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Purpose: Radiation has many potential long-term effects on cancer survivors. Female cancer patients may experience decreased fertility depending on the site irradiated. Oncologists should be aware of these consequences and discuss options for fertility preservation before initiating therapy., Methods and Materials: A comprehensive review of the existing literature was conducted. Studies reporting the outcomes for female patients treated with cranio-spinal, abdominal, or pelvic radiation reporting fertility, pregnancy, or neonatal-related outcomes were reviewed., Results: Cranio-spinal irradiation elicited significant hormonal changes in women that affected their ability to become pregnant later in life. Women treated with abdomino-pelvic radiation have an increased rate of uterine dysfunction leading to miscarriage, preterm labor, low birth weight, and placental abnormalities. Early menopause results from low-dose ovarian radiation. Ovarian transposition may decrease the rates of ovarian dysfunction., Conclusions: There is a dose-dependent relationship between ovarian radiation therapy (RT) and premature menopause. Patients treated with RT must be aware of the impact of treatment on fertility and explore appropriate options.

Purpose: Contouring clinical target volume (CTV) from medical images is an essential step for radiotherapy (RT) planning. Magnetic resonance imaging (MRI) is used as a standard imaging modality for CTV segmentation in cervical cancer due to its superior soft‐tissue contrast. However, the delineation of CTV is challenging as CTV contains microscopic extensions that are not clearly visible even in MR images, resulting in significant contour variability among radiation oncologists depending on their knowledge and experience. In this study, we propose a fully automated deep learning–based method to segment CTV from MR images. Methods: Our method begins with the bladder segmentation, from which the CTV position is estimated in the axial view. The superior–inferior CTV span is then detected using an Attention U‐Net. A CTV‐specific region of interest (ROI) is determined, and three‐dimensional (3‐D) blocks are extracted from the ROI volume. Finally, a CTV segmentation map is computed using a 3‐D U‐Net from the extracted 3‐D blocks. Results: We developed and evaluated our method using 213 MRI scans obtained from 125 patients (183 for training, 30 for test). Our method achieved (mean ± SD) Dice similarity coefficient of 0.85 ± 0.03 and the 95th percentile Hausdorff distance of 3.70 ± 0.35 mm on test cases, outperforming other state‐of‐the‐art methods significantly (p‐value < 0.05). Our method also produces an uncertainty map along with the CTV segmentation by employing the Monte Carlo dropout technique to draw physician's attention to the regions with high uncertainty, where careful review and manual correction may be needed. Conclusions: Experimental results show that the developed method is accurate, fast, and reproducible for contouring CTV from MRI, demonstrating its potential to assist radiation oncologists in alleviating the burden of tedious contouring for RT planning in cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: Brachytherapy combined with external beam radiotherapy (EBRT) is the standard treatment for cervical cancer and has been shown to improve overall survival rates compared to EBRT only. Magnetic resonance (MR) imaging is used for radiotherapy (RT) planning and image guidance due to its excellent soft tissue image contrast. Rapid and accurate segmentation of organs at risk (OAR) is a crucial step in MR image‐guided RT. In this paper, we propose a fully automated two‐step convolutional neural network (CNN) approach to delineate multiple OARs from T2‐weighted (T2W) MR images. Methods: We employ a coarse‐to‐fine segmentation strategy. The coarse segmentation step first identifies the approximate boundary of each organ of interest and crops the MR volume around the centroid of organ‐specific region of interest (ROI). The cropped ROI volumes are then fed to organ‐specific fine segmentation networks to produce detailed segmentation of each organ. A three‐dimensional (3‐D) U‐Net is trained to perform the coarse segmentation. For the fine segmentation, a 3‐D Dense U‐Net is employed in which a modified 3‐D dense block is incorporated into the 3‐D U‐Net‐like network to acquire inter and intra‐slice features and improve information flow while reducing computational complexity. Two sets of T2W MR images (221 cases for MR1 and 62 for MR2) were taken with slightly different imaging parameters and used for our network training and test. The network was first trained on MR1 which was a larger sample set. The trained model was then transferred to the MR2 domain via a fine‐tuning approach. Active learning strategy was utilized for selecting the most valuable data from MR2 to be included in the adaptation via transfer learning. Results: The proposed method was tested on 20 MR1 and 32 MR2 test sets. Mean ± SD dice similarity coefficients are 0.93 ± 0.04, 0.87 ± 0.03, and 0.80 ± 0.10 on MR1 and 0.94 ± 0.05, 0.88 ± 0.04, and 0.80 ± 0.05 on MR2 for bladder, rectum, and sigmoid, respectively. Hausdorff distances (95th percentile) are 4.18 ± 0.52, 2.54 ± 0.41, and 5.03 ± 1.31 mm on MR1 and 2.89 ± 0.33, 2.24 ± 0.40, and 3.28 ± 1.08 mm on MR2, respectively. The performance of our method is superior to other state‐of‐the‐art segmentation methods. Conclusions: We proposed a two‐step CNN approach for fully automated segmentation of female pelvic MR bladder, rectum, and sigmoid from T2W MR volume. Our experimental results demonstrate that the developed method is accurate, fast, and reproducible, and outperforms alternative state‐of‐the‐art methods for OAR segmentation significantly (p < 0.05). [ABSTRACT FROM AUTHOR]

