1Department of Neurosurgery, Yale New Haven Hospital, New Haven, Connecticut.
2Memorial Sloan Kettering Cancer Center, New York, New York; and.
J Neurosurg. 2019 Feb 15;132(2):512-517. doi: 10.3171/2018.10.JNS181371. Print 2020 Feb 1.
Concurrent use of anti-PD-1 therapies with stereotactic radiosurgery (SRS) have been shown to be beneficial for survival and local lesional control in melanoma patients with brain metastases. It is not known, however, if immunotherapy (IT) confers the same outcome advantage in lung cancer patients with brain metastases treated with SRS.
The authors retrospectively reviewed 85 non-small cell lung cancer (NSCLC) patients with brain metastases who were treated with SRS between January 2006 and December 2016. Thirty-nine PD-L1 antibody-positive patients received anti-PD-1 therapy with SRS (IT group) and 46 patients received chemotherapy (CT) with SRS (CT group). Results were obtained using chi-square, Kaplan-Meier, and Mann-Whitney U tests and Cox regression analyses.
Median survival following first radiosurgical treatment in the whole study group was 11.6 months (95% CI 8-15.5 months). Median survival times in the IT group and CT group were 10 months (95% CI 8.3-13.2 months) and 11.6 months (95% CI 7.7-15.6 months), respectively (p = 0.23). A Karnofsky Performance Status (KPS) score < 80 (p = 0.001) and lung-specific molecular marker Graded Prognostic Assessment (lungmol GPA) score < 1.5 (p = 0.02) were found to be predictive of worse survival.Maximal percent lesional shrinkage and time to maximal shrinkage were not significantly different between the CT and IT groups. Of the lesions for which a complete response occurred, 94.8% had pre-SRS volumes < 500 mm3. The amount of lesion shrinkage and time to maximal shrinkage were not different between the IT and CT groups for lesions with volumes < 500 mm3. However, in lesions with volume > 500 mm3, 90% of lesions shrank after radiosurgery in the IT group compared with 47.8% in the CT group (p = 0.001). Median times to initial response and times to maximal shrinkage were faster in the IT group than in the CT group: initial response 49 days (95% CI 33.7-64.3 days) versus 84 days (95% CI 28.1-140 days), p = 0.001; maximal response 105 days (95% CI 59-150 days) versus 182 days (95% CI 119.6-244 days), p = 0.12.
Unlike patients with melanoma, patients with NSCLC with brain metastases undergoing SRS showed no significant benefit-either in terms of survival or total amount of lesional response-when anti-PD-1 therapies were used. However, in lesions with volume > 500 mm3, combining SRS with IT may result in a faster and better volumetric response which may be particularly beneficial in lesions causing mass effect or located in neurologically critical locations.
在脑转移的黑色素瘤患者中，抗 PD-1 治疗联合立体定向放射外科（SRS）的同时使用已被证明对生存和局部病变控制有益。然而，对于接受 SRS 治疗的脑转移肺癌患者，免疫治疗（IT）是否具有相同的获益优势尚不清楚。
作者回顾性分析了 2006 年 1 月至 2016 年 12 月期间接受 SRS 治疗的 85 例非小细胞肺癌（NSCLC）脑转移患者。39 例 PD-L1 抗体阳性患者在 SRS 治疗中接受了抗 PD-1 治疗（IT 组），46 例患者接受了 SRS 治疗联合化疗（CT 组）。结果采用卡方检验、Kaplan-Meier 法和 Mann-Whitney U 检验和 Cox 回归分析。
在整个研究组中，首次放射外科治疗后的中位生存时间为 11.6 个月（95%CI 8-15.5 个月）。IT 组和 CT 组的中位生存时间分别为 10 个月（95%CI 8.3-13.2 个月）和 11.6 个月（95%CI 7.7-15.6 个月）（p = 0.23）。Karnofsky 表现状态（KPS）评分<80（p = 0.001）和肺特异性分子标志物分级预后评估（lungmol GPA）评分<1.5（p = 0.02）被发现与生存预后较差相关。最大病变缩小百分比和最大缩小时间在 CT 组和 IT 组之间无显著差异。完全缓解的病变中，94.8%的病变在 SRS 前体积<500mm3。对于体积<500mm3 的病变，IT 组和 CT 组之间的病变缩小量和最大缩小时间无差异。然而，对于体积>500mm3 的病变，在 IT 组中，90%的病变在放射外科治疗后缩小，而 CT 组中只有 47.8%（p = 0.001）。IT 组的初始反应和最大缩小时间均快于 CT 组：初始反应 49 天（95%CI 33.7-64.3 天）与 84 天（95%CI 28.1-140 天），p = 0.001；最大反应 105 天（95%CI 59-150 天）与 182 天（95%CI 119.6-244 天），p = 0.12。
与黑色素瘤患者不同，接受 SRS 治疗的脑转移 NSCLC 患者，无论在生存还是总病变反应方面，使用抗 PD-1 治疗均未显示出显著获益。然而，对于体积>500mm3 的病变，SRS 联合 IT 治疗可能会导致更快更好的体积反应，这对于引起占位效应或位于神经关键部位的病变可能特别有益。
