Observed‐to‐expected incidence ratios of second malignant neoplasms after radiation therapy for medulloblastoma: A Surveillance, Epidemiology, and End Results analysis

Abstract

BACKGROUND The authors analyzed the incidence and types of second malignant neoplasms (SMNs) in patients treated for medulloblastoma. METHODS The authors compared the incidence of SMNs after radiotherapy (RT) for medulloblastoma in patients treated in 1973‐2014 with the incidence in the general population with the multiple primary–standardized incidence ratio function of Surveillance, Epidemiology, and End Results 9. Observed‐to‐expected incidence (O/E) ratios and 95% confidence intervals (CIs) were reported for the entire cohort and by disease site according to age at diagnosis, treatment era, and receipt of chemotherapy. P values < .05 were considered statistically significant. RESULTS Of the 1294 patients with medulloblastoma who received RT, 68 developed 75 SMNs. The O/E ratio for SMNs among all patients was 4.49 (95% CI, 3.53‐5.62; P < .05). The site at highest risk was the central nervous system (CNS; O/E, 40.62; 95% CI, 25.46‐61.51), which was followed by the endocrine system (O/E, 15.95; 95% CI, 9.12‐25.91), bone (O/E, 14.45; 95% CI, 1.75‐52.21), soft tissues (O/E, 9.01; 95% CI, 1.09‐32.56), the digestive system (O/E, 5.03; 95% CI, 2.51‐9.00), and the lymphatic/hematopoietic system (O/E, 3.37; 95% CI, 1.35‐6.94). The O/E ratio was higher for patients given chemotherapy and RT (O/E, 5.52; 95% CI, 3.75‐7.83) than for those given RT only (O/E, 3.96; 95% CI, 2.88‐5.32). CONCLUSIONS Patients with medulloblastoma are at elevated risk for SMNs in comparison with the general population. Variations in O/E for SMNs by organ systems were found for treatment modality, age at diagnosis, and time of diagnosis. The most common site, the CNS, was involved more often in younger patients and those given chemotherapy with RT.

Overall survival and secondary malignant neoplasms in children receiving passively scattered proton or photon craniospinal irradiation for medulloblastoma

“…16 Others have suggested a higher SMN rate with the use of alkylating agents in addition to RT for medulloblastoma. 11,17 Finally, the OS rates were the same as those for patients with medulloblastoma in this study and were comparable to rates reported in the existing photon and proton literature, validating the efficacy of PT for this tumor. 11,14,17 Whether the incidence of SMN after RT can be reduced by using passively scattered protons requires further study and longer follow-up.…”

“…11,17 Finally, the OS rates were the same as those for patients with medulloblastoma in this study and were comparable to rates reported in the existing photon and proton literature, validating the efficacy of PT for this tumor. 11,14,17 Whether the incidence of SMN after RT can be reduced by using passively scattered protons requires further study and longer follow-up. Chung et al performed a retrospective cohort study of 558 patients who received passive scatter PT at the Harvard Cyclotron matched by age, sex, year of treatment, histology, and site with 558 patients who received photons from the SEER data.…”

Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis

“…Finally, there is some controversy regarding radiation-induced tumors and the role of chemotherapy in contributing to their development. The combination of radiation and chemotherapy has been reported to have a synergistic effect on the development of treatment-induced gliomas 4 , 97 or result in a shorter latency period. 16 In contrast, others report statistically significant increases in the risk of glioma development with increasing radiation dose, but no further increased risk with the addition of chemotherapy.…”

“… 6 A recent study of 1294 medulloblastoma patients treated with radiation therapy between 1973 and 2014 reported that these patients developed second central nervous system (CNS) tumors at 40 times the rate expected in the general population. 4 Furthermore, several large cohort studies have demonstrated a direct correlation between the cumulative dose of radiation received and the risk of subsequent CNS tumor development. 5 , 7 , 8 This is particularly pertinent for young children, as those under 5 years of age are more susceptible to the development of radiation-associated gliomas compared with children receiving radiotherapy at a later age.…”

“… 5 , 17 Over 50% of RIGs are diagnosed during adulthood, 16 and arise more frequently in patients who received radiotherapy early in life. 4 , 5 , 17 …”