Long-Term Morbidity and Mortality Among Survivors of Neuroblastoma Diagnosed During Infancy: A Report From the Childhood Cancer Survivor Study

Authors

Danielle Novetsky Friedman
Pamela J Goodman
Wendy M Leisenring
Lisa R Diller
Susan L Cohn
Rebecca M Howell
Susan A Smith
Emily S Tonorezos
Suzanne L Wolden
Joseph P Neglia
Kirsten K Ness
Todd M Gibson
Paul C Nathan
Brent R Weil
Leslie L Robison
Kevin C Oeffinger
Gregory T Armstrong
Charles A Sklar
Tara O Henderson

Publication Date

3-10-2023

Journal

Journal of Clinical Oncology

Abstract

Purpose: To describe the risk of late mortality, subsequent malignant neoplasms (SMNs), and chronic health conditions (CHCs) in survivors of neuroblastoma diagnosed in infancy by treatment era and exposures.

Methods: Among 5-year survivors of neuroblastoma in the Childhood Cancer Survivor Study diagnosed age < 1 year between 1970 and 1999, we examined the cumulative incidence of late (> 5 years from diagnosis) mortality, SMN, and CHCs (grades 2-5 and 3-5). Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs by decade and treatment (surgery-alone v chemotherapy with or without surgery [C ± S] v radiation with or without chemotherapy ± surgery [R ± C ± S]) among survivors and between survivors and 5,051 siblings.

Results: Among 1,397 eligible survivors, the 25-year cumulative incidence of late mortality was 2.1% (95% CI, 1.3 to 3.9) with no difference by treatment era. Among 990 participants who completed a baseline survey, fewer survivors received radiation in more recent eras (51.2% 1970s, 20.4% 1980s, and 10.1% 1990s; P < .001). Risk of SMN was elevated only among individuals treated with radiation-containing regimens compared with surgery alone (HR[C ± S], 3.2 [95% CI, 0.9 to 11.6]; HR[R ± C ± S], 5.7 [95% CI, 1.2 to 28.1]). In adjusted models, there was a 50% reduction in risk of grade 3-5 CHCs in the 1990s versus 1970s (HR, 0.5 [95% CI, 0.3 to 0.9]; P = .01); individuals treated with radiation had a 3.6-fold risk for grade 3-5 CHCs (95% CI, 2.1 to 6.2) versus those treated with surgery alone. When compared with siblings, risk of grade 3-5 CHCs for survivors was lowest in the most recent era (HR[1970s], 4.7 [95% CI, 3.4 to 6.5]; HR[1980s], 4.6 [95% CI, 3.3 to 6.4]; HR[1990s], 2.5 [95% CI, 1.7 to 3.9]).

Conclusion: Neuroblastoma survivors treated during infancy have a relatively low absolute burden of late mortality and SMN. Encouragingly, risk of CHCs has declined in more recent eras with reduced exposure to radiation therapy.

Keywords

Child, Infant, Humans, Cancer Survivors, Retrospective Studies, Survivors, Neuroblastoma, Morbidity, Incidence, Neoplasms, Second Primary

DOI

10.1200/JCO.22.01732

PMID

36525618

PMCID

PMC10043581

PubMedCentral® Posted Date

12-16-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes