MDB-03. Outcome of Group 4 medulloblastomas of early childhood treated with high dose chemotherapy and craniospinal irradiation sparing approach.

Abstract Background Group 4 medulloblastoma (MB) are rare in young children and their outcome when treated with radiation avoidance strategies is unknown. Method This retrospective international cohort included children with molecularly characterized group 4 treated with high-dose chemotherapy(HDC) and CSI sparing approach. Results The cohort includes 38 patients (26M/12F) diagnosed at a median age of 46.4 months (25.9-78). Twenty-four (63.2%) were M0 and 26(68.4%) underwent initial gross total resection. The most common consolidation used was three cycles of HDC (carboplatin, thiotepa) in 76.3% or one cycle of HDC (carboplatin, etoposide, thiotepa) in 21.1%. Twenty patients (52.6%) relapsed at a median time of 24.9 months from diagnosis, providing a 5 years PFS of 40.9%(±9.2%). Patients who underwent 3 cycles of HDC, who received carboplatin and thiotepa or who achieved complete response at treatment completion had a better PFS. High-dose methotrexate during induction and metastatic status did not impact PFS. Relapse was local in 45%. Eighteen patients underwent radiation-based salvage therapy (2 focal, 16 CSI) in intent to cure. The median dose of CSI was 36 Gy (18-36). However, 7(43.7%) patients received CSI dose 24 Gy. The 5 years post-relapse survival was 60.3% (±14.8%). At median follow-up of 39.9 months from diagnosis, 29 (76.3%) patients were alive, seven died of disease and two of toxicity, leading to 5 years OS of 72.7% (±8.6%). Using the SIOP-Boston scale, grades 2, 3 and 4 ototoxicity were reported in 18.7%, 31.2% and 25%. Mean FSIQ for patients without relapse or evaluated prior relapse was 86.5 (range 69-97; N = 6) and 2 had age appropriate cognitive and intellectual skills. Conclusions HDC and CSI sparing approaches led to a high rate of relapse (52.6%). However, 72.2% patients were salvaged with radiation-based therapy given at a median time of 2 years after initial diagnosis.