Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India.

PURPOSE: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non-high-income setting, with international input to evaluate the necessity of MTB in clinical practice. METHODS: We collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented. RESULTS: Seventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases). CONCLUSION: The discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.

Cervical Cancer in SAARC Countries.

Purvish M. ParikhIn the year 2020, a total of 342 000 women were estimated to die of cervical cancer, of which 90%) were expected amongst low- and middle-income countries (LMIC). Globally incidence of cervical cancer has reduced as a result of improved personal hygiene, better living conditions and higher application of opportunistic screening programs. Yet GLOBOCAN shows that absolute number of cases are still increasing. We therefore conducted a 21 question multiple choice questionnaire online survey in Jan 2023 amongst 9 SAARC countries. A total of 367 replies were received and the representative answers for each country are being reported in this manuscript. A good possibility of achieving World Health Assembly target (Nov 17, 2020) was felt only by Bhutan and Nepal. For screening, most countries (Bhutan, India, Myanmar, Nepal, Pakistan and Sri Lanka) recommend for all asymptomatic eligible patients. Public health experts have suggested VIA / VILI as the best solution for LMICs. However, a dual screening strategy (HPV DNA plus) cytology was preferred by doctors in Afghanistan, Bhutan, India, Myanmar, Pakistan and Sri Lanka. Screening, triage and then treatment was the preferred by Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka. HPV vaccination was recommended in all girls between ages 10 to 26 years in Bangladesh, India, Myanmar, Nepal, Pakistan and Sri Lanka. All the 9 countries would use HPV vaccination to all eligible patients if the cost of the vaccine was reasonably low. Our survey clearly outlines challenges faced in tackling cervical cancer in SAARC countries. We also provide consensus regarding several potential solutions that can be used in both public and private cervical cancer control programs.

Distinct patterns of occurrence, common associations, and survival of patients with second primary maligancies: A 5-year single institute experience with review of literature.

BACKGROUND: Multiple primary malignancy (MPM) is defined as occurrence of two or more synchronous or metachronous primary malignancies. With the rise in cancer burden and meticulous screening of index primary malignancy (IPM) during treatment, increased incidence of second primary malignancy (SPM) is expected. This study was undertaken with an attempt to analyze the incidence, commonest associations, management strategies, and clinical outcomes of MPM. MATERIALS AND METHODS: This is an observational retrospective study carried out in a single institute with patients registered between 1st January 2015 and 31st August 2019. The International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC) definition was used for identification of IPM and SPM. Synchronous SPM was defined as malignancy occurring within 6 months from the diagnosis of IPM. RESULTS: Out of 16,461 registered patients during the study interval, 44 (0.26%) cases were found to have MPM. A total of 31 (70.5%) cases were women and 13 (29.5%) cases were men. Median age at presentation of IPM was 48 years and of SPM was 56 years, with median duration between two primaries being 38 months. Seven patients (15.9%) had synchronous malignancies. Gynecological tumors were the most common site of IPM presentation (n = 14, 31.8%) followed by breast (n = 09, 20.5%) and head and neck tumors (n = 07, 15.9%), respectively. The most common SPM was gynecological tumors (n = 12, 27.3%) followed by gastrointestinal malignancies (n = 10, 23.3%). Curative treatment was offered to 88% of patients with IPM and 70% patients with SPM. At a median follow-up of 365 days, 21 (47.72%) patients were disease free, six (13.6%) died of disease and nine (20.5%) were lost to follow-up. CONCLUSION: The study emphasizes the importance of detecting SPM as a result of improved diagnostic and screening procedures. Clinicians should be aware of it and offer multidisciplinary management.

Pazopanib in metastatic soft tissue sarcomas: Testing the waters in developing world.

BACKGROUND: In metastatic soft tissue sarcoma (M-STS), pazopanib has demonstrated promising activity; however, there is dearth of data from lower and middle income countries. It is important to explore the feasibility (toxicity, acceptance), efficacy (response rates, survival), and optimal dose requirement of pazopanib in M-STS in India. METHODS: All patients who received pazopanib for M-STS in 2013-2018 in Tata Memorial Centre were included. Institutional ethics committee approval was obtained. Assessment for response with contrast computed tomography scans was done as per the response evaluation criteria in solid tumors (RECIST) 1.1 criteria. Pazopanib was continued until progression or unacceptable toxicity. Clinical benefit rates and survival were evaluated by Kaplan-Meier method. All statistical calculations were done using SPSS version 21.0. RESULTS: Seventy-two consecutive patients with a median follow-up of 17 (4-40) months were included in this study. Median lines of prior therapy were 2 (0-2). Among 50 evaluable patients, there were 12/50 (24%) partial responses, 25/50 (50%) stable disease, and 15/50 (30%) progressive disease. Median progression-free survival was 5 (95% confidence interval (CI) 3-6.9) months and median overall survival was 11 (95% CI 6.8-15.2) months. Adverse effects (G2/G3) in patients: hand foot syndrome-28%, hyperbilirubinemia/transaminitis-10%, diarrhea-20%, hypertension-17%, hypothyroidism-15%, anemia-6%, and fatigue-17%. Notably, 40% patient required dose reduction and median dose was 600 (200-800) mg daily. CONCLUSION: Pazopanib was found a feasible treatment option for M-STS in India with internationally comparable outcomes. However, significant patients required dose modifications, and median tolerated dose was lower than the standard 800 mg dose. This novel finding merits confirmation in larger cohorts for reproducibility.