CLINICAL STUDY Repeated stereotactic radiosurgery for patients with progressive brain metastases Giuseppe Minniti 1,2 • Claudia Scaringi 2 • Sergio Paolini 1 • Enrico Clarke 2 • Francesco Cicone 3 • Vincenzo Esposito 2 • Andrea Romano 4 • Mattia Osti 2 • Riccardo Maurizi Enrici 2 Received: 24 April 2015 / Accepted: 8 September 2015 Ó Springer Science+Business Media New York 2015 Abstract In the present study we have evaluated the effi- cacy and toxicity of repeated stereotactic radiosurgery (SRS) in patients with recurrent/progressive brain metas- tases. Between March 2006 and October 2014, 43 patients (21 men and 22 women) with 47 lesions received a second course of SRS given in three daily fractions of 7–8 Gy. With a follow-up study of 19 months, the 1- and 2-year survival rates from repeated SRS were 37 and 20 %, respectively, and the 1- and 2-year local control rates were 70 and 60 %, respectively. Actuarial local control was significantly better for breast and lung metastases as compared with melanoma metastases; specifically, 1-year local control rates were 38 % for melanoma, 78 % for breast carcinoma and 73 % for non-small cell lung cancer (NSCLC) metastases (p = 0.01). The cause of death was progressive sys- temic disease in 25 patients and progressive brain disease in 11 patients. Stable extracranial disease (p = 0.01) and Karnofsky performance status (KPS; p = 0.03) were pre- dictive of longer survival. Radiologic changes suggestive of brain radionecrosis were observed in 9 (19 %) out of 47 lesions, with an actuarial risk of 34 % at 12 months. Neu- rological deficits (RTOG Grade 2 or 3) associated with brain necrosis occurred in 14 % of patients. In conclusion, a second course of SRS given in three daily fractions is a feasible treatment for selected patients with recurrent/pro- gressive brain metastases. Further studies are needed to explore the efficacy and safety of different dose-fractiona- tion schedules, especially in patients with melanoma or large metastases. Keywords Stereotactic radiosurgery Á Brain metastases Á Fractionated stereotactic radiotherapy Á Reirradiation Á Brain radionecrosis Introduction Stereotactic radiosurgery (SRS) has been increasingly used for the treatment of patients with brain metastases, with a reported local control of 70–90 % at 12 months [1–5]. Two randomized trials showed similar survival benefits and functional independence between patients with 1–4 brain metastases treated with SRS alone or SRS plus whole brain radiation therapy (WBRT) [3, 5], indicating that brain metastases can be managed initially with SRS alone, potentially avoiding the decline of neurocognitive function and quality of life associated with WBRT [6]. For patients whom brain metastases recur after SRS, the evidence regarding the safety and efficacy of salvage therapies is limited. Treatment options include WBRT (3,5), surgery [7, 8] or SRS [9–16]. For patients with recurrent/progressive brain metastases receiving salvage SRS, a few studies report a variable survival time of 7–10 months (9–16); however, most of the series include metastases that recur after WBRT or distant from the irradiated tumor site. Thus, the efficacy and risk of radia- tion-induced toxicity following a second course of SRS for recurrence/progression at the previously irradiated sites remain unsubstantiated. & Giuseppe Minniti gminniti@ospedalesantandrea.it 1 IRCCS Neuromed, 86077 Pozzilli, IS, Italy 2 Radiation Oncology Unit, Sant’ Andrea Hospital, University Sapienza, Via di Grottarossa 1035, 00189 Rome, Italy 3 Nuclear Medicine Unit, Sant’ Andrea Hospital, University Sapienza, 00189 Rome, Italy 4 Neuroradiology Unit, Sant’ Andrea Hospital, University Sapienza, 00189 Rome, Italy 123 J Neurooncol DOI 10.1007/s11060-015-1937-4