Five rare cases of Ewing sarcoma, including with epithelial differentiation, involving the female genital tract, displaying EWSR1 rearrangement: Diagnostic challenge and treatment implications.

We present clinicopathological and molecular cytogenetic features of five rare cases of Ewing sarcomas, occurring in the female genital tract. A 40 year-old lady presented with a 5.4 cm-sized vaginal mass of 3 months duration, which was histopathologically diagnosed as ES. She defaulted chemotherapy and 8 months later, presented with a recurrence. She underwent chemotherapy and radiotherapy. A 45 year-old lady presented with recurrent vaginal bleeding, for which she underwent total abdominal hysterectomy (TAH) and unilateral salpingo-oophorectomy (USO), 2 and 1/2 years back. Subsequent vaginal biopsy was reported inconclusively, elsewhere. Thereafter, a 5 cm-sized, residual cervicovaginal mass was reported as ES. She completed induction chemotherapy with a significant response. A 35 year-old-lady was referred with a 4 cm-sized cervical mass, for which she underwent TAH-USO with pelvic and para-aortic lymphadenectomy. A 39 year-old-lady presented with a right labial lesion, which recurred. She underwent initial excision, chemotherapy, wide excision and brachytherapy. A year later, she developed multiple metastases; received palliative radiotherapy and died-of-disease. A 16 year-old girl presented with perineal swelling of 4 months duration. She underwent surgical excision of a recurrent right-sided labial cyst, followed by chemotherapy. On histopathological review, all 5 cases were malignant round cell tumors. Immunohistochemically, tumor cells displayed MIC2/CD99 and Fli1 positivity, along with focal positivity for pan cytokeratin (AE1/AE3) (cases 1 and 2) and p63 (case 2). Furthermore, tumor cells in the 1st, 2nd, 3rd and 5th cases displayed EWSR1 rearrangement. Five uncommon cases of ES involving the female genital tract are presented with diagnostic challenges and therapeutic implications.

Diffusion-weighted imaging of gynecologic tumors: diagnostic pearls and potential pitfalls.

Conventional magnetic resonance (MR) imaging has an established role in gynecologic imaging. However, increasing clinical demand for improved lesion characterization and disease mapping to optimize patient management has resulted in the incorporation of newer sequences, such as diffusion-weighted (DW) imaging, into routine protocols for pelvic MR imaging. DW imaging provides functional information about the microenvironment of water in tissues, hence augmenting the morphologic information derived from conventional MR images. It can depict shifts of water from extracellular to intracellular compartments, altered cell membrane permeability, disruption of cell membrane depolarization, and increased cellular density. Such changes may be associated with tumors. DW imaging has emerged as an important cancer biomarker and takes the role of the radiologist from the level of mere macroscopic diagnosis to more active participation in determining patient prognosis and management through a better understanding of the tumor microenvironment. With the growing acknowledgment of DW imaging as a pivotal tool in the radiologist's armamentarium, radiologists must be familiar with the appearances of various gynecologic tumors at DW imaging and understand the implications of this sequence for improving diagnostic accuracy and predicting and monitoring treatment response. Although positron emission tomography/computed tomography is extremely useful for detecting tumor recurrence in cervical and ovarian carcinomas, it has a limited specificity in the immediate posttreatment setting. DW imaging may aid in detection of residual or recurrent tumors in such situations. DW imaging is a potentially useful adjunct to conventional MR imaging for evaluation of gynecologic tumors, thus improving overall diagnostic accuracy, tumor staging, prediction of response to therapy, and treatment follow-up.

Clinical outcome of early-stage endometroid adenocarcinoma: a tertiary cancer center experience.

