Youlong Wang, Huang Qi, Zhong Guangqing, Lv Jun, Guo Qinzhi, Ma Yifei, Wang Xinjia, Zeng Jiling
Hainan Hospital of PLA General Hospital, Department of General Surgery, Haitang District, Sanya, China.
Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Oncol. 2023 Dec 21;13:1191611. doi: 10.3389/fonc.2023.1191611. eCollection 2023.
The efficacy of immune checkpoint inhibitors (ICIs), including toripalimab and pembrolizumab, has not been confirmed in the treatment of cancer of unknown primary (CUP), which has a very poor prognosis. Combined with anti-angiogenic therapies, ICIs are hypothesized to be effective in prolonging overall survival. The study aims to give evidence on the treatment effects of sunitinib combined with ICIs, find pathological biomarkers associated with changes in volumetric F FDG PET/CT parameters, and investigate inner associations among these markers associated with response on PET/CT.
The study recruited patients receiving combined treatment (ICIs + sunitinib), compared the effects of combined treatment with those of separate treatment and age-matched negative controls, and analyzed propensity score-matched (PSM) pairs. Markers associated with survival were identified, and their inner associations were tested using structural equation modeling.
A total of 292 patients were enrolled in the final analysis, with 53 patients receiving combined treatment. Survival analysis demonstrated significantly prolonged survival in either combined or separate treatment, with the combined arm showing better response when PSM-paired using pre-treatment whole-body PET/CT parameters. The angiogenic markers KDR and VEGF mediate the PD-1 blockade impact on volumetric value changes in positive and negative manners.
The anti-angiogenic agent sunitinib may potentiate PD-1 blockade by diminishing angiogenesis or its downstream effects. The combined separate treatment increased the survival of CUP patients, and the responses could be evaluated using volumetric PET/CT parameters.
包括托瑞帕利单抗和帕博利珠单抗在内的免疫检查点抑制剂（ICI）在治疗预后极差的未知原发癌（CUP）方面的疗效尚未得到证实。ICI与抗血管生成疗法联合使用时，被认为可能有效延长总生存期。本研究旨在提供关于舒尼替尼联合ICI治疗效果的证据，寻找与容积性氟代脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（FDG PET/CT）参数变化相关的病理生物标志物，并研究这些与PET/CT反应相关的标志物之间的内在关联。
本研究招募接受联合治疗（ICI+舒尼替尼）的患者，将联合治疗的效果与单独治疗及年龄匹配的阴性对照的效果进行比较，并分析倾向评分匹配（PSM）对。识别与生存相关的标志物，并使用结构方程模型测试它们的内在关联。
共有292例患者纳入最终分析，其中53例接受联合治疗。生存分析表明，联合治疗或单独治疗均可显著延长生存期，在使用治疗前全身PET/CT参数进行PSM配对时，联合治疗组显示出更好的反应。血管生成标志物激酶插入域受体（KDR）和血管内皮生长因子（VEGF）以正负两种方式介导程序性死亡蛋白1（PD-1）阻断对容积值变化的影响。
抗血管生成药物舒尼替尼可能通过减少血管生成或其下游效应来增强PD-1阻断作用。联合或单独治疗均可提高CUP患者的生存率，并且可以使用容积性PET/CT参数评估反应。
