Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients with unresectable stage III/IV NSCLC who received first-line systemic therapy, we sought to assess the association between the site of metastases with patterns of response and progression. Data regarding demographics, tumour characteristics (including site, size, and volume of metastases), treatment, and outcomes were examined at two cancer care centres. The endpoints included organ site-specific response rate, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Two-hundred and eighty-five patients were included in the analysis. In a multivariate analysis, patients with bone metastases had a reduced ORR, PFS, and OS. Primary resistance was also more likely in patients with bone metastases. Patients with bone or liver metastases had a shorter OS when receiving ICIs with or without chemotherapy, but not with chemotherapy alone, suggesting an immunological basis for therapeutic resistance. A directed assessment of the tumour microenvironment in these locations and a deeper understanding of the drivers of organ-specific resistance to immunotherapy are critical to optimise novel combination therapies and sequencing in these patients.
晚期非小细胞肺癌（NSCLC）患者对免疫检查点抑制剂（ICIs）联合或不联合化疗的治疗反应存在异质性。目前，对于NSCLC中转移灶分布对系统性联合治疗方案疗效的影响仍知之甚少。本研究通过回顾性队列分析，纳入接受一线系统性治疗的不可切除III/IV期NSCLC患者，旨在探讨转移部位与治疗反应模式及疾病进展之间的关联。研究收集了两家癌症诊疗中心患者的基线资料、肿瘤特征（包括转移部位、大小及体积）、治疗方案及临床结局数据。评估终点包括器官特异性缓解率、客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。共285例患者纳入分析。多变量分析显示，骨转移患者的ORR、PFS和OS均显著降低，且更易出现原发性耐药。在接受ICIs联合或不联合化疗（而非单纯化疗）的患者中，骨转移或肝转移患者的OS更短，提示治疗耐药可能存在免疫学机制。对这些部位肿瘤微环境进行定向评估，并深入理解免疫治疗器官特异性耐药的驱动因素，对于优化此类患者的联合治疗方案及治疗顺序至关重要。
肿瘤(癌症)患者之家