OBJECTIVE: Endometrial cancer (EC) outcome data from developing countries are sparse. We undertook this retrospective analysis to report outcome in our patient population. MATERIALS AND METHODS: Two hundred forty-nine patients with stage I and II and type I histology ECs referred/treated at our institution from 1998 to 2004 were analyzed. All the details including demographic profile, surgical and histopathological details, as well as International Federation of Gynecology and Obstetrics stage and adjuvant therapy were compiled. The 1988 International Federation of Gynecology and Obstetrics staging and risk stratification were performed on the basis of PORTEC risk groups. RESULTS: With a median age of 54 years (26-72 years), 136 patients (55%) underwent surgery elsewhere; 118 (47.3%) underwent a complete surgical staging. There were 60 (24.1%), 124 (49.8%), 65 (26.1%) patients in the low-risk (LR), intermediate-risk (IR), and high-risk (HR) groups, respectively. Adjuvant radiation was given in 160 patients (LR, 18; IR, 85; and HR, 57). With a median follow-up of 36 months (mean, 40 months), 10 patients had vault recurrences, (LR, 3; IR, 4; and HR, 3), 11 had nodal (5 also had local recurrence; LR, 2; IR, 4; and HR, 5), and 16 had distant recurrences (3 also had nodal; LR, 4; IR, 5; HR, 7). The 5-year disease-free survival (DFS) and overall survival (OAS) rates were 80% and 95%, respectively. The DFS and OAS rates at 5 years were 84% and 97%, 85% and 98%, and 60% and 85% for the LR, IR, and HR groups, respectively. On multivariate analysis, grade (P = 0.002) and type of radiation (P = 0.027) had significant impact on DFS and OAS. Late toxicities (grade 3/4) were vaginal stenosis in 4 (1%) and radiation proctitis in 3 (1%) patients. CONCLUSIONS: In our study, ECs are seen in relatively younger population. There is a trend toward incomplete staging surgery outside the oncological referral network. However, the clinical outcome for early-stage type I histology ECs within our population are similar to those reported in the literature.

Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic features, terminology, immunohistochemical profile, and clinical outcomes in a series of 50 cases from a single institution in India.

Neuroendocrine carcinomas of the cervix are uncommon, characterized by a histomorphological spectrum and, mostly, an aggressive clinical course. There are only few substantial studies on such cases documented from our country, where cervical cancer is the second most common cancer affecting women. Herein, we present a spectrum of 50 cervical neuroendocrine carcinomas, including histopathologic features, terminology, immunohistochemical (IHC) profile, and clinical outcomes, wherever available. Fifty tumors occurred in women, with their age ranging from 23 to 69 years (mean, 48.6 years; median, 46.5 years). Stagewise, among 25 cases, most cases (6, or 24%) presented with stage IB. Average tumor size was 4.7 cm. On histopathologic review, 26 tumors (52%) were classified as small cell carcinoma (SMCA); 14 (28%), as large cell neuroendocrine carcinomas (LCNECs); 4 (8%), as SMCA+LCNECs; and 6, as mixed carcinomas, including 3 tumors (6%) with SMCA and squamous cell carcinoma (SCC), 2 tumors (4%) with LCNEC and adenocarcinoma, and a single tumor (2%) with LCNEC and squamous cell carcinoma. On IHC performed in 41 tumors (82%), 36 tumors (87.8%) were positive for at least a single neuroendocrine marker, and 22 (53.6%) expressed 2 neuroendocrine markers. Synaptophysin was positive in 22 (59.4%) of 37 tumors; chromogranin, in 27 (72.9%) of 37; CD56, in 8 (100%) of 8; and neuron-specific enolase in 7 (87.5%) of 8 tumors. Treatment wise, among 30 patients (60%), 6 (20%) underwent surgery, including Wertheim hysterectomy (5) and simple hysterectomy (1); 8 (26.6%) underwent surgery with adjuvant treatment, and 10 patients (33.3%) were offered chemotherapy and/or radiotherapy. On follow-up (27 patients, or 54%) over 1 to 144 months, 16 patients (59.2%) were alive with disease over median duration of 9 months, and 7 (25.9%) were free of disease over median duration of 26.5 months. There were 5 recorded deaths. Thirteen tumors (48.1%) metastasized, most commonly to liver. In cases with early stage disease and adjuvant treatment, including radiotherapy, LCNEC histology fared well. This study forms the largest documented series on cervical neuroendocrine carcinomas from our country, testifying the current histopathologic classification system. Although SMCAs can be recognized on morphology, LCNECs need to be correctly identified because these can be misdiagnosed in the absence of neuroendocrine markers. Synaptophysin, chromogranin, and CD56 are optimal IHC markers. Small cell carcinomas, pure or mixed, are relatively more aggressive. All these tumors are best treated with multimodal therapy. Early stage disease treated with radical surgery and adjuvant treatment seems to increase survival. Despite aggressive treatment, prognosis is dismal.

Clinical outcomes of patients treated with template-based high-dose-rate interstitial brachytherapy boost for post-operative recurrent gynecological malignancies: A retrospective analysis.

