Development of second primary tumors and outcomes in medulloblastoma by treatment modality: A Surveillance, Epidemiology, and End Results analysis

Abstract

Background As treatment modalities for medulloblastoma have developed and overall survival (OS) has improved, there are relatively limited data on the impact of long‐term effects such as risk of second primary tumors (SPT). To address the knowledge gap, we analyzed factors associated with the risk of SPT and OS by treatment modality for medulloblastoma. Methods We queried the Surveillance, Epidemiology, and End Results (SEER)‐18 database for patients diagnosed with medulloblastoma in 1973‐2014. Patients were then grouped by age, gender, race, geographic region, histology, adjuvant treatment (no radiation [RT] and no chemotherapy [CT], RT and CT, RT alone, or CT alone), era of diagnosis (1973‐1994 or 1995‐2014), and survival time. Cumulative incidence, factors associated with SPT and OS were analyzed. Results Of 2271 patients, 146 developed SPT, of which 42 were benign. The incidence of SPT was 3.1% and 4.9% at 10 and 15 years, respectively. The incidence of SPT was 3.1% with RT + CT versus 3.7% with RT alone at 10 years. The most common site for an SPT was the central nervous system. Female gender (P = 0.01) and longer OS of ≥21 years (P < 0.01) were associated with higher risk of SPT. RT + CT led to better OS than RT only (66.1% and 61.4% vs 55.6% and 49.7% at 10 and 15 years) (P < 0.01). Conclusions Medulloblastoma patients have a relatively low risk of SPT at 10 years with treatment. Use of RT + CT led to better OS with no statistical difference in SPT compared with the RT alone.

Safety and efficacy of concurrent carboplatin during full‐dose craniospinal irradiation for high‐risk/metastatic medulloblastoma in a resource‐limited setting

“…Reassuringly, there was no treatment-related mortality during the concurrent phase in our study, although three toxic deaths were documented during adjuvant chemotherapy. Development of second new primary and late noncancer mortality (excluding toxic deaths) that appear seemingly high in our study was quite similar to that reported from the Childhood Cancer Survivor Study (CCSS) 30 and Surveillance Epidemiology and End Results (SEER) analysis 31 with mature and long-term follow-up. In conclusion, our understanding, definition, and management of high-risk/metastatic medulloblastoma have evolved considerably over the last four decades resulting in progressive and consistent improvement in survival.…”

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

“…Therefore, the youngest age group may have been exposed to less RT than the other groups. Similarly, data from SEER 18 showed that patients in the 11‐ to 20‐year‐old group had the highest percentage of SPTs in comparison with other age groups 12 …”

“…In the Childhood Cancer Survivor Study, the cumulative incidence at 30 years of SPTs among 381 medulloblastoma survivors, treated in 1970‐1985, was 7.8% 13 . Next, the percentage risk from other SEER data for patients diagnosed from 1973 to 2014 were SPT incidence rates of 3.1% and 4.9% at 10 and 15 years, respectively 12 . Another population‐based study of patients with medulloblastoma from the United States and Sweden showed a 5.5‐fold excess incidence of SMNs 14 .…”

“…Accordingly, survivors, especially children (who constitute most patients with medulloblastoma), can develop treatment‐related toxic effects over their lifetimes 9,10 . One of the most concerning late toxic effects is second primary tumors (SPTs), 11,12 especially second malignant neoplasms (SMNs), which could shorten survival times 13‐15 . Both RT and some systemic treatments have been linked to SMNs 16,17 …”

“…Even though medulloblastoma is the most common central nervous system (CNS) malignancy in childhood, this disease is still rare 18 . In a large population database of patients treated over a more than 4‐decade span from 1973 to 2014, the incidence of SPTs among patients with medulloblastoma was 4.9% at 15 years 12 . Another population‐based study showed an excess incidence of SMNs among patients with medulloblastoma 14 .…”