Guiding Principles for Community Building in Global Oncology.

With the escalating incidence and prevalence of cancer worldwide disproportionately affecting low- and middle-income countries, there is an urgent need for the global oncology community to foster bidirectional partnerships and an equitable exchange of knowledge, resources, and expertise. A dedicated Global Oncology Community of Practice (CoP) can serve as a self-organizing, grassroots approach for members, with common goals and values, to coordinate efforts, maximize impact, and ensure sustainable outcomes. It is imperative, however, when outlining goals and priorities to adhere to an ethical and appropriate framework during community building efforts to avoid perpetuating inequities and power imbalances. This article reviews the core guiding principles for ASCO's Global Oncology CoP which includes responsibility, amplification, accessibility, sustainability, and decolonization.

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.

Local Sociocultural Practice Specific Financial Toxicity Assessment Tool for Cancer: An Emerging Need.

It is relevant to study the financial toxicity of cancer to address it. However, the existing tools fail to capture the financial destruction of cancer on patients and their families in resource-limited countries. The authors discuss the need for a new tool in this article.

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 burden shared: the financial, psychological, and health-related consequences borne by family members and caregivers of people with cancer in India.

In India, approximately 1.4 million new cases of cancer are recorded annually, with 26.7 million people living with cancer in 2021. Providing care for family members with cancer impacts caregivers' health and financial resources. Effects on caregivers' health and financial resources, understood as family and caregiver "financial toxicity" of cancer, are important to explore in the Indian context, where family members often serve as caregivers, in light of cultural attitudes towards family. This is reinforced by other structural issues such as grave disparities in socioeconomic status, barriers in access to care, and limited access to supportive care services for many patients. Effects on family caregivers' financial resources are particularly prevalent in India given the increased dependency on out-of-pocket financing for healthcare, disparate access to insurance coverage, and limitations in public expenditure on healthcare. In this paper, we explore family and caregiver financial toxicity of cancer in the Indian context, highlighting the multiple psychosocial aspects through which these factors may play out. We suggest steps forward, including future directions in (1) health services research, (2) community-level interventions, and (3) policy changes. We underscore that multidisciplinary and multi-sectoral efforts are needed to study and address family and caregiver financial toxicity in India.

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.

Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis.

BACKGROUND: The increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques especially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity. METHODS: A diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP, and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings. RESULTS: A total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1, and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2, and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10 and 56%, the panel sensitivity values reported across studies were higher with an estimated range of 60-87%. CONCLUSION: Findings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2, and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.

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.

Cancer Medicines: What Is Essential and Affordable in India?

PURPOSE: The WHO essential medicines list (EML) guides selection of drugs for national formularies. Here, we evaluate which medicines are considered highest priority by Indian oncologists and the extent to which they are available in routine practice. METHODS: This is a secondary analysis of an electronic survey developed by the WHO EML Cancer Medicine Working Group. The survey was distributed globally using a hierarchical snowball method to physicians who prescribe systemic anticancer therapy. The survey captured the 10 medicines oncologists considered highest priority for population health and their availability in routine practice. RESULTS: The global study cohort included 948 respondents from 82 countries; 98 were from India and 67 were from other low- and middle-income countries. Compared with other low- and middle-income countries, the Indian cohort was more likely to be medical oncologist (70% v 31%, P < .001) and work exclusively in the private health system (52% v 17%, P < .001). 14/20 most commonly selected medicines were conventional cytotoxic drugs. Universal access to these medicines was reported by a minority of oncologists; risks of significant out-of-pocket expenditures for each medicine were reported by 19%-58% of oncologists. Risk of catastrophic expenditure was reported by 58%-67% of oncologists for rituximab and trastuzumab. Risks of financial toxicity were substantially higher within the private health system compared with the public system. CONCLUSION: Most high-priority cancer medicines identified by Indian oncologists are generic chemotherapy agents that provide substantial improvements in survival and are already included in WHO EML. Access to these treatments remains limited by major financial burdens experienced by patients. This is particularly acute within the private health system. Strategies are urgently needed to ensure that high-quality cancer care is affordable and accessible to all patients in India.

A comparative study of cancer drug approvals in india and high-income countries.

BACKGROUND: The new drug approval in every country is closely monitored and regulated by central authorities which regulates drug development, approval, and marketing. In this study, we aim to analyze and compare the approval status of drugs that are approved for medical use in India by the Central Drugs Standard Control Organization (CDSCO) with the drug approval organizations of Western Countries. METHODS: We conducted a retrospective cross-sectional study. We queried the CDSCO website and database for new drugs and anti-cancer drugs that are approved for use in India by CDSCO during 2010-2019. We compared the approval status of those drugs in the FDA (Food and Drug Administration), EMA (European Medicines Agency), and Health Canada (HC) databases. RESULTS: A total of 257 new drugs (including 47 anti-cancer drugs) are approved for use in India by the CDSCO during the period 2010-2019. Out of these, only 69.6% (n = 179) new drugs were approved by the FDA, 62.65% (n = 161) were approved by EMA and 63.40% were approved by Health Canada (n = 163). Most of the anti-cancer drugs that are approved for use in India are approved by these agencies except 2 drugs that are not approved by FDA and HC. CONCLUSION: Majority of cancer drugs approved for use in India are approved for use in the USA, Europe and Canada. However, a significant number of non-cancer drugs approved for use in India are not approved in these regions. POLICY SUMMARY: We recommend a comprehensive assessment of India's drug regulatory processes and policies to improve patient safety.

