Jaya Ghosh

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India

BACKGROUND This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. MATERIALS AND METHODS The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. RESULTS A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. CONCLUSIONS The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study

Background Angiosarcomas are rare malignant tumors of vascular origin that represent a genuine therapeutic challenge. Recently, the combination of metronomic chemotherapy and drug repositioning has been proposed as an attractive alternative for cancer patients living in developing countries. Methods In vitro experiments with transformed endothelial cells were used to identify synergistic interactions between anti-hypertensive drug propranolol and chemotherapeutics. This led to the design of a pilot treatment protocol combining oral propranolol and metronomic chemotherapy. Seven consecutive patients with advanced/metastatic/recurrent angiosarcoma were treated with this combination for up to 12 months, followed by propranolol-containing maintenance therapy. Findings Gene expression analysis showed expression of ADRB1 and ADRB2 adrenergic receptor genes in transformed endothelial cells and in angiosarcoma tumors. Propranolol strongly synergized with the microtubule-targeting agent vinblastine in vitro, but only displayed additivity or slight antagonism with paclitaxel and doxorubicin. A combination treatment using bi-daily propranolol (40 mg) and weekly metronomic vinblastine (6 mg/m2) and methotrexate (35 mg/m2) was designed and used in 7 patients with advanced angiosarcoma. Treatment was well tolerated and resulted in 100% response rate, including 1 complete response and 3 very good partial responses, based on RECIST criteria. Median progression-free and overall survival was 11 months (range 5–24) and 16 months (range 10–30), respectively. Interpretation Our results provide a strong rationale for the combination of β-blockers and vinblastine-based metronomic chemotherapy for the treatment of advanced angiosarcoma. Furthermore, our study highlights the potential of drug repositioning in combination with metronomic chemotherapy in low- and middle-income country setting. Funding This study was funded by institutional and philanthropic grants.

Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature

We report a case of an acute non-ST elevation myocardial infarction (AMI) induced by paclitaxel in a patient with ovarian cancer. A 45-year-old premenopausal lady without any co-morbidity was started on the first cycle of neoadjuvant chemotherapy with paclitaxel-based regimen for advanced stage ovarian cancer. The patient developed chest pain 3 h after paclitaxel infusion with characteristic electrocardiographic changes of antero-apical myocardial infarction. The patient recovered on conservative medical management with reversion of electrocardiogram (ECG) changes. Cardiac ischemia and myocardial infarction, possibly due to coronary vasospasm, are rare adverse effects of paclitaxel with reported incidence of 0.26%. We have reported a case of paclitaxel-induced myocardial infarction with reversible cardiac dysfunction. The possibility of myocardial infarction should be considered in patients who develop chest pain or other symptoms after paclitaxel infusion.

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.

Oligometastatic breast cancer: A mini review.

With few exceptions such as germ cell tumors, trophoblastic neoplasms and colonic cancers, metastatic solid tumors are considered largely incurable. It is increasingly appreciated that oligometaststic cancer differs from multi-metastatic disease in prognosis and survival. Oligometastatic breast cancer (OMBC) is, therefore, sometimes considered as an intermediate biological state between localized and widely metastatic disease. There is no strict definition of OMBC with studies using different criteria. Treatment of OMBC is still controversial in view of sparse data that is retrospective. However, there is an increasing shift toward individualized, multidisciplinary management of OMBC with the intent to cure some patients. This article will concisely review the subject of OMBC from points of view of biology and practical management recommendations.

Clinico-pathological spectrum of primary ovarian malignant mixed mullerian tumors (OMMMT) from a tertiary cancer institute: A series of 27 cases

AIMS AND OBJECTIVES To study the clinico-pathological characteristics of primary ovarian malignant mixed mullerian tumor (OMMMT) and assess the prognostic factors associated with treatment outcome and survival. MATERIALS AND METHODS The pathology database was searched for primary ovarian carcinosarcoma diagnosed and/or managed at our institute from period of January 2004 to July 2010. The histological sections were reviewed, with emphasis on type and grade of epithelial and sarcomatous components. The medical records were retrospectively analyzed for clinical details and follow up. RESULTS A total of 27 cases of primary ovarian carcinosarcoma were identified. The median age at diagnosis was 51 years. Fourteen patients had advanced stage (stage III and IV) at presentation. Cytoreductive surgery was done in 18 cases, and 7 had received upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50% epithelial component) and 11 had sarcoma predominance. The most frequent epithelial component was endometroid type, and most common sarcoma component was rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen prominently in 15 cases. Three cases showed germ cell /yolk sac-like areas. Eighteen cases had follow up with a median of 15 months (4-40 months). The recurrence-free survival in advanced stage and sarcoma predominant was 10.5 months in comparison to 13 months in early stage and epithelial predominant OMMMT. CONCLUSION Primary ovarian carcinosarcoma is a rare biphasic malignancy with variable proportions of epithelial and spindle elements. Presence of hyaline droplets within spindle sarcoma in a biopsy from ovarian mass should alert the pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.

