Gerber Naamit K, Young Robert J, Barker Christopher A, Wolchok Jedd D, Chan Timothy A, Yamada Yoshiya, Friguglietti Leigh, Beal Kathryn
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
J Neurooncol. 2015 Jan;121(1):159-65. doi: 10.1007/s11060-014-1617-9. Epub 2014 Oct 2.
Brain metastases (BM) frequently develop in patients with melanoma and are associated with a poor prognosis. Whole brain radiation therapy (WBRT) is a standard intervention for intracranial disease, particularly in patients with multiple BM. Ipilimumab improves survival in patients with advanced melanoma. The purpose of this study is to investigate the safety and efficacy of concurrent WBRT and ipilimumab. A retrospective analysis was conducted of 13 consecutive patients treated with WBRT within 30 days of ipilimumab administration. Radiographic response, as measured by serial magnetic resonance imaging scans post-treatment, was graded by modified World Health Organization (mWHO) and immune-related response criteria (irRC) in the 9 patients with follow-up imaging. Treatment-related toxicity was prospectively assessed during treatment. Four of nine patients (44 %) experienced partial response or stable central nervous system (CNS) disease as measured by mWHO criteria. This number increased to 5 patients (56 %) when irRC criteria were used. Rates of treatment-related neurologic toxicity were low with only one patient experiencing grade 3-4 neurologic toxicity. There was a high rate of intratumoral hemorrhage in this patient population, with 10 of 10 patients with post-treatment imaging demonstrating new or increased intratumoral bleeding after WBRT. This retrospective study demonstrates that the primary pattern of CNS response to WBRT and ipilimumab is stable disease and not regression of BM. Furthermore, while the combination of WBRT and ipilimumab may offer promising efficacy, prospective studies are needed to further assess efficacy and toxicity.
脑转移瘤（BM）在黑色素瘤患者中经常出现，且与预后不良相关。全脑放射治疗（WBRT）是颅内疾病的标准干预措施，尤其是对于多发性BM患者。伊匹单抗可提高晚期黑色素瘤患者的生存率。本研究的目的是调查同步进行WBRT和伊匹单抗治疗的安全性和疗效。对13例在伊匹单抗给药后30天内接受WBRT治疗的连续患者进行了回顾性分析。通过治疗后的系列磁共振成像扫描测量的影像学反应，在9例接受随访成像的患者中，根据改良世界卫生组织（mWHO）和免疫相关反应标准（irRC）进行分级。在治疗期间对治疗相关毒性进行前瞻性评估。根据mWHO标准，9例患者中有4例（44%）出现部分缓解或中枢神经系统（CNS）疾病稳定。使用irRC标准时，这一数字增至5例（56%）。治疗相关神经毒性发生率较低，只有1例患者出现3-4级神经毒性。该患者群体中瘤内出血发生率较高，10例接受治疗后成像的患者中有10例在WBRT后出现新的或增加的瘤内出血。这项回顾性研究表明，CNS对WBRT和伊匹单抗反应的主要模式是疾病稳定，而非BM消退。此外，虽然WBRT和伊匹单抗联合使用可能具有有前景的疗效，但仍需要前瞻性研究来进一步评估疗效和毒性。
