Late effects after novel therapies for childhood cancer: Anticipating the future landscape of health outcomes for survivors

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ID: 331742
2026
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Abstract
Five-year survival rates for childhood cancer now exceed 85%, with recent improvements driven by advances in understanding of tumor biology allowing for molecular risk stratification. The introduction of novel therapies, including antibodies, antibody-drug conjugates, immune checkpoint inhibitors, cellular therapy, and targeted small molecule inhibitors into early-phase and pivotal trials has the potential to further improve survival. Although these agents have transformed outcomes for some children with cancer, their long-term toxicity profiles remain poorly defined. Large cohort studies have characterized the late effects of conventional cytotoxic chemotherapies and radiation, informing survivorship guidelines and risk-based surveillance strategies. In contrast, the distinct mechanisms of action of targeted and immune-based therapies introduce new and potentially persistent toxicities affecting cardiovascular, neurologic, endocrine, gastrointestinal, and immune systems. This review synthesizes current evidence on acute toxicities of novel therapies and summarizes available data about persistent long-term toxicities and new onset late effects outcomes, including growth impairment, persistent immune dysfunction, and subsequent malignancies in children treated with these agents. We focus on therapies with U.S. Food and Drug Administration approval for pediatric indications. Current evidence from acute toxicity profiles, limited pediatric long-term follow-up, and emerging data from adult populations highlights the urgent need for systematic evaluation of long-term outcomes in children treated with these therapies. As the use of novel agents continues to expand, extending established survivorship cohorts to include children exposed to novel therapies, while developing complementary approaches to detect previously unrecognized toxicities, will be essential for defining late effects and informing evidence-based surveillance and intervention strategies.
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Authors Amy M. Berkman, David T. Teachey, Matthew J. Ehrhardt, Ching‐Hon Pui, Hiroto Inaba, Seth E. Karol, Sharon M. Castellino, Stephanie B. Dixon, Jun J Yang, Thomas G. Gross, Sara Michele Federico, Roger J. Packer, Alberto S. Pappo, Ibrahim A. Qaddoumi, Ralph Salloum, Stephanie M Smith, Todd M. Cooper, Tara Olive Henderson, Douglas S. Hawkins, Paul Craig Nathan, Eric Jessen Chow, Elizabeth Fox, Gregory T. Armstrong
Journal JNCI Journal of the National Cancer Institute
Year 2026
DOI
10.1093/jnci/djag371
URL
https://doi.org/10.1093/jnci/djag371
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