P17.38 * THE EFFECT OF TIMING OF RADIOTHERAPY (RT) IN PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) RECEIVING TEMOZOLOMIDE (TMZ): AN ANALYSIS BASED ON THE UCSF EXPERIENCE

Abstract

BACKGROUND: The effect of timing of initiation of radiotherapy (RT) after surgery on the outcome of patients with glioblastoma (GBM) remains controversial. Most neurosurgeons and neuro-oncologists believe that early initiation of RT may result in clinical benefits. However, certain reports suggested that delayed RT may be positively associated with survival for GBM patients. To further explore this issue, we analyzed three clinical trials for newly diagnosed GBM patients receiving temozolomide (TMZ) conducted at UCSF. METHODS: From 2004 through 2010, 207 adult patients with supratentorial GBM were enrolled into 3 clinical trials which consisted of RT plus TMZ and an experimental agent. Timing of RT was defined as the time interval between definitive surgery and commencement of RT, which was intended to be within 6 weeks per protocol eligibility. Overall survival (OS) and Progression-free survival (PFS), measured from study registration, were estimated using the Kaplan-Meier method. Analysis by classification and regression trees was used to determine the cut-off values for timing of RT at which there was a significant difference in OS and PFS. Cox proportional hazards model was used to assess the effect of RT timing (in days) on clinical outcomes, adjusting for treatment protocol, age, KPS, and extent of resection. RESULTS: The median wait time between surgery and RT was 29.5 days (range: 7-89 days). There was no significant difference in timing of RT with respect to baseline variables, except for resection extent: patients who were given RT earlier were more likely to have undergone a biopsy than more extensive surgery. Unexpectedly, a short delay in RT administration (at 30-34 days) was predictive of prolonged OS (HR = 0.58, p < 0.02) as well as prolonged PFS (HR = 0.55, p < 0.001), compared to early initiation of RT (<29 days), after adjusting for protocol and baseline prognostic variables, including extent of resection. Interestingly, a longer delay of RT initiation past 34 days was not associated with improved OS or PFS compared to early initiation (HR = 0.89, p = 0.54, HR = 0.76, p = 0.14, respectively). CONCLUSIONS: We conclude that there may be an optimal window in which a short delay in start of RT may be associated with prolonged OS and PFS. Caution should be exercised in interpreting these results since it is well known that secondary analyses may be influenced by unknown confounding factors.