10020 Background: Relapse remains the leading cause of treatment failure and mortality in pediatric acute myeloid leukemia (pAML). In AML, relapse is common and is increasingly recognized as a consequence of therapy-driven clonal evolution rather than mere persistence of the diagnostic clone. This study aimed to delineate mutational trajectories from diagnosis to relapse and identify relapse-associated genomic alterations of potential clinical relevance. Methods: This prospective study was conducted from July 2021 to December 2025. Bone marrow or peripheral blood samples were collected from children ≤18 years at diagnosis and relapse. Genomic DNA from paired samples was sequenced exomically to identify somatic mutations. Longitudinal comparative analyses assessed clonal persistence, emergence of relapse-specific mutations, and pathway-level enrichment. Results: A total of 100 children with AML were enrolled. Paired longitudinal analysis (n=18) identified 133 mutated genes. Seventy-nine (59.4%) were shared between diagnosis and relapse, forming a conserved truncal genomic backbone. Fifty genes (37.6%) were exclusive to diagnosis, while only four (3.0%) were exclusive to relapse, suggesting strong therapeutic selection pressure rather than widespread genomic diversification. At diagnosis, missense variants predominated (88.4%), followed by in-frame insertions/deletions (6.5%), nonsense (2.4%), and frameshift alterations (2.5%). Relapse samples showed further enrichment of missense variants (90.5%) and a relative depletion of truncating events, consistent with selection for functionally adaptive mutations. Truncal alterations were consistently observed in epigenetic regulators TET2 and KMT2C, supporting their role as early leukemogenic events. In contrast, relapse samples showed enrichment of signaling and transcriptional regulators, including FLT3 and PTPN11, along with relapse-exclusive emergence of WNT pathway components (FZD7, LEF1) and the PI3K regulator PIK3R1. Functional enrichment analysis revealed that diagnostic samples were primarily enriched for DNA damage response, p53 signaling, apoptosis, and cell-cycle checkpoint pathways (p<0.05). At relapse, these core programs persisted alongside marked enrichment of oncogenic signaling pathways (WNT, PI3K–AKT, FLT3) and metabolic processes, including glycolysis and ATP generation. Reactome analysis highlighted convergence on FLT3- and AKT-driven signaling, TP53-mediated DNA repair, and escape from apoptosis. Conclusions: Longitudinal genomic profiling demonstrates that pAML relapse is driven by the persistence of early truncal mutations, coupled with the selective expansion of signaling- and metabolism-adapted subclones. Enrichment of WNT, PI3K–AKT, and FLT3-associated pathways at relapse reveals potential targets for relapse-directed precision strategies.

PURPOSE The Pediatric Relapse Prediction and Risk Evaluation for Acute Lymphoblastic Leukemia (PREPARE-ALL) tool aims to predict relapse in pediatric ALL by integrating clinical expertise with artificial intelligence and machine learning (ML), particularly Extreme Gradient Boosting (XGBoost). PREPARE-ALL demonstrates that multicenter, protocol-driven clinical and laboratory data can be used through ML to generate reproducible relapse predictions with greater sensitivity than individual clinician assessments. METHODS PREPARE-ALL was developed using data from the ICiCLe ALL-14 pretrial cohort across five centers, incorporating 33 clinical and laboratory features. RESULTS Among 2,252 patients enrolled in the study, 565 (25.1%) relapsed. Using an 80:20 train-test split, XGBoost achieved a sensitivity of 68.5% (245/447 relapses detected). Additional metrics included a positive predictive value of 31.3%, a negative predictive value of 82.8%, an accuracy of 54.8%, and a specificity of 50.3%. Key predictors of relapse included high hyperdiploidy and BCR-ABL1 fusion positive, positive measurable residual disease status at the end of induction, sex, age, highest presenting WBC, and final risk group. Three clinicians scored the validation data set; the developed model achieved a higher recall (68.5%) compared with clinical judgment (approximately 31%-36%). CONCLUSION PREPARE-ALL identifies twice as many relapses as clinicians and serves as a practical decision-support tool for early relapse triage and treatment planning, enabling timely therapeutic adjustments and improved outcomes in pediatric ALL.

