Late Morbidity and Mortality in Survivors of Medulloblastoma
In a report from the Childhood Cancer Survivor Study published in the Journal of Clinical Oncology, Salloum et al found that changes in medulloblastoma therapy over 3 decades that have improved survival have also increased risk for subsequent neoplasms and debilitating health conditions. As noted by the investigators, treatment of medulloblastoma has evolved from surgery and radiotherapy to incorporate multimodality treatments.
In the study, the cumulative incidence of late mortality (≥ 5 years from diagnosis), subsequent neoplasms, and chronic health conditions was evaluated among 5-year survivors of medulloblastoma diagnosed between 1970 and 1999. Outcomes were analyzed by treatment exposure, including historical therapy (craniospinal irradiation [CSI] ≥ 30 Gy, no chemotherapy), high-risk therapy (CSI ≥ 30 Gy plus chemotherapy), and standard-risk therapy (CSI < 30 Gy plus chemotherapy); and by treatment decades (1970s, 1980s, and 1990s).
Late Mortality and Morbidity
Among the 1,311 eligible survivors, median age was 29 years (range = 6–60 years) and median time from diagnosis was 21 years (range = 5–44 years). The 15-year cumulative incidence rate of all-cause late mortality was 23.2% among patients treated in the 1970s vs 12.8% among those treated in the 1990s (P = .002), with recurrence-related mortality rates of 17.7% vs 9.6% (P = .008). Lower late mortality rates as a result of other health-related causes among those diagnosed in more recent years were not observed.
Among 997 survivors completing a baseline survey, the 15-year cumulative incidence of subsequent neoplasms was higher among survivors who received standard-risk multimodal therapy vs those receiving historical treatment with radiotherapy alone (9.5% vs 2.8%, P = .03; cumulative incidence = 4.1% in those receiving high-risk therapy). The cumulative incidence of severe, disabling, life-threatening, and fatal chronic health conditions was 56.5% among patients treated in the 1990s vs 39.9% among those treated in the 1970s (P < .001), with those treated in the 1990s being more likely to develop multiple conditions (rate ratio [RR] = 2.89, 95% confidence interval [CI] = 1.31–6.38). Survivors who received standard-risk therapy were less likely to use special education services than those who received high-risk therapy (RR = 0.84, 95% CI = 0.75–0.93).
The investigators concluded, “The [study] provides evidence that historical changes in medulloblastoma therapy that improved 5-year survival have resulted in an increased risk for severe, life-threatening, and disabling chronic health conditions, including [subsequent neoplasms]. Now, the challenge for the pediatric neuro-oncology community is to reduce risk while maintaining or improving survival rates.”
Ralph Salloum, MD, of the Brain Tumor Center, Cincinnati Children’s Hospital Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and the American Lebanese-Syrian Associated Charities. The study authors' full disclosures can be found at jco.ascopubs.org.
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