Secondary Malignant Neoplasms in Patients with Medulloblastoma

Abstract

To analyze the incidence and types of second malignant neoplasms (SMN) in patients treated for medulloblastoma. Using the multiple primary-standardized incidence ratio (MP-SIR) session from SEER 9 registry data (1973-2014), we compared the incidence of SMN in patients with medulloblastoma treated with radiotherapy (RT) to the general population. Observed-to-expected incidence ratios (O/E ratios) and 95% confidence intervals (CI) were reported for the overall cohort and classified by disease sites according to age, era treated and use of chemotherapy (CT). We report organ systems or disease sites with statistically significant elevated O/E ratios of p <0.05. Of 1294 patients with medulloblastoma who received RT, 68 developed a SMN. A total of 75 SMN was reported, with 4 patients having 2 SMN and 1 having 4 SMN. The O/E ratio for SMN was 4.49 (CI 3.53-5.62) for all patients diagnosed with medulloblastoma (p<0.05). The highest risk for developing a SMN was in the central nervous system (CNS; O/E 40.62; CI 25.46 –61.51), followed by endocrine (O/E 15.95; CI 9.12-25.91), bone (O/E 14.45; CI 1.75-52.21), soft tissues (O/E 9.01; 95% 1.09-32.56), digestive (O/E 5.03; CI 2.51-9.00) and lymphatic/hematopoietic (O/E 3.37; CI 1.35-6.94) systems. Patients receiving chemotherapy had a higher O/E compared to RT alone (O/E 5.52, CI 3.75-7.83 vs. 3.96, CI 2.88-5.32); chemotherapy patients also had a higher O/E for SMN in the CNS, salivary gland, and acute non-lymphocytic leukemia compared to RT alone patients. After accounting for differences in length of follow-up with standardized incidence ratios, patients treated before 1995 and younger age at diagnosis were associated with a higher O/E for SMN. The O/E for ages 0-10 years, 11 to 20 years and > 20 years at time of RT were 11.48 (CI 7.85-16.21), 8.85 (CI 5.55-13.4) and 1.84 (CI 1.14-2.81) (p < 0.05 individual O/E ratios). The CNS, thyroid and salivary gland had higher O/E in the younger age groups compared to those > 20 years. Medulloblastoma patients have an elevated risk for SMN compared to the general population. Variations by organ systems most at risk were observed based on treatment modality, age at diagnosis and time period. The CNS is the most common site of SMN and is seen more frequently in younger patients and those receiving chemotherapy.