of standardized guidelines and an online contouring teaching atlas for performing 3D image-based brachytherapy has created a universal platform for communication and training. This has resulted in a uniform approach to using image-guided brachytherapy for treatment and an internationally accepted format for reporting clinical outcomes. Significant improvements in survival and reductions in toxicity have been reported with the addition of image guidance to increase dose to tumor and decrease dose to the critical OAR. Future improvements in individualizing patient treatments should include a more precise definition of the target. This will allow dose modulation based on the amount of residual disease visualized on images obtained at the time of brachytherapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To analyze margin status and prognostic factors for complications in patients undergoing vulvectomy for invasive squamous cell cancer (iSCC) with and without plastic-assisted closure., Methods: Demographic and clinical data were collected on 94 patients with iSCC who underwent vulvectomy between 2004 and 2013. All pathology slides were re-reviewed by two gynecologic pathologists. Data were analyzed using XLSTAT-Pro v2014.2.02., Results: Of 88 eligible patients, 15 (17%) had plastic-assisted vulvar closure and 73 (83%) did not. There were significantly more patients in the plastics group with recurrent disease (53% v 10%) and history radiation therapy prior to surgery (40% versus 5%). Plastic-assisted closure was associated with larger tumors (3.73 cm versus 2.03 cm, p<0.01) and a higher frequency of adequate margins (53% versus 29%, p=0.06). For tumors≥3.0 cm, plastic-assisted closure was significantly associated with adequate margins (44% versus 6%, p=0.03). Prior radiation use was associated with plastic-assisted closure, larger tumors, older age, and recurrent disease. Complications occurred in 36 patients (41%) and significantly more occurred in those with plastic-assisted closure (67% versus 36%, p=0.04). On multivariate analysis including age, tumor size, recurrent disease, plastic-assisted closure, and history of radiation, only history of radiation therapy was a significant predictor of complications (OR=17, 95%CI 2.05-141.35; p=0.01)., Conclusions: Plastic-assisted vulvectomy closure was more often utilized in cases involving past radiation therapy and larger tumors. Plastic-assisted closure significantly increased the frequency of adequate margins in tumors≥3 cm and did not impact complications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To summarize the literature on quality of life for patients treated with definitive radiation for gynecologic cancers, with a specific focus on patient reported outcomes., Methods: A literature review was performed to summarize studies about patient-reported outcomes and quality of life in women with gynecologic malignancies who were treated with definitive radiation therapy. Summaries are by disease site, including endometrial, cervical and vulvar cancers., Results: Over 20 different survey instruments have been used to describe patient-reported outcomes for women treated with radiation for gynecologic cancer. Regardless of disease site, all patients describe a degree of compromise in physical and social functioning, as well as sexual dysfunction. Specific symptoms which are most bothersome for patients vary by disease site, such as bowel concerns predominating for endometrial cancer patients, while body image is more concerning for cervical cancer patients., Conclusions: Several quality of life concerns exist for women treated with radiation therapy for gynecologic malignancies. Significant overlap exists in the QOL issues affecting these patients. Whether to combine or separate surveys by diagnosis, treatment type, age, or time point should be explored further. Assessing patients' psychological, emotional, and physical concerns helps to understand long-term adjustment, enabling incorporation of these domains into future trials that will ultimately improve patient well-being., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To identify clinical predictors of long-term survival in women with FIGO Stage IVB uterine papillary serous carcinoma (UPSC) confined to the abdomen, Methods: Records were reviewed for 48 patients with Stage IVB UPSC diagnosed from 1/1980 to 12/2011. Study inclusion required hysterectomy, salpingo-oophorectomy and negative chest imaging. Disease-free (DFS) and overall (OS) survival rates were calculated using the Kaplan-Meier method. Multivariate analysis (MVA) was performed using Cox