ATCT-17IMPACT OF ADVERSE RADIOLOGICAL AND HISTOPATHOLOGIC CHARACTERISTICS ON OUTCOME OF AGGRESSIVE ADULT LOW GRADE GLIOMAS TREATED UNIFORMLY WITH RADIOTHERAPY AND CONCURRENT AND ADJUVANT TEMOZOLOMIDE: AN ANALYSIS OF 47 PATIENTS

Abstract

BACKGROUND: We investigate the impact of adverse radiology and histopathologic characteristics in adult low-grade gliomas (LGG) treated uniformly with post-operative radiotherapy with concurrent and adjuvant Temozolomide (TMZ). We also compare outcomes with published RTOG-9802 and RTOG-0424 trials data. METHODS: Between February 2009 to March 2014, 47 patients with supratentorial aggressive LGG selected meticulously based on predefined high-risk features on pre-operative MRI and histomorphology [nuclear pleomorphism suggesting atypical histology, high cellularity/mitosis, high Mib-1 index, and/or radiological features like definite gadolinium enhancement or considerable heterogeneity on T2 fluid-attenuated inversion recovery (FLAIR)]) were treated with post-operative RT with concurrent (75mg/m2) and adjuvant TMZ (150-200 mg/m2) for 6-12 cycles. All patients had either subtotal resection/biopsy/or had 3 or more Pignatti's high risk factors. RESULTS: Median age of the cohort was 35 years. Histologies included astrocytoma in 17 patients, oligodendrogliomas in 11 patients and mixed in remaining. Median RT dose was 55.8 Gy, median TMZ cycles were 6. The median Mib-1 index was 4 (range 2-15%). P53 mutation was present in 19/25 tested samples. 1p19q co-deletion was found in 11/22 tested samples. IDH 1 was mutated in 5/9 cases tested. At a mean follow up of 31 months, the 3 year and 5 year OS was 86% and 73% respectively, while PFS was 82% and 61% respectively. For 31 patients having 3 or more Pignatti's high risk factors, 3 year OS and PFS were 85% and 73% respectively. Five patients had clinic-radiological progression, while two patients had transformation to glioblastoma. No grade III/beyond toxicity was reported. CONCLUSION: Our experience of employing TMZ in concurrent and adjuvant setting along with focal irradiation in aggressive adult LGG, based on adverse radiological and histopathologic factors, even without all molecular markers is encouraging. Future work will include late follow-up data and impact of molecular markers in this cohort.