Meenakshi Thakur

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.

Role of ultrasonography to detect axillary node involvement in operable breast cancer

Prompted by the concern about unnecessary axillary dissections, we prospectively studied the accuracy of clinical examination (CE) and conventional ultrasonography (USG, 7.5 MHz), to diagnose pre-operatively metastatic axillary lymph nodes in 200 operable breast cancer patients. USG had higher specificity (90% vs 77%, P = 0.025) and higher positive predictive value (ppv = 90% vs 76%, P = 0.02) than CE. Together, CE + USG had higher sensitivity (82% vs 58%, P = 0.00005) and higher negative predictive value (npv = 76% vs 58%, P = 0.008) than CE alone. In women < 45 years, CE + USG had higher sensitivity (91% vs 76%, P = 0.037) and npv (89% vs 67%, P = 0.018) than in older women. The sensitivity and npv of CE + USG to detect > 1 positive node were 97% (for both) in women < 45 years compared to 81% and 79% in older women. The high sensitivity of CE + USG (82% for the whole group) is probably due to the higher proportion of young women (median age = 45) in our population. It suggests that using CE + USG to avoid axillary dissection in some patients is feasible.

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 radiologists 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.

Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation for conformal intracavitary brachytherapy in carcinoma of the uterine cervix

PURPOSE Trans-abdominal ultrasonography (US) is capable of determining size, shape, thickness, and diameter of uterus, cervix and disease at cervix or parametria. To assess the potential value of US for image-guided cervical cancer brachytherapy, we compared US-findings relevant for brachytherapy to the corresponding findings obtained from MR imaging. MATERIALS AND METHODS Twenty patients with biopsy proven cervical cancer undergoing definitive radiotherapy with/without concomitant Cisplatin chemotherapy and suitable for brachytherapy were invited to participate in this study. US and MR were performed in a similar reproducible patient positioning after intracavitary application. US mid-sagittal and axial image at the level of external cervical os was acquired. Reference points D1 to D9 and distances were identified with respect to central tandem and flange, to delineate cervix, central disease, and external surface of the uterus. RESULTS Thirty-two applications using CT/MR compatible applicators were evaluable. The D1 and D3 reference distances which represent anterior surface had a strong correlation with R=0.92 and 0.94 (p<0.01). The D2 and D4 reference distances in contrast, which represent the posterior surface had a moderate (D2) and a strong (D4) correlation with R=0.63 and 0.82 (p<0.01). Of all, D2 reference distance showed the least correlation of MR and US. The D5 reference distance representing the fundal thickness from tandem tip had a correlation of 0.98. The reference distances for D6, D7, D8, and D9 had a correlation of 0.94, 0.82, 0.96, and 0.93, respectively. CONCLUSIONS Our study evaluating the use of US, suggests a reasonably strong correlation with MR in delineating uterus, cervix, and central disease for 3D conformal intracavitary brachytherapy planning.

Determinants of Compliance in a Cluster Randomised Controlled Trial on Screening of Breast and Cervix Cancer in Mumbai, India

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.

Percutaneous computed tomography-guided core biopsy for the diagnosis of mediastinal masses

AIM: To describe various approaches of computed tomography (CT)-guided core biopsy and evaluate its ability to obtain adequate tissue for the assessment of mediastinal masses. MATERIALS AND METHODS: Between February 2004 and October 2006, 83 percutaneous CT-guided biopsies of mediastinal lesions were performed on 82 patients under local anesthesia. Coaxial needles were used and minimum of 3-4 cores were obtained. Post-biopsy CT scan was performed and patients observed for any complications. Tissue samples were taken to Pathology Department in formalin solution. RESULTS: From the 83 biopsies, adequate tissue for histological diagnosis was obtained in 80 (96%), and the biopsy was considered diagnostic. Of the 80 diagnostic biopsies, 74 biopsy samples were definitive for neoplastic pathology and 6 biopsy samples revealed no evidence of malignancy. There were no major complications. Minor complications were recorded in 5 patients. CONCLUSION: Percutaneous image-guided core biopsy of mediastinal lesions is an accurate, safe and cost-effective tool for the initial assessment of patients with mediastinal masses.

Osteoradionecrosis of the mandible: through a radiologist's eyes.

Head and neck malignancies constitute a major cause of morbidity and mortality all over the world. Radiotherapy plays a pivotal role in the management of these tumours; however, it has associated complications, with mandibular osteoradionecrosis (ORN) being one of the gravest orofacial complications. Early diagnosis, extent evaluation, and detection of complications of ORN are imperative for instituting an appropriate management protocol. ORN can closely mimic tumour recurrence, the differentiation of which has obvious clinical implications. The purpose of the present review is to acquaint the radiologist with the imaging features of mandibular ORN and the ways to differentiate ORN from tumour recurrence.

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.

Guidelines for locoregional therapy in primary breast cancer in developing countries: The results of an expert panel at the 8(th) Annual Women's Cancer Initiative - Tata Memorial Hospital (WCI-TMH) Conference.

Background: Limited guidelines exist for breast cancer management in developing countries. In this context, the Womens Cancer Initiative - Tata Memorial Hospital (WCI-TMH) organised its 8th Annual Conference to update guidelines in breast cancer. Materials and Methods: Appropriately formulated guideline questions on each topic and subtopic in the surgical, radiation and systemic management of primary breast cancer were developed by the scientific committee and shared with the guest faculty of the Conference. Majority of the questions had multiple choice answers. The opinion of the audience, comprising academic and community oncologists, was electronically cumulated, followed by focussed presentations by eminent national and international experts on each topic. The guidelines were finally developed through an expert panel that voted on each guideline question after all talks had been delivered and audience opinion elicited. Separate panels were constituted for locoregional and systemic therapy in primary breast cancer. Results: Based on the voting results of the expert panel, guidelines for locoregional therapy of breast cancer have been formulated. Voting patterns for each question are reported. Conclusions: The updated guidelines on locoregional management of primary breast cancer in the context of developing countries are presented in this article. These recommendations have been designed to allow centers in the developing world to improve the quality of care for breast cancer patients.