To assess the impact of adding rituximab on outcomes in children with aggressive mature B-non Hodgkin’s lymphoma (B-NHL) in resource-challenged settings. This retrospective study was conducted at a tertiary care cancer center in India. Children aged < 18 y with newly diagnosed advanced mature B-NHL between January 2004-June 2023 were included. Patients treated in December 2016 or after were included in the post-rituximab group and those treated prior were included in the pre-rituximab group. Clinical details were compiled from hospital records. Patients in the pre- and post-rituximab groups were matched using 1:1 propensity score matching to minimize baseline differences. The impact of rituximab on event-free survival (EFS) and overall survival (OS) was examined using multivariable Cox proportional hazards regression on the matched cohort. The cohort included 138 patients in the pre-rituximab and 82 in the post-rituximab groups of median age eight years. The 5-year EFS was 56.7

BACKGROUND & AIMS:Malnutrition is common among children with cancer in low- and middle-income countries (LMICs). Although baseline undernutrition has been associated with complications and inferior outcomes, prospective data evaluating how longitudinal nutritional changes relate to survival are limited. In this study we aimed to study the longitudinal changes in anthropometric measures during treatment of childhood cancer and their association with event-free survival (EFS) and overall survival (OS). METHODS:Children aged 18 years or younger with a new diagnosis of malignancy between August 1, 2016, and April 30, 2021, were enrolled in this prospective cohort study conducted at a tertiary care hospital in New Delhi, India. Serial measurements of weight, height, and mid-upper arm circumference were obtained at diagnosis and during follow-up visits up to one year after diagnosis. Multivariable Cox regression models adjusted for age, sex, malignancy type, and baseline anthropometric status were used to evaluate associations between longitudinal nutritional changes and survival in a landmark cohort of patients alive and event-free at 6 months after diagnosis. RESULTS:A total of 1931 children (median [IQR] age, 8 [0.1-18] years; 1374 [71.2%] male) were included, of whom 996 formed the landmark analysis cohort. The 5-year EFS and OS of the overall cohort was of 49.1% and 53.3%, respectively. At diagnosis, 328 children (17.0%) had wasting (body mass index-for-age Z-score < -2 SD), 417 (21.6%) had stunting (height-for-age Z-score < -2 SD), and 979 (55.5%) had mid-upper arm circumference Z-scores < -2 SD. Weight loss greater than 5% was observed in 312 patients (22.1%) at 3 months, 157 (15.1%) at 6 months, 61 (8.6%) at 9 months, and 31 (6.4%) at 12 months among those with available follow-up data. In the landmark cohort, weight loss >5% at or after six months was independently associated with inferior EFS (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.22-2.33; P = 0.002) and OS (aHR, 1.92; 95% CI, 1.37-2.68; P < 0.001). Similarly, children who had wasting at or after six months had inferior EFS and OS compared with those without wasting. CONCLUSION:Weight loss >5% after six months is independently associated with inferior overall survival. Ongoing nutritional monitoring is essential to improve outcomes in children with cancer in LMICs.