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. • Vaginal necrosis occurs after a high dose of radiation. • Conservative treatment includes antibiotics, hydrogen peroxide douching. • When clinically refractory, hyperbaric oxygen, debridement or pelvic exenteration may be required. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) refusal is known to have deleterious effects on survival for multiple cancer types. Factors associated with RT refusal by patients with gynecologic malignancies have not been well described. This study aimed to examine factors associated with and the survival impact of documented RT refusal among patients with gynecologic cancers. This study analyzed data from the National Cancer Database (NCDB) of patients with gynecologic cancers diagnosed between 2004 and 2020. Patients were included if they had complete survival data and a documented RT recommendation by their treating physician in the NCDB. Patients coded as received RT were compared with those coded as refused RT in the NCDB using a multivariate log binomial regression with robust variance to yield incidence rate ratios (IRR). Overall survival was analyzed using a multivariate (MV) Cox proportional hazards model to yield hazard ratios. This study identified 209,976 patients. A total of 5.75% (n = 12,081) patients were coded as refusing RT. Multivariable IRR showed that documentation of RT refusal was positively associated with older age (MV IRR, 1.04; 95% CI, 1.041-1.045), Native Hawaiian Pacific Islander race (1.72 [1.27-2.32]), and increased morbidity (score = 1: 1.06 [1.02-1.11]; score = 2: 1.20 [1.12-1.29]; score ≥3: 1.26 [1.14-1.38]). Negative associations were seen with Hispanic ethnicity (0.74 [0.67-0.80]), having insurance (0.58 [0.53-0.63]), and annual income >$74,063 (0.85 [0.81-0.90]). During the 16-year period, a statistically significant test for trend (P =.001) for increasing RT refusal was noted. RT refusal was associated with a significantly higher risk of death (MV hazard ratio, 1.59 [1.55-1.63]). For patients with gynecologic malignancies diagnosed from 2004 to 2020, an increase in documented RT refusal is associated with decreased overall survival in all disease types. Targeted interventions aimed at mitigating potential sociodemographic barriers to receipt of RT are warranted. [ABSTRACT FROM AUTHOR]

Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: Lower extremity lymphedema adversely affects quality of life by causing discomfort, impaired mobility and increased risk of infection. The goal of this study is to investigate factors that influence the likelihood of lymphedema in patients with endometrial cancer who undergo adjuvant radiation with or without chemotherapy. Methods: A retrospective chart review identified all stage I-III endometrial cancer patients who had a hysterectomy with or without complete staging lymphadenectomy and adjuvant radiation therapy between January 2006 and February 2013. Patients with new-onset lymphedema after treatment were identified. Logistic regression was used to find factors that influenced lymphedema risk. Results: Of 212 patients who met inclusion criteria, 15 patients (7.1%) developed new-onset lymphedema. Lymphedema was associated with lymph-node dissection (odds ratio [OR], 5.6; 95% CI, 1.01 to 105.5; p=0.048) and with the presence of pathologically positive lymph nodes (OR, 4.1; 95% CI, 1.4 to 12.3; p=0.01). Multivariate logistic regression confirmed the association with lymph-node positivity (OR, 3.2; 95% CI, 1.0007 to 10.7; p=0.0499) when controlled for lymph-node dissection. Median time to lymphedema onset was 8 months (range, 1 to 58 months) with resolution or improvement in eight patients (53.3%) after a median of 10 months. Conclusion: Lymph-node positivity was associated with an increased risk of lymphedema in endometrial cancer patients who received adjuvant radiation. Future studies are needed to explore whether node-positive patients may benefit from early lymphedema-controlling interventions. [ABSTRACT FROM AUTHOR]

