Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: A contemporary single-institution experience

Abstract

Background: Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity.

Methods: A single-center, retrospective study was conducted of patients age ≥18 years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses.

Results: Fifty-nine patients met criteria, with median age of 25 years (range 18-62 y) and median follow-up of 6.5 years (range 0.7-23.1 y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6 Gy (relative biological effectiveness [RBE]), median total dose was 54.0 Gy (RBE), 80% received proton radiotherapy; 81% received chemotherapy. 5 year PFS and OS were 86.5% and 95.8%, respectively; 10 year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (P = .04). Among eight recurrences, 25% presented after 5 years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (P = .05).

Conclusions: Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae.

Keywords: adult medulloblastoma; late toxicity; medulloblastoma; outcomes.

Fig. 1

Survival of total population. (A) Kaplan-Meier Curve for overall survival from diagnosis of medulloblastoma to event, with 5 year OS of 95.8% and 10 year OS of 90.7%. (B) Kaplan-Meier Curve for progression-free survival from diagnosis of medulloblastoma to recurrence, with 5 year PFS of 86.5% and 10 year PFS of 83.9%. (C) Kaplan-Meier Curve for progression-free survival from diagnosis of medulloblastoma to event, stratified by anaplastic histology. The 5 year PFS for non-anaplastic MB was 89.3% compared with 76.9% for anaplastic MB.

Fig. 2

Patterns of Failure in Adult Medulloblastoma. Forty-seven-year-old male with standard-risk, anaplastic, SHH-activated MB treated with GTR and craniospinal proton RT (36.0 Gy [RBE] CSI, 19.8 Gy [RBE] PF boost) without concurrent or adjuvant chemotherapy. He experienced concurrent local failure of posterior fossa, as seen on axial and coronal MRI Brain images (A) as well as nodular recurrence within cord at C1-2, as seen on axial and sagittal MRI Spine images (B), 65 months after diagnosis. Twenty-four-year-old female with standard-risk, desmoplastic, SHH-activated MB treated with GTR, craniospinal proton RT (23.4 Gy [RBE] CSI, 30.6 Gy [RBE] PF boost) with concurrent (weekly vincristine) and adjuvant (vincristine/lomustine/cisplatin) chemotherapy for six cycles. She experienced extraneural recurrence within left parotid bed, as seen on coronal and axial PET images (C) and fused axial PET/CT and axial CT images (D), 56 months after diagnosis.