Purpose: To report the clinical outcomes in patients treated with Martinez universal perineal interstitial template (MUPIT)-based interstitial brachytherapy boost for primary and recurrent vault and vaginal cancers, and to perform a comparative analysis with our previously published series of similar patients. Material and methods: One hundred and seventeen patients treated between January, 2009 and December, 2015 were evaluated. Descriptive statistics for the patterns of relapse, local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and late toxicities were carried out. Kaplan-Meier curves were used for survival analysis. All variables with the potential to affect outcomes were tested using log-rank test for statistical significance. Results: At a median follow-up of 63 months, LRFS, DFS, and OS at 3/5 years were 77.1%/74.7%, 61%/52%, and 72.3%/63.1%, respectively. Overall treatment time (OTT) of 56 days did not affect outcomes. Bulky tumors and OTT > 63 days adversely affected LRFS. Overall treatment time also significantly impacted DFS and OS. Grade 3-4 late bladder toxicities were observed in 1.7% patients, and grade 3-4 late rectal toxicities in 5% patients. Compared to our previous series, the outcome in the current series is better in terms of severe late toxicities (5% improvement in rectal toxicity, and 2.7% improvement in bladder toxicity) and OS by 10%. This could be attributed to the increasing use of concurrent chemotherapy and relative optimization strategies for organs at risk. Conclusions: Patients with primary and recurrent vault and vaginal cancers treated with high-dose-rate interstitial brachytherapy boost using MUPIT resulted in modest clinical outcomes and acceptable late toxicities. OTT was the most important factor affecting the outcomes.

Quality of life in long term survivors of cervical cancer: A cross sectional study.

BACKGROUND: Quality of life (QOL) is an important parameter to evaluate and modify in patients treated for cervical cancer as long-term survival is excellent in early-stage and reasonably good in locally advanced stage compared to other solid cancers. The aim of the study was the cross sectional evaluation of the quality of life in survivors completing at least 3 years of follow-up after curative therapy for cervical cancer at a tertiary cancer institute. METHODS: All patients, following primary curative treatment with no evidence of recurrence and completing at least 3 years follow-up, were assessed for QOL using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30 and its cervical cancer module (Cx24). Patients were subdivided based on the modality of treatment. Analysis was done using Kruskal-Wallis and Mann-Whitney U test. RESULTS: One hundred seven patients were analyzed out of the 113 patients initially included. Treated patients showed good global QOL (mean value: 84.07) and functional scores (covering all domains). In the cervical cancer module, sexual activity, sexual enjoyment, and sexual function were low in the majority of the respondents. Chronic lymphedema, symptom experience, and sexual worry were significant across all the treatment arms. CONCLUSION: Cervical cancer survivors have an overall good QOL. However, certain concerns related to the sexual quality of life, symptom experience, and chronic lymphedema need to be addressed appropriately.

Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial.

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

A cluster randomized, controlled trial of breast and cervix cancer screening in Mumbai, India: methodology and interim results after three rounds of screening.

Cervix and Breast cancers are the most common cancers among women worldwide and extract a large toll in developing countries. In May 1998, supported by a grant from the NCI (US), the Tata Memorial Hospital, Mumbai, India, started a cluster-randomized, controlled, screening-trial for cervix and breast cancer using trained primary health workers to provide health-education, visual-inspection of cervix (with 4% acetic acid-VIA) and clinical breast examination (CBE) in the screening arm, and only health education in the control arm. Four rounds of screening at 2-year intervals will be followed by 8 years of monitoring for incidence and mortality from cervix and breast cancers. The methodology and interim results after three rounds of screening are presented here. Good randomization was achieved between the screening (n = 75360) and control arms (n = 76178). In the screening arm we see: High screening participation rates; Low attrition; Good compliance to diagnostic confirmation; Significant downstaging; Excellent treatment completion rate; Improving case fatality ratios. The ever-screened and never-screened participants in the screening arm show significant differences with reference to the variables religion, language, age, education, occupation, income and health-seeking behavior for gynecological and breast-related complaints. During the same period, in the control arm we see excellent participation rate for health education; Low attrition and a good number of symptomatic referrals for both cervix and breast.

