Medulloblastoma: conventional radiation therapy in comparison to chemo radiation therapy in the post-operative treatment of high-risk patients

Abstract

The aim of this study is to assess treatment results of 48 pediatric high-risk medulloblastoma cases that were treated by surgery, radiotherapy with or without chemotherapy. The impact of adjuvant combination chemotherapy on treatment results will be assessed. Forty-eight cases of pediatric high-risk medulloblastoma treated from July 2001 to July 2004 were randomized into two groups. The first (group I) included 21 patients who received postoperative craniospinal radiation therapy (36Gy+boost 20Gy to the posterior fossa). The second (group II) included 27 cases who received postoperative combination cranio-spinal radiation therapy (with the same dose as the first group) and chemotherapy (vincristine, etoposide, cisplatin). Both groups were compared as regards overall survival (OS), disease free survival (DFS), response rate and treatment toxicity. In-group I, complete remission (CR) was achieved in 71.4% of the cases; partial remission (PR) in 14.3% of the patients; stationary disease (SD) in 14.3% and none of the cases suffered from progressive disease. The three-year OS was 69.5% and the three-year DFS was 61.3%. In-group II, CR was achieved in 59.3% of the cases; PR in 3.7%; SD in 3.7% and PD in 37.3% of the cases. The three-year OS was 48.4% and the 3-year DFS was 48.9%. Regarding acute treatment toxicity in group I, nine patients (31.5%) developed grade I myelo-suppression and seven cases (24.5%) developed grade II myelo-suppression with three to five days treatment interruption. Whereas in group II, 13 patients (45.5%) developed grade I myelosuppression and seven cases (24.5%) developed grade II myelo-suppression requiring interruption of treatment for a period ranging from five to seven days with spontaneous recovery. In group I no other acute toxicity was recognized, whereas in group II other toxicities related to chemotherapy were noticed. For example, three patients (11%) developed peripheral neuritis during the course of treatment and two patients (7%) developed renal impairment, which responded to medical treatment. Late treatment toxicity, manifested as reduction in intelligence quotient (IQ), was noticed, which makes conventional treatment of medulloblastoma unsatisfactory. In group I; 13 patients (62%) suffered a reduction of 8-20% in IQ in comparison to their normal siblings, whereas in Group II; 13 patients (48%) developed a reduction in IQ ranging from 12-21%.

Conclusion: The current treatment of medulloblasotma has a detrimental effect on long-term survivors. Whereas acute toxicity is considered mild and tolerable, late toxicity regarding diminution in IQ makes current treatment unsatisfactory because of the long-term mental disability of the cured patients. We believe that, the poorer outcome in the chemo-radiation group was due to the treatment interruption during radiation therapy caused by myelosuppression since the incidence of myelosuppression was higher in the chemo-radiation group and the recovery time was longer.