Abstract 5336: Change in pattern of relapse following anti-angiogenic therapy in high grade gliomas

Purpose:. Local recurrence (LR) accounts for >90% at the time of relapse in high grade glioma (HGG) following conventional therapy. Anti-angiogenic therapy with bevacizumab has shown impressive radiological and clinical responses in HGG. However, an apparent increase in diffuse invasive relapse (DIR) following therapy necessitated a detailed analysis of pattern of recurrence following therapy. Methods: One hundred and sixty five consecutive patients with HGG, either newly diagnosed (n=75) or recurrent (n= 90) received therapy with bevacizumab at 10 mg/kg every two weeks along with conventional chemotherapy ± involved field radiotherapy. The treatment was continued till the time of disease progression or the patient developed dose limiting toxicity. Treatment evaluation was done with neurological examination and magnetic resonance imaging at base line and every 8 weeks subsequently. Pattern of recurrence and time to relapse were the primary aims of the study. DIR was defined as involvement of multiple lobes ± crossing the midline. Survival was calculated from the start of bevacizumab therapy. Results: With a mean follow-up of 6.8 months (range 1-58), 100 of the 165 patients (60.6%) have relapsed with 76 as DIR and 70 have died. The median progression free survival (PFS) and overall survival (OS) were 5 and 9 months respectively. Of the 62 patients who failed initially as LR, 38 (61.3%) patients subsequently developed DIR. 38/75 (50.7%) patients with newly diagnosed and 38/90 (42.2%) of recurrent HGG failed ultimately as DIR. All 9 patients who presented with multicentric HGG relapsed as DIR. The median OS for the patients who failed as DIR was 9 months Vs 6 months for patients with LR alone (p=0.06). While the hazard risk for LR remained linear over time, the risk of DR increased exponentially with time (R2 = 0.933). Biopsies done on eight of these patients at the time of recurrence showed decreased expression of Olig-2 in 6, increased expression of SDF-1 in 5 and a variable expression of CXCR-4 in 6 patients. No change in expression of HIF-1, p53, PDGF or CD163 was seen. Conclusion: Invasion remains a dominant process in HGG as demonstrated by both imaging and pathology. Angiogenic blockade that results in increased invasiveness of HGG is worrisome and needs to be addressed in future clinical trials. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5336.