Small Cell Carcinoma of Ovary, Hypercalcemic Type (Malignant Rhabdoid Tumor of Ovary) with Loss of SMARCA4 (BRG1) Expression: Report of Two Cases.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) / malignant rhabdoid tumor of the ovary (MRTO) is a rare tumor affecting young women. It is frequently misdiagnosed due to overlapping morphological and immunohistochemical features with many other ovarian tumors. The prognosis of the tumors is very poor; hence an accurate diagnosis is of utmost importance. Recently, the loss of BRG1 protein by immunohistochemistry has been shown to be a useful diagnostic marker. We present here two cases of SSCOHT/MRTO, in young women 22 and 32 years of age, where several differential diagnoses were considered on morphology and immunohistochemistry but were confirmed as SCCOHT/MRTO by the demonstration of loss of BRG1. As the prognosis of SCCOHT is very dismal, and accurate diagnosis is of necessity, we recommend the inclusion of BRG1 immunohistochemistry in the diagnostic armamentarium of poorly differentiated ovarian tumors, particularly in young adults.

Compliance to treatment guidelines and survival in women undergoing interval debulking surgery for advanced epithelial ovarian cancer.

BACKGROUND: One of the primary treatment strategies for advanced epithelial ovarian cancers includes neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy. Compliance to treatment is important to possibly improve outcomes. AIM: To audit treatment compliance and its effect on overall survival (OS) and disease free survival (DFS) in women undergoing IDS. METHODS AND RESULTS: Women diagnosed with advanced epithelial ovarian cancer undergoing IDS were included. Details of compliance to chemotherapy and surgery as per standard guidelines were assessed, and correlation with survival was studied. Reasons for protocol deviation at various levels were documented and analysed. A total of 182 patients were included. The total number of deviations was 134 with deviation at any level being 89 (48.9%) and at all levels 5%. Both patient- and treatment-related factors contributed towards deviation. Deviation or noncompliance towards treatment resulted in a significantly reduced 5-year OS (34.4% vs 58.2%; P = .001) compared with compliant patients, which retained its significance on multivariate analysis (P = .024) as well. CONCLUSION: Deviation from treatment guidelines resulted in a significantly lower 5-year OS compared with those who remained treatment compliant. Both patient- and treatment-related factors contributed towards noncompliance and hence towards lower survival.

Feasibility of laparoscopic abdomino-perineal resection for large-sized anorectal cancers: a single-institution experience of 59 cases.

BACKGROUND: Laparoscopic surgery for anorectal carcinoma is steadily gaining acceptance. While feasibility has already been reported, there are no reports addressing the impact of the actual size of large tumors on laparoscopic resectability. AIM: To assess the feasibility and short-term results (including oncological surrogate end points) of performing laparoscopic abdomino-perineal resection (APR) for large rectal cancers. MATERIALS AND METHODS: Data of 59 patients undergoing laparoscopic APR (LAPR) for anorectal malignancies were reviewed retrospectively. Outcomes were evaluated considering the surgical procedure, surface area of the tumor and short-term outcomes. RESULTS: Of the 59 cases, LAPR could be completed in 53 (89.8%) patients. Thirty-one (58.4%) patients had Astler-Coller C2 stage disease. The mean surface area of the tumors was 24+/-17.5 (4-83) cm2. The number of median lymph nodes harvested per case was 12 (1-48). Circumferential resection margin (CRM) was positive in 11 (20.7%) patients. No mortality was reported. CONCLUSION: This appears to be the first report analyzing the impact of the size of the rectal tumor in LAPR. The data clearly indicates that LAPR is not hampered by the size of the tumor. There appears to be a need for preoperative radiotherapy and chemotherapy before undertaking surgery on larger tumors in view of the higher circumferential resection margin positivity.

Cisplatin Chemoradiotherapy vs Radiotherapy in FIGO Stage IIIB Squamous Cell Carcinoma of the Uterine Cervix: A Randomized Clinical Trial.

