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

Objectives 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). Patients and Methods Twenty-one patients with recurrent or progressive APTs (n = 17) and PCs (n = 4) who received combined TMZ and re-SRT, 36 Gy/18fractions or 37.5 Gy/15fractions, were retrospectively evaluated. TMZ was given at a dose of 75 mg/m(2)given concurrently to re-SRT, and then 150-200 mg/m(2)/day for 5 days every 4 weeks or 50 mg/m(2)daily for 12 months. Local control (LC) and overall survival (OS) were calculated from the time of re-SRT by Kaplan-Meier method. Results With a median follow-up of 27 months (range 12-58 months), 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 14 months.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. Conclusion 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.