Oregon Health & Science University, Portland, OR.
Am J Clin Oncol. 2019 Mar;42(3):253-257. doi: 10.1097/COC.0000000000000509.
The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control.
We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined.
In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed.
Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.
抗 CTLA-4 和抗程序性细胞死亡-1（PD-1）疗法显著改善了转移性黑色素瘤患者的生存率。然而，关于免疫疗法（IT）和立体定向放射外科（SRS）在脑转移患者中的相互作用的数据有限，特别是联合治疗如何影响毒性和颅内肿瘤控制的数据有限。
我们回顾性分析了 2011 年至 2017 年间接受免疫检查点抑制剂和 SRS 治疗脑转移的 26 例转移性黑色素瘤患者。我们评估了同时（30 天内）和序贯接受 SRS 和 IT 治疗的病变。评估总生存期（OS）、局部控制率（LC）和区域无进展生存期（RPFS）。
共 26 例患者和 90 个病变接受了 pembrolizumab、nivolumab 和/或 ipilimumab 序贯或同时治疗。中位随访时间为 18.9 个月（范围，4.9 至 62.3 个月）。中位总生存期为 26.1 个月。有 3 例局部失败，但两组之间无显著差异。与非同期治疗相比，同步 SRS 和免疫治疗后患者的颅内无进展生存期明显延长，分别为 19 个月和 3.4 个月（P<0.0001）。未观察到 4-5 级毒性。
接受 SRS 和免疫检查点抑制剂治疗的脑转移黑色素瘤患者的中位生存时间为 26.1 个月，优于历史对照。与接受序贯治疗的患者相比，在 SRS 后 30 天内接受免疫治疗的患者区域颅内无进展生存期明显改善。我们的发现表明检查点抑制剂免疫疗法与放射外科之间存在协同作用。需要进一步的研究来证实这些发现。
