The BRCA mutation spectrum among breast and ovarian cancers in India: highlighting the need to screen BRCA1 185delAG among South Indians.

Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers. We also aimed to identify population specific BRCA1/2 mutation hotspots, to enable the development of more affordable testing strategies. We identified 921 patients with breast and ovarian cancer who underwent mutation testing. The target enrichment was followed by targeted NGS in 772 patients and an allele-specific PCR (ASPCR) based genotyping for BRCA1:c.68_69delAG (or 185delAG), was carried out in 149 patients. We identified 188 (20.4%) patients with BRCA1/2 variants: 118 (62.8%) with pathogenic/likely pathogenic and 70 (37.2%) with VUS. The 185delAG was identified as a recurrent mutation in the Southern Indian population, accounting for 24.6% of the pathogenic variants. In addition, a family history of breast, ovary, pancreas, or prostate (BOPP) cancer was found to be associated with an increased risk of identifying a deleterious BRCA1/2 variant [OR = 2.11 (95% CI 1.45-3.07) p ≤ 0.001]. These results suggest that Targeted NGS is a sensitive and specific strategy for BRCA testing. For Southern Indian patients, a two-tiered approach can be considered: Initial screening with ASPCR for BRCA1 185delAG followed by NGS for those testing negative. Expanding the gene panel and identifying other population-specific mutation hot spots is a promising area with potential for improvements in testing and treatment strategies.

Adrenocortical Carcinoma: a Therapeutic Challenge - 44 Cases from a Single Tertiary Care Center in India.

This study was conducted among patients with adrenocortical carcinoma (ACC) to analyze their clinico-pathological profile, management outcomes, and risk factors for local recurrence, systemic metastasis, and survival. The data of patients with ACC who were managed at a single institution between January 2004 and December 2016 was retrospectively collected and analyzed using STATA 13.1. Forty-four patients with a diagnosis of ACC were included in the study. The mean age at presentation was 38.5 ± 14.6 (9-74) with a male preponderance. Functioning tumors represented 59.1% (n = 26), cortisol being the most common hormone secreted. Forty patients (90.9%) underwent surgery, 14 (35%) of whom required an en bloc resection of adjacent organs. Fifteen (37.5%) received radiation (RT) to the postoperative bed while chemotherapy and mitotane were administered in 12 (27.3%) and 9 (20.5%) respectively. The mean follow-up was 34.3 ± 32.7 months. Twelve (30%) patients developed local recurrence, 21 (55.3%) had systemic metastasis, and 15 (34.1%) expired. The mean 1-year and 5-year overall survival rates were 77% and 65.7% respectively. On multivariate analysis, patients with ENSAT stage III/IV were significantly associated with local recurrence (p = 0.011) and metastasis (p = 0.037). Age > 50 (p = 0.003) and ENSAT III/IV (p = 0.017) were significantly associated with mortality on univariate analysis but not on multivariate analysis. In our study population, patients presented at a younger age with a male preponderance. Ninety percent underwent surgery, a subset (35%) requiring resection of adjacent organs to ensure R0 resection. Patients presenting at ENSAT stage I/II have better outcomes.

Aggressive malignant phyllodes tumor of breast with omental metastases - A case report.

Distant metastasis from malignant Phyllodes tumour (PT) is rare. They generally metastasize to the lung, bone, pleura, and liver. We present a very rare case of a 25-year-old woman with intraabdominal metastases from malignant phyllodes tumour of the breast. She presented with left breast lump and the biopsy was Phyllodes tumour. She underwent a two staged surgery; left modified radical mastectomy followed by left latissimus dorsi musculocutaneous flap cover. She received adjuvant radiation therapy to left chest wall. Following which she developed intrabdominal mass which was proven to be metastasis from Phyllodes tumour. She was then advised palliative chemotherapy. Malignant Phyllodes with distant metastases has a dismal prognosis. We propose it is preferable to have a CT Thorax and Abdomen as a staging workup for patients with malignant PT to identify those with poor prognosis.

A new strategy for craniospinal axis localization and adaptive dosimetric evaluation using cone beam CT.

BACKGROUND AND AIM: Computational complexities encountered in craniospinal irradiation (CSI) have been widely investigated with different planning strategies. However, localization of the entire craniospinal axis (CSA) and evaluation of adaptive treatment plans have traditionally been ignored in CSI treatment. In this study, a new strategy for CSI with comprehensive CSA localization and adaptive plan evaluation has been demonstrated using cone beam CT with extended longitudinal field-of-view (CBCTeLFOV). MATERIALS AND METHODS: Multi-scan CBCT images were acquired with fixed longitudinal table translations (with 1 cm cone-beam overlap) and then fused into a single DICOM-set using the custom software coded in MatLab™. A novel approach for validation of CBCTeLFOV was demonstrated by combined geometry of Catphan-504 and Catphan-604 phantoms. To simulate actual treatment scenarios, at first, the end-to-end workflow of CSI with VMAT was investigated using an anthropomorphic phantom and then applied for two patients (based on random selection). RESULTS: The fused CBCTeLFOV images were in excellent agreement with planning CT (pCT). The custom developed software effectively manages spatial misalignments arising out of the uncertainties in treatment/setup geometry. Although the structures mapped from pCT to CBCTeLFOV showed minimal variations, a maximum spatial displacement of up to 1.2 cm (and the mean of 0.8 ± 0.3 cm) was recorded in phantom study. Adaptive plan evaluation of patient paradigms showed the likelihood of under-dosing the craniospinal target. CONCLUSION: Our protocol serves as a guide for precise localization of entire CSA and to ensure adequate dose to the large and complex targets. It can also be adapted for other complex treatment techniques such as total-marrow-irradiation and total-lymphoid-irradiation.

