Background. Medulloblastoma is a rare disease in adult patients, with an annual incidence rate of 0.05 per 100,000 per year. Results are, therefore, sparse and comprise small series over long periods. The real survival rate, the prognostic factors, the optimal postoperative radiation dose, and the role of adjuvant chemotherapy are still unknown for this disease in adults. Methods. The authors collected 156 cases of histologically proven medulloblastoma in patients older than 18 years of age who were treated between January 1975 and December 1991 in 13 French institutions. They analyzed the prognostic factors for survival and the impact of postoperative treatment on survival. Results. The 5‐ and 10‐year event free survival rates, 61 and 48%, respectively, are similar to those observed in children. The median time to recurrence is 30 months, but late relapses after 5 years remain frequent. Multivariate analysis identified postoperative performance status, spinal axis radiation dose, fourth ventricular floor involvement, and desmoplastic histologic subtype as factors significantly correlated with event free survival. No benefit of concomitant chemotherapy was demonstrated, and complete resection resulted only in severely reduced postoperative performance status. Conclusions. The prognostic factors in adult medulloblastoma are comparable to those of medulloblastoma in children, but a new parameter, postoperative performance status, was identified in this adult series. Postoperative craniospinal irradiation remains the standard treatment for adults with medulloblastoma. A reduced dose to the supratentorial compartment should be tested in a prospective protocol.

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Recent studies suggest the possibility of a direct antiangiogenic effect of anti -epidermal growth factor receptor (EGFR) drugs due to the presence of EGFR on endothelial cells. The aim of this study was to analyze the direct effect on endothelial cells of associating EGFR targeting, vascular endothelial growth factor receptor (VEGFR)-2 targeting, and irradiation. We examined both the cytotoxic effects and the effect on molecular markers resulting from the combined action of gefitinib (Iressa; anti-EGFR), ZM317450 [VEGFR tyrosine kinase inhibitor (VTKI); anti-VEGFR-2], and irradiation (radiation therapy) on HMME7 cells, an immortalized microvascular endothelial cell of human origin. The presence of a functional EGFR pathway sensitive to gefitinib was shown in HMME7 cells (gefitinib-induced decrease in phospho-EGFR, phospho-p42/p44, and phospho-Akt). The stimulation of VEGFR-2 pathway led to an increase in Akt phosphorylation that was inhibited by VTKI. Of note, a post -radiation therapy induction of phospho-p42/p44 was observed on HMME7 cells, and this effect was inhibited by a pretreatment with gefitinib. Based on combination indexes (Chou and Talalay analyses), the associations gefitinib-radiation therapy, VTKI-radiation therapy, VTKI-gefitinib, and gefitinib-VTKI-radiation therapy were found to be additive, slightly synergistic, and markedly synergistic, respectively, for the cytotoxicity on HMME7 cells. Among molecular explanatory factors that were examined, the combination gefitinib-radiation therapy totally abolishes DNA-dependent protein kinase expression, and gefitinib attenuates the radiation therapy -induced enhancement of ERCC1 and augments the VTKI-induced CD95 enhancement.

Home ZOL therapy was well tolerated. Both patient and nurse satisfaction were very high. However, better compliance with best practice should be encouraged.

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