Brown Lauren Julia, Ahn Julie, Gao Bo, Gee Harriet, Nagrial Adnan, Hau Eric, Silva Inês Pires da
Department of Medical Oncology, Westmead Hospital, Sydney, NSW 2145, Australia.
Blacktown Cancer and Haematology Centre, Blacktown Hospital, Sydney, NSW 2148, Australia.
Cancers (Basel). 2024 Jun 4;16(11):2136. doi: 10.3390/cancers16112136.
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（ICI）无论联合或不联合化疗均有不同反应。在NSCLC中，转移部位分布及对全身治疗联合方案的反应仍了解甚少。在一项针对接受一线全身治疗的不可切除III/IV期NSCLC患者的回顾性队列研究中，我们试图评估转移部位与反应和进展模式之间的关联。在两个癌症治疗中心检查了有关人口统计学、肿瘤特征（包括转移部位、大小和体积）、治疗及结局的数据。终点指标包括器官部位特异性反应率、客观反应率（ORR）、无进展生存期（PFS）和总生存期（OS）。285例患者纳入分析。在多变量分析中，骨转移患者的ORR、PFS和OS降低。骨转移患者也更易出现原发性耐药。骨或肝转移患者在接受ICI联合或不联合化疗时OS较短，但单纯化疗时并非如此，提示治疗耐药存在免疫基础。对这些部位的肿瘤微环境进行定向评估以及更深入了解器官特异性免疫治疗耐药的驱动因素对于优化这些患者的新型联合治疗及治疗顺序至关重要。
