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.

Immunotherapy in Older Patients with Cancer: A Narrative Review.

Purpose: Immunotherapies have revolutionized cancer treatment; however, relatively little is known about their efficacy and toxicity in the elderly, a cohort accounting for more than half of total cancer cases. In this review, we aim to provide insight into the current knowledge base regarding the clinical utility and side effects of immunotherapies in the geriatric population as well as identify key gaps in the literature where further research is essential. Methods: We conducted a rapid critical review of available literature, focusing on studies reporting on use of immunotherapy in cancer patients aged ≥65 years. The review assessed studies that included different types of cancer, were of multiple study types (although predominantly retrospective), had different study duration, and reported different outcomes of interest. Owing to this heterogeneity, meta-analysis and a direct comparison between studies were not feasible. Results: Overall, the review findings indicate that certain malignancies have shown comparable survival rates in younger and older age groups when managed with immunotherapeutic drugs, the incidence of immunotherapy-related side effects varies only slightly by age groups, and in general there is a lack of studies on the determinants of the clinical outcomes of immunotherapy in or including geriatric patients. Conclusion: Enhanced clinical benefits along with better tolerability associated with immunotherapies make it an attractive alternative to conventional chemotherapeutic drugs, especially in elderly patients. There is currently a limited number of studies assessing the clinical outcomes of immunotherapies, particularly in the elderly. Overall, our findings reflect a need for further prospective studies focussing on geriatric patients representative of the real-life population, in order to derive a more precise understanding of the clinical utility, toxicity profile, and cost-effectiveness of immune checkpoint inhibitors in older patients with cancer.

Proportion of papillary thyroid microcarcinoma in Kerala, India, over a decade: a retrospective cohort study.

Background: Overdiagnosis is a phenomenon where an indolent cancer is diagnosed that otherwise would not have caused harm to the patient during their lifetime. The rising incidence of papillary thyroid cancer (PTC) in various regions of the world is attributed to overdiagnosis. In such regions, the rates of papillary thyroid microcarcinoma (PTMC) are also rising. We aimed to study whether a similar pattern of rising PTMC is found in Kerala, a state in India, where there has been a doubling of thyroid cancer incidence over a decade. Methods: We conducted a retrospective cohort study in two large government medical colleges, which are tertiary referral facilities in the state of Kerala. We collected data on the PTC diagnosis in Kozhikode and Thrissur Government Medical colleges from 2010 to 2020. We analysed our data by age, gender and tumor size. Results: The incidence of PTC at Kozhikode and Thrissur Government Medical colleges nearly doubled from 2010 to 2020. The overall proportion of PTMC in these specimens was 18.9%. The proportion of PTMC only marginally increased from 14.7 to 17.9 during the period. Of the total incidence of microcarcinomas, 64% were reported in individuals less than 45 years of age. Conclusion: The rise in the number of PTCs diagnosed in the government-run public healthcare centres in Kerala state in India is unlikely to be due to overdiagnosis since there was no disproportionate rise in rates of PTMCs. The patients that these hospitals cater to may be less likely to show healthcare-seeking behavior or ease of healthcare access which is closely associated with the problem of overdiagnosis.

A novel strategy to downstage breast cancer: impact of a phone helpline.

Breast cancer incidence rates in India are rising. The majority of breast cancers are still diagnosed in later stages. There is also a burden of neglected cancers in India, where patients neglect their symptoms due to fear, ignorance, financial insecurity and lack of access to medical care. This results in greater morbidity and mortality from breast cancer. Systematic screening programs have been tested in an Indian setting, with limited success. An effective strategy to downstage breast cancer is an area of unmet need. We aimed to explore the effectiveness of an anonymous nurse-led telephone helpline in identifying patients with possible breast malignancies and to encourage them to seek healthcare. We created a telephone helpline system by training junior public health nurses (JPHNs) to provide counselling to women who may call with breast-related symptoms. We then created a short video message on the initiative and disseminated it using social media platforms. During the 1-year study period, 434 calls were received from individuals who reported having some breast symptoms. Among them, 28% (122 callers) had never consulted a doctor for their symptoms. 78 callers consulted a nearby doctor upon the advice of the JPHN. Among them, 14 callers (18%) were advised by the doctor to undergo investigations to rule out malignancy, while 64 (82%) of them were found to have some benign/normal breast conditions. 3 (21%) out of the 14 patients who underwent further evaluation were eventually diagnosed with breast cancer. Our study provides evidence that an anonymous nurse-led telephone helpline can be an effective strategy to reduce the incidence of neglected breast cancers and downstage the diagnoses.