Background: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer.Methods: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]).Results: A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months.Conclusions: Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: 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 (≥1cm), 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 49months. 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 ≥56Gy had a lower risk of relapse than those who received ≤50.4Gy (p<0.05). Though recurrences were noted with margins up to 9mm, the highest risk of vulvar recurrence was associated with margins ≤5mm (p=0.002). Conclusions: Close or positive margins were associated with a significantly increased risk of vulvar recurrence. Radiation with a dose ≥56Gy may decrease the risk of vulvar recurrence. [Copyright &y& Elsevier]

Background: It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT) or concurrent chemoradiation therapy (CRT). Methods: Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS) and disease-free survival (DFS) rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. Results: The median age at diagnosis was 61 years (range, 18–92 years) and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011). Twenty-three patients (45%) in the RT group had a relapse at any site compared to 3 (15%) in the CRT group (p = 0.027). With regard to the sites of first relapse, 10 patients (14%) had local only, 4 (6%) had local and regional, 9 (13%) had regional only, 1 (1%) had regional and distant, and 2 (3%) had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10–0.97; p = 0.04)). Conclusions: Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: 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 5.5years (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 &y& Elsevier]

The article focuses on a study concerning computed tomography-based radiation therapy of ovarian remnants for symptomatic persistent endometriosis. It examines three patients with endometriosis causing incapacitating pelvic pain who received 3D-imaging-based external beam radiation to doses of 1,500 to 2,100 cGy. In addition, the study concludes that radiation therapy effectively induced menopause and relieved refractory pain from endometriosis.

Purpose: To examine the relationship between margin status and local recurrence (LR) or any recurrence after radical hysterectomy (RH) in women treated with or without radiotherapy (RT) for Stage IB cervical carcinoma. Methods and Materials: This study included 284 patients after RH with assessable margins between 1980 and 2000. Each margin was scored as negative (≥1 cm), close (>0 and <1 cm), or positive. The outcomes measured were any recurrence, LR, and relapse-free survival. Results: The crude rate for any recurrence was 11%, 20%, and 38% for patients with negative, close, and positive margins, respectively. The crude rate for LR was 10%, 11%, and 38%, respectively. Postoperative RT decreased the rate of LR from 10% to 0% for negative, 17% to 0% for close, and 50% to 25% for positive margins. The significant predictors of decreased relapse-free survival on univariate analysis were the depth of tumor invasion (hazard ratio [HR] 2.14/cm increase, p = 0.007), positive margins (HR 3.92, p = 0.02), tumor size (HR 1.3/cm increase, p = 0.02), lymphovascular invasion (HR 2.19, p = 0.03), and margin status (HR 0.002/increasing millimeter from cancer for those with close margins, p = 0.03). Long-term side effects occurred in 8% after RH and 19% after RH and RT. Conclusion: The use of postoperative RT may decrease the risk of LR in patients with close paracervical margins. Patients with other adverse prognostic factors and close margins may also benefit from the use of postoperative RT. However, RT after RH may increase the risk of long-term side effects. [Copyright &y& Elsevier]

: PurposeTo analyze the sites of relapse, relapse-free survival, and overall survival in children with Group III rhabdomyosarcoma treated with or without radiotherapy (RT).: Methods and materialsThe outcomes of 48 children with Group III rhabdomyosarcoma treated between 1980 and 1997 were evaluated. The median overall survival follow-up was 7.3 years. Of the 48 patients, 65% had embryonal histology. Local treatment after induction chemotherapy included complete surgical resection (CSR) alone in 9 (19%), CSR plus RT in 13 (27%), partial resection or rebiopsy plus RT in 10 (21%), and RT alone in 15 patients (31%). One child developed distant disease before completing local therapy.: ResultsOf the 48 patients, 12 developed relapse at local (n = 3), regional (n = 4), or distant (n = 5) sites. All 9 patients treated with CSR after induction chemotherapy had embryonal/botryoid histology. Only 1 of these 9 patients developed relapse. No statistically significant difference was found in overall survival (p = 0.95) or relapse-free survival (p = 0.67) between patients treated with or without RT. The Kaplan-Meier estimate of 5-year overall survival and relapse-free survival was 76% ± 7% and 74% ± 7%, respectively. Significant predictors of relapse-free survival on univariate analysis included CSR (p = 0.03), nodal positivity (p = 0.001), and embryonal histology (p = 0.0003). On multivariate analysis, embryonal histology was the most significant predictor of relapse-free (p = 0.001) and overall (p = 0.01) survival.: ConclusionThe overall survival for children with Group III rhabdomyosarcoma in this series was favorable. Embryonal/botryoid histology was the most significant predictor of both overall and relapse-free survival. We found that for a selected subgroup of children with embryonal histology, induction chemotherapy followed by complete surgical resection alone may be adequate local therapy. [Copyright &y& Elsevier]

