Clinical Audit of Survival Outcomes and Prognostic Factors in Adolescents and Adults with Medulloblastoma

Abstract

Purpose: Medulloblastomas, comprising 20%-25% of all primary brain tumors in children are much rarer in adulthood. Disease biology varies substantially across different age groups; however, owing to rarity, adults with medulloblastoma are traditionally treated using pediatric protocols. This is a retrospective audit of adolescent and adult medulloblastoma from a comprehensive cancer center. Methods: Data regarding demography, clinical presentation, imaging characteristics, histopathological features, molecular profiling, risk stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analysis of relevant prognostic factors was done with p value <0.05 being considered statistically significant. Results: A total of 162 patients ≥15 years of age with medulloblastoma were included. The median age was 25 years (range: 15-59 years) with leptomeningeal metastases seen in 31 (19%) patients at initial diagnosis. Following surgery, patients were treated with appropriate risk-stratified adjuvant therapy comprising of craniospinal irradiation plus boost with or without systemic chemotherapy. At a median follow-up of 50 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 53.5% and 59.5%, respectively. The addition of adjuvant systemic chemotherapy did not impact upon survival in standard-risk medulloblastoma. High-risk (HR) disease and anaplastic histology emerged as significant and independent predictors of poor survival on multivariate analysis. Conclusion: Medulloblastoma is a rare tumor in adolescents and adults with key differences in disease biology and resultant outcomes compared with the pediatric population. Contemporary management comprising maximal safe resection followed by appropriate risk-stratified adjuvant therapy provides acceptable survival outcomes.

Keywords: biology; medulloblastoma; outcomes; risk-stratification.

FIG. 1.

Schematic representation of patterns of failure following risk-stratified therapy in adolescent and adult medulloblastoma.

FIG. 2.

Kaplan–Meier curves of progression-free survival (A) and overall survival (B) for the entire study cohort of adolescent and adult medulloblastoma.

FIG. 3.

Kaplan–Meier curves of progression-free survival (A) and overall survival (B) stratified by risk category (high-risk vs. standard-risk).

FIG. 4.

Kaplan–Meier curves of progression-free survival (A) and overall survival (B) stratified by histological subtype (large-cell/anaplastic vs. nonanaplastic).

FIG. 5.

Kaplan–Meier curves of progression-free survival (A) and overall survival (B) stratified by molecular subgrouping (WNT vs. SHH vs. non-WNT/non-SHH). SHH, sonic hedgehog; WNT, wingless.

FIG. 6.

Kaplan–Meier curves of progression-free survival (A) and overall survival (B) stratified by time interval from surgery to radiotherapy (<6 vs. ≥6 weeks).