Complete response to nivolumab in Kirsten rat sarcoma virus oncogene KRAS-G12C mutant metastatic lung adenocarcinoma: a case report.

BACKGROUND: The advent of immunotherapies has ushered in a new era in the treatment of non-small cell lung carcinoma. Although immunotherapies are associated with improved clinical outcomes, studies report a median overall survival of 11 months with progression-free survival of 2.5 months with the use of nivolumab for pretreated metastatic non-small cell lung cancer. Herein, we describe a case of advanced non-small cell lung carcinoma that has shown exceptional response to immunotherapy, with the patient being in complete response for the past 6 years since commencement of nivolumab. CASE PRESENTATION: We report the case of a 58-year-old female Caucasian, an ex-smoker with 40-pack-year history of smoking, who presented with cough and chest pain and was subsequently diagnosed with metastatic pulmonary adenocarcinoma. The tumor was positive for Kirsten rat sarcoma virus oncogene KRAS-G12C mutation and had high programmed death-1 ligand expression. She was commenced on first-line chemotherapy with carboplatin and gemcitabine with disease response, then continued on maintenance pemetrexed. She was then commenced on immunotherapy with nivolumab, with complete response for a total of 6 years. She does not report any adverse events. Currently, she shows no evidence of recurrence of non-small cell lung carcinoma. CONCLUSION: The exceptional response to immunotherapy seen in this case may be explained by the presence of Kirsten rat sarcoma virus oncogene mutation, which is associated with enhanced clinical response to programmed death-1 ligand inhibitors. This report emphasizes the urgent need for further studies evaluating the role of Kirsten rat sarcoma virus oncogene mutation in determining the clinical efficacy of immunotherapies. This would enable us to make effective evidence-based clinical interventions in the treatment of non-small cell lung carcinoma.

Value-Based Care in Systemic Therapy: The Way Forward.

The rising cost of cancer care has shed light on an important aspect of healthcare delivery. Financial toxicity of therapy must be considered in clinical practice and policy-making. One way to mitigate the impact of financial toxicity of cancer care is by focusing on an approach of healthcare delivery that aims to deliver value to the patient. Should value of therapy be one of the most important determinants of cancer care? If so, how do we measure it? How can we implement it in routine clinical practice? In this viewpoint, we discuss value-based care in systemic therapy in oncology. Strategies to improve the quality of care by incorporating value-based approaches are discussed: use of composite tools to assess the value of drugs, alternative dosing strategies, and the use of Health Technology Assessment in regulatory procedures. We propose that there must be a greater emphasis on value of therapy in determining its use and its cost.

Financial toxicity in cancer care in India: a systematic review.

Although financial toxicity is widely acknowledged to be a potential consequence of costly cancer treatment, little is known about its prevalence and outcome among the Indian population. In this study, we systematically reviewed the prevalence, determinants, and consequences of financial toxicity among patients with cancer in India. 22 studies were included in the systematic review. The determinants of financial toxicity include household income, type of health-care facility used, stage of disease, area of residence, age at the time of diagnosis, recurrent cancer, educational status, insurance coverage, and treatment modality. Financial toxicity was associated with poor quality of life, accumulation of debts, premature entry into the labour market, and non-compliance with therapy. Our findings emphasise the need for urgent strategies to mitigate financial toxicity among patients with cancer in India, especially in the most deprived sections of society. The qualitative evidence synthesised in this systematic review could provide a basis for the development of such interventions to reduce financial toxicity among patients with cancer.