Role of extra cranial stereotactic body radiation therapy in the management of Stage IV melanoma.

BJR Received: 10 April 2017 © 2017 The Authors. Published by the British Institute of Radiology Revised: 13 June 2017 Accepted: 19 June 2017 https://doi.org/10.1259/bjr.20170257 Cite this article as: Franceschini D, Franzese C, De Rose F, Navarria P, D’Agostino GR, Comito T, et al. Role of extracranial stereotactic body radiation therapy in the management of Stage IV melanoma. Br J Radiol 2017; 90: 20170257. FULL PAPER Role of extracranial stereotactic body radiation therapy in the management of Stage IV melanoma 1 DAVIDE FRANCESCHINI, MD, 1CIRO FRANZESE, MD, 1FIORENZA DE ROSE, MD, 1PIERINA NAVARRIA, MD, GIUSEPPE R D’AGOSTINO, MD, 1TIZIANA COMITO, MD, 1ANGELO TOZZI, MD, 2MARIA C TRONCONI, MD, 3 LORENZA DI GUARDO, MD, 3MICHELE DEL VECCHIO, MD and 1,4MARTA SCORSETTI, MD 1 1 Department of Radiotherapy and Radiosurgery, Humanitas Clinical and Research Center, Rozzano-Milan, Italy Department of Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy 3 Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 4 Department of Biomedical Sciences, Humanitas University, Rozzano-Milan, Italy 2 Address correspondence to: Dr Davide Franceschini E-mail: Objective: To investigate the role of extracranial stereotactic body radiation therapy (SBRT) in the management of oligometastatic melanoma. Methods: Patients affected by Stage IV melanoma, with less than three extracranial metastatic lesions, who received SBRT were included in this analysis. Acute and late toxicity, local control (LC), overall survival (OS) and progression-free survival (PFS) were analysed. Results: 31 patients were included in the study. 16 patients (51.6%) were treated for lung meta stases, 8 patients for liver metastases (25.8%) and 7 (22.6%) for nodal metastases. 38 lesions were irradiated. With a median follow-up time of 13 months, 11 patients (35.4%) were still alive, in four cases (12.9%) with no evidence of disease. Median OS was 10.6 months, and OS at 6, 12 and 24 months was 77, 41 and 21% respectively. LC at 12 and 24 months was 96.6 and 82.8%. 23 patients (74.2%) developed distant metastases. Median PFS was 5.8 months, and PFS at 6, 12 and 24 months was 48.2, 18.5 and 13.9% respectively. Number of irradiated lesions showed a statistically significant correlation only with LC (p = 0.03). Response of the irradiated lesion was related to OS (p = 0.019). Local response showed also a borderline correlation with PFS (p = 0.07). Conclusion: SBRT for extracranial metastases from melanoma is feasible and well tolerated. Response of the irradiated lesions is predictive of OS. Advances in knowledge: SBRT for melanoma extracranial metastases is feasible and the response of the irradiated lesions is predictive of OS. INTRODUCTION Stage IV melanoma is characterized by poor prognosis. The presence of distant metastatic disease is associated with a 10-year survival rate of only 7%.1 other forms of cancer in oligometastatic patients6,7 a similar use of RT is also conceivable in stage IV oligometastatic melanoma patients. This is particularly appealing, considering the well-established radioresistance of melanoma cells,8 which makes the typical high doses per fraction used with SBRT necessary for the ablation of metastatic deposits. However, almost all published experiences of ablative RT in metastatic melanoma focused on brain metastases, with excellent local control rates and good survival outcomes.9 Very few data are available regarding extracranial sites. Patients with metastatic disease are often treated with various forms of chemotherapy, targeted therapy or immunotherapy. In recent years, the introduction in clinical practice of immunotherapeutic agents, such as ipilimumab,2 nivolumab and pembrolizumab,3,4 and of targeted therapies, such as the combination dabrafenib–trametinib significantly improved OS and outcomes of patients.5 However, most patients ultimately experience disease progression, so that more effective approaches, may be a combination of already available therapies, are warranted. In this scenario, the role of stereotactic body radiotherapy (SBRT) is still unclear. According to the results obtained in With this background, we performed this retrospective analysis on melanoma patients treated with SBRT for pulmonary, hepatic or nodal metastases. We analysed safety, local control (LC), overall survival (OS) and progression-free survival (PFS), with focus on the possible prognostic impact of local approaches in patients also receiving systemic treatments. Franceschini et al BJR METHODS AND MATERIALS Patients with Stage IV melanoma treated with SBRT for extracranial metastases were identified retrospectively from the institutional database. Inclusion criteria were (i) oligometastatic diseases (up to 3 metastatic sites); (ii) at least 6 months of follow-up for the surviving patients; and (iii) good performance status (PS): 0, 1 or 2. Patients with active cerebral disease were excluded. Any kind of previous or subsequent systemic therapy was allowed and recorded. The study was approved by the Institutional Ethical Committee. All patients were treated according to the Helsinki declaration. All patients were staged before SBRT, commonly with total body CT and in most cases positron emission tomography/CT. For simulation purposes, patients underwent simulation CT, with contrast medium in case of nodal or liver metastases. For lung metastases CT without medium of contrast was required, except in the case of central lesions. All patients were simulated in supine position with individualized thermoplastic mask. In case of lung or liver SBRT, in order to account for respiratory motion, 4D CT was performed. In all patients who underwent 4D CT scan, an internal target volume (ITV) was defined as the envelope of all gross tumour volumes identified in the different respiratory phases. In these cases, the treatment dose plans were optimized on the average CT. The planning target volume was generated from the ITV by adding an overall isotropic margin of 5 mm from the ITV. In all other cases, gross tumour volume was identified on simulation CT, and then a isotropic margin of 5 mm was added to obtain the planning target volume. Treatment was performed with linear accelerator. Volumetric modulated arc therapy was utilized. One or more partial or completed arcs were used to obtain the required target coverage and to spare as much as possible the organs at risk. Daily conebeam CT was used for treatment verification. Patients were clinically evaluated on the first and last days of treatment or more often if needed. Toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. Patients were followed up at 2 months after the end of treatment and then every 3 months for the first year, every 4 months during the second year and then every 6 months. Contrast-enhanced CT scan imaging was performed within 2 months af (...truncated)