Three Decade Single-Institution Experience of Safety and Efficacy of Radiotherapy and Adjuvant Chemotherapy for Young Adult Patients with Medulloblastoma

Abstract

The rarity of medulloblastoma in the adult population limits information on optimal treatment and clinical outcomes. Adjuvant chemoradiation has been correlated to improved overall survival (OS) in a recent National Cancer Database (NCDB) analysis. We performed a retrospective safety and efficacy analysis of radiation (RT) +/- adjuvant chemotherapy (aCTH) in young adult patients with medulloblastoma to better understand outcomes, prognostic factors, and possibly optimal treatment strategies. We conducted an IRB-approved retrospective chart review on young adult (age ≥18 - 39 years old) patients with medulloblastoma treated at our institution (1992-2018) with a minimum follow-up of 6 months from completion of therapy. We gathered data on patient and disease characteristics, treatment, and clinical outcomes, including OS, progression-free survival (PFS), local control (LC), and freedom from distant metastasis (FDM). We employed Cox regression model for univariable and multivariable analyses and Kaplan-Meier (KM) test methods for survival analyses, using JMP version 15.0 software. Thirty-one patients were treated with postoperative RT including craniospinal irradiation (median dose: 2340 cGy/13 fractions) followed by tumor bed/posterior fossa (median total dose: 5580 cGy/31 fractions) either alone (n = 9; 29%) or with adjuvant chemotherapy (aCTH: n = 22; 71%); mostly as per COG A9961 Regimen A: oral lomustine, intravenous cisplatin, and intravenous vincristine (n = 12). 54.6% (n = 12) were known to complete the full aCTH course. Common RT acute toxicities included G1-2 nausea and/or vomiting (N/V; n = 8) and G1-2 fatigue (n = 6). Common aCTH acute toxicities included G1-2 N/V (n = 7) and peripheral neuropathy: G1-2 (n = 6) and G3 (n = 3). Late adverse events were primarily G1-2 peripheral neuropathy and gait imbalance (22.6%), G1-2 hormonal disturbances (19.4%) and G1-2 neurocognitive impairment (16.1%). Male patients had worse OS, PFS, FDM, and LC. Age at diagnosis, tumor location (lateral vs. central), and completion of aCTH course were shown on uni- and multi-variable analysis to be significantly associated with OS; p<0.05. KM survival analysis revealed superior 10-year PFS and OS in patients who completed aCTH compared to those who received RT alone or did not complete aCTH: 72.9% vs 59.3% vs 42%, p = 0.461, and 74.1% vs 63.5% vs 40%, p = 0.033, respectively. A similar trend was noted for LC and FDM. Our series provides a report of acute and late side effects of treatment of young adult patients with medulloblastoma. Significant OS and PFS advantage are seen of aCTH completion in this patient population. Since optimal treatment of these patients is still an unmet need, prospective studies for this rare disease entity are needed.