OBJECTIVES:Lacrimal gland adenoid cystic carcinoma (ACC) is a rare and lethal malignancy associated with a poor prognosis, with no known therapeutic targets. The clinical relevance of Myb, Sox4, c-Kit protein expression, and the MYB::NFIB fusion gene in lacrimal gland ACC is not well known. The current study aims to investigate the prognostic significance of Myb, Sox-4, c-Kit protein, and the MYB::NFIB fusion gene in lacrimal gland ACC. METHODS:A total of 30 histopathologically diagnosed lacrimal gland ACC cases were included in this study. Myb, Sox4, c-Kit expression, and MYB::NFIB gene fusion were evaluated by immunohistochemistry and fluorescence in situ hybridization, respectively. The results were correlated with clinicopathologic features and patient survival. RESULTS:Immunoexpression of Myb, Sox4, and c-Kit was observed in 70%, 63%, and 63% of ACC cases, respectively. Myb expression showed a significant association with the solid and cribriform histologic patterns, Sox-4 expression, and disease-free survival. On univariate analysis, Myb expression, solid histologic pattern, bone erosion, intracranial extension, and advanced tumor stage were indicators of poor prognosis. c-Kit expression showed a significant association with advanced tumor stage. MYB::NFIB fusion, detected in 47% of cases, was significantly associated with intracranial extension. CONCLUSIONS:Myb protein emerged as a prognostic indicator in the pathogenesis and clinical outcomes of patients with lacrimal gland ACC.

PURPOSEChildhood 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.METHODSWe 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.RESULTSWe 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.CONCLUSIONFor 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.

Introduction: Deficiency of the dihydropyrimidine dehydrogenase enzyme can result in capecitabine-related toxicity due to genetic alterations in the DPYD gene, leading to complete or partial DPD deficiency and poor or intermediate metabolizer phenotypes. The distribution of DPYD variants varies across populations. While routine DPYD genotyping is recommended in Western populations, data from India, particularly from next-generation sequencing (NGS)-based studies, remain limited. Methods: This exploratory analysis was conducted within the D-TORCH trial, a randomized, double-blind, placebo-controlled study evaluating topical diclofenac for prevention of capecitabine-induced hand-foot syndrome. Germline whole-exome sequencing was performed in consenting patients prior to capecitabine initiation. DPYD variants were identified using an NGS pipeline, annotated via ANNOVAR and PharmGKB, and classified according to CPIC guidelines. Results: Seventy-six patients underwent DPYD sequencing; 54 (71%) carried at least one variant and 22 (29%) were wild-type. Thirteen coding or splice-site variants were identified, including three (3.9%) associated with an intermediate metabolizer phenotype; no poor metabolizers were detected. The most common variants were classified as normal metabolizers. Grade 2 toxicity occurred in 63.6% of variant carriers and 55.6% of wild-type patients, with diarrhea and mucositis being most frequent. No significant association was observed between DPYD variant status and toxicity. Discussion: This first NGS-based DPYD report from India highlights the low prevalence of clinically actionable variants. Larger studies are required to validate these findings and guide population-specific fluoropyrimidine dosing strategies.

Background/Objectives: Juvenile myelomonocytic leukemia (JMML) is a rare, highly aggressive form of pediatric myelodysplastic/myeloproliferative neoplasm characterized by molecular heterogeneity and constitutive activation of the RAS signaling pathway. This study aimed to characterize the mutational landscape, driver genes, mutational signatures, functional pathways, and therapeutic potential of mutated epigenetic regulator genes in JMML. Methods: Tumor and matched buccal swab samples were collected from 35 JMML patients, and whole-exome sequencing was performed. Somatic variants were called with GATK-Mutect2 and annotated with ANNOVAR. maftools and OncodriveCLUST were used for mutational profiling, co-occurrence analysis, driver gene identification, and protein domain mapping. Drug-gene interactions were explored using DGIdb, mutational signatures for genes were characterized by MutationalPatterns, and functional enrichment analysis was performed by the clusterProfiler package. Results: A total of 28 variants were detected in epigenetic regulator genes, with missense mutations being the most common class of variants and a C>T nucleotide substitution pattern being the most frequent. EP300, SETD2, and DNMT3B were the genes most frequently altered, with 8.57% of cases each, followed by ASXL1, BCORL1, ATRX, KMT2A, and TET2 (5.71% each). Driver gene analysis identified ASXL1 as the top candidate driver gene, followed by BCORL1, EP300, and SETD2. Functional enrichment analysis revealed a high number of genes involved in chromatin organization, histone modification, transcriptional regulation, and oncogenic signaling pathways. The mutational signatures identified were SBS5-like, which are dominated by C>T and T>C transitions, indicating endogenous mutational processes. Analysis of drug-gene interactions revealed KMT2A, EP300, and ATRX as the most interconnected and potentially actionable therapeutic targets. Conclusions: This study provides a comprehensive characterization of epigenetic regulator gene alterations in JMML and highlights the importance of epigenetic dysregulation in disease pathogenesis.

