Department of Radiation Oncology, Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin.
NRG Oncology Statistics and Data Management Center.
Int J Radiat Oncol Biol Phys. 2022 Oct 1;114(2):266-274. doi: 10.1016/j.ijrobp.2022.05.048. Epub 2022 Jun 5.
The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes.
Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT.
Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027).
Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.
放射治疗（RT）后免疫炎症状态与不良预后相关。我们使用放射治疗肿瘤学组（RTOG）0521 的血清标本进行了一项预先设计的验证研究。假设预处理炎症状态与临床结局相关。
RTOG 0521 的患者储存了血清以备生物标志物验证。这项研究旨在验证先前的发现，即 C 反应蛋白（CRP）升高与较短的生化无病生存期（bDFS）相关。在预处理样本中测量 CRP 水平。还测量了一组相关细胞因子的探索性面板，包括：单核细胞趋化蛋白-1、粒细胞-巨噬细胞集落刺激因子、干扰素-γ、白细胞介素（IL）-1b、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12、IL-13、IL-17A、IL-23 和肿瘤坏死因子。主要终点是 bDFS。其他探索性终点包括总生存期、远处转移和归因于 RT 的毒性事件。
RTOG/NRG 0521 中有 202 名患者有血清样本。中位年龄为 66 岁（48-83），90%的患者为白人。CRP 与 bDFS 之间无关联（调整后的危险比[HR]，每增加 1 对数 CRP 增加 1.07；95%置信区间，0.83-1.38；P=0.60）。在探索性、无计划的分析中，预处理 IL-10 与较差的 bDFS（调整后的 HR，每增加 1 对数增加 1.61；P=0.0027）和远处转移（HR，每增加 1 对数增加 1.55；P=0.028）显著相关。在多重调整后，IL-10 与 bDFS 的相关性得以维持。预处理干扰素-γ、IL-1b、IL-2、IL-13、IL-23 水平的探索性分析与 2 级或更高的尿频（调整后的优势比，0.64、0.65、0.71、0.72 和 0.74，均 P<0.05）呈负相关，IL-6 与 2 级或更高的勃起功能障碍（优势比，0.62；P=0.027）呈负相关。
预处理 CRP 与 RT 后 bDFS 较差无关。在假设生成分析中，较高的基线 IL-10 水平与较低的 bDFS 发生率相关。这些发现需要进一步的前瞻性评估。
