Late Major Surgical Intervention in Survivors of Childhood Cancer

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In an analysis from the Childhood Cancer Survivor Study (CCSS) reported in The Lancet Oncology, Dieffenbach et al found that childhood cancer survivors had a heavy cumulative burden of late major surgical interventions.

Study Details

The study involved data from the CCSS on 5-year survivors of childhood cancer diagnosed before age 21 years between January 1970 and December 1999. A group of nearest-age siblings of survivors was randomly selected for comparison. The primary outcome was any self-reported late major surgical intervention—defined as any anesthesia-requiring operation—occurring at ≥ 5 years after the primary cancer diagnosis.  

Key Findings

A total of 25,656 survivors and 5,045 siblings were included in the analysis. Among survivors, median age at diagnosis was 6.1 years (interquartile range [IQR] = 3.0–12.4 years) and median follow-up was 21.8 years (IQR = 16.5–28.4 years).   

Survivors underwent 28,202 late major surgical interventions, and siblings underwent 4,110. The 35-year mean cumulative counts of late major surgical intervention were 206.7 (95% confidence interval [CI] = 202.7–210.8) per 100 survivors vs 128.9 (95% CI = 123.0–134.7) per 100 siblings (adjusted rate ratio [RR] = 1.8, 95% CI = 1.7–1.9).

Among survivors, females were more likely to undergo surgical intervention than males (adjusted RR = 1.4, 95% CI = 1.4–1.5). Diagnosis of cancer in the 1990s among survivors was associated with an increased risk of late surgery vs diagnosis in the 1970s (adjusted RR = 1.4, 95% CI = 1.3–1.5); no significant relationship was observed among sibling controls (adjusted RR = 1.1, 95% CI = 0.9–1.3). Among survivors, the highest cumulative burdens of late surgical intervention expressed as 35-year mean cumulative counts per 100 survivors were observed for Hodgkin lymphoma (333.3, 95% CI = 320.1–346.6), Ewing sarcoma (322.9, 95% CI = 294.5–351.3), and osteosarcoma (269.6, 95% CI = 250.1–289.2).  

Survivor treatment involving locoregional surgery, radiotherapy, or both at the time of the initial cancer diagnosis was associated with undergoing late surgical intervention in the same body region or organ system. Survivors underwent late interventions more frequently vs sibling controls in most body regions or organ systems, including the central nervous system (adjusted RR = 16.9, 95% CI = 9.4–30.4), endocrine system (adjusted RR = 6.7, 95% CI = 5.2–8.7), cardiovascular system (adjusted RR = 6.6, 95% CI = 5.2–8.3), respiratory system (adjusted RR = 5.3, 95% CI = 3.4–8.2), spinal region (adjusted RR = 2.4, 95% CI = 1.8–3.2), breast region (adjusted RR = 2.1, 95% CI = 1.7–2.6), renal or urinary system (adjusted RR = 2.0, 95% CI =  1.5–2.6), musculoskeletal system (adjusted RR = 1.5, 95% CI =1.4–1.7), gastrointestinal system (adjusted RR = 1.4, 95% CI = 1.3–1.6), and head and neck region (adjusted RR = 1.2, 95% CI = 1.1–1.4).  

The investigators concluded, “Childhood cancer survivors have a significant burden of late, major surgical interventions, a late effect that has previously been poorly quantified. Survivors would benefit from regular health-care evaluations aiming to anticipate impending surgical issues and to intervene early in the disease course when feasible.”

Brent R. Weil, MD, of the Department of Surgery, Boston Children’s Hospital and Harvard Medical School, is the corresponding author for The Lancet Oncology article. 

Disclosure: The study was funded by the National Institutes of Health, National Cancer Institute, American Lebanese Syrian Associated Charities, and St. Jude Children’s Research Hospital. For full disclosures of the study authors, visit

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