PURPOSE: Childhood cancer is an under-recognized public health priority in low- and middle-income countries. India bears a substantial share of the global burden, yet survival outcomes are poorly documented. This scoping review synthesizes survival outcomes across childhood cancers in India, assesses geographic disparities, and benchmarks against international standards to inform national policy and system strengthening. METHODS: We searched PubMed, Scopus, Web of Science, and Embase (January 1994 to December 2023) for studies reporting survival outcomes among childhood cancers (0-18 years) in India. Two reviewers independently screened records, extracted data, and conducted descriptive synthesis by cancer type excluding case reports and registry summaries. Exploratory forest plots were created where ≥3 studies reported comparable end points. The protocol was prospectively registered on Open Science Framework. RESULTS: Of 6,505 records screened, 182 studies (22,886 children) were included. Most were retrospective (78%) and single-center (94%), concentrated in four tertiary hospitals. Exploratory pooled estimates derived from descriptive analyses showed that the 5-year overall (OS) and event-free survival were 67.1% (95% CI, 56.9 to 77.2) and 59.2% (95% CI, 48.0 to 70.3) for ALL and 93.1% (95% CI, 91.7 to 94.4) and 85.3% (95% CI, 81.3 to 89.3) for Hodgkin lymphoma (HL). The pooled median OS for AML and Ewing sarcoma was 25.4 months (95% CI, 16.8 to 33.9) and 21.2 months (95% CI, 14.6 to 27.7), respectively, whereas the 3-year OS for neuroblastoma was 56.9% (95% CI, 45.7 to 68.0). Reporting was inconsistent, with frequent omission of CIs and heterogeneity across regions. CONCLUSION: Childhood cancer survival in India remains variable, with HL nearing global benchmarks, but leukemias and solid tumors show inferior outcomes. Strengthening national cancer registries, research infrastructure, and political commitment is critical for achieving equity in childhood cancer care.

Background: Childhood and adolescent acute lymphoblastic leukemia (ALL) survival outcomes have improved significantly, but treatment-related toxicities (TRTs) remain a major concern affecting dose intensity and quality of life. Germline pharmacogenetic variations contribute to inter-individual differences in chemotherapy response, yet consistent replication of associations has been limited by differences in treatment protocols, ethnic backgrounds, and toxicity definitions. Methods: This systematic review and meta-analysis (PROSPERO CRD42021229748) included 68 studies in the qualitative synthesis, with 42 high-quality studies undergoing structured synthesis and, where appropriate, quantitative meta-analysis. Studies focused on the toxicities of thiopurines, methotrexate, glucocorticoids, vincristine, and asparaginase. Results: Meta-analyses showed strong evidence linking the NUDT15 rs116855232 variant to thiopurine-induced myelosuppression (OR 19.0, 95% CI 1.6–224; I² = 86.5%) and a significant association between the TYMS enhancer repeat polymorphism and osteonecrosis (OR 6.66, 95% CI 3.67–12.11; I² = 0%). In contrast, MTHFR variants and VDR polymorphisms showed no significant associations with methotrexate-induced myelosuppression or osteonecrosis, respectively. Narrative synthesis highlighted clinically actionable associations: TPMT and NUDT15 with thiopurine toxicity; CEP72 with vincristine neuropathy; and HLA haplotypes with asparaginase hypersensitivity. Population allele frequency comparisons (IndiGenomes, gnomAD, UK Biobank) showed strong concordance (r = 0.919–0.997), supporting the broad generalisability of identified variants, which remains to be evaluated prospectively. The main limitations included heterogeneous toxicity definitions, non-uniform genetic models, evolving treatment protocols, population heterogeneity, and a lack of harmonised reporting. Conclusions: The review supports routine TPMT and NUDT15 genotyping and highlights the need for harmonised definitions, multi-ethnic studies, standardised data representation, and prospective validation. A literature-based candidate gene list for future PGx association studies was generated.

PURPOSE: Childhood cancer has high cure rates; however, data on long-term socioeconomic challenges faced by survivors, particularly in low- and middle-income countries, are limited. We aimed to identify issues related to educational disruption, employment, and financial hardship among childhood cancer survivors. METHODS: We conducted a cross-sectional study of survivors enrolled in the Childhood Cancer Survivorship Program at a tertiary cancer center in India (December 2020-March 2025). Eligible survivors were aged 21 years and younger at diagnosis and had completed therapy. Clinical and sociodemographic data were abstracted from records and structured proforma. Logistic regression with forward stepwise modeling was used to identify predictors of educational, financial, and employment challenges. RESULTS: We included 1,098 survivors. The median age was 16 years at evaluation, and 74.7% were male. Among those diagnosed at age 5-21 years (n = 764), 85% reported educational disruption (median 1.75 years). Relocation from the hometown for therapy (odds ratio [OR], 1.8; P = .01) and job loss within the family (OR, 2.1; P = .01) independently predicted educational disruption, whereas maternal education until or above high school was associated with lower odds of educational disruption (OR, 0.29; P = .001). Catastrophic health expenditure occurred in 91.3%. Younger age at diagnosis (OR, 1.03; P = .003) and relocation (OR, 1.61; P = .001) independently predicted higher treatment costs, ≥$3,385 US Dollars. Cancer-related employment difficulties affected 30.2% of working-age survivors, with older age at diagnosis (OR, 1.15; P < .001) and longer time since treatment completion (OR, 1.08; P = .02) being independent predictors. CONCLUSION: For Indian childhood cancer survivors, cure carries hidden costs of disrupted education, financial strain, and workplace barriers. Survivorship care in resource-constrained settings should integrate school reintegration, financial protection, and vocational support.