Radiotherapy outcomes are strongly influenced by the DNA damage response (DDR), a coordinated network of signalling proteins, that detects breaks in DNA, and governs DNA repair, cell cycle checkpoint activation and cell-fate decisions. While canonical DDR control has traditionally been attributed to protein kinases such as ataxia-telangiectasia mutated (ATM), ATM and rad3-related (ATR), and DNA-dependent protein kinase catalytic subunit (DNA-PKcs), accumulating evidence demonstrates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and emerging small RNA classes, serve as important upstream regulators of these pathways. In this review, we synthesise current evidence on how ncRNAs regulate core DDR signalling networks and direct the balance between homologous recombination (HR) and non-homologous end joining (NHEJ), thereby influencing repair fidelity and overall cellular responses to radiation. We outline how ncRNAs regulate early DDR events in response to ionizing radiation, including the sensing of DNA double-strand breaks and the chromatin remodelling required for efficient recruitment of repair factors. In addition, we summarise emerging radiation-responsive RNA species such as DNA damage response RNAs (DDRNAs), vault RNAs (vtRNAs), and tRNA-derived fragments (tRFs) that contribute to genome stability and stress adaptation. Clinically, circulating ncRNAs represent minimally invasive biomarkers of radiation response, and their targeted modulation offers an opportunity for improving radiotherapy outcome, highlighting the translational relevance of defining ncRNA-mediated DDR regulation.

BACKGROUND:Delayed platelet recovery remains a frequent and clinically significant complication following hematopoietic stem cell transplantation (HSCT) in children, contributing to increased transfusion burden, bleeding risk, and prolonged hospitalization. Thrombopoietin receptor agonists (TPO-RAs), including romiplostim, have demonstrated activity in post-transplant thrombocytopenia; however, prospective pediatric data on their early post-transplant use are limited. We evaluated the safety and potential effects of early romiplostim administration on platelet and hematopoietic recovery following pediatric HSCT. METHODS:In this prospective, open-label, randomized pilot study conducted at a tertiary care center in India, children aged 1-18 years undergoing autologous or allogeneic HSCT were randomized (1:1) to receive standard post-transplant care with or without romiplostim. Romiplostim (5 µg/kg subcutaneously) was administered on Days +1 and +8 post-transplant (or Days +5 and +12 for haploidentical transplants with post-transplant cyclophosphamide). The primary endpoint was time to platelet engraftment (platelet count ≥20 × 109/L for 3 consecutive days without transfusion). Secondary endpoints included platelet transfusion requirements, platelet nadir, platelet counts on Day +28, time to platelet count ≥50 × 109/L, neutrophil recovery, bleeding, and thrombotic events. RESULTS:Thirty-two children were enrolled (romiplostim n = 17; control n = 15). Median time to platelet engraftment was comparable between the romiplostim and control groups (12 vs. 12.5 days; p = 0.88), with no significant difference on Kaplan-Meier analysis. Platelet transfusion requirements, platelet nadir, and time to platelet count ≥50 × 109/L were also similar between groups. By Day +28, higher platelet counts were observed in the romiplostim arm, with exploratory subgroup analysis demonstrating higher platelet counts following allogeneic HSCT. Romiplostim recipients also demonstrated higher absolute neutrophil counts on Day +28. No thrombotic events, severe bleeding episodes, or drug-related serious adverse events were observed. CONCLUSION:Early administration of romiplostim following pediatric HSCT was safe and well tolerated, with no significant treatment-related toxicity observed. Although it did not shorten time to platelet engraftment, exploratory analyses demonstrated higher Day +28 platelet and neutrophil counts, generating the hypothesis that romiplostim may support sustained hematopoietic recovery. These findings require confirmation in larger, adequately powered multicenter studies before conclusions regarding efficacy can be drawn.

