The Impact Of Temozolomide On Post Radiation Therapy Progression Free Survival In Low Grade Glioma

Low-grade gliomas, classified as WHO grade II gliomas, are relatively slow-growing brain tumors for which the optimal timing of radiation therapy (RT) has not been well established. With increasing use of temozolomide (TMZ) over the past 10 years, our institutional paradigm for the post-operative management of low-grade glioma has evolved from RT alone, to early TMZ followed by RT at progression/recurrence, and finally to concurrent TMZ and RT. The purpose of this study was to evaluate the effects of TMZ and timing of RT on post-radiation therapy progression-free survival (post-RT PFS) and overall survival (OS). Records were reviewed of 182 patients, age ≥ 12 years, with pathologically-proven WHO grade II glioma and treated at a single institution from 01/1986 to 04/2014. Post-operatively, 79 (43.4%) patients were treated with up-front TMZ followed by RT at progression/recurrence, 39 (21.4%) patients received concurrent TMZ and RT, and 19 (10.4%) patients underwent RT alone. Time to RT, post-RT PFS, and OS were analyzed for each group. Date of progression was defined as the date of radiographic progression. At a median follow-up of 60.6 months, 118 (64.8%) patients had progressed. Among patients who received TMZ prior to RT, average time to RT was 18.1 months, post-RT PFS was 14.8 months, and OS was 44.4 months. Among patients who received concurrent TMZ and RT, the average time to RT was 9.8 months, post-RT PFS was 71.2 months, and OS was 44.5 months (9 patients died). A statistically significant difference in post-RT PFS was seen in patients who received early TMZ compared to those who did not receive TMZ prior to RT (p=0.0002). Both the median age and proportion of astrocytoma histology were higher in patients who received early TMZ (49.8 years, 53.6%) compared to those who did not receive TMZ prior to RT (44.9 years, 46.4%). Time to RT, post-RT PFS and OS were 37.9, 47.8, and 141.1 months, respectively, (7 patients died) in patients who underwent early RT alone. Our preliminary results suggest that up-front TMZ and delay of RT for the management of low grade glioma has a deleterious effect on post-RT PFS. While TMZ may facilitate delay of RT, such deferral may preclude a more efficacious opportunity for early intervention with radiation therapy. Patients who received TMZ were also found to have a worse OS, which may be attributed to the larger proportion of prognostically-poor astrocytoma histology as well as the higher median age in that group. Ongoing studies are investigating the impact of tumor characteristics and molecular markers on disease response to chemotherapeutic and radiotherapeutic interventions.