proportional hazards., Results: Median age at diagnosis was 70 years (range, 53-87). Optimal cytoreduction (Opt) to <1cm residual disease was performed in 36 patients (75%). With a median follow-up of 21 months for all patients and 99 months for survivors, 36 (75%) experienced disease progression or relapse, most commonly intraperitoneal (16, 44%). At 5 years, DFS and OS rates were 12% and 19%, respectively. Five patients (10%) were long-term survivors without relapse at a median of 124 months. All 5 had Opt and carboplatin/paclitaxel chemotherapy, and 4 received radiotherapy (2 pelvic, 1 whole-abdominal, 1 brachytherapy). On MVA in the chemotherapy-treated population, Opt (HR 0.09, 95% CI 0.02-0.35) and radiotherapy (HR 0.36, 0.15-0.80) were associated with decreased rates of recurrence or progression. Opt (HR 0.09, 0.02-0.38) was prognostic for OS when adjusted for age., Conclusions: Clinical predictors of long-term survival for Stage IVB UPSC confined to the abdomen include optimal cytoreduction and adjuvant platinum and paclitaxel chemotherapy. Radiotherapy may decrease rates of recurrence or progression. Despite intra-abdominal involvement, disease remission and long-term survival may be achieved in some patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To determine the toxicity and survival rates in a trial of concurrent bevacizumab and external beam radiation (EB) for patients with recurrent endometrial or ovarian cancer., Methods: Nineteen women with recurrent endometrial (n = 15) or ovarian (n = 4) cancer with gross disease involving the vaginal cuff, and/or pelvic nodes and/or para-aortic nodes, cancer were enrolled between 2008 and 2010. All patients received bevacizumab during radiation. Toxicity was assessed at baseline, weekly during treatment and every 3 months for at least 1 year after treatment., Results: All patients completed EB on schedule. For the 15 patients with recurrent endometrial cancer, the 1- and 3-year progression-free survival (PFS was) 80%/67% and overall survival (OS) was 93%/80%. Patients that had a vaginal cuff recurrence alone had a 1- and 3-year PFS of 75%/63% and OS of 100%/75%. Two patients with pelvic node involvement did not recur throughout the entire follow-up period. The 5 patients with para-aortic node involvement had a 1- and 3-year PFS of 80%/60% and OS of 80%/80%. Of the 4 ovarian cancer patients 3 relapsed with 1- and 3-year PFS of 80%/40% and OS of 100%/60%. Toxicities included thrombosis and 1 embolic event in the setting of metastatic disease. No gastrointestinal perforations were noted., Conclusions: Delivering bevacizumab with concurrent radiation provides excellent local tumor control and survival for women with recurrent endometrioid endometrial cancer, particularly those with unresectable nodes. Caution must be used in those at highest risk of developing metastatic disease given the increased risk of thromboembolic events. This regimen may be considered for recurrent gynecologic malignancies in future trials., (© 2013.)

Purpose: To evaluate clinical outcomes for women with recurrent endometrial cancer treated with 3D image-guided brachytherapy, Methods and Materials: 44 women, of whom 13 had received prior RT, received salvage RT for vaginal recurrence from 9/03 to 8/11. HDR or LDR interstitial brachytherapy was performed under MR or CT guidance in 35 patients (80%); 9 (20%) had CT-guided HDR cylinder brachytherapy. The median cumulative dose in EQD2 was 75.5 Gy. Actuarial estimates of local failure (LF), disease-free (DFS) and overall survival (OS) were calculated by Kaplan-Meier., Results: Histologic subtypes were endometrioid (EAC, 33), papillary serous/clear cell (UPSC/CC, 5) and carcinosarcoma (CS, 6). The 2-year DFS/OS rates were 75%/89% for EAC and 11%/24% for UPSC/CC/CS (both p<0.01). On MVA, high tumor grade was associated with recurrence (HR 3.2 for grade 2, 9.6 for grade 3, p<0.01). The LF rate at 2 years was 4% for patients without versus 39% for those with prior RT (p=0.1). Patients who had prior RT received lower cumulative doses at recurrence (66.5 Gy vs. 74.4 Gy, p<0.01). The 2-year DFS/OS rates with and without prior RT were 26%/55% and 72%/80% (both p=0.1). Four patients (9%) experienced grade 3 late toxicity, including 3 of 13 (23%) in the re-irradiation setting and 1 of 31 (3%) with no prior radiotherapy., Discussion: 3D image-guided brachytherapy results in excellent local control for women with recurrent endometrial cancer, particularly with cumulative EQD2 doses greater than 70 Gy. Successful salvage of vaginal recurrence is related to tumor grade and histologic subtype., (© 2013.)

