Treatment of extracranial rhabdoid tumor with intensive ifosfamide-containing chemotherapy regimens

Introduction: Extracranial malignant rhabdoid tumors (MRT) and rhabdoid tumors of the kidney (RTK) are rare pediatric solid tumors characterized by aggressive behavior and poor prognosis. Case reports have demonstrated successful outcomes using ifosfamide-containing chemotherapy regimens, leading some clinicians to incorporate this alkylating agent into treatment plans. We assessed our institutional experience treating MRT and RTK using ifosfamide-containing regimens. Methods: Fifteen patients with histologically confirmed MRT or RTK and loss of INI1 who were treated at Children's National Hospital (CNH) between 2009 and 2025 were reviewed retrospectively. Results: The median age at diagnosis was 16 months (range: 3-171 months). Eleven patients (73.3%) had MRT and four (26.7%) had RTK. Treatment involved multimodal therapy, including surgical resection when feasible, radiation therapy, and intensive chemotherapy. Eleven patients received regimens including ifosfamide, in some cases with higher-dose cyclophosphamide compared to recent Children's Oncology Group and European Soft Tissue Sarcoma Study Group protocols. Three-year event-free survival (EFS) and overall survival (OS) were 42.4% (95% CI: 22.7-79.3%) and 40.4% (95% CI: 20.8-78.5%), respectively. No significant difference in 3-year EFS was observed with ifosfamide (43.6%, 95% CI: 21.8-87.4%) versus without ifosfamide (37.5%, 95% CI: 8.4-100%; p=0.85). Second and third-line treatment regimens included tazemetostat (n=3), temozolomide/irinotecan +/- vincristine (n=3), alisertib (n=1), and cemiplimab (n=1); however, no responses were observed. Conclusion: Ifosfamide-containing regimens did not appear to improve outcomes for MRT or RTK. Novel, targeted therapeutic strategies are urgently needed to improve survival for patients with rhabdoid tumor, particularly those with stage III/IV disease.