Clinical Benefit of Comprehensive Genomic Profiling for Advanced Cancers in India.

PURPOSE: Comprehensive genomic profiling (CGP) assay is increasingly used in low-middle-income countries to detect clinically relevant genomic alterations despite its clinical benefits not being well known. Here, we describe the proportion of patients with advanced cancer in India who received targeted therapy for an actionable genetic alteration identified on CGP assays. METHODS: This was a multicenter, retrospective cohort study in adult patients with advanced nonhematologic malignancies who underwent a CGP test. If patients received a targeted therapy for ≥ 6 months, they were considered to have obtained a clinical benefit from the medication, whereas those continuing for ≥ 12 months were considered to have attained an exceptional response. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. RESULTS: During 2019-2020, 12 medical oncologists provided CGP reports for 297 patients; 221 met the inclusion criteria. Patients received a median of two lines (range: 0-5) of prior systemic therapy. On the basis of the CGP assay, 21 patients (10%) received targeted therapy. Among them, 33% was for human epidermal growth factor receptor 2 (HER2) amplification (nonbreast cancer) and 19% for HER2 or epidermal growth factor receptor exon 20 insertion mutation (lung cancer). After excluding patients with HER2 or epidermal growth factor receptor exon 20 insertions, 8% of 217 patients received targeted therapy. In the overall cohort of 221 patients, clinical benefit was seen in nine patients (4%), of whom two were exceptional responders (1%). CONCLUSION: We observed that in a low-middle-income country setting, 10% of patients received targeted therapy on the basis of CGP assay. Only 4% of patients who underwent CGP testing obtained a clinical benefit.

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.

Polycythemia Vera Presenting as Hemorrhagic Stroke.

Patients with polycythemia vera are at high risk for vaso-occlusive events including cerebral ischemia and hemorrhage. Cerebral ischemic events are due to increased blood viscosity and platelet activation within the central nervous system arterial vessels. We present a case of a 65-year-old woman who presented to the emergency department with seizures followed by left-sided weakness. Hematologic investigations revealed a hyperviscous state, and magnetic resonance imaging (MRI) was consistent with bilateral hemorrhagic infarction. Genetic studies were positive for polycythemia vera mutation. Symptoms improved with phlebotomy and antiplatelet agents. Through this case, we aim to highlight polycythemia vera as a cause of hemorrhagic stroke and the importance of blood counts in the routine evaluation of the same.

Clinical Trial Access in Low- and Middle-Income Countries: A Case Study on India.

The global burden of cancer is estimated to be more than 20 million cases by 2030, the majority occurring in low- and middle- income countries (LMICs). LMICs account for 64% of global cancer deaths and 80% of disability-adjusted-life-years lost. Despite this, only 5% of the global cancer resources are spent in LMICs causing a high mortality-to-income ratio. Despite the burgeoning number of clinical trials in the HICs, there are several reasons to conduct clinical trials in LMICs. In this commentary, we discuss the problem of access to clinical trials in LMICs using India as a case study.

Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry.

The state of Kentucky has the highest cancer incidence and mortality in the United States. High-risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution. Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure was 78.3% and 14.5%, respectively. TP53 (62.3%), CDKN1B/2A (40.5%), NOTCH and PIK3 (33.3%) were the most common alterations in tumors. 67.4% were PDL1 positive and 59.4% had intermediate-high tumor mutational burden (TMB). Median TMB (12.6) was twofold to fourfold compared to clinical trials. The prevalence of mutations associated with smoking, homologous recombinant repair and PIK3/AKT/mTOR pathway mutations was higher compared to historic cohorts. PDL1 expression had no significant effect on radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended toward statistical significance (median 18 vs. 40 weeks. HR = 1.43. 95%CI 0.93, 4.46). Median PFS was higher in the high-TMB cohort compared to low-intermediate TMB (median not reached vs. 26 weeks; HR = 0.37. 95%CI 0.13, 1.05). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR = 2.51. 95%CI 1.23, 5.14). This was independent of tumor mutational burden (TMB) status or PDL1 expression status. PIK3 mutants had a higher overall response rate than the wild type (69.6% vs. 43.5%, OR 0.34; p = 0.045). The results should prompt further evaluation of these potential biomarkers and more widespread real-world data publications which might help determine biomarkers that could benefit specific populations.