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Grill, J. et al.

Grill, Sainte-Rose, Jouvet, Gentet, Lejars, Frappaz, Doz, Rialland, Pichon, Bertozzi, Chastagner, Couanet, Habrand, Raquin, Le Deley, Kalifa,

Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children.

BACKGROUND: Morbidity and mortality are high in young children with medulloblastoma who receive craniospinal radiotherapy. We aimed to assess whether adjuvant treatment with protracted chemotherapy alone could replace radiotherapy. METHODS: We enrolled 79 children aged younger than 5 years who had had surgical resection of medulloblastoma onto a multicentre trial. Patients were treated with combination chemotherapy, which did not include methotrexate, for more than 16 months irrespective of the extent of disease. Early postoperative imaging defined three groups: R0M0 (no residual disease, no metastasis), R1M0 (radiological residual disease alone), and RXM+ (presence of metastases). Patients who did not relapse did not receive radiotherapy. Patients who relapsed or had disease progression received salvage treatment, which consisted of high-dose chemotherapy and stem-cell transplantation followed by local or craniospinal radiotherapy. For children classified as R0M0, the primary endpoint was 5-year overall survival and the secondary endpoint was 5-year progression-free survival. For children classified as R1M0 or RXM+, the primary endpoint was best radiological response and the secondary endpoints were 5-year overall survival and 5-year progression-free survival. Analyses were done by intention to treat. FINDINGS: Two of 15 patients classified as RXM+ and four of 17 patients classified as R1M0 had a complete radiological response. 5-year progression-free survival was 29% (95% CI 18-44) in the R0M0 group, 6% (1-27) in the R1M0 group, and 13% (4-38) in the RXM+ group. 5-year overall survival was 73% (59-84) in the R0M0 group, 41% (22-64) in the R1M0 group, and 13% (4-38) in the RXM+ group. In the R0M0 group, 5-year progression-free survival was 41% (26-58) for the 34 patients who underwent gross total resection compared with 0% for the 13 patients who had subtotal resection (relative risk 2.7 [1.3-5.6], p=0.0065). INTERPRETATION: Conventional chemotherapy alone can be used to cure children with non-metastatic medulloblastoma who have gross total resection confirmed by early radiological assessment, but is not sufficient for treatment of those with metastatic or incompletely resected medulloblastoma. Salvage treatment followed by posterior-fossa radiotherapy can effectively treat local relapses or progression.[1]

References

Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Grill, J., Sainte-Rose, C., Jouvet, A., Gentet, J.C., Lejars, O., Frappaz, D., Doz, F., Rialland, X., Pichon, F., Bertozzi, A.I., Chastagner, P., Couanet, D., Habrand, J.L., Raquin, M.A., Le Deley, M.C., Kalifa, C. The lancet oncology. (2005) [Pubmed]

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