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Late Mortality, Subsequent Malignant Neoplasms, and Chronic Health Conditions Among Survivors of Neuroblastoma Diagnosed During Infancy


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In an analysis from the Childhood Cancer Survivor Study reported in the Journal of Clinical Oncology, Friedman et al found low rates of late mortality and subsequent malignant neoplasms in survivors of neuroblastoma treated in infancy. The risk of severe chronic health conditions decreased during more recent years with reduced use of radiotherapy.

Study Details

The analysis included 1,397 eligible 5-year survivors of neuroblastoma diagnosed at age < 1 year between 1970 and 1999; the total cohort was assessed for incidence of late mortality (> 5 years from diagnosis). A total of 990 survivors with completed baseline surveys and up to 6 follow-up questionnaires were evaluated for subsequent malignant neoplasms and grade 3 to 5 chronic health conditions. Multivariate analysis was performed to derive hazard ratios (HRs) for outcomes by treatment eras (1970s, 1980s, 1990s) and by treatment (surgery alone vs chemotherapy with or without surgery [C ± S] vs radiation with or without chemotherapy or with or without surgery [R ± C ± S]) among survivors and between survivors and 5,051 siblings.

Key Findings

Among the 1,397 survivors, the 25-year cumulative incidence of late mortality was 2.1% (95% confidence interval [CI] = 1.3%–3.9%). No significant differences were observed according to treatment era or treatment. By 25 years after diagnosis, neuroblastoma survivors were 2.1 times more likely to die vs matched U.S. population controls (standardized mortality ratio = 2.1, 95% CI = 1.5–3.1). Among 990 patients with a completed baseline survey, the proportion who received radiation declined from 51.2% in the 1970s, to 20.4% in the 1980s, and then to 10.1% in the 1990s (P < .001).

The 25-year cumulative incidence of subsequent malignant neoplasms was 1.2% in patients diagnosed during the 1970s, 3.5% for those diagnosed in the 1980s, and 0.0% for those diagnosed in the 1990s. Compared with surgery alone, the risk of subsequent malignant neoplasms was significantly elevated among those receiving radiation-containing regimens: hazard ratios were 5.7 (95% CI = 1.2–28.1) for those receiving R ± C ± S and 3.2 (95% CI = 0.9–11.6) for those receiving C ± S.

The 20-year cumulative incidence of grade 3 to 5 chronic health conditions was 21.9% among survivors diagnosed in the 1970s, 23.2% among those diagnosed in the 1980s, and 17.4% among those diagnosed in the 1990s; it was 10.6% among those receiving surgery alone, 20.1% among those receiving C ± S, and 39.5% among those receiving R ± C ± S. In adjusted analysis, compared with survivors diagnosed in the 1970s, those diagnosed in the 1990s had a significantly reduced risk of grade 3 to 5 chronic health conditions (HR = 0.5, 95% CI = 0.3–0.9); no significant difference was observed for those diagnosed in the 1980s (HR = 0.97, 95% CI = 0.6–1.5). Compared to patients receiving surgery alone, those treated with radiation-containing regimens had a significantly increased risk of grade 3 to 5 chronic health conditions. Hazard ratios were 3.6 (95% CI = 2.1–6.2) among those receiving R ± C ± S and 1.4 (95% CI = 0.8–2.5) among those receiving C ± S. 

Compared with siblings, the risk of grade 3 to 5 chronic health conditions among survivors decreased from hazard ratios of 4.7 (95% CI = 3.4–6.5) among those diagnosed in the 1970s and 4.6 (95% CI = 3.3–6.4) among those diagnosed in the 1980s to 2.5 (95% CI = 1.7–3.9) among those diagnosed in the 1990s.

The investigators concluded, “Neuroblastoma survivors treated during infancy have a relatively low absolute burden of late mortality and subsequent malignant neoplasms. Encouragingly, risk of chronic health conditions has declined in more recent eras with reduced exposure to radiation therapy.”

Danielle Novetsky Friedman, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article. 

Disclosure: The study was supported by the National Cancer Institute and American Lebanese-Syrian Associated Charities. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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