1. Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the Childhood Cancer Survivor Study.
- Author
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Friedman, Danielle Novetsky, Goodman, Pamela J, Leisenring, Wendy M, Diller, Lisa R, Cohn, Susan L, Howell, Rebecca M, Smith, Susan A, Tonorezos, Emily S, Wolden, Suzanne L, Neglia, Joseph P, Ness, Kirsten K, Gibson, Todd M, Nathan, Paul C, Turcotte, Lucie M, Weil, Brent R, Robison, Leslie L, Oeffinger, Kevin C, Armstrong, Gregory T, Sklar, Charles A, and Henderson, Tara O
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NEUROBLASTOMA , *CHILDHOOD cancer , *CANCER survivors , *STEM cell transplantation , *MORTALITY , *REGRESSION analysis - Abstract
Background Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described. Methods Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings. Results Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1]). Conclusion Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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