Killer cell immunoglobulin-like receptor (KIR) gene contents: Are they associated with cervical cancer?

Killer cell immunoglobulin-like receptors (KIRs) are required for natural killer cell function against virus-infected cells or tumor cells. KIR gene content polymorphisms in Indian women with cervical cancer (CaCx) remain unexplored. Hence, we analyzed the frequencies of KIR genes, KIR haplotypes, and Bx subsets to draw their association with CaCx. The polymerase chain reaction-sequence-specific primer method was used for KIR genotyping in three groups of women: healthy controls (n = 114), women with human papillomavirus (HPV) infection (n = 70), and women with CaCx (n = 120). The results showed that the frequency of KIR2DS5 was significantly higher in women with CaCx compared to women with HPV infection (p = 0.02) and healthy controls (p = 0.01). Whereas the frequency of KIR2DL5B was significantly higher in healthy controls than in women with HPV infection (p = 0.02). The total number of activating KIR genes was higher in women with CaCx than in healthy controls (p = 0.006), indicating their positive association with CaCx. Moreover, the C4T4 subset was higher in women with CaCx than in women with HPV infection, though not significant. In conclusion, our findings highlight KIR2DS5, the C4T4 subset, and activating KIR genes are susceptible factors or positively associated with CaCx. Besides KIR2DL5B, this study also reported for the first time significantly high frequency of KIR2DL1 in healthy controls, indicating its possible protective association against CaCx. Further, significantly high frequency of KIR2DL3 observed in HPV-infected women might be also a promising biomarker for viral infections. Thus, the study confirms the association of KIR genes with cervical cancer in women with HPV infection.

Secondary cytoreduction in platinum sensitive relapsed ovarian cancer: an individual patient level meta-analysis.

OBJECTIVE: To synthesize the role of secondary cytoreduction in recurrent ovarian cancer from the results of randomized studies. METHODS: We conducted a meta-analysis of randomized controlled trials which compared secondary cytoreductive surgery versus no surgery in patients with platinum sensitive relapsed ovarian cancer. Individual patient data for overall survival and progression free survival were manually extracted from published survival curves, for whole study populations and subgroups based on completeness of surgical resection and bevacizumab use, using WebPlotDigitizer software. Overall survival and progression free survival curves for each study and the combined population were reconstructed from extracted data. RESULTS: Three studies with 1249 patients were included, of whom complete resection was achieved in 427 (34.2%) patients. In individual patient data analysis of the whole study population with 562 deaths, there was no significant difference in overall survival between the surgery and no surgery groups (median 52.8 vs 52.1 months, respectively, hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.80 to 1.11; p=0.5) but the surgery group had significantly longer progression free survival compared with the no surgery group (median 18.3 vs 14.4 months, respectively, HR 0.70, 95% CI 0.62 to 0.80; p<0.001). In subgroup analyses, overall survival was significantly longer in the complete cytoreduction subgroup compared with the no surgery group (median 62.0 vs 52.1 months, respectively, HR 0.70, 95% CI 0.57 to 0.92; p<0.001) while overall survival was significantly worse in the incomplete cytoreduction subgroup compared with the no surgery group (median 34.2 vs 52.1 months, respectively, HR 1.72, 95% CI 1.38 to 2.14; p<0.001). In the no bevacizumab subgroup, there was no significant overall survival difference between the surgery and no surgery groups (median 49.3 vs 47.0 months, HR 0.86, 95% CI 0.67 to 1.10; p=0.25). CONCLUSIONS: Secondary cytoreductive surgery among women with platinum-sensitive relapsed ovarian cancer did not lead to significant benefit in overall survival although it increased progression free survival. However, overall survival was significantly longer among patients in whom complete cytoreduction was possible compared with no surgery.

Role of education and income on disparities of time-to-treatment initiation and its impact on cervical cancer survival.

Background: In India, cervical cancer is the second-leading cause of cancer incidence among women. Socioeconomic factors play a vital role in cervical cancer survival. Objectives: This study assessed the role of education and income on disparities in time-to-treatment initiation (TTI) and its impact on cervical cancer survival. Materials and Methods: This was a retrospective facility-based record study conducted among newly treated cervical cancer patients registered in a tertiary medical care center in Mumbai between 2014 and 2016. Adjusted hazard ratio with a 95% confidence interval was reported. Results: In total, 1947 cervical cancer patients with a mean age of 52.89 (±10.55) years were included. The average number of days for TTI among highly educated patients was 27 versus 35 days for patients with no formal education. An increasing trend in survival was observed as education levels shift from no formal to higher education category (75.54%, 77.30%, and 85.10%, P = 0.01). All cause mortality was lower in cervical cancer patients with secondary education and above than illiterates (hazard ratio [HR] = 0.63, P < 0.01), among those with higher income (HR = 0.78, P = 0.04) than lower income and among who started on treatment within 30 days (HR = 0.90, P = 0.29) than patients who started treated after 30 days. Conclusions: Inferior survival is found for cervical cancer patients with lower education and income and who initiated treatment after 30 days. Hence, it is important to improve awareness and screening activities, especially among the lower socioeconomic groups, for early diagnosis and better treatment outcomes.

Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future.

BACKGROUND: Cisplatin-based concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. In view of the difficulties associated with implementation of standard radiation protocols in low- and middle-income countries and the associated toxicities of chemoradiation, neoadjuvant chemotherapy followed by surgery has been tried as an alternative treatment for locally advanced cervical cancer. METHODS: A comprehensive review was undertaken of the existing literature, caveats and potential avenues of neoadjuvant chemotherapy followed by surgery compared with chemoradiation in locally advanced cervical cancer. RESULTS: Randomized studies conducted in the pre-chemoradiation era comparing neoadjuvant chemotherapy followed by surgery with definitive radiotherapy alone showed favorable outcomes with the chemo-surgical approach. However, contemporary studies evaluating the role of neoadjuvant chemotherapy followed by surgery have failed to establish this approach as the standard. About 25-30% of patients who undergo neoadjuvant chemotherapy remain inoperable and require definitive chemoradiation. A similar proportion of patients would require adjuvant (chemo)radiation after neoadjuvant chemotherapy followed by surgery, resulting in excessive morbidity. Evaluation of time trends across the past few decades reveals that the advancements in delivery of radiation (external beam and brachytherapy) have translated into improvement in outcomes for locally advanced cervical cancer, while a similar trend was not observed for surgery or chemotherapy. CONCLUSION: Neoadjuvant chemotherapy followed by surgery cannot be considered a standard of care in patients with locally advanced cervical cancer. This approach needs further clinical research to generate robust high-quality evidence especially for the sub-sets that might potentially benefit in terms of survival, toxicity and quality of life, against the gold standard treatment of concomitant chemoradiation.

Surgery for cervical cancer: consensus & controversies.

Surgery plays an important role in the management of early-stage cervical cancer. Type III radical hysterectomy with bilateral pelvic lymph node dissection using open route is the standard surgical procedure. There is level I evidence against the use of laparoscopic/robotic approach for radical hysterectomy for cervical cancer. Emerging data support the use of sentinel lymph node biopsy and nerve sparing radical hysterectomy in carefully selected patients with early-stage disease. In locally advanced cervical cancer patients, the use of neoadjuvant chemotherapy (NACT) followed by radical surgery yields inferior disease-free survival compared to definitive concurrent chemoradiation therapy. Therefore, definitive concurrent chemoradiation is the standard treatment for locally advanced disease. Fertility preserving surgery is feasible in highly selected young patients. Role of less-radical surgical procedures in patients' with low-stage disease with good prognostic factors is under evaluation.

Implications of the revised cervical cancer FIGO staging system.

The 2018 revised International Federation of Gynaecology and Obstetrics (FIGO) staging of cervical cancer has brought about a paradigm shift by offering the option of adding imaging and pathology to clinical staging. This makes it applicable to all types of resource situations across geographies with implications for all stakeholders, including gynaecologists, gynaecologic oncologists, radiologists, pathologists and radiation and medical oncologists. The new staging classification has more granularity, with three sub-stages of stage IB and a new category of stage IIIC for all cases with lymph node (LN) involvement. The major limitations of clinical staging were inaccurate assessment of tumour size and inability to assess pelvic and para-aortic LNs with the limited investigations permitted by FIGO to change the stage. This resulted in understaging of stages IB-III, and overstaging of stage IIIB, which has been largely overcome by incorporating imaging findings. Although any imaging modality can be used, magnetic resonance imaging appears to be the best imaging modality for early-stage disease owing to its better soft-tissue resolution. However, the use of contrast-enhanced computed tomography or ultrasonography are also feasible options, depending on the availability and resources. But wherever pathological evaluation is possible, it supersedes clinical and radiological findings.

Outcomes of Elective Major Cancer Surgery During COVID 19 at Tata Memorial Centre: Implications for Cancer Care Policy.

BACKGROUND: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. METHODS: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. FINDINGS: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV - VI).Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties.Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection. INTERPRETATION: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India.

Evaluation of outcomes in patients of cervical Cancer with lower one third vaginal involvement: A single institutional experience.