Protocol for a phase III randomised trial of image-guided intensity modulated radiotherapy (IG-IMRT) and conventional radiotherapy for late small bowel toxicity reduction after postoperative adjuvant radiation in Ca cervix

Introduction External beam radiation followed by vaginal brachytherapy (±chemotherapy) leads to reduction in the risk of local recurrence and improves progression-free survival in patients with adverse risk factors following Wertheims hysterectomy albeit at the risk of late bowel toxicity. Intensity Modulated Radiotherapy (IMRT) results in reduction in bowel doses and has potential to reduce late morbidity, however, needs to be confirmed prospectively in a randomised trial. The present randomised trial tests reduction if any in late small bowel toxicity with the use of IMRT in postoperative setting. Methods and analysis Patients more than 18 years of age who need adjuvant (chemo) radiation will be eligible. Patients with residual pelvic or para-aortic nodal disease, history of multiple abdominal surgeries or any other medical bowel condition will be excluded. The trial will randomise patients into standard radiation or IMRT. The primary aim is to compare differences in late grades II–IV bowel toxicity between the two arms. The secondary aims of the study focus on evaluating correlation of dose–volume parameters and late toxicity and quality of life. The trial is planned as a multicentre randomised study. The trial is designed to detect a 13% difference in late grades II–IV bowel toxicity with an α of 0.05 and β of 0.80. A total of 240 patients will be required to demonstrate the aforesaid difference. Ethics and dissemination The trial is approved by institutional ethics review board and will be routinely monitored as per standard guidelines. The study results will be disseminated via peer reviewed scientific journals, conference presentations and submission to regulatory authorities. Registration The trial is registered with clinicaltrials.gov (NCT 01279135).

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.

Leptomeningeal metastasis in solid tumors with a special focus on lung cancer

Leptomeningeal metastasis is a common problem in advanced solid tumor malignancies. A significant number of patients have underlying lung cancer. With the advent of better therapies, the management of leptomeningeal metastasis is gained more importance to improve survival and quality of live. This review article focuses on the epidemiology, clinical features, diagnostics and the recent management strategies directed towards leotomeningela metastasis from solid tumor, esp lung cancer.

Impact of adjuvant radiation therapy photon energy on quality of life after breast conservation therapy: Linear accelerator versus the cobalt machine

BACKGROUND Breast conservative therapy (BCT) is a standard treatment option in early operable breast cancers (OBC) and a select group of large or locally advanced tumors. The present study deals with prospective evaluation of quality of life (QOL) score in consecutive patients treated with BCT employing adjuvant RT treated with either a cobalt machine or a linear accelerator (LA). MATERIAL AND METHODS Patients of carcinoma breast who underwent BCT were taken into the study. Patients with larger breasts (inter-field separation >18-20 cm) were treated on LA and those with smaller breasts were treated on cobalt machine. All patients received a uniform RT dose (45-50 Gy/25#/5 weeks) to whole breast followed by tumor bed boost with suitable energy electrons. Prospective evaluation of QOL was done using EORTC QLQ C30 and breast cancer-specific EORTC QLQ BR23. QOL evaluation was done at pre-RT, at half completion of RT treatment (at 20-23 fractions) and at completion of RT. RESULTS Pre-RT evaluation GQOL scores in patients treated with cobalt and LA were 71.6 and 71.7, respectively (P = 0.8). QLQ C30 functional and symptom domain scores were also similar in the groups. At RT completion, Global quality of life (GQOL) scores were 67.7 in patients treated with cobalt as compared to 77.7 in patients treated with LA (P = 0.75). Physical function domain scores in cobalt and LA patients were 70.8 and 80.3, respectively (P = 0.26). Fatigue score was higher in patients treated with cobalt (39.1 versus 29.7; P = 0.9). However, there was no difference in other functional and symptom domains. There was no significant change in any of the EORTC QLQ C30 domains at RT completion as compared to the pre-RT scores. CONCLUSION There is no significant difference in QOL domains between appropriately selected patients treated with cobalt and LA. There are no significant changes in QOL domain scores at RT conclusion as compared to pre-RT baseline in patients treated with cobalt or LA source. A cobalt machine may be effectively used to deliver adjuvant RT in appropriately selected BCT patients especially in developing countries with limited resources.