BACKGROUND:Delays in diagnosis and treatment, driven in part by limited geographic access to specialized care, continue to hinder childhood cancer outcomes. In this study, we aimed to evaluate motorized travel times for children seeking care at three referral childhood cancer centers in India. METHODS:This multi-center retrospective study analyzed individual-patient level data for children (aged ≤19 years) diagnosed with cancer between 2005 and 2019 at three tertiary hospitals in India: All India Institute of Medical Sciences (AIIMS) and Rajiv Gandhi Cancer Institute (RGCI) in New Delhi, and Women's Indian Association (WIA) Cancer Institute in Chennai. Patient residential addresses were geocoded, and travel times were estimated using Malaria Atlas Project friction surface rasters and Dijkstra's algorithm. An exploratory logistic regression analysis was performed to identify factors associated with prolonged motorized travel time (>60 min). RESULTS:A total of 22,328 patients with a median age of 10 years (IQR 4-15), 32·5% (n = 7261) female, and 54·2% (n = 12,093) with solid malignancies were included. The median motorized travel time was 161 min (IQR 27-430), with 73·5% of patients traveling > 60 min. Male sex (aOR 1·23, 95% CI: 1·15-1·31; p < 0·001) and solid malignancies (aOR 1·09, 95% CI: 1·03-1·16; p = 0·004) were associated with prolonged travel time. Compared with AIIMS, WIA had higher odds (aOR 2·79, 95% CI: 2·58-3·03) and RGCI had lower odds (aOR 0·69, 95% CI: 0·65-0·74) of prolonged travel time (p < 0·001). CONCLUSION:Children with cancer in India face a substantial travel time burden to access cancer care, highlighting the need for expansion of pediatric oncology services. POLICY SUMMARY:There is a need for policies that expand pediatric oncology capacity beyond major urban referral centers, strengthen regional treatment networks, and improve referral systems to reduce delays and disparities in diagnosis and treatment and improve childhood cancer outcomes.

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.

The interaction of cellular organelles is crucial for maintaining intracellular homeostasis, particularly highlighting the impact of the cytoskeleton on mitochondrial dynamics. The aim of our study is to find direct molecular connections between cytoskeletal disturbance and mitochondrial failure which are inadequately characterized particularly in B-ALL. We investigated the effects of cytoskeleton inhibition on mitochondria in B-ALL using Pironetin (an alpha-tubulin inhibitor) and Latrunculin B (an actin inhibitor). Our findings indicate that these inhibitors caused mitochondrial fragmentation, characterized by smaller, rounder mitochondria with disordered cristae, increased Drp1 expression (fission protein), and decreased Mfn 1/2 and OPA 1 (fusion proteins) together with significantly modified the expression of essential mitochondrial transporters, such as VDAC and ANT2. These alterations were linked to increased mitochondrial membrane depolarization & mitochondrial reactive oxygen species and gradual mtDNA depletion, indicative of impaired oxidative phosphorylation (increased non-mitochondrial oxygen consumption, decreased mitochondrial reserve capacity) and diminished mitochondrial functionality. These mitochondrial alterations indicate that communication between the cytoskeleton and mitochondria is essential for preserving mitochondrial homeostasis. This study potentially enhances our understanding of how cancer cells modulate mitochondrial function during progression or therapeutic interventions.