Objective: The role of F-18-fluorothymidine (FLT) PET-CT imaging in the evaluation of gynecologic cancers has not been established. We sought to evaluate (FLT) PET-CT imaging in gynecologic cancers by comparing standard uptake values (SUVs) of FLT with F-18-fluorodeoxyglucose (FDG) PET in the primary tumor at diagnosis, and assess FLT uptake immediately following concurrent chemoradiotherapy (chemoRT). Methods: In this pilot study, patients treated for cervical (5) or vaginal (1) cancer underwent FLT-PET and FDG-PET scanning at diagnosis (FLT1 and FDG1). Five patients (4 cervical and 1 vaginal) also underwent FLT-PET within 1–3 weeks after chemoRT before brachytherapy (FLT2). Wilcoxon rank-sum test was used to compare the FLT1 and FDG1 parameters. Results: Median age at diagnosis was 61-years (range, 33–72). Cervical cancers were staged as IB2 (n = 1, 20%), IIB (n = 1, 20%), IIIB (n = 1, 20%) and IVA (n = 2, 40%) and the single vaginal cancer was staged IIIB. The most common histology was squamous cell carcinoma (n = 3, 50%) followed by adenocarcinoma (n = 2, 33%) and clear-cell adenosquamous carcinoma (n = 1, 17%). Median tumor SUVmax at diagnosis was 7.8 on FLT1-PET (3.9–14.2) versus 11.6 (5.9–23.2) on FDG1-PET (p = 0.15). Tumor SUVmax of FLT declined 54%–100% after chemoRT. Conclusion: The tumor SUV of FLT at diagnosis was lower than that of FDG-PET. FLT uptake was markedly decreased after chemoRT. Results indicate that there may not be a significant effect of inflammation on FLT uptake in gynecologic cancers. FLT may be a useful tool when assessing the effects of chemoRT on gynecologic malignancies and planning for postchemoRT brachytherapy treatments.

Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival (p = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings. [ABSTRACT FROM AUTHOR]

Purpose: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base.Methods and Materials: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis.Results: We identified 3075 patients with a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779).Conclusions: Patients with vulvar squamous cell carcinoma and positive surgical margins derive an OS benefit from aRT with a seemingly optimal dose in the range of 54.0 to 59.9 Gy. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. • OTT of adjuvant radiation therapy is an independent risk factor for death in women with resected, node-positive vulvar cancer • Each additional day between surgery and completion of adjuvant radiation contributes to higher risk of death • This is the first study to evaluate the impact of OTT on overall survival in this population of patients [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]

To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic. 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. 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. 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. • An international panel of gynecologic radiation oncologists offer recommendations for RT during the COVID-19 pandemic. • Recommendations for cervical cancer, uterine cancer, vulvar cancer, vaginal cancer and ovarian cancer have been provided. • Recommendations for RT timing, fractionation, and dose have been provided for external beam radiation and brachytherapy. • The panel emphasizes strategies to reduce risk of transmission of the novel SARS-CoV-2 to patients and healthcare workers. • These recommendations may be used any time an event occurs which limits healthcare resources, including natural disasters. [ABSTRACT FROM AUTHOR]

