Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcin
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CLINICAL STUDY
Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcinomas Giuseppe Minniti1,2 · Sergio Paolini2 · Marie Lise Jaffrain Rea3 · Andrea Isidori4 · Claudia Scaringi5 · Ivana Russo6 · Mattia Falchetto Osti7 · Luigi Cavallo8 · Vincenzo Esposito2 Received: 10 May 2020 / Accepted: 29 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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/m2 given concurrently to re-SRT, and then 150–200 mg/m2/day for 5 days every 4 weeks or 50 mg/m2 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)-MethylguanineDNA 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. Keywords Fractionated stereotactic radiotherapy · Aggressive pituitary adenomas · Pituitary carcinomas · Re-irradiation · Temozolomide
Introduction * Giuseppe Minniti [email protected] 1
Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy
2
IRCCS Neuromed, Pozzilli, IS, Italy
3
Biotechnological and Applied Clinical Sciences Department, University of L’Aquila, L’Aquila, Italy
4
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
5
UPMC Hillman Cancer Center, San Pietro Hospital FBF, Rome, Italy
6
UPMC Hillman Cancer Center, Villa Maria, Mirabella, AV, Italy
7
Radiation Oncology Unit, Sant’ Andrea Hospital, “Sapienza” University, Rome, Italy
8
Division of Neurosurgery, Università degli Studi di Napoli “Federico II”, Naples, Italy
Most secreting and nonfunctioning pituitary adenomas are successfully treated by surgery and medical therapy, given alone or in combination [1–4]. Radiation therapy (RT), either fractionated RT or stereotactic radios
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