Kiess Ana P, Wolchok Jedd D, Barker Christopher A, Postow Michael A, Tabar Viviane, Huse Jason T, Chan Timothy A, Yamada Yoshiya, Beal Kathryn
Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland; Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Int J Radiat Oncol Biol Phys. 2015 Jun 1;92(2):368-75. doi: 10.1016/j.ijrobp.2015.01.004. Epub 2015 Mar 5.
Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi.
From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations.
Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but in only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20% of patients.
Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly because of an enhanced immunomodulatory effect.
伊匹单抗（Ipi）是一种抗细胞毒性T淋巴细胞抗原4的单克隆抗体，已被证明可提高转移性黑色素瘤患者的生存率。在这项单机构研究中，我们调查了立体定向放射外科（SRS）对同时接受Ipi治疗的黑色素瘤脑转移（BMs）患者的安全性和疗效。
2005年至2011年，46例黑色素瘤患者接受了Ipi治疗，并对BMs进行了单次分割SRS。共治疗了113个BMs（91%为完整病灶，9%为术后病灶），中位剂量为21 Gy（范围15 - 24 Gy）。Ipi的给药剂量为3 mg/kg（54%）或10 mg/kg（46%），中位给药4次（范围1 - 21次）。使用不良事件通用术语标准3.0记录不良事件。采用Kaplan-Meier方法估计生存率，采用Cox回归研究相关性。
15例患者在接受Ipi期间接受了SRS，19例在接受Ipi之前接受了SRS，12例在接受Ipi之后接受了SRS。总生存期（OS）与SRS/Ipi的时间（P = 0.035）和黑色素瘤特异性分级预后评估（P = 0.013）显著相关。在接受Ipi期间或之前接受SRS治疗的患者比在接受Ipi之后接受SRS治疗的患者具有更好的OS和更低的区域复发率（1年OS分别为65%、56%和40%，P = 0.008；1年区域复发率分别为69%、64%和92%，P = 0.003）。与在接受Ipi之前或之后进行SRS相比，在接受Ipi期间进行SRS也有局部复发率更低的趋势（1年局部复发率分别为0%、13%和11%，P = 0.21）。在磁共振成像中，在接受Ipi期间或之前接受治疗的患者中有50%的患者BM直径增加至>150%，而在接受Ipi之后接受治疗的患者中仅为13%。20%的患者出现3 - 4级毒性反应。
总体而言，Ipi和SRS联合使用似乎耐受性良好。Ipi和SRS同时应用与良好的局部区域控制相关，可能生存期更长。它也可能导致肿瘤大小暂时增加，可能是由于免疫调节作用增强。
