Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, United States.
Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, United States.
Radiother Oncol. 2018 Aug;128(2):266-273. doi: 10.1016/j.radonc.2018.06.017. Epub 2018 Jun 27.
Preclinical studies have suggested that radiation therapy (RT) enhances antitumor immune response and can act synergistically when administered with immunotherapy. However, this effect in melanoma brain metastasis is not well studied. We aim to explore the clinical effect of combining RT and immunotherapy in patients with melanoma brain metastasis (MBM).
Patients with MBM between 2011 and 2013 were obtained from the National Cancer Database. Patients who did not have identifiable sites of metastasis and who did not receive RT for the treatment of their MBM were excluded. Patients were separated into cohorts that received immunotherapy versus patients who did not. Univariable and multivariable analyses were performed using Cox model to determine predictors of OS. Kaplan-Meier method was used to compare OS. Univariable and multivariable analyses using logistic regression model were used to determine the factors predictive for the use of immunotherapy. Propensity score analysis was used to account for differences in baseline patient characteristics between the RT and RT + immunotherapy groups. Significance was defined as a P value ≤ 0.05.
A total of 1104 patients were identified: 912 received RT alone and 192 received RT plus immunotherapy. The median follow-up time was 6.4 (0.1-56.8) months. Patients with extracranial disease (OR 1.603, 95% CI 1.146-2.243, P = 0.006), and patients receiving SRS (OR 1.955, 95% CI 1.410-2.711, P < 0.001) as compared to WBRT, had a higher likelihood of being treated with immunotherapy. The utilization of immunotherapy had nearly doubled between 2011 and 2013 (12.9-22.8%). On multivariable analysis, factors associated with superior OS were younger age, lower medical comorbidities, lack of extracranial disease, and treatment with immunotherapy and SRS. The median OS was 11.1 (8.9-13.4) months in RT plus immunotherapy vs. 6.2 (5.6-6.8) months in RT alone (P < 0.001), which remained significant after propensity score matching.
An increase in trend for the use of immunotherapy was noted, however, an overwhelming majority of the patients with this disease are still treated without immunotherapy. Addition of immunotherapy to RT is associated with improved OS in MBM. Given the selection biases that are inherent in this analysis, prospective trials investigating the combination of RT, especially SRS and immunotherapy are warranted.
临床前研究表明,放射治疗(RT)可增强抗肿瘤免疫反应,并与免疫疗法联合使用时具有协同作用。然而,这种作用在黑色素瘤脑转移中尚未得到很好的研究。我们旨在探讨 RT 联合免疫疗法在黑色素瘤脑转移(MBM)患者中的临床效果。
从国家癌症数据库中获取了 2011 年至 2013 年间患有 MBM 的患者。排除了无法识别转移部位且未接受 RT 治疗 MBM 的患者。将患者分为接受免疫治疗的队列和未接受免疫治疗的队列。使用 Cox 模型进行单变量和多变量分析,以确定 OS 的预测因素。使用 Kaplan-Meier 法比较 OS。使用逻辑回归模型进行单变量和多变量分析,以确定预测免疫治疗使用的因素。采用倾向评分分析来解释 RT 组和 RT+免疫治疗组之间患者基线特征的差异。定义 P 值≤0.05 为具有统计学意义。
共确定了 1104 名患者:912 名接受 RT 单独治疗,192 名接受 RT+免疫治疗。中位随访时间为 6.4(0.1-56.8)个月。与 WBRT 相比,有颅外疾病(OR 1.603,95%CI 1.146-2.243,P=0.006)和接受 SRS(OR 1.955,95%CI 1.410-2.711,P<0.001)的患者更有可能接受免疫治疗。2011 年至 2013 年间,免疫治疗的使用率几乎翻了一番(12.9-22.8%)。多变量分析显示,与 OS 相关的因素包括年龄较小、合并症较少、无颅外疾病以及接受免疫治疗和 SRS。RT+免疫治疗组的中位 OS 为 11.1(8.9-13.4)个月,RT 单独治疗组为 6.2(5.6-6.8)个月(P<0.001),在倾向评分匹配后仍然具有统计学意义。
尽管注意到免疫治疗使用率呈上升趋势,但该疾病的绝大多数患者仍未接受免疫治疗。RT 联合免疫治疗可改善 MBM 的 OS。鉴于该分析中存在选择偏倚,有必要进行前瞻性试验研究 RT,特别是 SRS 和免疫治疗的联合应用。