Mb-11 * Impact of Molecular Sub-Type and Craniospinal Irradiation (Csi) Dose on Relapse of Medulloblastoma

Abstract

PURPOSE: To evaluate the impact of craniospinal irradiation (CSI) dose and molecular sub-type on medulloblastoma relapse rates. METHODS: 115 medulloblastoma patients were treated with 18-≥ 36 Gy CSI. Molecular subtyping data was done by nanostring assay [WNT, SHH, and Group 3/4 non-WNT/non-SHH (NWNS)]. A CSI dose schema based on prognostic implications of molecular subtype was devised: ≥36 Gy for M+ or Group 3;≤18 Gy for non-disseminated WNT; 23.4 Gy all others. Relapse rates were assessed and correlated with CSI dose. RESULTS: After excluding patients with incomplete data, the final cohort included 36 subjects with median age 8.7 years (range 3.3 -16.9) and median follow-up 4.1 years (0.2-3.7). Molecular subtypes were as follows: 2-WNT, 6-SHH, 28-NWNS. CSI dose was 18 Gy(11 cases), 23.4 Gy(9), and ≥36 Gy(16). CSI dose was divergent from the proposed schema in 18 cases (14-lower, 4-higher). There were 14 relapses (by molecular subtype: 0-WNT, 1-SHH, 13-NWNS; by histology: 8-classic, 5-LC/A, 1-EN), with median time to relapse 18.5 months (0.43-62). Seven of 14 tumors treated to a lower dose relapsed (1 SHH; 6 NWNS); only 1 (NWNS) of 4 patients with higher divergent dose relapsed. Six of 18 patients treated to similar dose relapsed; all were NWNS, and 4/6 had M3 disease. Eleven of 14 patients who relapsed died. CONCLUSION: Molecular subtyping may help avoid under-treating some NWNS tumors but innovative strategies for metastatic NWNS are needed. We confirm that histological subtypes may hold some predictive value as 5/7 LC/A relapsed and no desmoplastic tumors relapsed. In this small sample, no WNT relapse occurred and only 1 SHH relapsed, suggesting that dose de-escalation can be cautiously explored for these subtypes. Future research directions include applying an MRI imagebased algorithm to subtype the entire cohort, and combining molecular data with other institutions to examine relapse patterns by subtype.