Abstract BACKGROUND Patients with relapsed/refractory central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) have poor prognosis. We explored prognostic factors to guide the management of these patients. METHODS We performed a multinational retrospective study of relapsed/refractory CNS NGGCTs. Data were summarized using standard descriptive statistics. Overall survival (OS) was evaluated using Kaplan-Meier and Fisher’s exact test to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS We identified 31 patients from eight centers. The median age at initial diagnosis was 11 years (interquartile range (IQR): 9-15.3). Twenty patients (64.5%) suffered a relapse, and 11 patients (35.5%) had refractory disease. The median follow-up time since relapse/progression was 17.5 months (range:1-295). The median time to relapse/progression was 12.1 months (IQR: 5.5-27.5). Ten patients (32.3%) received high-dose chemotherapy (HDCx) with stem cell rescue. Sixteen patients (51.6%) received re-irradiation at relapse/progression. Nine patients (29%) achieved complete remission (CR). Ten patients (32.3%) were alive at the time of the last follow-up. Among the ten survivors, the median serum and cerebrospinal fluid (CSF) alpha-fetoprotein levels were 2.3 ng/dl (range: 0-17) and 2.1 ng/dl (range: 0-55), respectively, the median serum and CSF beta-human chorionic gonadotropin were 23 IU/L (0-168) and 139 IU/L(0-601), none underwent gross total resection, eight received HDCx, and seven received radiotherapy (craniospinal irradiation (n=6), abdominal radiotherapy (n=1)). HDCx (OR=19.8, 95%CI: 2.7-145.7; p=0.01) and achieving CR at the end of relapse treatment (OR=160, 95%CI: 8.9-2880.5; p=<0.001) were associated with a survival benefit. Re-irradiation (OR=3.3 95%CI: 0.53-20.9; p=0.24) was not associated with a survival benefit. CONCLUSIONS A subset of patients with relapsed NGGCTs are salvageable at relapse. HDCx and achieving CR at the end of relapse therapy were associated with a survival benefit. More studies are required to identify these patients who would benefit from salvage therapy.
