Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcinomas.

Abstract

To evaluate the efficacy of a second course of fractionated stereotactic radiotherapy (re-SRT) and temozolomide (TMZ) as salvage treatment option in patients with aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs). Twenty-one patients with recurrent or progressive APTs (n = 17) and PCs (n = 4) who received combined TMZ and re-SRT, 36Gy/18fractions or 37.5Gy/15fractions, were retrospectively evaluated. TMZ was given at a dose of 75mg/m2 given concurrently to re-SRT, and then 150-200mg/m2/day for 5days every 4weeks or 50mg/m2 daily for 12months. Local control (LC) and overall survival (OS) were calculated from the time of re-SRT by Kaplan-Meier method. With a median follow-up of 27months (range 12-58months), 2-year and 4-year LC rates were 73% and 65%, respectively; 2-year and 4-year survival rates were 82% and 66%, respectively. A complete response was achieved in 2 and partial response in 11 patients. Six patients recurred with a median time to progression of 14months. O(6)-Methylguanine-DNA methyltransferase (MGMT) status and tumor volume emerged as prognostic factors. Grade 3 radiation-related toxicities occurred in 3 (14%) patients. Grade 2 or 3 hematologic toxicities during chemotherapy occurred in 8 (38%) patients. Re-SRT and TMZ is a safe treatment offering high LC in patients with progressive APTs and PCs. The potential advantages of combined chemoradiation as up-front or salvage treatment need to be explored in prospective trials.