Comparing Outcomes of Patients Treated With Radiation Therapy With or Without Concurrent and Adjuvant Temozolomide After Surgical Resection for Newly Diagnosed WHO Grade 3 Anaplastic Astrocytoma

Abstract

Treatment of patients (pts) with WHO grade III anaplastic astrocytomas (AA) includes maximal safe tumor resection and adjuvant radiation therapy (RT). The role of chemotherapy in this patient population has become of increasing interest in recent years, and has been the subject of multiple ongoing randomized clinical trials. The utility of temozolomide (TMZ) has been of particular interest given its established survival benefit in patients with WHO grade IV glioblastoma. This study investigates outcomes from our institutional experience treating patients with WHO grade III AA with surgery and RT, with or without concurrent TMZ. 152 patients with WHO grade III AA treated with surgical resection and adjuvant RT from 2004-2014 were analyzed retrospectively. Patients were divided into 2 groups, surgery followed by RT alone (n= 51 pts) and surgery followed by RT + concurrent TMZ (n= 101 pts). The decision to use TMZ was made based on the preference of the patient’s treating medical oncologist. When used, TMZ was administered at a dose of 75 mg/m2 daily concurrent with RT and at 150-200 mg/m2 during the maintenance phase for 6 cycles or as tolerated. Median RT dose was 59.4 Gy delivered in 1.8 Gy daily fractions. Overall survival (OS) and progression-free survival (PFS) from time of RT were estimated using the Kaplan Meier method and compared using the log-rank test. Patients were also stratified by 1p/19q co-deletion status and the effect of TMZ on OS and PFS were compared using the same technique. The median age at diagnosis for the TMZ and non-TMZ group was 52 and 50 years respectively. The median Karnofsky Performance Status (KPS) was 80 for both groups. Intensity modulated RT was used in approximately 25% of patients in both groups, with the remainder treated with forward-planned 3D-conformal technique. The majority of patients in the TMZ group subsequently received adjuvant TMZ, typically for a 6 month course at a dose of 150-200 mg/m2. Median PFS was 35 months for the TMZ group and 33 months for the non-TMZ group. This difference was not statistically significant with a p-value of 0.7. Median OS was 50 months for the TMZ group and 48 months for the non-TMZ group. This difference was not statistically significant with a p-value of 0.85. Of the patients with 1p/19q co-deletion (n=11 out of 46 with co-deletion status reported), no difference was observed in PFS when comparing those treated with or without concurrent TMZ (p=0.75). In our institutional experience of 152 patients with WHO grade III AA, we did not observe a difference in OS or PFS with the concurrent use of TMZ with RT after maximal safe resection. There was similarly no difference observed in PFS for patients with 1p/19q co-deletion present, although the sample size for this subset is small. Current ongoing clinical trials will be useful to investigate this question further in a prospective manner.