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Int. J. Mol. Sci. 2018, 19(9), 2653; https://doi.org/10.3390/ijms19092653

Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases under Simultaneous Anti-PD-1 Treatment

1
Department of Radiation Oncology and Cyberknife Center, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
2
Center for Integrated Oncology (CIO Köln Bonn), University of Cologne, 50937 Cologne, Germany
3
Radio Immune-Oncology Consortium (RIO), University Hospital of Cologne, 50937 Cologne, Germany
4
Department of Stereotaxy and Functional Neurosurgery, Centre of Neurosurgery, University Hospital of Cologne, 50937 Cologne, Germany
5
Institute for Neuroscience and Medicine, Research Center Juelich, Wilhelm-Johnen-Str., 52425 Juelich, Germany
6
Department of Dermatology and Allergology, Ludwig-Maximilians University (LMU), Frauenlobstr. 9-11, 80377 Munich, Germany
7
Department III of Internal Medicine, Hematology and Oncology, University Hospital Munich, Ludwig-Maximilians University (LMU), 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
Received: 10 August 2018 / Revised: 28 August 2018 / Accepted: 3 September 2018 / Published: 7 September 2018
(This article belongs to the Special Issue Partnership of Radiotherapy and Immunotherapy)
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Abstract

Combination concepts of radiotherapy and immune checkpoint inhibition are currently of high interest. We examined imaging findings, acute toxicity, and local control in patients with melanoma brain metastases receiving programmed death 1 (PD-1) inhibitors and/or robotic stereotactic radiosurgery (SRS). Twenty-six patients treated with SRS alone (n = 13; 20 lesions) or in combination with anti-PD-1 therapy (n = 13; 28 lesions) were analyzed. Lesion size was evaluated three and six months after SRS using a volumetric assessment based on cranial magnetic resonance imaging (cMRI) and acute toxicity after 12 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE). Local control after six months was comparable (86%, SRS + anti-PD-1, and 80%, SRS). All toxicities reported were less than or equal to grade 2. One metastasis (5%) in the SRS group and six (21%) in the SRS + anti-PD-1 group increased after three months, whereas four (14%) of the six regressed during further follow-ups. This was rated as pseudoprogression (PsP). Three patients (23%) in the SRS + anti-PD-1 group showed characteristics of PsP. Treatment with SRS and anti-PD-1 antibodies can be combined safely in melanoma patients with cerebral metastases. Early volumetric progression of lesions under simultaneous treatment may be related to PsP; thus, the evaluation of combined radioimmunotherapy remains challenging and requires experienced teams. View Full-Text
Keywords: brain metastases; malignant melanoma; robotic stereotactic radiosurgery; SRS; Cyberknife®; pseudoprogression; checkpoint inhibition; immunotherapy; radioimmunotherapy brain metastases; malignant melanoma; robotic stereotactic radiosurgery; SRS; Cyberknife®; pseudoprogression; checkpoint inhibition; immunotherapy; radioimmunotherapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Trommer-Nestler, M.; Marnitz, S.; Kocher, M.; Rueß, D.; Schlaak, M.; Theurich, S.; von Bergwelt-Baildon, M.; Morgenthaler, J.; Jablonska, K.; Celik, E.; Ruge, M.I.; Baues, C. Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases under Simultaneous Anti-PD-1 Treatment. Int. J. Mol. Sci. 2018, 19, 2653.

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