In a report from the Childhood Cancer Survivor Study published in the Journal of Clinical Oncology, Weil et al found that splenectomy and splenic radiation significantly increased the risk of infection-related late mortality among 5-year survivors of childhood cancer.
The study included 20,026 5-year survivors of childhood cancer diagnosed at < 21 years of age between 1970 and 1999. Patients had a median age at diagnosis of 7.0 years (range = 0–20 years) and median follow-up of 26 years (range = 5–44). Splenic radiation was approximated using average direct or indirect dose to the left upper-abdominal quadrant.
Within 5 years of diagnosis, 1,354 survivors (6.8%) had a splenectomy and 9,442 (46%) had splenic radiation without splenectomy. Overall, there were 62 late deaths attributable to infection, with 55 occurring in patients with splenectomy or splenic radiation.
The cumulative incidence of infection-related late mortality at 35 years was 1.5% after splenectomy and 0.6% after splenic radiation, compared with 0.2% among patients with neither intervention. In multivariate analysis, splenectomy was independently associated with late infection-related mortality (relative rate [RR] = 7.7, P < .001).
Splenic radiation was associated with increasing risk in a dose-related manner: RR = 2.0 (P = .08) for 0.1 to 9.9 Gy; RR = 5.5 (P = .001) for 10 to 19.9 Gy; and RR = 6.0 (P = .004) for ≥ 20 Gy. High alkylator chemotherapy exposure (cyclophosphamide equivalent dose) was also independently associated with increased risk of infection-related mortality (RR = 1.9, P = .018).
The investigators concluded, “Splenectomy and splenic radiation significantly increase risk for late infection-related mortality. Even low- to intermediate-dose radiation exposure confers increased risk, suggesting that the spleen is highly radiosensitive. These findings should inform long-term follow-up guidelines for survivors of childhood cancer, and should lead clinicians to avoid or reduce radiation exposure involving the spleen whenever possible.”
The study was supported by grants from the National Cancer Institute and American Lebanese Syrian Associated Charities.
Brent R. Weil, MD, of Boston Children’s Hospital, Harvard Medical School, is the corresponding author for the Journal of Clinical Oncology article.
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