Ipilimumab and Stereotactic Radiosurgery with CyberKnife® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience.

Marcello Serra,Vito Vanella,Paolo Muto,Esmeralda Scipilliti,Fabrizio Cammarota,Lucia Festino,Maria Grazia Vitale,Angela Petito,Emma D'Ippolito,Valentina Borzillo,Sara Falivene,Paolo A. Ascierto,Diana Giannarelli,Antonio M. Grimaldi,Gabriele Madonna,Claudia Trojaniello,Rossella Di Franco,Ester Simeone

doi:10.3390/cancers13081857

Abstract

Simple SummaryRetrospective studies have shown a survival advantage in combining ipilimumab with radiotherapy in patients with melanoma brain metastases (MBMs). However, these studies did not clarify the correct timing between the two methods. The aims of our study were to demonstrate the efficacy and toxicity of stereotactic radiotherapy/radiosurgery on MBMs in combination with ipilimumab and estimate the correct timing of treatments to improve patients’ outcomes.The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.

Highlights

The brain is frequently a site of metastases in melanoma malignancy, which represents the third most frequent cause of brain metastases after lung and breast cancers [1]
Retrospective analysis demonstrates an advantage in median overall survival (OS) with the association of ipilimumab and radiotherapy in patients with melanoma brain metastases (MBMs), without clarifying the optimal timing of these two modalities [24,25,26,27,28,29,30,31,32,33,34,35,36]. In this monoinstitutional retrospective analysis, we reported efficacy and toxicity data from patients with MBMs treated with the SRS/stereotactic radiotherapy (SRT) CyberKnife® (CK) System with or without ipilimumab
Chemotherapy alone has been proven to be ineffective for the treatment of MBMs with a median survival of 2.2 months due to the inability to penetrate across the blood–brain barrier (BBB) [40,41]

Summary

Introduction

The brain is frequently a site of metastases in melanoma malignancy, which represents the third most frequent cause of brain metastases after lung and breast cancers [1]. Immune checkpoint inhibitors and molecular target agents, introduced in the treatment of metastatic melanoma, have been proven effective against brain metastases, leading to median overall survival times of 14 to 23 months [2,3,4,5,6,7] Local treatments, such as radiotherapy (RT) and surgery, remain important in the management of MBMs and, in combination with new systemic therapies, can improve the outcomes of MBMs patients

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