Background: Understanding interindividual variability in treatment response and toxicity is essential for optimizing outcomes in pediatric acute lymphoblastic leukemia (ALL). Molecular and pharmacogenetic markers hold promise in predicting treatment efficacy and adverse effects, particularly in genetically diverse populations. This protocol outlines the methodology for a prospective, nonrandomized observational cohort designed to evaluate molecular and pharmacogenetic factors associated with treatment response and toxicity in Indian children diagnosed with ALL. Objective: The primary objective is to identify genetic markers associated with treatment-related toxicity and therapeutic response. Secondary objectives include evaluating associations between the occurrence of early toxicities and quality of life during active ALL treatment, specific pharmacogenetic variants, and survival outcomes along with generating data to support the future implementation of personalized treatment strategies in Indian children with ALL. Methods: In this prospective, observational cohort, 556 children (≤18 years of age) with newly diagnosed ALL treated under the Indian Childhood Collaborative Leukemia–Acute Lymphoblastic Leukemia 2014 (ICiCLe-ALL-14) protocol at two Indian centers will be enrolled, aiming for a minimum of 500 evaluable children. Eligible participants will be enrolled prior to the initiation of chemotherapy and followed longitudinally throughout treatment. Clinical and laboratory data (demographics, nutritional assessment, quality of life, comorbidities, treatment regimen, toxicity graded by Common Terminology Criteria for Adverse Events v5.0, remission status, and survival) will be collected at predefined intervals up to day 100 of the maintenance phase. Germline and somatic DNA will be sampled at diagnosis and remission. The first phase will use whole-exome sequencing to discover candidate variants by implementing a candidate gene prioritization strategy. The second phase will genotype the top candidates in the full cohort using array technology. Associations with early treatment–related toxicities, steroid response, and survival will be tested by multivariable regression and Cox models. A machine learning approach with pharmacogenetic predictors as classifiers will be implemented further with cross-validation and sensitivity analyses. Results: Ethical committees approved the protocol version 1.0 in 2020: IEC-1167/06.11.2020 (All India Institute of Medical Sciences, New Delhi), JIP/IEC/2020/201 (Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry), and AO_2021-00048 (UNIGE, Geneva). Funding was received from Swiss National Science Foundation, Switzerland; Department of Biotechnology, India; and CANSEARCH Foundation, Switzerland. Recruitment began in December 2022 and is likely to conclude by 2027. A comprehensive analysis of the complete study cohort is anticipated to be completed by 2027. Conclusions: The MPGx-INDALL (Molecular and Pharmacogenetic Marker Evaluation in Relation to the Toxicity and Clinical Response of Acute Lymphoblastic Leukemia Treatment in Indian Children) study will generate actionable insights for individualized ALL therapy in India via systematically evaluating germline and somatic markers in a large ethnically distinct cohort.

BACKGROUND Understanding inter-individual variability in treatment response and toxicity is essential for optimizing outcomes in pediatric acute lymphoblastic leukemia (ALL). Molecular and pharmacogenetic markers hold promise in predicting treatment efficacy and adverse effects, particularly in genetically diverse populations. This protocol outlines the methodology for a prospective, non-randomized observational cohort designed to evaluate molecular and pharmacogenetic factors associated with treatment response and toxicity in Indian children diagnosed with ALL. OBJECTIVE The primary objective is to identify genetic markers associated with treatment-related toxicity and therapeutic response. Secondary objectives include evaluating associations between occurrence of early toxicities and quality of life during active ALL treatment, specific pharmacogenetic variants and survival outcomes along with generating data to support future implementation of personalized treatment strategies in Indian children with ALL METHODS In this prospective, observational cohort 556 children (≤18 years) with newly diagnosed ALL treated under the ICiCLe-ALL-14 protocol at two Indian centers will be enrolled to have minimum of 500 evaluable children. Eligible participants will be enrolled prior to the initiation of chemotherapy and followed longitudinally throughout treatment. Clinical and laboratory data (demographics, nutritional assessment, quality of life, comorbidities, treatment regimen, toxicity graded by CTCAE v5.0, remission status, and survival) will be collected at predefined intervals up to day 100 of the maintenance phase. Germline and somatic DNA will be sampled at diagnosis and remission. The first phase will use whole-exome sequencing to discover candidate variants by implementing candidate gene prioritization strategy. The second phase will genotype the top candidates in the full cohort using array technology. Associations with early treatment related toxicities, steroid response, and survival will be tested by multivariable regression and Cox models. A machine-learning approach with pharmacogenetic predictors as classifiers will be implemented further with cross-validation and sensitivity analyses. RESULTS Ethical committees approved the protocol in 2020 (IEC-1167/06.11.2020 (AIIMS, New Delhi), JIP/IEC/2020/201 (JIPMER-Puducherry) and AO_2021-00048 (UNIGE, Geneva). Funding was received from SNSF-Switzerland, DBT-India, CANSEARCH Foundation-Switzerland. Recruitment began in December 2022 and is likely to conclude before May 2026. Data analysis is expected with manuscript submission in 2027. CONCLUSIONS MPGx-INDALL will generate actionable insights for individualized ALL therapy in India via systematically evaluating germline and somatic markers in a large, ethnically distinct cohort. CLINICALTRIAL ClinicalTrials.gov NCT05512169; https://clinicaltrials.gov/study/NCT05512169