OBJECTIVE(S): The objective of this study was to evaluate the clinical outcomes and prognostic factors affecting survival of cervical cancer patients presenting with lower third vaginal involvement. MATERIALS/METHODS: The patients with histologically proven invasive cervical cancer with clinical FIGO-2009 stage IIIA and IIIB with lower one-third vaginal involvement, treated with radio (chemo) therapy between 2010 and 2016 at our institution were retrospectively analyzed. RESULTS: There were 118 cervical cancer patients with lower third vaginal involvement with median age of 56.5 years (Range: 33-77 years). Forty-five patients were of FIGO stage IIIA, 73 patients staged as stage IIIB at diagnosis with predominant squamous histology. At a median follow up of 30 months, 12 patients (10.1%) developed local vaginal recurrences and 4 patients (3.3%) had developed loco regional recurrences, 27 patients (23%) developed distant and 2 patients developed loco-regional and distant relapses. The 3- year DFS and OS rates were 61.5% and 69.8% respectively. The 3-year DFS and OS of patients with IIIA was significantly better than IIIB patients (71% vs 56%, p: 0.02 and 76% vs 66%, p: 0.01 respectively) on univariate analysis. Concurrent chemotherapy and absence of persistent disease emerged as independent predictors of survival on multi-variate analysis. CONCLUSION: The outcome of patients with FIGO IIIA is better than IIIB with lower vaginal involvement. Elderly patients, patients not receiving concomitant chemotherapy and presence of residual disease at BT are associated with poorer outcomes.

Enhanced Recovery After Surgery (ERAS) in gynecologic oncology: an international survey of peri-operative practice.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) programs have been shown to improve clinical outcomes in gynecologic oncology, with the majority of published reports originating from a small number of specialized centers. It is unclear to what degree ERAS is implemented in hospitals globally. This international survey investigated the status of ERAS protocol implementation in open gynecologic oncology surgery to provide a worldwide perspective on peri-operative practice patterns. METHODS: Requests to participate in an online survey of ERAS practices were distributed via social media (WhatsApp, Twitter, and Social Link). The survey was active between January 15 and March 15, 2020. Additionally, four national gynecologic oncology societies agreed to distribute the study among their members. Respondents were requested to answer a 17-item questionnaire about their ERAS practice preferences in the pre-, intra-, and post-operative periods. RESULTS: Data from 454 respondents representing 62 countries were analyzed. Overall, 37% reported that ERAS was implemented at their institution. The regional distribution was: Europe 38%, Americas 33%, Asia 19%, and Africa 10%. ERAS gynecologic oncology guidelines were well adhered to (>80%) in the domains of deep vein thrombosis prophylaxis, early removal of urinary catheter after surgery, and early introduction of ambulation. Areas with poor adherence to the guidelines included the use of bowel preparation, adoption of modern fasting guidelines, carbohydrate loading, use of nasogastric tubes and peritoneal drains, intra-operative temperature monitoring, and early feeding. CONCLUSION: This international survey of ERAS in open gynecologic oncology surgery shows that, while some practices are consistent with guideline recommendations, many practices contradict the established evidence. Efforts are required to decrease the variation in peri-operative care that exists in order to improve clinical outcomes for patients with gynecologic cancer globally.

Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India.

There are few comprehensive studies from Asia on clinicopathologic features of mismatch repair (MMR)-deficient endometrial carcinomas, including rarely from our country. One hundred and four cases of endometrial carcinomas were tested for four MMR proteins by immunohistochemistry. Among 50 MMR-deficient (MMRd) tumors(48%), age-range was 27-68 years(median = 53) and tumor size(n = 34) varied from 1.2-10 cm(average = 4.6). Lower uterine segment(LUS) was involved in 21/31 cases(67.7%). Histopathologically, all cases were endometrioid adenocarcinomas(EMACs), of FIGO grade 2(low-grade)(18 cases) and 3(high-grade)(32 cases), displaying de-differentiated, undifferentiated and lymphoepithelioma(LE)-like patterns, in 24 cases(48%). Tumor infiltration ≥ half of myometrium was seen in 30/44 cases (68.1%); lymphovascular emboli in 19/43 cases(44.1%); and lymph node metastasis in 7/22(31.8%) cases. Uncommonly, clear cell component(n = 2) and focal neuroendocrine differentiation (n = 2) were observed. Immunohistochemically, tumor cells showed paired loss of MLH1 and PMS2 in 33(66%) and MSH2 and MSH6 in 14(28%) cases, along with loss of MSH2 and PMS2, in two and a single case, respectively. Nine patients(18%) were treated for another cancer and 9/33(27.2%) disclosed familial history of cancer. MSH2 was the most frequently lost MMR protein in those cases. Additionally, tumor cells displayed ER positivity in 41/50 cases(82%), PR in 38/41cases(92.6%) and wild-type p53 staining in 24/28 cases(85.7%). Tumor with LE-pattern showed PDLI immunoexpression. Certain clinicopathologic features suggestive for MMRd associated ECs, such as relatively large-sized tumors, involving LUS; especially high-grade, infiltrative EMACs, with undifferentiated/de-differentiated, and LE-like patterns; showing deep muscle invasion, frequent PR immunoexpression and invariably, wild-type p53 immunostaining can be useful in screening cases of Lynch syndrome. This constitutes the first report on these tumors from our country.

