CLINICAL STUDY Fractionated stereotactic radiosurgery for patients with brain metastases Giuseppe Minniti • Rolando M. D’Angelillo • Claudia Scaringi • Luca E. Trodella • Enrico Clarke • Paolo Matteucci • Mattia Falchetto Osti • Sara Ramella • Riccardo Maurizi Enrici • Lucio Trodella Received: 13 November 2013 / Accepted: 22 January 2014 / Published online: 1 February 2014 Ó Springer Science+Business Media New York 2014 Abstract Stereotactic radiosurgery (SRS) delivered in 2–5 fractions (multi-fraction SRS) has been employed in patients with brain metastases as an alternative to single- fraction SRS with the aim to reduce late radiation-induced toxicity while maintaining high local control rate. In the present study we have evaluated the efficacy and toxicity of multi-fraction SRS in patients with 1–3 brain metastases. Between March 2006 and October 2012, 135 patients (63 men and 72 women) with 171 brain metastases have been treated with multi-fraction SRS (3 9 9 Gy or 3 9 12 Gy). At a median follow-up of 11.4 months, 16 lesions recurred locally. The 1- and 2-year local control rates were 88 and 72 %, respectively. The 1- and 2-year survival rates were 57 and 25 %, and respective distant failure rates were 52 and 73 %. Seventy-eight percent of patients succumbed to their extracranial disease and 22 % died of progressive intracranial disease. Multivariate analysis showed that melanoma histology was predictive of local failure (p = 0.02; HR 6.1, 95 % CI 1.5–24). Specifically, the 1-year local control rates were 68 % for melanoma, 92 % for breast carcinoma, and 88 % for NSCLC, respectively. Stable extracranial disease (p = 0.004) and Karnofsky performance status (p = 0.01) were predictive of longer survival. Radiologic changes suggestive of radionecrosis occurred in 12 (7 %) out of 171 lesions, with an actuarial risk of 9 % at 1 year and 17 % at 2 years, respectively. In conclusion, multi-fraction SRS appears to be an effective and safe treatment modality for brain metastases. It may represent an alternative to single-dose SRS for patients with large lesions or lesions located near critical structures. Keywords Stereotactic radiosurgery Á Brain metastases Á Fractionated stereotactic radiotherapy Á Brain radionecrosis Introduction Brain metastases have been reported in up to 40 % of patients with cancer, and treatment options include sup- portive care, surgery and radiotherapy [1]. Most patients receive whole brain radiotherapy (WBRT) with a reported median survival of 3–6 months, and with a significant proportion of patients who die of intracranial progressive disease a few months after treatment [2]. The efficacy of stereotactic radiosurgery (SRS) alone or in association with WBRT for patients with brain metastases has been inves- tigated in several studies [3–6]. Two randomized trials showed similar survival benefits and functional indepen- dence between patients with 1–4 brain metastases treated with SRS alone or SRS plus WBRT [5, 6], suggesting that WBRT could be omitted in the initial management of brain metastases. Although SRS offers an effective treatment for patients with brain metastases, single large doses may be associated with an increased risk of neurologic morbidity from radi- ation necrosis [7–9], and this is of concern especially for lesions larger than 2.5–3.0 cm or of any size that are in close proximity to critical structures, such as optic chiasm G. Minniti (&) Á C. Scaringi Á E. Clarke Á M. F. Osti Á R. M. Enrici Radiation Oncology Unit, Sant’ Andrea Hospital, University ‘‘Sapienza’’, Via di Grottarossa 1035, 00189 Rome, Italy e-mail: gminniti@ospedalesantandrea.it G. Minniti IRCCS Neuromed, 86077 Pozzilli, IS, Italy R. M. D’Angelillo Á L. E. Trodella Á P. Matteucci Á S. Ramella Á L. Trodella Radiotherapy and Oncology Department, Campus Bio-Medico University, 00128 Rome, Italy 123 J Neurooncol (2014) 117:295–301 DOI 10.1007/s11060-014-1388-3