Patterns Of Failure And Prognostic Factors Of Adult Medulloblastoma Treated With Radiation Therapy

Abstract

Medulloblastoma (MB) is a rare adult malignancy of the central nervous system (CNS). Treatment guidelines are not well-established, as most practice is extrapolated from experience in the pediatric population. We reviewed our single institutional experience in managing adult MB to define clinical outcomes and identify potential prognostic factors. We identified and reviewed records of all adult MB patients aged ≥18 years who received upfront postoperative radiotherapy (RT) from 1997-2017 at a single institution. A total of 50 consecutive patients (29 male) were identified with histologically proven MB, reviewed at our institution but without consistent molecular classification available, and disease confined to the craniospinal axis at presentation. A total of 33 patients were classified as standard-risk, and 17 patients were classified as high-risk; 7 patients had M+ disease by Chang staging. Gross total resection was achieved in 37 patients with subtotal resection (STR) in the remaining 13 patients. Median craniospinal irradiation (CSI) dose was 36Gy (RBE) with a median tumor bed or posterior fossa dose boosted to 54Gy (RBE). Thirty-nine patients were treated with proton beam RT, 9 with photon-based RT, and 2 with mixed proton/photon RT. Eleven patients did not receive any adjuvant chemotherapy (CHT), 25 patients received concurrent and adjuvant CHT, 8 received only adjuvant CHT (after RT), and 6 received a combination of neoadjuvant CHT with concurrent and adjuvant CHT. With a median follow up of 5.3 years, 7 patients had disease recurrence: 5 within the craniospinal axis and 2 patients with extraneural recurrence. Two patients died, both from disease progression. Overall survival (OS) at 5 years was 96.3%, and event-free survival (EFS) at 5 years was 80.7%. Twenty-nine percent (2/7) of recurrences occurred after 5 years. In the seven patients with disease recurrence, all were classified as standard risk and M0 on presentation; 86% (6/7) were treated with 36Gy to CSI and 54Gy to boost volume; 4 had anaplastic histology and 3 had desmoplastic histology. Two patients deferred adjuvant CHT, four were treated with concurrent and adjuvant CHT, and one with adjuvant CHT only. Both patients with extraneural recurrence received concurrent and adjuvant CHT. On univariate analysis, time to start of RT >35 days from diagnosis was associated with worse EFS (HR 8.46, 95% CI 1.01-70.70, p = 0.049). There was no statistically significant trend for worse EFS or OS with histology, STR, high-risk, M+ disease, RT duration, or use of adjuvant CHT. Adults with MB have survival rates similar to their pediatric counterparts, but late and distant relapses are not uncommon. RT is a major component of the treatment of adult MB, however better prognostic factors, possibly from molecular subtyping, may help to define better personalized treatments for adult MB with high risk of recurrence.