CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Presurgical Ablative Radiation Is Associated with Local Control and Immune Response in Pancreatic Cancer.
Presurgical Ablative Radiation Is Associated with Local Control and Immune Response in Pancreatic Cancer.
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新辅助 SAbR 与改善的病理结局、增强的局部控制以及维持生存相关，同时诱导了独特的免疫反应。需要足够效力的研究来阐明其临床获益。
比较胰腺癌患者在新辅助（NA）化疗后接受手术的结局和分子特征，包括接受和不接受立体定向消融放疗（SAbR）的患者。深入了解可能有助于阐明SAbR的获益，并为未来的治疗方案提供分子指导。
这项单中心、三级医疗学术中心的队列研究纳入了2012年至2023年间所有接受NA化疗、伴或不伴SAbR治疗的胰腺癌患者。我们比较了治疗反应，进行了患者匹配，并采用Cox模型分析以识别组间差异。我们通过RNA测序评估分子反应，以识别SAbR诱导的生物学差异。
在133例接受化疗的患者和48例接受化疗+SAbR的患者中，分别有29例和14例患者有RNA测序数据。尽管基线疾病更为晚期，SAbR组的治疗后病理结果更好，总生存期相似[HR=0.97，95%置信区间（CI），0.58-1.60，P=0.9]。患者匹配分析表明，SAbR改善了局部区域无复发生存期（HR=0.24，95%CI，0.07-0.88，P=0.009）。动脉受累增加了单纯化疗的局部失败风险（HR=3.37，95%CI，1.74-6.54，P<0.001），而SAbR显著降低了该风险（HR=0.28；95%CI，0.12-0.68；P=0.005）。基因集富集分析显示免疫激活，CD8和NK/NKT细胞特征与局部控制相关，Treg特征与较差的局部控制相关。
To compare outcomes and molecular characteristics of patients who had surgery after neoadjuvant (NA) chemotherapy, with and without stereotactic ablative radiotherapy (SAbR), for pancreatic cancer. Insight could clarify the benefits of SAbR and provide molecular guidance for future therapeutic regimens. EXPERIMENTAL DESIGN: This single-institution, tertiary care academic center cohort study included all patients diagnosed with pancreatic cancer between 2012 and 2023 treated with NA chemotherapy, with or without SAbR. We compared therapeutic responses, performed patient matching, and conducted Cox modeling to identify differences between groups. We assessed molecular response using RNA sequencing to identify SAbR-induced biologic differences.
Among 133 patients receiving chemotherapy and 48 receiving chemotherapy + SAbR, RNA sequencing was available for 29 and 14 patients, respectively. Despite more advanced baseline disease, the SAbR group showed better posttreatment pathology and similar overall survival [HR = 0.97, 95% confidence interval (CI), 0.58-1.60, P = 0.9]. Patient matching indicated that SAbR improved locoregional recurrence-free survival (HR = 0.24, 95% CI, 0.07-0.88, P = 0.009). Arterial involvement raised local failure risk with chemotherapy alone (HR = 3.37, 95% CI, 1.74-6.54, P < 0.001), which was significantly reduced with SAbR (HR = 0.28; 95% CI, 0.12-0.68; P = 0.005). Gene set enrichment analysis showed immune activation, with CD8 and NK/NKT cell signatures associated with local control and Treg signatures associated with worse control.
NA SAbR is associated with improved pathologic outcomes, enhanced local control, and maintained survival while inducing a distinct immune response. Well-powered studies are needed to clarify its clinical benefits.
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