IMPORTANCE: The evidence for concurrent chemoradiotherapy (CT-RT) in International Federation of Gynecology and Obstetrics (FIGO) stage IIIB squamous cell carcinoma of the uterine cervix is not robust. This study reports the final results of a randomized clinical trial of concurrent cisplatin-based CT-RT and radiotherapy alone (RT) in women with FIGO stage IIIB squamous cell carcinoma of the uterine cervix. OBJECTIVE: To investigate the benefit of concurrent CT-RT in FIGO stage IIIB squamous cell carcinoma of the uterine cervix. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 open-label randomized clinical trial accrued 850 women in Mumbai, India, between July 7, 2003, and September 22, 2011. Of 2121 screened, 850 women with FIGO stage IIIB squamous cell carcinoma of the uterine cervix suitable for concurrent cisplatin chemotherapy were randomly assigned to CT-RT and RT using block randomization (1:1). The data were updated for a minimum follow-up period of 5 years until December 2016. The final analyses were performed in February and March 2017. This single-institution study was conducted at a tertiary cancer center setting. INTERVENTIONS: Randomization to receive RT (RT arm), comprising a combination of external beam RT (50 Gy in 25 fractions over 5 weeks) and brachytherapy, or to receive in addition to the same RT concurrent weekly cisplatin chemotherapy (40 mg/m2 per week) (CT-RT arm). MAIN OUTCOMES AND MEASURES: The primary end point was 5-year disease-free survival (DFS), defined as the time between the date of randomization and the date of any recurrence or death (whichever occurred first) in the intent-to-treat population. RESULTS: This trial included 424 women assigned to CT-RT (mean [SD] age, 49.4 [7.9] years) and 426 women assigned to RT (mean [SD] age, 49.3 [7.9] years). At a median follow-up of 88 months (interquartile range, 61.3-113.1 months), there were 222 recurrences and 213 deaths in the CT-RT arm and 252 recurrences and 243 deaths in the RT arm. The 5-year DFS was significantly higher in the CT-RT arm (52.3%; 95% CI, 52.2%-52.4%) compared with the RT arm (43.8%; 95% CI, 43.7%-43.9%), with a hazard ratio for relapse or death of 0.81 (95% CI, 0.68-0.98) (P = .03). Similarly, the 5-year overall survival (OS) was significantly higher in the CT-RT arm (54.0%; 95% CI, 53.9%-54.1%) compared with the RT arm (46.0%; 95% CI, 45.9%-46.1%), with a hazard ratio for death of 0.82 (95% CI, 0.68-0.98; P = .04). After adjusting for prognostic factors, CT-RT continued to be significantly superior to RT for DFS and OS. There was a higher incidence of acute hematological adverse effects in the CT-RT arm. CONCLUSIONS AND RELEVANCE: Chemoradiotherapy using weekly cisplatin results in significantly better DFS and OS compared with RT in women with stage IIIB squamous cell carcinoma of the uterine cervix. This study provides level 1 evidence in the largest clinical trial reported so far in favor of concurrent weekly cisplatin chemotherapy in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00193791.

Locally advanced cervical cancer: A study of 5-year outcomes.

BACKGROUND: Cervical cancer is the second most common cancer among Indian women. This present retrospective study was conducted to report patient outcomes with locally advanced cervical cancer treated in the year 2010. MATERIALS AND METHODS: Case records of cervical cancer patients registered from January 1, 2010, to December 31, 2010 were retrieved. A total of 1200 patients were registered, of which 583 received either definitive or adjuvant radiotherapy (RT). Of these, 345 patients who received complete treatment at our hospital were included for outcome analysis. Descriptive statistics were used to summarize patient- and treatment-related variables, and Kaplan-Meier analysis was performed for survival analysis. RESULTS: The median age was 56 years (range: 33-90). Squamous carcinoma was the most common histology (91.4%) and the majority were FIGO Stage III (45.4%). Median follow-up of the cohort was 44 months (1-85 months). The 5-year disease-free survival (DFS) across stages was 50%. Most important predictor of DFS was FIGO staging (Stage II vs. Stage III: 62% vs. 45%) and use of concurrent chemoradiotherapy (CTRT) l (RT vs. CTRT: 32% vs. 57%, respectively). Patients aged >70 years had a significantly poor DFS at 5 years; however, did not have any effect on survival. Grade 3 or more late toxicity was seen in only 5% of the patients. CONCLUSION: Five-year DFS of 62% and 45% of Stage II and III patients treated under routine care represents comparable stage-matched results to the rest of the world, respectively.

Outcomes of advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy.

