Standard-risk Medulloblastoma Research Articles

Impact of radiotherapy (RT) parameters on outcome in the international society of paediatric oncology (SIOP)/united kingdom children’s cancer study group (UKCCSG) PNET-3 study of pre-radiotherapy chemotherapy for M0-1 medulloblastoma

Purpose/Objective: The main study aim was to determine whether four cycles of pre-RT chemotherapy with vincristine, etoposide and carboplatin alternating with cyclophosphamide would improve outcome for patients with M0-1 medulloblastoma compared with RT alone. The present study is an analysis of the impact of RT parameters on outcome. Materials/Methods: Following maximal surgical resection patients were randomized to RT either alone, or preceded by four cycles of chemotherapy with vincristine 1.5 mg/m2 weekly for three weeks, etoposide 100mg/m2 daily for 3 days and carboplatin 500 mg/m2 daily for 2 days alternating with cyclophosphamide 1.5 g/m2. RT consisted of craniospinal RT 35 Gy in 21 fractions of 1.67 Gy followed by a boost to the entire posterior fossa (PF) of 20 Gy in 12 fractions of 1.67 Gy. The total RT dose to the posterior fossa was 55 Gy in 33 fractions of 1.67 Gy. The RT protocol specified standard field placements for craniospinal and posterior fossa RT. Craniospinal and PF planning films were reviewed by two radiation oncologists. Accuracy of cribriform fossa and skull base coverage and PF field placement were assessed. Results: Between March 1992 and January 2000, 217 patients were randomised and 179 eligible for analysis. Median age at time of treatment was 7.67 years and median follow-up for the study group is 4.71 years. For eligible patients overall survival (OS) was 78.9% at 3 years and 71.4% at 5 years. Event free survival (EFS) was 71.5% at 3 years and 66.7% at 5 years. A significant difference in EFS was demonstrated for patients treated by chemotherapy + RT when compared with RT alone. For chemotherapy + RT, EFS was 78.7% and 73.4% at 3 and 5 years respectively compared with 64.2% and 60.0% at 3 and 5 years respectively for RT alone (p=0.0419). Overall survival at 3 years was 83.8% for patients completing RT within 50 days compared with 69.7% for those taking more than 50 days to complete RT. This survival benefit almost reached the level of statistical significance (p=0.0513). There was a significantly better EFS (p=0.0184) for patients completing RT within 50 days compared with those taking more than 50 days to complete RT, with a 3-year EFS of 78.1% vs 55.0%. Multivariate analysis identified complete resection (p=0.0398), use of chemotherapy (p=0.0228) and duration of RT of 50 days or less (p=0.0056) as factors predictive of better EFS. There was no significant effect of surgery-RT interval on outcome in either arm. RT planning films were reviewed for 131 of the 176 (74.4%) irradiated patients. Sixty-five (49.6%) had no targeting deviations, 58 (44.3%) had one or more targeting deviations and for 8 (6.1%) targeting was not assessable. Placement of cribriform fossa shielding was assessable for 131 patients, and 29 (22.1%) had over-shielding. Placement of skull base shielding was assessable for 130 patients and 22 (16.9%) had over-shielding. PF field placement was assessable for 112 patients and 32 (28.6%) had a deviation from the protocol. PF recurrence was seen in 11 of 32 (34.4%) patients who had a PF targeting deviation compared with 3 of 80 (16.3%) who did not (p=0.043). There was no statistically significant impact of other targeting deviations on the risk of recurrence or EFS. Conclusions: This study has demonstrated the feasibility and benefits of administering intensive adjuvant pre-RT chemotherapy in patients with standard risk medulloblastoma and has also confirmed the importance of avoiding gaps in RT for medulloblastoma. Attention to detail when planning RT is important, as illustrated in this study in the case of PF field placement.

Treatment of standard risk medulloblastoma with craniospinal irradiation, carboplatin, and vincristine

Background Improved outcome for children with medulloblastoma requires new treatment protocols which incorporate chemotherapeutic agents that are capable of eradicating minimal residual disease in the primary posterior fossa site and in the leptomeninges and whose toxicities are tolerable. Procedure We treated 25 children with nondisseminated medulloblastoma with complete or near complete surgical resection of the posterior fossa tumor, 3,600 cGy craniospinal irradiation (CSRT) and 5,400 cGy posterior fossa irradiation followed by adjuvant chemotherapy with carboplatin and vincristine. Results The estimated 3-year progression-free survival (PFS) was 0.73 (S.E. ± 0.09) compared with a 3-year PFS of 0.69 in historical controls treated with surgical resection and CSRT but without chemotherapy. Six relapses occurred outside the posterior fossa and one relapse occurred both in the posterior fossa and in the lateral ventricle. The major acute toxicities were myelosuppression, anorexia and neuropathy. Conclusions Our experience with this adjuvant chemotherapy regimen with carboplatin and vincristine, as used by us, does not encourage its adoption in future clinical trials. Med. Pediatr. Oncol. 29:563–567, 1997. © 1997 Wiley-Liss, Inc.