GCT-06. THE OUTCOMES OF PATIENTS WITH DISSEMINATED GERMINOMA TREATED ON ACNS0232: A REPORT FROM THE CHILDREN’S ONCOLOGY REPORT

Abstract

Abstract BACKGROUND Central nervous system (CNS) germinomas are curable with craniospinal irradiation (CSI). However, concerns about long-term sequelae led to investigations into neoadjuvant chemotherapy. The ACNS0232 study, a phase III trial, evaluated the efficacy of neoadjuvant chemotherapy followed by response-based radiotherapy (RT) in patients with germinomas. METHODS Patients aged 3-21 years with newly-diagnosed histologically-confirmed germinoma were randomized to standard RT alone (Regimen A: 24 Gy CSI with a boost of 21 Gy) or neoadjuvant chemotherapy followed by response-based RT (Regimen B: 2 cycles of carboplatin/ etoposide, and if not in complete response (CR), two additional cycles of of cisplatin/ cyclophosphamide were administered followed by 21 Gy CSI with boost of 9 Gy). The study objectives included comparing event-free (EFS), overall survival (OS) and evaluating response to pre-RT chemotherapy. RESULTS Twenty-two patients (10 in Regimen A, 12 in Regimen B) were randomized between January 2007 and May 2009, including 13 with disseminated disease (5 in Regimen A, 8 in Regimen B). The study closed early due to low accrual. The median study follow-up time was 5.8 years. The 5-year EFS estimates were 0.89 (95% CI 0.47, 0.98) for Regimen A and 0.92 (95% CI 0.47, 0.99) for Regimen B. Regimen B was well-tolerated and demonstrated a 72.7% CR rate. CONCLUSION Despite the premature closure of the study, ACNS0232 provides valuable insights into the role of neoadjuvant chemotherapy with response-based RT in the treatment of disseminated germinoma. However, it is crucial to acknowledge the limitations of drawing conclusions with such a small sample size. The COG oncology community was not supportive of the proposed phase 3 design, but there is value in expanding the limited experience using Regimen B in a single arm phase 2 study to validate the safety and efficacy of neoadjuvant chemotherapy strategies in patient’s with disseminated CNS germinoma.