BACKGROUND: Ovarian cancer is the fourth most common cancer in Indian women. Majority of these are epithelial ovarian cancers (EOCs), most of which present in advanced stage. Women with poor performance status and/or those unlikely to achieve optimal debulking at upfront surgery, benefit from neoadjuvant chemotherapy (NACT) followed by interval cytoreduction, with lesser surgical morbidity and equal survival rates as compared to primary cytoreduction. METHODOLOGY: This was a retrospective analysis of patients with advanced ovarian cancer, treated with NACT followed by interval debulking surgery at Tata Memorial Hospital from January 2014 to December 2014. RESULTS: Epithelial cancers constituted 84.4% (n = 406) of all cases of ovarian malignancies. Of these, overwhelming majority (84.3%, n = 342) were in the advanced stage. Sixty percent of all EOC patients received NACT. The mean baseline serum CA-125 level in women treated with NACT was 4294.7 U/ml (range, 11-151,200 U/ml). The median number of NACT cycles (paclitaxel + carboplatin) was 3. Optimal cytoreduction was achieved in 81.5% cases. The rates of Grade 3 or 4 intraoperative and postoperative complications were 4% each. The median postoperative stay was 5 days and the median time between surgery and adjuvant chemotherapy was 20 days. The median progression-free survival (PFS) was 15.15 months (95% confidence interval [CI]: 12.95-17.34), and the median overall survival (OS) was 34.73 months. Multivariate analysis revealed that optimal cytoreduction (hazard ratio [HR] = 2.04 [95% CI: 1.15-3.62]; P = 0.015) and number of NACT cycles (3 vs. >3; HR = 1.51 [95% CI: 1.06-2.16]; P = 0.022) were significantly associated with PFS, and optimal cytoreduction (HR = 3.21 [95% CI: 1.53-6.73]; P = 0.002) and ECOG status (0-1 vs. ≥2; HR = 2.64 [95% CI: 1.25-5.55]; P = 0.011) with OS. CONCLUSIONS: High rates of optimal cytoreduction were achieved at interval cytoreductive surgery after NACT, with acceptable surgical morbidity, early start of adjuvant chemotherapy, and survival outcomes comparable to international standards.

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial.

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

National Cancer Grid of India Consensus Guidelines on the Management of Cervical Cancer.

Standard guidelines for the management of early and locally advanced cervical cancer are available from various academic consortiums nationally and internationally. However, implementing standard-of-care treatment poses unique challenges within low- and middle-income countries, such as India, where diverse clinical care practices may exist. The National Cancer Grid, a consortium of 108 institutions in India, aims to homogenize care for patients with cervical cancer by achieving consensus on not only imaging and management, but also in addressing potential solutions to prevalent challenges that affect the homogenous implementation of standard-of-care treatment. These guidelines therefore represent a consensus statement of the National Cancer Grid gynecologic cancer expert group and will assist in homogenization of the therapeutic management of patients with cervical cancer in India.

Determinants of compliance in a cluster randomised controlled trial on screening of breast and cervix cancer in Mumbai, India. 1. Compliance to screening.

OBJECTIVES: This study aims to investigate the efficacy of screening by low-cost technology in down-staging and reducing mortality due to breast and cervix cancer. METHODS: The present trial is a community-based, cluster randomised controlled cohort study on screening for breast and cervix cancers (clinical breast examination and visual inspection of the cervix after application of 4% acetic acid). Univariate and multivariate logistic regression analyses are conducted to identify the predictors of participation in screening. RESULTS: The average compliance is 71.43 and 64.93% for breast and cervix cancer screening, respectively, with the highest compliance in round 1. At the end of 3 screening rounds, 94 and 84% of the eligible women were screened at least once for breast and cervix cancer, respectively. Younger women, women from other than Hindu and Muslim communities, school level-educated women, women belonging to lower-income families, Marathi-speaking women, married women and women who had previously consulted for any breast or gynaecological complaints had higher compliance to participation in screening. CONCLUSIONS: Good compliance rates to screening have been demonstrated in the trial, reflecting acceptance of the study by the society, which has implications while translating the trial into a programme.

Determinants of compliance in a cluster randomised controlled trial on screening of breast and cervix cancer in mumbai, India. 2. Compliance to referral and treatment.

