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PURPOSE Evaluation of the treatment outcome after radiosurgery (RS) alone or in combination with whole-brain radiotherapy (WBRT) with special attention to prescribed dose and its influence on local control and survival. PATIENTS AND METHODS Between September 1984 and January 1997, 236 patients with 311 brain metastases treated with radiosurgery met the following inclusion criteria: one to three brain metastases per patient; no previous WBRT; and Kamofsky performance status (KPS) > or = 50%. One hundred fifty-eight patients treated only with RS received a median dose of 20 Gy prescribed to the 80% isodose line; 78 patients received RS with a median dose of 15 Gy/80% and an additional course of WBRT. RESULTS For the entire series, overall median survival was 5.5 months, with control of CNS disease achieved in 92% of the treated brain metastases; the results were not significantly different between patients treated by RS with or without WBRT. However, in patients without evidence of extracranial disease, median survival was increased for patients who received WBRT (15.4 vs 8.3 months; P=.08). Additionally, there was a suggestion that increased doses for patients treated with RS only resulted in improved outcome. Four lesions were suspicious for radiation necrosis by magnetic resonance imaging (MRI); in one of the four lesions, radiation necrosis was confirmed histologically. The incidence of transient low-grade toxicity was 18%; symptoms could be treated by the temporary administration of steroids. CONCLUSION RS is an effective, noninvasive means of controlling brain metastases when used alone or in combination with WBRT. There is a trend for superior local control and especially in patients without extracranial disease for superior survival when RS is used in conjunction with WBRT. Randomized trials would seem to be warranted, comparing the benefit of RS with or without additional WBRT.

4065 Background: Evaluation of the HPV infection- and transformation-status as a predictor of the response to definitive radio-chemotherapy for anal cancer. Methods: 80 patients (54 fm, 26 m) with histologically confirmed anal cancer and known HPV-Infection- (determined by PCR) and p16-expression-status (determined by immunohistochemistry) were analyzed. All pts. were treated with definitive radio-chemotherapy (RCT) with 5-FU/MMC, median age 60ys (35–86), median follow up 54mo (4–180). 41 pts. were HPV+ and p16+ (group 1), 10 pts. were HPV-/p16+ (group 2), 9 pts. were HPV+/p16- (group 3) and 17 pts. were HPV+/p16- (group 4). Endpoints were local control (LC) at 5ys and overall survival (OS) at 5ys. In addition to HPV/p16 status, the influence of T-stage and tumor localization (canal vs. margin) was analyzed. Results: More women than men were HPV+ (fm 77% vs. m 33%) while gender was evenly distributed among HPV-pts. (fm 48% vs. m 53%). Upon univariate analysis, gender, HPV+ and p16+ were significant predictors of both LC and OS (p

13125 Background: In a current clinical study, the tyrosine kinase (TK) inhibitor, imatinib mesylate, is given alternately with radiotherapy in inoperable glioblastoma patients. Imatinib inhibits phosphorylation of certain protein TKs including activated Bcr-Abl, c-kit, and the PDGF receptor. To study the interaction between imatinib and irradiation, a translational study on glioblastoma cells in vitro was conducted in parallel with the clinical study. The purpose of the present work was to study the effect of simultaneous or sequential treatment of the two agents. Methods: U343MG glioblastoma cells were grown in medium supplemented with 10% foetal bovine serum (FBS) or 5% platelet poor plasma (PPP). The colony formation assay was used to test the cytostatic effect of imatinib alone and clonogenic cell survival after irradiation. The surviving fraction as function of dose was fitted by the linear-quadratic model. Results: Irradiation in dilute culture conditions showed a moderate enhancement of radiation-induced cell inactivation by 3–10 μM imatinib. The sensitising effect was similar when the medium was supplemented with PPP instead of FBS. The inhibitory effect on colony formation was the same whether imatinib was added before or after irradiation. However, the inhibitor was required to be present during colony formation since no significant effect was observed when the inhibitor was present only during irradiation and repair. Pretreatment of mass cultures with imatinib for 2–5 days had no effect on the radiosensitivity in delayed plating experiments where imatinib was absent during colony formation. Conclusions: Imatinib showed a synergistic effect in combination with radiation but did not act as a classical radiosensitiser. We suggest that the interaction of imatinib with radiation may be associated with an inhibitory effect on cell proliferation. [Table: see text]