RARE-12TOXICITY AND RESPONSE IN PATIENTS TREATED ACCORDING TO THE DUTCH SOCIETY FOR NEURO-ONCOLOGY (LWNO) MEDULLOBLASTOMA TREATMENT PROTOCOL WITH NEOADJUVANT CHEMOTHERAPY, RADIATION AND ADJUVANT CHEMOTHERAPY

BACKGROUND: In 2009 the Dutch Society for Neuro-Oncology set up a treatment protocol for newly diagnosed high-risk adult medulloblastoma patients in order to uniformize treatment. The protocol consists of surgery, neoadjuvant carboplatin-etoposide, neuraxis radiotherapy combined with vincristine, and four adjuvant cycles of carboplatin-vincristine-cyclophosphamide. Centers were free to also use the protocol in patients with supratentorial primitive neuro-ectodermal tumors (sPNETs). METHODS: We retrospectively collected clinical data of all patients treated according to the new protocol during the period July 2009-july 2014. We evaluated toxicity, feasibility, response, and outcome of these patients. RESULTS: Ten patients with high-risk medulloblastoma, and 6 with sPNETs were included. Median age at diagnosis was 35.4 years; median Karnofsky performance score (KPS) after surgery was 90. Fourteen of 16 patients received neoadjuvant carboplatin-etoposide, all in full dose. None showed progression during these courses. All received radiotherapy. Thirteen patients started with adjuvant chemotherapy, and 7 completed all cycles. Overall, treatment was stopped in 8 patients; in 6 because of toxicity (decreased performance score (2), bone marrow suppression (3), polyneuropathy (1)). The dose adjuvant chemotherapy was reduced in all but 1 patient because of prolonged myelosuppression. After treatment, 5 patients showed complete remission, 4 partial response and 2 stable disease. Median follow-up of all patients was 1.92 years, with 50% (8/16) patients still alive. One-year survival rate from start of therapy was 88%. CONCLUSIONS: Neo-adjuvant chemotherapy was feasible and did not compromise radiotherapy. During the adjuvant chemotherapy a high percentage of toxicity was found, necessitating dose reduction in nearly all patients. In adult patients the use of adjuvant chemotherapy needs a critical appraisal considering more mature data on survival with respect to the feasibility of these courses.