OBJECTIVES: The study aims to investigate the efficacy of screening by low-cost technology in down-staging and reduction of mortality due to breast and cervix cancer. METHODS: The present trial is a community-based, cluster randomised controlled cohort study on screening for breast and cervix cancers (clinical breast examination and visual inspection of the cervix after application of 4% acetic acid). Univariate and multivariate logistic regression analyses are conducted to identify the predictors of compliance to referral among screen-positive women and to treatment among cancer cases. RESULTS: The compliance to diagnostic investigations is 73% among screen-positive women referred for breast cancer and 79% among women referred for cervix cancer. Younger women, women working in service or being self-employed, school level-educated women, mother tongue Marathi, participation in screening in all 3 rounds and women referred as screen positive for cervix cancer had higher compliance to diagnostic investigations. The compliance to treatment completion is higher in women diagnosed with breast cancer, at 95%, compared to 86% for cervix cancers and 81% for cervix pre-cancers. CONCLUSIONS: Good compliance rates along with a proper system of referral, further investigations, confirmation of diagnosis and treatment as demonstrated in this trial are crucial for successful screening programmes.

Dose-volume correlation of cumulative vaginal doses and late toxicity after adjuvant external radiation and brachytherapy for cervical cancer.

PURPOSE: To investigate dose-response relationship between vaginal doses and long-term morbidity. METHODS AND MATERIALS: Patients receiving adjuvant pelvic (chemo) radiation and brachytherapy for cervical cancer from January 2011 to December 2014 were included. Baseline vaginal length was determined clinically and from imaging at BT planning. Dose points were defined along mucosa and at 5 mm depth at 12, 3, 6, and 9 'o' clock positions at every 2 cm from apex to introitus. Cumulative equivalent doses in 2 Gy were calculated. Vaginal stenosis was reported in reference to baseline length according to CTCAE version 3.0. Receiver operator characteristics curve was used to identify dose thresholds for univariate and multivariate analysis. RESULTS: Overall, 78 women with median age of 49 (32-71) years were included. The median dose at vaginal apex mucosa and 5 mm depth was 118 Gy3 (78-198) and 81 Gy3 (70-149) respectively. At median follow-up of 36 (18-60) months, vaginal stenosis ≥25%, and grade ≥ II telangiectasia was observed in 33.3% and 45.7%, respectively. On receiver operator characteristics analysis, apical mucosal dose >142 Gy3 and recto-vaginal point dose >86 Gy3 predicted for stenosis on univariate (p = 0.02, p = 0.06) and multivariate analysis (p = 0.04). The probability of stenosis increased from 32% at 70 Gy3, 38% at 80 Gy3, and 45% at 90 Gy3 rectovaginal point dose. No correlation was observed between vaginal doses and telangiectasia and vaginal stenosis and sexual quality of life. CONCLUSION: Vaginal apex mucosal dose >142 Gy3 independently predicts for vaginal stenosis.

Squamous carcinoma coexistent with teratoma of ovary: a clinicopathological study of 12 cases diagnosed over a 10-year period at a tertiary cancer referral center.

BACKGROUND: Somatic malignancy in an ovarian teratoma including a squamous carcinoma (SCC) is rare. Clinicopathological features of 12 ovarian teratomas with coexistent SCCs are presented. MATERIALS AND METHODS: Over a 10-year-period, 12 ovarian teratomas with coexistent SCCs were reviewed and analyzed. RESULTS: The age range was 31-68 years (median, 49), and the tumor size (nine cases) varied from 10 to 18 cm (mean, 12.4). Stage-wise (10 cases), 7 cases (70%) were in stage I; a single case (10%) in stage II, and two (20%) cases were in stage III. Microscopically, all 12 tumors revealed mature teratoma with SCC, as a discrete tumor (6, 50%), or arising from the epithelium of the teratoma in six (50%) cases. SCC component was commonly moderately differentiated (eight cases) or poorly differentiated (three cases). P63 immunostaining reinforced squamous differentiation in a single poorly differentiated SCC and CK5/6 in another tumor. All patients underwent surgery. Two cases revealed positive lymph nodes and contiguous colonic involvement. Three patients (stages II and III) underwent adjuvant chemotherapy (CT). Outcomes (seven patients) (3-58 months) included five patients who are free-of-disease (all stage I) and two patients who are alive-with-disease (stages I and III). CONCLUSION: SCC and coexistent ovarian teratomas are rare. Most cases present at an early stage, commonly in perimenopausal women. Teratomas occurring in such patients should be optimally sampled for SCC. Teratomas coexistent with SCC are invariably mature-type. P63 is useful in differentiating poorly differentiated SCC from germ cell tumor components. Surgery forms the treatment mainstay. Adjuvant CT may be offered in high-stage that forms as an adverse prognostic parameter.