Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Shandong Academy of Medical Science, Jinan, Shandong, China; Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania.
Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):196-203. doi: 10.1016/j.ijrobp.2020.01.032. Epub 2020 Feb 7.
Research to elucidate predictive factors of the abscopal effect is an essential first step toward potentially modifying these factors to increase the incidence of systemic antitumor effects. This study, using data from 3 institutional phase 1/2 trials, examined the predictive capacity of recorded parameters in patients undergoing combined radiation therapy (RT) and immunotherapy and explored outcomes based on those predictive factors.
All patients underwent combined immunotherapy and RT and had at least 1 nonirradiated noncontiguous lesion to evaluate out-of-field (abscopal) responses, defined as the best Response Evaluation Criteria in Solid Tumors response.
Altogether, 153 patients met study criteria, and the median follow-up was 21.1 months. The most common cancer types were non-small cell lung carcinoma (n = 62), small cell lung carcinoma (n = 25), head and neck cancers (n = 16), and renal cell carcinoma (n = 13). Immunotherapies included ipilimumab (n = 98) and pembrolizumab (n = 55). Multivariable linear regression indicated that post-RT absolute lymphocyte count (ALC), when analyzed as a continuous variable, correlated with abscopal responses (P < .001). For post-RT ALC, the abscopal response rate was 34.2% in the cohort with ALC higher than the median value, compared with 3.9% in patients with ALC lower than the median (P < .0001). Corresponding figures for pre-RT ALC were 30.3% versus 7.8%, respectively (P = .0004). Cox multivariate analysis confirmed that lower post-RT ALC also associated with poorer progression-free survival (P = .009) and overall survival (P = .026).
Lymphopenia, measured as the continuous variable of post-RT ALC, may affect the occurrence of abscopal responses and thus influence prognosis in patients treated with RT and immunotherapy. Although this hypothesis-generating finding requires corroboration by additional data, it suggests the importance of ALC monitoring and the potential of therapeutic manipulation of this parameter to induce abscopal effects.
阐明远隔效应预测因素的研究是朝着可能改变这些因素以增加全身抗肿瘤效应发生率迈出的重要第一步。本研究使用来自 3 项机构性 1/2 期试验的数据，研究了接受联合放射治疗（RT）和免疫治疗的患者中记录参数的预测能力，并根据这些预测因素探讨了结果。
所有患者均接受联合免疫治疗和 RT，并至少有 1 个未照射的非相邻病变，以评估场外（远隔）反应，定义为实体瘤反应评价标准的最佳反应。
共有 153 例患者符合研究标准，中位随访时间为 21.1 个月。最常见的癌症类型为非小细胞肺癌（n=62）、小细胞肺癌（n=25）、头颈部癌（n=16）和肾细胞癌（n=13）。免疫治疗包括伊匹单抗（n=98）和派姆单抗（n=55）。多变量线性回归分析表明，RT 后绝对淋巴细胞计数（ALC）作为连续变量分析时，与远隔反应相关（P<0.001）。对于 RT 后 ALC，ALC 值高于中位数的患者远隔反应率为 34.2%，而 ALC 值低于中位数的患者为 3.9%（P<0.0001）。相应的 RT 前 ALC 分别为 30.3%和 7.8%（P=0.0004）。Cox 多变量分析证实，较低的 RT 后 ALC 也与无进展生存期（P=0.009）和总生存期（P=0.026）较差相关。
淋巴细胞减少症，以 RT 后 ALC 的连续变量来衡量，可能影响远隔反应的发生，从而影响接受 RT 和免疫治疗的患者的预后。尽管这一假设生成的发现需要更多数据的证实，但它表明了 ALC 监测的重要性，以及通过治疗性干预该参数以诱导远隔效应的潜力。
