P04.06.a a phase ii monocentric study of limited use of high dose of chemotherapy and proton therapy in pediatric high risk medulloblastoma and other embryonal cancers

BACKGROUND Despite the multimodal approach, medulloblastoma remains a leading cause of cancer-related death in children. We proposed the preliminary data of an interventional, open-label, phase II study to evaluate the safety and efficacy of standard and high-dose chemotherapy associated with craniospinal proton therapy in patients with metastatic medulloblastoma and other embryonal cancers. MATERIAL AND METHODS A total of 19 patients have been enrolled from the beginning of the study from February 2018 to May 2022 . The median age was 7,5 years (range; 13 males and 6 female). The protocol predicted the first phase of induction with 4 cycles of chemotherapy. After induction patients with favorable histology without evidence of disease were enrolled to proton therapy (with concomitant vinorelbine biweekly). The maintenance phase with Lomustine repeated every 9 weeks and vinorelbine every 3 weeks for overall 12-18 months (PR). Conversely LC/A MB, pineoblastoma or other high risk embryonic tumors were subjected to consolidation phase with high dose of chemotherapy with tiothepa followed by autologous HSC transplant and successive maintenance phase of 6 months. RESULTS At December 2022, the median follow up was 23 months. 18 patients had high risk medulloblastoma and one had a primary leptomeningeal primitive neuroectodermal tumor. After the induction phase 14 patients showed CR, 3 PR, 1PD, 1SD. At subsequent re-evaluations two of the three patients with PR, showed disease control, one CR and the other SD and the patient with PD showed CR. At the end of proton therapy 18 patients had CR. During the reporting period three patient died for progression of the underlying disease. At 15 months from the start of treatment the PFS and OS were 68.8% (95% CI: 34.1% - 87.6%) and 94.7% (95% CI: 68.1% - 99.2%) respectively. The principal expected side effects of chemotherapy were hematology toxicity (fever and neutropenia prevalent after etoposide and carboplatin plus vinorelbine). Among the unexpected side effect was CMV retinopathy with complete blindness and leukoencephalopathy after high dose of thiotepa and proton irradiation. CONCLUSION As the study did not reveal any safety issues, proton therapy combined with intensive chemotherapy, and myeloablative chemotherapy only in selected cases and always before irradiation, proved feasible and successful in treating high-risk medulloblastomas and other embryonal tumors.