Abstract Background Acute pain syndrome (APS) is a common side effect of paclitaxel therapy. To date, there is no standard of care to prevent APS in patients receiving paclitaxel. Through this study, we aim to assess whether oral duloxetine reduces the incidence of paclitaxel-induced APS (P-APS) as compared to placebo. Methods This is a multi-centric, randomized (1:1), double-blind, placebo-controlled, parallel-group superiority trial. A total of 204 patients with breast cancer planned to receive paclitaxel will be randomly assigned to receive either oral duloxetine or a matched placebo for 7 days after paclitaxel infusions for 4 cycles. The primary objective of the study is to compare the proportion of patients who develop P-APS in two groups. Key secondary objectives are to compare the quality of life (using the FACT-B scale), the incidence of peripheral neuropathy, the safety profile, and adherence with duloxetine. Patient-reported outcomes for P-APS and neuropathy will be assessed at the end of each cycle using BPI-SF and EORTC-CIPN20 questionnaires, respectively. Discussion The DOPA study is designed to evaluate whether oral duloxetine can reduce the occurrence of APS in patients receiving paclitaxel chemotherapy for breast cancer. Limited trials have assessed P-APS prevention using etoricoxib, dexamethasone, and pregabalin, but no pharmacological measure is effective. If the trial successfully meets its primary endpoint, oral duloxetine could become the new standard of care for preventing paclitaxel-induced APS. Trial registration Clinical Trials Registry of India – CTRI/2024/10/075636. Registered on 22 October 2024.

PURPOSEChildhood 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.METHODSWe 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.RESULTSOf 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.CONCLUSIONChildhood 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.

10017 Background: Dexamethasone, with a 5-HT3 receptor antagonist and a neurokinin-1 antagonist, is the guideline-recommended prophylaxis for chemotherapy-induced nausea and vomiting (CINV) in children and adolescents receiving highly emetogenic chemotherapy (HEC), but is associated with clinically relevant toxicities. The role of olanzapine as a dexamethasone-sparing agent for pediatric CINV prophylaxis remains uncertain. Methods: This investigator-initiated, multicenter, open label, phase III randomized non-inferiority (NI) trial (INPHOG-SUPP-22-03) enrolled patients aged 4–18 years receiving single or multi-day HEC. Patients were randomized 1:1 (single chemotherapy cycle) to receive dexamethasone, palonosetron, and fosaprepitant (DEX; standard-of-care) or olanzapine, palonosetron, and fosaprepitant (OLANZ; dexamethasone-free). The primary endpoint was complete response (CR) to vomiting (no vomiting and no rescue anti-emetics) during the overall period (0–120 h after the last chemotherapy dose). A NI margin of −15% was prespecified based on adult dexamethasone-sparing trials. Assuming a control CR rate of 70% from prior pediatric studies, 310 patients provided 80% power at a one-sided α of 0.025, allowing for 5% dropout. Absolute differences in CR rates were analyzed using the Miettinen–Nurminen method; NI was concluded if the lower bound of the 95% confidence interval (CI) was above −15%. Results: Between December 2022 and January 2026, 310 patients were randomized (DEX, n=156; OLANZ, n=154). The per-protocol (PP) population included 299 patients (DEX, n=151; OLANZ, n=148). Median age was 13 years; 62.2% were male, and 56.8% received multi-day HEC. In the PP population, the CR rate for vomiting during the overall period was 56.9% in the DEX arm and 63.5% in the OLANZ arm (absolute difference, 6.6%; 95% CI, −4.5% to 17.7%). Non-inferiority was demonstrated, as the lower 95% CI (−4.5%) was above −15%. Results were consistent in the intention-to-treat population. For secondary endpoints, CR to vomiting during the acute period (0-24 h) was 64.2% vs 68.9%, and during the delayed period (24-120 h) 78.8% vs 79.1%, in the DEX and OLANZ arms, respectively. CR to nausea during the overall period was 54.3% vs 53.4%, during the acute period 59.6% vs 59.5%, and during the delayed period 69.5% vs 68.9%, respectively. Grade ≥2 non-hematologic and hematologic laboratory toxicities were uncommon and similar between arms. Any-grade somnolence was significantly higher with OLANZ than DEX (52.0% vs 25.8%), with all events being ≤ grade 2. Conclusions: A dexamethasone-free antiemetic regimen was non-inferior to standard dexamethasone-based prophylaxis for prevention of vomiting in children and adolescents receiving HEC. These findings support the use of olanzapine as an effective steroid-sparing alternative. Clinical trial information: CTRI/2022/08/045009.

