18F-fluorodeoxyglucose PET-CT-guided pelvic chemoradiation therapy using helical tomotherapy for locally advanced carcinoma cervix without para-aortic nodal disease: Clinical and patient-reported outcomes from a prospective phase 2 study.

INTRODUCTION: Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic information from 18 fluro-deoxyglucose positron emission tomography combined with contrast-enhanced computerized tomography (FDG PET-CT) may potentially augment treatment decision-making for LACC. This study ascertained FDG-PET CT influence on chemoradiation therapy (CTRT) decisions in LACC. We report oncologic and patient-reported outcome measures (PROMs). METHODS: FDG PET-CT scans were reviewed independently by two nuclear medicine specialists and two radiation oncologists. Pelvic CTRT plan digressions were documented and therapy was adapted accordingly. Pelvis radiation (50 Gy/25#/5 weeks) using tomotherapy with weekly cisplatin was used in node-negative disease. Dose-escalated simultaneous integrated boost (SIB) 60 Gy/25#/5 weeks was delivered to involved pelvic nodes. All received brachytherapy. Post-treatment PET-CT scans were at 6 months. Functional assessment of cancer therapy scores were calculated at baseline, treatment completion, 3 months, 1 year and 3 years. RESULTS: Between November 2015 and January 2018, 85 patients were screened, and 77 consented. Extrapelvic disease was seen in 12 (16%) patients (9 para-aortic nodes, 2 distant metastases and 1 synchronous carcinoma breast); 60 patients were included in the final analysis. Decision changes were seen in 10/77 (13%) screened, 8/60 (13%) included and 32 (53.3%) received SIB. Post-treatment, 27 (45%) had grade 2 GI/GU/GYN toxicity, one (2%) had grade 3 GI and five (8.3%) had grade 3 neutropenia. At median overall survival of 54.2 months (95% CI 52.8-58.3), 5-year local failure, pelvic nodal and para-aortic nodal-free survival were 86.8% (95% CI 78.0-96.6), 85.2% (95% CI 76.1-95.3) and 85.2% (95% CI 76.2-95.4). Functional assessment of cancer therapy trial outcome index (FACT TOI) improved by 10.43 at 3 months with no further decline. Grade 3 toxicity was noted for abdominal pain in one (1.7%), cystitis in four (6.7%) and lymphoedema in one (1.7%) at 5 years. CONCLUSION: PET-CT resulted in major decision changes in 13%. PET-adapted CTRT was associated with acceptable toxicity, encouraging long-term survival and improvement in PROMS.

Multidisciplinary management of ovarian germ cell tumours-a single institutional study from India.

BACKGROUND: Ovarian germ cell tumours constitute a heterogeneous group of neoplasm with malignant potential being seen in 5% of cases. There is limited data on treatment outcomes of patients with malignant ovarian germ cell tumours (MOGCT). Here, we present our hospital audit of patients with MOGCT. MATERIAL AND METHODS: This is a retrospective data review of patients with MOGCT treated between May 2011 and December 2019. Patients were treated with staging laparotomy and adjuvant chemotherapy, wherever applicable. Surveillance was allowed for those at low risk for recurrence. Clinicopathologic features and treatment details were recorded, and survival analysis was performed. RESULTS: Sixty-five patients with a median age of 25 years (range: 11-52 years) were treated during the study period. The most common histology was immature teratoma in 35.3% of cases. International Federation of Gynecology and Obstetrics stage IC was the most common stage of presentation (47%). Surveillance was advised for 12.3% of cases. Systemic therapy was given in 51 (78%) patients. At a median follow-up of 46 months (range: 1-109 months), the median progression-free survival (PFS) was not reached. Five-year PFS was 79.3% (95% CI: 65.8-88). The most common toxicity was febrile neutropenia (22%) among those who received systemic therapy. CONCLUSION: Immature teratoma was the most common histology in our series. The majority presented in the early stage. MOGCT is a highly curable disease with surgery and systemic therapy.

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. METHODS: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. CONCLUSION: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.