Survival outcomes with 12 weeks of adjuvant or neoadjuvant trastuzumab in breast cancer

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6–90 months), the median age was 46 (24–65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56–75%) and the OS was 76% (95% CI 67–85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

Breast cancer in a tertiary cancer center in India - An audit, with outcome analysis

Background: Surgery is the mainstay in the management of thyroid cancer. Surgical outcomes need to be tempered against the excellent prognosis of the disease. Aims: This study aims to study the surgical outcomes including the 30-day morbidity and 5-year survival of thyroid cancer patients. Settings and Design: Retrospective analysis of a prospectively maintained surgical database in a tertiary cancer center in India. Materials and Methods: We analyzed 221 surgically treated patients in the year 2012. Statistical Analysis: Used IBM SPSS 24.0 (Armonk, NY) with p < 0.05. Results: The median age was 40 years with predominantly papillary thyroid carcinoma (55%). Localized disease in 47% of cases, locoregional disease in 42.5% and distant metastasis in 10.2% of cases at presentation was noted. Treatment naïve patients were 71% and revision surgeries were done in 29% patients. Extended thyroidectomy constituted 11% of the surgeries. Temporary hypocalcemia was seen in 30.8% of patients, 5% requiring intravenous calcium supplementation. Vocal cord palsy as per nerve at risk and chyle leak were seen in 4.5% and 3.1%, respectively. Aggressive histology, extended thyroidectomy, and inadvertent parathyroidectomy were significant factors associated with complications. Five year estimated overall survival with median follow-up of 50 months was 98%, and event-free survival was 84.8%. Advanced age, distant metastasis at presentation and aggressive histology connoted poor outcomes. Conclusion: Thyroid cancer, irrespective of the extent of disease, has good prognosis. Aggressive histology, the extent of thyroid surgery, distant metastasis and age are important factors, which should be factored in the algorithm of thyroid cancer management.

Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: An animal trial.

Purpose: The purpose of the study is to compare the intra-vitreal concentrations of carboplatin, post peri-ocular injections of commercially available carboplatin (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate carboplatin (NPC), in either eye, as a model system for treatment of advanced intra-ocular retinoblastoma (RB). Design: Experimental, comparative, animal study. Materials and Methods: Polymethylmethacrylate nanoparticles were prepared by free radical emulsion polymerization of methyl methacrylate in aqueous solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6 weeks and 3 months were enrolled. The right eye of each rat was injected peri-ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology. Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. Analysis of data was done with paired t-test. Results: The intra-vitreal concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all animals, on all the days (P < 0.05). Conclusion: A higher trans-scleral permeability gradient is obtained with the novel nanoparticles than with the commercial drug, leading to sustained higher levels of carboplatin in the vitreous. Peri-ocular injection of NPC could thus have an adjuvant effi cacy in the treatment for advanced clinical RB, specifi cally those with vitreous seeds.

Establishment & characterization of lymphoblastoid cell lines from patients with multiple primary neoplasms in the upper aero-digestive tract & healthy individuals.

Background & objectives: A major drawback for genetic studies as well as long-term genotype-phenotype correlation studies in cancer is lack of representative human cell lines providing a continuous source of basic biomolecules and a system to carry out various experimental investigations. This can be overcome to some extent by establishing lymphoblastoid cell lines (LCLs) by infecting peripheral blood lymphocytes with Epstein Barr virus (EBV) which is known to immortalize human resting B cells in vitro giving rise to actively proliferating B-lymphoblastoid cell lines. The present study involves preparation and characterization of LCLs generated from patients with multiple primary neoplasms (MPN) of upper aero-digestive tract (UADT). Methods: Thirty seven LCLs were established from UADT MPN patients and healthy age, sex and habit matched controls using EBV crude stock. Characterization was done with respect to expression of CD-19 (Pan B-cell marker), CD3 (T cell specific marker), CD56 (NK-cell specific marker), cell morphology, ploidy analysis, genotype and gene expression comparison with the parent lymphocytes. Results: LCLs showed rosette morphology with doubling time of approximately 24 h. Ploidy analysis showed diploid DNA content which was maintained for at least 30 population doublings. When compared with parent lymphocytes there appeared no change at genetic and gene expression level. Interpretation & conclusions: Our results show that lymphoblastoid cell lines are a good surrogate of isolated lymphocytes bearing their close resemblance at genetic and phenotypic level to parent lymphocytes and are a valuable resource for understanding genotype-phenotype interactions.

Radiotherapy-induced depigmentation in a patient with breast cancer.

Vitiligo is a common dermatological disorder. A middle-aged woman with preexisting vitiligo was diagnosed with breast carcinoma. After surgery and chemotherapy she received regional radiotherapy. Six months after the completion of radiotherapy she developed depigmentation in the irradiated area. This article discusses the etiology for this phenomenon and the literature in this regard.

Age related macular degeneration: a study of patients managed with radiotherapy.

INTRODUCTION: Age-related macular degeneration (ARMD) is the leading cause of blindness in the west. Radiotherapy affects the evolution of exudative macular degeneration directly by its effect on the endothelium and inflammation modulation. We conducted a retrospective study to evaluate the improvement in visual acuity and healing of sub retinal neovascular membrane (SRNV) following fractionated radiotherapy. MATERIALS AND METHODS: 47 patients (58 eyes) of ARMD were retrospectively analyzed. One of the following radiotherapy fractionation schedules was employed in all the patients in this study. a) 15 Gy/5 fractions/1 week (five patients) b) 20 Gy/5 fractions/1 week (19 patients) c) 22.5 Gy/5 fractions/1 week (21 patients) d) 25 Gy/5 fractions/1 week (two patients). VA and funduscopy was taken at each follow-up for objective improvement and to assess the healing of SRNV. RESULTS: The median follow-up was 7.23 months. The mean improvement in the VA in the entire group was of 0.44 line. (Median 1, SD 1.04). Overall 75% of the eyes showed either steady vision or an improvement in subjective vision analysis. The deterioration free survival was significantly better in the group that had a relatively short duration of symptoms (P = 0.01). Scarring at presentation was a significant adverse factor for improvement in vision after radiotherapy (P = 0.001). CONCLUSIONS: In patients of ARMD treated with radiotherapy, the initial duration of symptoms and scarring of eyes at presentation were significant prognostic variables for improvement in VA after radiotherapy.

Genotype, phenotype and cancer: role of low penetrance genes and environment in tumour susceptibility.

Role of heredity and lifestyle in sporadic cancers is well documented. Here we focus on the influence of low penetrance genes and habits, with emphasis on tobacco habit in causing head and neck cancers. Role of such gene-environment interaction can be well studied in individuals with multiple primary cancers. Thus such a biological model may elucidate that cancer causation is not solely due to genetic determinism but also significantly relies on lifestyle of the individual.