Objective: To evaluate the effect of margin status and radiation dose in patients treated with radiation therapy (RT) for vulvar cancer. Clinical outcomes included vulvar recurrence (VR), relapse-free survival (RFS) and overall survival (OS)., Methods: We retrospectively reviewed the records of 300 patients with Stage I-IVA vulvar cancer treated between 1988 and 2009. Slides were reviewed and margin status was scored as negative (≥ 1 cm), close (<1cm) or positive after formalin fixation. Cox proportional hazards models were constructed to determine significant prognostic factors for vulvar relapse., Results: Of 205 eligible patients, 69 (34%) had negative surgical margins, 116 (56%) had close margins and 20 (10%) had positive margins. Median follow-up time was 49 months. The 4-year RFS rate was 53% and OS was 73%. Of 78 recurrences, 62 had the vulva as the first site of recurrence. The 4-year rates of freedom from vulvar recurrence were 82%, 63% and 37% for those with negative, close and positive margins, respectively (p for trend=0.005). On multivariate analysis, close margins (HR=3.03, 95% CI 1.46-6.26) and positive margins (HR=7.02, 95% CI 2.66-18.54) were associated with a significantly increased risk of vulvar relapse. Those who received a dose ≥ 56 Gy had a lower risk of relapse than those who received ≤ 50.4 Gy (p<0.05). Though recurrences were noted with margins up to 9 mm, the highest risk of vulvar recurrence was associated with margins ≤ 5 mm (p=0.002)., Conclusions: Close or positive margins were associated with a significantly increased risk of vulvar recurrence. Radiation with a dose ≥ 56 Gy may decrease the risk of vulvar recurrence., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To report clinical outcomes following adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) for early-stage uterine papillary serous (UPSC) and clear cell (CC) endometrial cancer., Methods: A retrospective study of Stage I and II papillary serous and clear cell endometrial cancer treated with post-operative HDR VB between October 2005 and May 2012 was performed. A total of 37 patients were identified, 26 with UPSC, 9 with CC and 2 with mixed UPSC/CC. After total hysterectomy and bilateral salpingo-oophorectomy, VB was administered without external-beam radiation with a dose of 24 Gy in 6 fractions prescribed to the vaginal surface. Chemotherapy was given to 30 patients (75%)., Results: The median follow up time was 24.8 months (range, 2.0 to 71.5 months). Four patients relapsed, 2 with UPSC and 2 with CC. The initial site of relapse was concurrent vagina, pelvic/para-aortic nodes and abdominal wall (1), pelvic/para-aortic nodes (1) and para-aortic nodes alone (2). The 2-year vaginal-control rate was 96.8%. The pelvic-control rate including vaginal and nodal relapse was 93.5%. The 2-year disease-free and overall survival rates were 89.3% and 100%, respectively., Conclusion: HDR VB as the sole adjuvant treatment modality for early-stage UPSC/CC is associated with a low rate of vaginal relapse and excellent survival outcomes. This novel low-dose regimen for VB is safe and effective., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen., Methods: We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method., Results: All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5-76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient., Conclusion: Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical outcomes for women with node-positive endometrioid adenocarcinoma of the uterus, Methods: Records were reviewed for 66 patients with Stage IIIC endometrioid adenocarcinoma diagnosed between 1/1995 and 12/2009. Study inclusion required TAH, BSO and negative chest imaging. Papillary serous and clear cell histologies were excluded. Adjuvant treatment was external beam radiation (RT) alone in 18 patients (27%), combined chemotherapy and RT in 44 (67%), chemotherapy alone in 1 (2%), and no adjuvant therapy in 3 (5%). The median follow-up was 48 months., Results: Of 66 patients, 56 (85%) had positive pelvic nodes only, 5 (8%) had positive para-aortic nodes only, and 5 (8%) had both. Of the 62 patients who received adjuvant RT, only 4 (6%) had an in-field recurrence, including 2 with residual disease after surgery. Disease-free (DFS) and overall (OS) survival rates at 5 years were 71% and 81%, respectively. By adjuvant treatment modality, 5-year DFS and OS rates were 63% and 67% for RT alone and 79% and 90% for combined modality therapy (p=0.15 and p<0.01). On multivariate analysis, combined modality therapy significantly improved DFS (HR 0.12, 95% CI 0.03-0.49, p<0.01) and OS (HR 0.20, 95% CI 0.05-0.75, p=0.02) compared to adjuvant RT alone., Conclusions: Compared to RT alone, combined modality therapy decreased recurrence and improved survival in patients with node-positive endometrioid adenocarcinoma of the uterus. In addition, external beam RT resulted in excellent local and regional control. Future studies are needed to define the optimal chemotherapy regimen, sequencing, and radiation fields., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To identify prognostic and predictive factors of overall survival (OS), relapse-free survival (RFS) and toxicity for patients with uterine papillary serous carcinoma (UPSC)., Materials and Methods: Patient, tumor, treatment and relapse characteristics of 135 women with Stages I-IVA UPSC treated between 1980 and 2006 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed using Cox regression models to determine prognostic and predictive factors for OS, RFS and toxicity., Results: Mean follow-up was 5.5 years (range, 0.01-25.2). Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression analysis, increasing age, stage, and myometrial invasion were prognostic factors associated with shorter OS and RFS. A paclitaxel-platinum chemotherapy regimen was significantly associated with longer OS (hazard ratio [HR]=0.34, 95% confidence interval [CI] 0.15-0.74, p=0.007) and RFS (HR=0.45, 95% CI 0.22-0.92, p=0.03). RFS was improved for patients treated with RT (HR=0.44, 95% CI 0.25-0.77, p=0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received RT and was 2.9% for those who did not (p=NS)., Conclusion: Uterine papillary serous cancer can be an aggressive tumor type with a poor prognosis. RFS was improved by radiation and chemotherapy with few grade 3 or higher complications. Using radiation and paclitaxel-platinum chemotherapy should be attempted whenever feasible for patients with UPSC who do not have distant metastases at diagnosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To compare outcomes in patients with squamous cell carcinoma (SCC) of the vulva treated with radiation (RT) and concurrent weekly platinum-based or every-3-4-week regimens containing 5-fluorouracil (5-FU)., Methods: Records of 44 patients with vulvar SCC treated with concurrent chemotherapy and radiation (chemoRT) from 1988 to 2008 were reviewed. Rates of disease-free survival (DFS), overall survival (OS), locoregional recurrence (LRR), and distant metastases (DM) were estimated using the Kaplan-Meier method., Results: The median age was 63 years (range, 44-90), 84.1% of patients had ECOG performance status 0-1, and patients had FIGO Stage II (n=6), III (n=31), or IVA (n=7) disease. Patients were treated preoperatively (n=10), postoperatively (n=10), or without surgery (n=24). The median RT dose to the vulva was 50.2 Gray (range, 22-75). Concurrent chemotherapy regimens included weekly platinum (n=16) or every 3-4 week regimens with 5-FU as the backbone (n=28). With a median follow-up of 31.5 months, there was no significant difference in 2-year OS (74.5% vs. 70.0%; p=0.65), DFS (61.9% vs. 56.0%; p=0.85), LRR (31.3% vs. 32.9%; p=0.93), or DM (6.3% vs. 10.6%; p=0.81) between the weekly platinum and every-3-4-week 5-FU regimens. Twenty patients (45.4%) recurred: 16 LRR, 2 DM, and 2 with both. The clinical and pathologic complete response rates were 58.8% (20/34), and 53.8% (14/26), respectively. There was a higher proportion of grade 3 or higher acute non-skin toxicities in patients receiving every-3-4-week 5-FU (46.1% vs. 13.3%; p=0.07), but more grade 3 or higher skin toxicity in patients receiving weekly platinum (62.5% vs. 32.0%; p=0.01)., Conclusion: OS, response rates, and recurrence rates were not significantly different after RT with concurrent weekly platinum-based versus every-3-4-week regimens containing 5-FU for vulvar SCC., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Vulvar synovial cell sarcomas are rare, with only four previously published cases in the literature. Traditionally, the primary management for these tumors has been surgery alone., Case: We report a case of a large vulvar synovial cell sarcoma in a 50-year-old woman treated with comprehensive combined multimodality management, including preoperative intensity-modulated radiation therapy, radical hemivulvectomy, flap reconstruction, interstitial low-dose-rate brachytherapy boost, and adjuvant chemotherapy., Conclusion: Based on this case and the limited data in the literature, multimodality treatment of advanced soft tissue sarcoma of the vulva may optimize local control and minimize toxicity while preserving sexual function.

Objectives: To analyze the sites of relapse and overall survival in women with neuroendocrine marker-positive small cell carcinoma of the cervix., Methods: The records of all women who had their initial treatment for cervical cancer at The University of Texas M.D. Anderson Cancer Center between 1980 and 2000 were reviewed. Fifty-one patients had stages I-III cancers that were originally described as "small cell" or "neuroendocrine." Histological material was available for reexamination in 45 cases; of these, 21 were found to have small cell neuroendocrine carcinoma (SCNEC) as indicated by positive staining for chromogranin, synaptophysin, or CD56. Local treatment consisted of a radical hysterectomy in six patients and radiation therapy in 15. Thirteen patients received chemotherapy as part of their initial treatment. The median follow-up for surviving patients was 83 months (range, 25-209 months)., Results: Fourteen (66%) of the 21 patients had a relapse. The median time to first relapse from the initiation of treatment was 8.4 months (range, 3.6-28 months). Most patients developed hematogenous distant metastases before their death. Only 2 of 15 patients who were treated with radiation therapy had a recurrence within the radiation fields. However, five patients had a recurrence above the radiation fields in the paraaortic lymph nodes, and two patients had a recurrence distal to the pelvic fields in the vagina. No patient had brain metastases as the sole site of first recurrence. However, two patients developed brain metastases concurrently with lung metastases. The overall survival rate was 29% at 5 years; none of the patients who had disease more extensive than stage IB1 or clinical evidence of lymph node metastases survived their disease., Conclusions: Patients with small cell neuroendocrine cervical cancer have a poor prognosis. Their course is frequently characterized by the development of widespread hematogenous metastases; locoregional recurrence outside irradiated fields is also frequent. Brain metastases were seen only in patients who also had lung metastases, suggesting that prophylactic cranial irradiation would be of little benefit.