Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: A report from the Childhood Cancer Survivor Study Journal Article
| Authors: | Friedman, D. N.; Goodman, P. J.; Leisenring, W. M.; Diller, L. R.; Cohn, S. L.; Howell, R. M.; Smith, S. A.; Tonorezos, E. S.; Wolden, S. L.; Neglia, J. P.; Ness, K. K.; Gibson, T. M.; Nathan, P. C.; Turcotte, L. M.; Weil, B. R.; Robison, L. L.; Oeffinger, K. C.; Armstrong, G. T.; Sklar, C. A.; Henderson, T. O. |
| Article Title: | Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: A report from the Childhood Cancer Survivor Study |
| 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. © The Author(s) 2024. Published by Oxford University Press. All rights reserved. |
| Keywords: | adolescent; adult; cancer chemotherapy; child; controlled study; preschool child; child, preschool; cancer surgery; young adult; major clinical study; mortality; united states; cancer radiotherapy; follow up; antineoplastic agent; cancer grading; antineoplastic metal complex; proportional hazards models; incidence; morbidity; cohort analysis; risk factors; alkylating agent; cyclophosphamide; autologous stem cell transplantation; retrospective study; risk factor; high risk patient; cancer survivor; proportional hazards model; neuroblastoma; thyroid cancer; hazard ratio; neoplasms, second primary; sibling; epidemiology; population dynamics; therapy; non-hodgkin lymphoma; sebaceous carcinoma; cancer survivors; intermediate risk patient; lymphoblastoma; childhood cancer survivor; acute myeloid leukemia; epipodophyllotoxin; low risk patient; humans; human; male; female; article; standardized mortality ratio; all cause mortality; second primary neoplasm |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 116 |
| Issue: | 6 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-06-01 |
| Start Page: | 885 |
| End Page: | 894 |
| Language: | English |
| DOI: | 10.1093/jnci/djae062 |
| PUBMED: | 38460547 |
| PROVIDER: | scopus |
| PMCID: | PMC11160496 |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is Danielle Novetsky Friedman -- Source: Scopus |
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