To understand the reasons behind current low utilization of brachytherapy for locally advanced cervical cancer in the United States. A 17-item survey was e-mailed to the American Brachytherapy Society (ABS) listserv of active members in 2018. Responses of attending physicians in the United States were included in the analysis. Among a total of 135 respondents, 81 completed the survey. Eighty-four percent agree/strongly agree that cervical brachytherapy is underutilized, and 46.9% disagree/strongly disagree that residents are receiving adequate training for brachytherapy; 75.3% agree/strongly agree that inadequate maintenance of brachytherapy skills is a major obstacle to brachytherapy use; and 71.6% agree/strongly agree that increased time requirement constitutes a major obstacle. Over 97% will recommend brachytherapy for most patients with cervical cancer if given access/time; 72.8% always perform their own brachytherapy, whereas 29.6% reported some type of barrier exists in performing brachytherapy themselves, with time required to perform brachytherapy (9.9%) being a leading factor. A quarter (24.7%) routinely refer to other radiation oncologists for brachytherapy. Even among ABS members, 37.0% reported that they would perform an intensity-modulated radiation therapy or stereotactic body radiation therapy boost in specific scenarios in potentially curable patients. The most common scenario is inability to place a uterine tandem (56.7%). The underutilization of brachytherapy in cervical cancer is widely recognized by ABS members with inadequate training during residency and inadequate maintenance of skills being possible major contributing factors. Even among ABS members, there are identifiable barriers. Continued advocacy and future initiatives in enhancing access to brachytherapy training and efficiency are needed. [ABSTRACT FROM AUTHOR]

Purpose: Chartrounds (www.chartrounds.com) was established in the United States in 2010 as a web-based platform for radiation oncologists to review cases with leading disease-site experts. However, the need for access to experts for peer review and education is not unique to the United States, and the Chartrounds platform was therefore adapted for improved global reach. Chartrounds was first expanded to India, and herein we report our initial experience with this initiative.Methods and Materials: The US Chartrounds platform was adapted to create Chartrounds India (ind.chartrounds.com). Through collaboration with the Association of Radiation Oncologists of India, India-based specialists were recruited, and the association's membership list was used to announce sessions to potential participants.Results: Between June 2017 and January 2018, 27 Chartrounds India sessions were completed, led by 21 different specialists (representing 10 centers in India) and covering 11 different disease sites/topics. A total of 240 members from 126 centers (private: 56%; teaching: 36%; public: 8%) across 24 states/territories participated in ≥1 session. Of the 240 members who participated in ≥1 session, 159 (66%) participated in ≥2 sessions and 60 (25%) participated in ≥5 sessions. The average number of participants per session was 34 (range, 13-72). On average, 80% of respondents rated the sessions as high or very high quality; 87% and 95% agreed or strongly agreed that the time was used effectively and that the sessions were relevant to daily practice, respectively. Seventy-six percent agreed or strongly agreed that the sessions will result in a change in their practice. The average feedback survey response rate was 32% (range, 17%-49%).Conclusions: Chartrounds has proven to be an effective resource for US-based radiation oncologists, and our initial experience with Chartrounds India suggests that an online platform for radiation oncology case review and education can be successfully implemented globally with use of local disease site experts. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the survival endpoints in women with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer who received adjuvant vaginal brachytherapy (VBT) alone using multi-institutional pooled data.Methods and Materials: We performed a multi-institutional analysis of surgically staged patients with FIGO stage II endometrioid-type endometrial cancer treated with VBT alone. Patient, tumor, and treatment characteristics were collected and analyzed. Univariable and multivariable frailty survival models were performed to assess clinicopathologic risk factors for recurrence and death.Results: One hundred six patients were included (92 VBT alone and 14 VBT with chemotherapy) with median follow-up of 39.0 months. Pelvic node dissection was performed in 89.6% of patients. One hundred four patients (98.1%) and 2 patients (1.9%) had microscopic and macroscopic cervical stromal invasion, respectively. Grade 1 or 2 disease occurred in 88.6% of patients. For patients treated with VBT without chemotherapy, the 5-year estimates of vaginal failure, pelvic nodal failure, and distant metastases were 2.6%, 4.2%, and 7.2%, respectively. Five-year progression-free survival and overall survival were 74.0% and 76.2%, respectively. On univariable and multivariable models for progression-free survival, increasing age and lack of pelvic node resection were hazardous (P < .05).Conclusions: Vaginal and pelvic failure rates were low in this selected population of stage II patients receiving adjuvant VBT without external beam radiation therapy. It is reasonable to consider adjuvant VBT alone in selected patients with grade 1 or 2 disease and microscopic cervical stromal invasion who underwent pelvic lymphadenectomy. [ABSTRACT FROM AUTHOR]

Purpose: We designed and built dedicated active magnetic resonance (MR)-tracked (MRTR) stylets. We explored the role of MRTR in a prospective clinical trial.Methods and Materials: Eleven gynecologic cancer patients underwent MRTR to rapidly optimize interstitial catheter placement. MRTR catheter tip location and orientation were computed and overlaid on images displayed on in-room monitors at rates of 6 to 16 frames per second. Three modes of actively tracked navigation were analyzed: coarse navigation to the approximate region around the tumor; fine-tuning, bringing the stylets to the desired location; and pullback, with MRTR stylets rapidly withdrawn from within the catheters, providing catheter trajectories for radiation treatment planning (RTP). Catheters with conventional stylets were inserted, forming baseline locations. MRTR stylets were substituted, and catheter navigation was performed by a clinician working inside the MRI bore, using monitor feedback.Results: Coarse navigation allowed repositioning of the MRTR catheters tips by 16 mm (mean), relative to baseline, in 14 ± 5 s/catheter (mean ± standard deviation [SD]). The fine-tuning mode repositioned the catheter tips by a further 12 mm, in 24 ± 17 s/catheter. Pullback mode provided catheter trajectories with RTP point resolution of ∼1.5 mm, in 1 to 9 s/catheter.Conclusions: MRTR-based navigation resulted in rapid and optimal placement of interstitial brachytherapy catheters. Catheters were repositioned compared with the initial insertion without tracking. In pullback mode, catheter trajectories matched computed tomographic precision, enabling their use for RTP. [ABSTRACT FROM AUTHOR]

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 58 months 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. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a survey of radiation oncologists in India, to better understand specific educational needs of radiation oncology in India and define areas of collaboration with US institutions.Methods and Materials: A 20-question survey was distributed to members of the Association of Indian Radiation Oncologists and the Indian Brachytherapy Society between November 2013 and May 2014.Results: We received a total of 132 responses. Over 50% of the physicians treat more than 200 patients per day, use 2-dimensional or 3-dimensional treatment planning techniques, and approximately 50% use image guided techniques. For education needs, most respondents agreed that further education in intensity modulated radiation therapy, image guided radiation therapy, stereotactic radiation therapy, biostatistics, and research methods for medical residents would be useful areas of collaboration with institutions in the United States. Other areas of collaboration include developing a structured training module for nursing, physics training, and developing a second-opinion clinic for difficult cases with faculty in the United States.Conclusion: Various areas of potential collaboration in radiation oncology education were identified through this survey. These include the following: establishing education programs focused on current technology, facilitating exchange programs for trainees in India to the United States, promoting training in research methods, establishing training modules for physicists and oncology nurses, and creating an Indo-US. Tumor Board. It would require collaboration between the Association of Indian Radiation Oncologists and the American Society for Radiation Oncology to develop these educational initiatives. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To develop recommendations for the use of adjuvant vaginal cuff brachytherapy after hysterectomy and update previous American Brachytherapy Society (ABS) guidelines. Methods and Materials: A panel of members of the ABS performed a literature review, supplemented their clinical experience, and formulated recommendations for adjuvant vaginal cuff brachytherapy. Results: The ABS endorses the National Comprehensive Cancer Network guidelines for indications for radiation therapy for patients with endometrial cancer and cervical cancer and the guidelines on quality assurance of the American Association on Physicists in Medicine. The ABS made specific recommendations for applicator selection, insertion techniques, target volume definition, dose fractionation, and specifications for postoperative adjuvant vaginal cuff therapy. The ABS recommends that applicator selection should be based on patient anatomy, target volume geometry, and physician judgment. The dose prescription point should be clearly specified. Suggested doses were tabulated for treatment with brachytherapy alone, and in combination with external beam radiation therapy, when applicable. A properly fitted brachytherapy applicator should be selected that conforms to the vaginal apex and achieves mucosal contact with optimal tumor and normal tissue dosimetry. Dose prescription points may be individually selected but doses should be reported at the vaginal surface and at 0.5-cm depth. Conclusions: Recommendations are made for adjuvant vaginal cuff brachytherapy. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their treatment and dose reporting policies. These recommendations will permit meaningful comparisons of reports from different institutions and lead to better and more appropriate use of vaginal brachytherapy. [Copyright &y& Elsevier]

Abstract: 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 63years (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 3–4week regimens with 5-FU as the backbone (n =28). With a median follow-up of 31.5months, 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. [ABSTRACT FROM AUTHOR]