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.

Impact of HPV 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy - A prospective observational study.

OBJECTIVE: With an aim to investigate the impact of Human Papilloma Virus (HPV) 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy, we undertook this prospective study. METHODS: Between May 2010 and April 2012, 150 histologically proven cervical cancer patients treated with radio (chemo) therapy were accrued. Cervical biopsies/brushings were collected at pre-treatment, end of treatment and at 3 monthly intervals up to 24months. Quantitative estimation of HPV 16/18 was done using real-time polymerase chain reaction (RT-PCR) and correlated with various clinical end-points. RESULTS: Out of 150 patients accrued, 135 patients were considered for final analysis. Pre-treatment HPV16/18 DNA was detected in 126 (93%) patients, with HPV-16 present in 91%. The mean log (±SD) HPV-16 and HPV-18 viral load at pre-treatment was 4.76 (±2.5) and 0.14 (±2.1) copies/10ng of DNA, respectively. Though significant decline in viral load was observed on follow-ups (p<0.0001); by 9-month follow-up, 89 (66%) patients had persistence of HPV infection. Patients with persistent HPV 16/18 infection had a significantly higher overall and loco-regional relapses [44/89 (49%) and 29/89 (32%)] as compared to HPV clearance by 9months [12/43 (28%) and 5/43 (11%)] with p=0.024 and p=0.02, respectively. Also, persistent HPV infection by 24-month showed a significant impact on loco-regional control (LRC) and recurrence-free survival (RFS). CONCLUSION: In locally advanced cervical cancers treated with radical radio (chemo) therapy, persistent HPV 16/18 infection is significantly high in immediate post-treatment period and correlated with higher loco-regional, overall relapses and was also associated with early relapses.

Poorly differentiated biphasic synovial sarcoma of the vulva, displaying SS18::SSX1 fusion and weak to absent (mosaic) INI1/SMARCB1 immunostaining: A rare case with literature review.

ABSTRACT: Synovial sarcoma (SS) is rarely documented in the female genital tract, especially confirmed by molecular testing for SYT::SSX translocation and TLE1 immunostaining. A 62-year-old lady presented with a progressively increasing lump and pain over her right groin, for 6-month duration. Radiologically, a well-defined, solid-cystic mass was seen involving the right labia with necrotic areas, sparing the underlying muscles and the overlying skin. She underwent a biopsy followed by a surgical excision. Histopathologic examination revealed a spindle cell sarcoma, including tumor cells exhibiting a prominent hemangiopericytomatous pattern. There were focal areas of epithelial differentiation (pseudoglandular) along with areas of round cell morphology and increased mitoses (poor differentiation) in the resected specimen. Immunohistochemically, the tumor cells were diffusely positive for TLE1, patchily positive for pan keratin (AE1/AE3) and EMA, the latter more in the areas of epithelial differentiation, while negative for CD34, SMA, desmin, S100P, and SOX10. INI1/SMARCB1 showed a characteristic weak to absent (mosaic) staining pattern. Furthermore, the tumor displayed SS18::SSX 1 fusion by RT-PCR. This constitutes one of the few reported cases of vulvar SS, confirmed by molecular testing and the first documented vulvar SS showing a mosaic pattern of INI1/SMARCB1 immunostaining. A review of the literature and diagnostic implications are presented herewith.

Longitudinal Costs of Image-Guided Intensity-Modulated Radiation Therapy Versus Three-Dimensional Conformal Radiation: Lessons From Phase III PARCER Trial for Shaping Resource-Stratified Guidelines in Low- and Middle-Income Countries.