BACKGROUND:Alterations in genes involved in homologous recombination repair (HRR) occur in approximately 20%-25% of patients with metastatic prostate cancer and are associated with aggressive biology, poor outcomes, and potential sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). However, frequency and variations in somatic HRR mutations in the Indian population are unknown. METHODS:We analyzed somatic HRR alterations in patients at the All India Institute of Medical Sciences, New Delhi, between 2022 and November 2024. Targeted next-generation sequencing of 15 HRR genes was performed on tumor tissue samples. Demographic and clinicopathological variables were retrieved from medical records, and their associations were assessed. RESULTS:Of 247 patients tested, 167 were evaluable (32.3% tissue failure due to poor DNA yield). Sixty-eight pathogenic HRR alterations were detected across 51 patients (30.5%). ATM was the most frequently altered gene (13.2%), followed by BRCA1 (5.3%), BRCA2 (4.2%), and CDK12 (4.2%). Variants of unknown significance (VUS) were detected in 12% (20) of patients. Patients with HRR alterations had higher baseline PSA values compared with the non-HRR cohort (median 150 vs 100 ng/mL, P = .012). No significant associations were observed with age, Gleason score, disease volume or risk category, or visceral metastases. CONCLUSIONS:This study provides the first comprehensive dataset on the spectrum of somatic HRR mutations in Indian patients with prostate cancer. The prevalence (30.5%) was somewhat higher than the global studies, ATM was the most frequently mutated gene, followed by BRCA1, in contrast to Western and Asian cohorts, where BRCA2 predominates. These findings suggest potential population-specific variations and underscore the need for broader HRR testing to better delineate the genomic landscape of prostate cancer in Indian patients.

PURPOSE:Dexamethasone combined with a 5-hydroxytryptamine-3 receptor antagonist and a neurokinin-1 receptor antagonist is the guideline-recommended prophylaxis for chemotherapy-induced nausea and vomiting (CINV) in children receiving highly emetogenic chemotherapy (HEC), but it is associated with clinically relevant toxicities. The role of olanzapine as a dexamethasone-sparing agent for pediatric CINV prophylaxis remains uncertain. METHODS:The Chemotherapy Induced Vomiting in Children-Prophylaxis Omitting Dexamethasone (CIVIC POD) was an investigator-initiated, multicenter, open-label, phase III, randomized noninferiority (NI) trial (INPHOG-SUPP-22-03) that enrolled patients age 4-18 years scheduled to receive single- or multiday HEC. Patients were randomly assigned 1:1 to dexamethasone, palonosetron, and fosaprepitant (DEX) or olanzapine, palonosetron, and fosaprepitant (OLANZ) for one chemotherapy cycle. The primary end point was complete response (CR) to vomiting (no vomiting and no rescue antiemetics) during the overall period (0-120 h after last chemotherapy). The prespecified NI margin was -15%. RESULTS:A total of 310 patients were randomly assigned (DEX, n = 156; OLANZ, n = 154). The median age was 13 years, 62.3% were male, and 51.9% received multiday chemotherapy. The per-protocol population included 299 patients (DEX, n = 151; OLANZ, n = 148). The overall-period CR to vomiting was 56.9% with DEX and 63.5% with OLANZ (absolute difference, 6.6% [95% CI, -4.5 to 17.7]), meeting NI criteria. Acute-period CR to vomiting was 64.2% versus 68.9%, and delayed-period CR was 78.8% versus 79.1% (DEX v OLANZ). CR to nausea during the overall, acute, and delayed periods was 54.3% versus 53.4%, 59.6% versus 59.5%, and 69.5% versus 68.9%, respectively. Any-grade somnolence was more frequent with OLANZ (50.7% v 17.2%). CONCLUSION:A dexamethasone-free regimen using olanzapine demonstrated noninferior control of vomiting compared with standard prophylaxis in children and adolescents receiving HEC, supporting olanzapine as a potential corticosteroid-sparing alternative for pediatric CINV prophylaxis.

