P14.03 Adult medulloblastoma: Influence of risk stratification and molecular subtypes on chemotherapy efficacy

Abstract

Abstract BACKGROUND Incidence of medulloblastoma (MB) in adults is about 1%. Optimal treatment for adult medulloblastoma has not been defined. Published datasets were acquired over a long period of time, during which there were changes in surgical technique, radiotherapy, chemotherapy regimens; often disease stage was not considered in the analyses. Recently discovered molecular subgroups are not taken into account in studies concerning treatment of medulloblastoma in adults. MATERIAL AND METHODS Study includes 64 patients with medulloblastoma (median age 26.5 years (15–62)), who were first admitted to Burdenko Neurosurgery Institute for surgery from 2000 to 2017. 100 % patients included in the study received radiotherapy - craniospinal irradiation, 36 Gy (20 x 1.8 Gy) with boost to primary site (2 cm around tumor bed) up to 55 Gy total dose. 41 patients (64%) received chemotherapy (ChT). Chemotherapy was started 4–6 weeks after finishing craniospinal irradiation, the regimen included cisplatin 25 mg/m2 days 1–4+etoposide 100 mg/m2 days 1–4+cyclophosphamide 600 mg/m2 days 1–4; the cycles repeating every 28 days, 6 cycles in total. Treatment volume didn’t correspond with risk group and/or molecular genetic subgroup (these parameters were determined retrospectively). Median follow-up time is 4.45 years. RESULTS 53% patients had classic histology MB, 27% - desmoplastic, 20% - large cell/anaplastic. High risk (HR), standard risk (SR) and unspecified risk (UR) groups included 23, 16 and 25 patients respectively. Molecular subgroup testing was performed in 39 cases: SHH-activated - 59%, WNT-activated - 18%, GROUP4 - 23%. Median time to tumor progression (MTTP) in patients who received radio-chemotherapy versus radiotherapy alone was 4.3 and 2.64 years, respectively (p=0.264). The differences in MTTP were the most pronounced in SR and UR patients who received radio-chemotherapy (5.5 and 6.0 months, respectively) versus radiotherapy alone (1.5 and 2.0 months, respectively). HR patients showed the least difference in MTTP for radiotherapy (2.0 years) versus radio-chemotherapy (2.5 years), p=0.093. The SHH-subgroup patients had MTTP of 3.1 years (3.1 and 3.0 years for ChT+ and ChT-, respectively). GROUP4 patients had MTTP of 4.3 years (4.3 and 1.5 years for ChT+ and ChT-, respectively). All WNT-subgroup patients received chemotherapy, MTTP was 9.0 years. Median overall survival cannot be defined in any of the subgroups. CONCLUSION Chemotherapy in adult medulloblastoma patients increases MTTP in SR and UR patients. Low efficacy of chemotherapy for high risk medulloblastoma urges search for more efficacious treatment protocols. WNT-activated adult medulloblastoma has the highest MTTP among other molecular subgroups.