Rare Cause of Stricture Esophagus-Sarcoma: A Case Report and Review of the literature.

Adenocarcinoma and squamous cell carcinoma account for the vast majority of oesophageal malignancies. Other malignancies known to occur in the oesophagus include melanoma, sarcoma, and lymphoma. Among the sarcomas, carcinosarcoma is the commonest with both carcinomatous and sarcomatous elements followed by leiomyosarcoma of mesenchymal origin. Other sarcomas reported in the literature are liposarcoma, synovial sarcoma, myxofibrosarcoma, Ewing's sarcoma, granulocytic sarcoma, histiocytic sarcoma, schwannoma rhabdomyosarcoma, and epithelioid sarcoma. We report a case of malignant spindle cell tumour of oesophagus. Sarcomas of esophagus present as a polypoid exophytic soft tissue mass. Our patient presented with a stricture which is a rare presentation. Locally aggressive treatment with surgery is beneficial, and local palliative treatment including radiotherapy is worthwhile.

Lobular carcinoma metastasis to endometrial polyp unrelated to tamoxifen. Report of a case and review of the literature.

Endometrial polyps are rare sites for metastatic breast carcinoma. Such cases have mostly been reported in tamoxifen-related polyps. We report a case of lobular carcinoma with metastasis to an endometrial polyp in a patient with no history of tamoxifen therapy. The histological features of the polyp in our case closely mimicked those of tamoxifen-related polyps, emphasizing the fact that although characteristic-these features are not specific for tamoxifen. This case also reiterates the need for careful evaluation of endometrial polyps, since inconspicuous deposits of lobular carcinoma can easily be missed.

Transient asymptomatic bradycardia in patients on infusional 5-fluorouracil.

The incidence of 5-fluorouracil (5-FU)-related cardiotoxicity seems to be dosage and schedule dependent. Although various other cardiac events have been reported in literature, a series of patients having transient asymptomatic bradycardia has not been reported in the literature as yet. We report such a series of patients who had transient asymptomatic bradycardia after being treated with continuous infusion 5-FU. We plan to do a Holter study during the period of bradycardia in subsequent patients and this may throw more light on the issue.

Endoluminal formalin application for haemorrhagic radiation proctitis.

BACKGROUND: Radiation proctitis is a common complication following radiation therapy for pelvic malignancies. This is associated with significant morbidity which adversely affects the quality of life. Local application of formalin has been used effectively in the treatment of radiation proctitis. METHODOLOGY: Thirty patients with haemorrhagic radiation proctitis who underwent endoluminal application of 4% formalin between January 1998 to October 2002 were followed up prospectively to assess the efficacy of the treatment. RESULTS: The follow up ranged from 5 to 36 months (mean 18.1 months). Nineteen (63.3%) patients had complete response to formalin application while 7 (23.3%) patients had partial response. There were 4 (13.3%) failures. No procedure related complication was observed. CONCLUSION: Local application of formalin is a simple, safe, inexpensive and fairly effective outpatient treatment modality for chronic radiation proctitis.

A multicenter phase II study of gemcitabine, paclitaxel, and cisplatin in chemonaïve advanced ovarian cancer.

OBJECTIVES: The objectives of this multicenter phase II study were to evaluate the effects of gemcitabine-paclitaxel-cisplatin combination chemotherapy on response rate, survival, and toxicity in patients with advanced epithelial ovarian cancer (AEOC). METHODS: Chemonaive AEOC patients with bidimensionally measurable disease or an elevated serum cancer antigen 125 level received cisplatin (70 mg/m(2)) on day 1 and paclitaxel (80 mg/m(2)) and gemcitabine (1000 mg/m(2)) on days 1 and 8, every 3 weeks. RESULTS: Between October 2000 and September 2001, 46 patients were enrolled. Sixteen patients underwent debulking surgery prior to chemotherapy. In 45 evaluable patients, overall response rate was 64.4% (7 CR and 22 PR). Median time-to-progression was 13.4 months (95% CI, 9.6-17.4 months); median progression-free survival was 12.3 months (95% CI, 8.8-15.6 months); median overall survival was 26.0 months (95% CI, 18 months-not reached); and 1-year survival was 74% (95% CI, 60-88%). The relative dose intensities of gemcitabine, paclitaxel, and cisplatin were 81.4%, 80.2%, and 89.8%, respectively. Grade 3/4 neutropenia was the predominant hematologic toxicity observed (73.9% of patients) followed by grade 3/4 leukopenia (56.5%), anemia (45.7%), thrombocytopenia (23.9%), and febrile neutropenia/neutropenic sepsis (26.1%). The predominant grade 3 nonhematologic toxicities were alopecia (43.5%) and diarrhea (19.6%). Grade 4 nonhematologic toxicities were nausea/vomiting, constipation, and uremia (2.2% each). Two treatment-related deaths occurred (neutropenic sepsis and uremia). CONCLUSION: Gemcitabine-paclitaxel-cisplatin combination chemotherapy is active with manageable toxicity in chemonaive patients with advanced ovarian cancer and should be explored in larger phase III trials.