BACKGROUND:Acute graft-versus-host disease (aGvHD) is a major immune complication of allogeneic hematopoietic stem cell transplantation (Allo-HSCT), driven by complex immune-cytokine interactions. This study employed machine learning (ML) algorithms to develop early predictive models for aGvHD using immune and cytokine profiles of Allo-HSCT recipients at the time of engraftment. MATERIALS AND METHODS:Seventy patients with hematological disorders undergoing their first Allo-HSCT were recruited prospectively. Peripheral blood immune subsets and cytokines were analyzed using flow cytometry and ELISA, respectively. ML models, including support vector classifier (SVC), decision tree, and random forest, were trained on 48 features: 34 immune subsets and 14 cytokines. RESULTS:Patients who developed aGvHD exhibited a reduced CD4+/CD8+ ratio, lower Tregs, elevated Th1, Th17, cytotoxic natural killer (NK) cells, dendritic cells (DCs), B cell, and increased proinflammatory cytokines (IFN-γ, IL-1β, IP-10, TNF-α, IL-17α, IL-12p70, MIP-1α, MIP-1β, and RANTES). ML models demonstrated excellent predictive performance, with cytokine profiles alone or combined with immune data achieving perfect accuracy (1.00), followed by T-cell (0.96), NK cell (0.93), DC (0.90), and B cell (0.86) models. CONCLUSION:Cytokine profiles emerged as superior predictors over immune subsets, supporting their integration into ML-based aGvHD risk prediction. These findings provide a foundation for developing biomarker-guided strategies for early aGvHD detection and management.

OBJECTIVES:To assess the trial-based cost-effectiveness of an intravenous fosaprepitant-based antiemetic regimen compared with oral aprepitant, in combination with ondansetron and dexamethasone, among children receiving highly emetogenic chemotherapy in India and the USA using individual patient-level data. METHODS:Costs were estimated from a private payer perspective in India and the USA. Health outcomes were expressed as quality-adjusted life-years (QALYs). Incremental cost-utility ratio (ICUR) and incremental net monetary benefit (iNMB) were calculated. Uncertainty was evaluated through one-way deterministic sensitivity analyses. RESULTS:A total of 140 and 139 children were enrolled in the fosaprepitant and aprepitant groups, respectively. Mean QALYs were marginally higher in the aprepitant group (0.0118 vs 0.0116; difference: 0.0002). In India, mean costs were $33.94 in the fosaprepitant arm vs $19.73 in the aprepitant arm (difference: $14.21). In the USA, mean costs were $615.92 vs $809.73, respectively, in the two arms (difference: $193.81), favouring fosaprepitant. iNMB values of fosaprepitant compared with aprepitant were -$15.59 in India and $173.81 in the USA, indicating lack of cost-effectiveness for fosaprepitant in India but cost-effectiveness in the USA. In sensitivity analyses, the ICUR was most sensitive to the cost of fosaprepitant in India and to the utility value of the complete protection health state in the USA. CONCLUSIONS:Intravenous fosaprepitant, administered in combination with ondansetron and dexamethasone, was not cost-effective compared with oral aprepitant-based combination therapy in India but demonstrated cost-effectiveness in the USA.