PURPOSE: The PARCER trial provided level I evidence for image-guided intensity-modulated radiation therapy (IG-IMRT) in patients with cervical cancer. Further information regarding long-term financial impact is imperative for adoption into the National Cancer Grid of India cervical cancer resource-stratified guidelines. METHODS: Patient data from the PARCER trial were analyzed to evaluate the cost implications of transitioning to IG-IMRT. Lacking differences in outcomes between the three-dimensional conformal radiation (3D-CRT) and IG-IMRT, differences in treatment costs, adverse event incidence, and toxicity management costs were examined. The overall financial impact was estimated by adding the treatment costs, toxicity management, and wage loss. This was extrapolated nationally to determine if a transition to IG-IMRT would be feasible for the Indian health care system. RESULTS: Of the 300 patients in the PARCER trial, 93 faced grades ≥2 adverse events (3D-CRT = 59, IG-IMRT = 34). Patients in the 3D-CRT and IG-IMRT arms spent an average of 2.39 years and 1.96 years in toxicity, respectively. The average toxicity management and the yearly financial impact per patient were, respectively, 1.50 and 1.44 times higher for 3D-CRT patients compared with IG-IMRT patients. Extrapolation to the national level showed that treatment with 3D-CRT led to a 2.88 times higher cost ratio when compared with treatment with IG-IMRT. CONCLUSION: Although the initial costs of IG-IMRT are high, on the basis of longitudinal data, it is financially inefficient to treat with 3D-CRT. Resource-stratified guidelines should include longitudinal health intervention costs rather than solely initial costs for policy decisions to implement advanced radiation technology.

Clinicopathological and Oncological Outcomes of Borderline Mucinous Tumours of Ovary: a Large Case Series.

The objective is to study the clinico-demographic profile, treatment patterns and oncological outcomes in borderline mucinous tumours of the ovary. Retrospective cohort analysis was carried out between January 2017 and December 2019 for patients with a diagnosis of borderline mucinous tumours of the ovary who were treated at our centre. Kaplan-Meier method was used for the estimation of the probability of DFS and OS. Univariate and multivariate analyses based on the Cox proportional hazard model were performed to identify factors associated with DFS and OS. A p-value ≤ 0.05 in a two-tailed test was considered statistically significant. The study population included 75 patients and the median follow-up time for the entire cohort was 24 months. The 5-year DFS for the entire cohort was 79.6% and OS was 90.5%, whereas for stage I disease, 5-year OS was 92.6% as opposed to 60% in the advanced stage. On univariate analysis, only the stage of the disease had a significant association with DFS and OS. Fertility-preserving surgeries had no impact on OS or DFS, and hence, it is suggested that fertility-sparing surgeries may be considered a viable option in young patients with mucinous ovarian tumours. Borderline mucinous tumours of the ovary have excellent survival outcomes and fertility-sparing surgeries should be done whenever feasible.

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.

High-grade endometrial stromal sarcoma displaying immunohistochemical expression of BCOR-A report of two cases of a novel tumor entity.

Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.

Clinical Observations and Outcomes in Advanced Low-Grade Serous Carcinoma of the Ovary: Case Series from a Tertiary Cancer Center.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype of ovarian cancer. We present detailed management of 15 cases of advanced LGSC from a tertiary cancer center of India. Fifteen cases of advanced LGSC who underwent cytoreductive surgery (CRS) were analyzed from a prospectively maintained database. Baseline demographic characteristics, surgical details, and chemotherapy details were recorded. Descriptive statistics were summarized, and progression-free survival (PFS) and overall survival (OS) were estimated. The median age was 37 years. Nine patients had received NACT. All cases were FIGO stage III. Mean PCI was 15. Eleven patients had a completeness of cytoreduction score of 0-1. The median surgical time was 7.5 h; nine patients required multiple gastrointestinal resections. Median blood loss was 2500 ml. Median postoperative ventilation, ICU stay, and hospital stays were 1, 2, and 16 days, respectively. One patient had a grade III complication. Four patients received adjuvant chemotherapy. There was no postoperative mortality at the end of 90 days of surgery. All the patients except one were offered hormonal maintenance therapy. At a median follow-up of 43 months, 4 patients were disease-free, 9 had a recurrence, one died of disease progression, and one was lost to follow-up. Most recurrences were locoregional in the peritoneal cavity or pelvis. Four-year OS and PFS were 71.8% and 29.7%, respectively. Advanced LGSCs occur mostly in young premenopausal women with favorable oncologic outcomes. Optimal CRS is the mainstay of treatment. Relative chemo-resistance and hormone receptor positivity provide an excellent therapeutic opportunity for endocrine therapy.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers.

PURPOSE: To evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. METHODS AND MATERIALS: Seventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. RESULTS: Median age at recurrence was 55 years (Range: 35-73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30-50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. CONCLUSION: The use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.