What question did this study set out to answer?

This study aims to determine if tandem marrow-ablative chemotherapy provides better survival outcomes in infants and young children with CNS embryonal tumors.

June 26, 2026Open Access

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), Pineoblastoma (Pb) and CNS Embryonal Tumors Nos, Treated on the “Head Start” 4 Protocol

Key Points

This study aims to determine if tandem marrow-ablative chemotherapy provides better survival outcomes in infants and young children with CNS embryonal tumors.
51 eligible patients with other CNS embryonal tumors enrolled in the HS-4 trial.
Patients received induction therapy followed by randomization to receive three tandem high-dose chemotherapy cycles or single high-dose chemotherapy.
Diagnosis confirmed by central pathology review and DNA methylation analysis.
2-year event-free survival (EFS) was 43.9% and overall survival (OS) was 53.6% for all patients.
For evaluable patients, 2-year EFS was 60.1% and OS was 76.2%; specifically, 80% OS for pineoblastoma patients.
Patients receiving three tandem HDCT cycles had a significantly higher EFS of 81.6% compared to 30% for those receiving a single cycle (p = 0.0099).

Abstract

Abstract 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.

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