ID #933 OUTCOMES OF INFANTS AND YOUNG CHILDREN WITH NEWLY DIAGNOSED CENTRAL NERVOUS SYSTEM (CNS) EMBRYONAL TUMORS OTHER THAN MEDULLOBLASTOMA AND ATYPICAL TERATOID/RHABDOID TUMOR (AT/RT), INCLUDING EMBRYONAL TUMOR WITH MULTI-LAYERED ROSETTES (ETMR), P
Girish Dhall, Sapuni Chandrasena, Parth Patel, Megan Blue, Daniel Boue, Benita Tamrazi, Liming Xu, Ben Ho, Mei Lu, Robert Siddaway, Megan Welling, Randal Olshefski, Priya Chan, Caroline Hastings, Stacie Stapleton, Andrew Walter, Chad Jacobsen, Sandeepkumar Kuril, Anne Bendel, Carl Koschmann, Diane Puccetti, Kristina Cole, Guy Brock, Marvin Nelson, Annie Huang, Jonathan FinlayAbstract
Background
“Head Start” 4 (HS-4) is a prospective clinical trial with a primary objective to determine whether tandem marrow-ablative Consolidation chemotherapy (HDCT), in a randomized comparison with single-cycle Consolidation, provides event-free and overall survival (EFS and OS) benefit for patients with non-Wnt/non-Shh medulloblastoma and Other central nervous system embryonal tumors (CNS-ETs) completing HS-4 Induction. We present the outcome of Other CNS-ETs enrolled on HS-4.
Methods
Fifty-one eligible patients with Other CNS-ETs, median age 2.61 years (range: 1.36-3.54), were enrolled on HS-4 (ETMR=21, PB = 13, Other CNS-ET NOS=17), and received three cycles (five cycles if < complete response) of Induction (vincristine/cisplatin/cyclophosphamide/etoposide/high-dose methotrexate) followed by randomization to either Consolidation with three tandem HDCT cycles (thiotepa/carboplatin) or single HDCT cycle (thiotepa/carboplatin/etoposide). Diagnosis was confirmed by central pathology review and DNA methylation. Twenty patients were deemed non-evaluable: progression=9, family/physician preference=8 and toxicity=3; all during induction.
Results
For Intent-to-Treat analysis of all 51 patients, the 2-year EFS and OS was 43.9% (95%CI: 31.6-61) and 53.6% (95%CI=41.3-69.5) overall, 39.7% (95%CI=22.4-70.3) and 38.1% (95%CI=22.1-65.7) for ETMR, 46.2% (95%CI=25.7-83.0) and 53.8% (95%CI=32.6-89.1) for PB, and 47.5% (95%CI=27.9-80.9) and 73.9% (95%CI=54.9-99.6) for Other CNS-ET NOS patients. For 31 evaluable patients completing Induction (ETMR=13, PB = 5, Other CNS ET, NOS=13), the 2-year EFS and OS were 60.1% (95%CI: 44.2-81.6) and 76.2% (95%CI=62.2-93.3) overall , 59.2% (95%CI=37.1-94.5) and 61.5% (95%CI=40.0-94.6) for ETMR, 80% (95%CI=51.6-100) and 100% for PB, and 51.9% (95%CI=28.7-93.9) and 82.1% (95%CI=62.1-100) for Other CNS-ET NOS patients. For 17 evaluable patients receiving three tandem HDCT cycles, 2-year EFS was 81.6% (95%CI=64.7-100), compared to 30% (95%CI=12-74.7) for 14 patients receiving single HDCT cycle (p = 0.0099).
Conclusion
We report excellent results for young children with Other CNS-ETs when treated with intensive Induction and HDCT Consolidation on HS-4 trial without irradiation, with improved EFS for patients receiving three tandem HDCT cycles.