Zhou Juan, Zhou Fei, Chu Xiangling, Zhao Jing, Wu Yan, Zhao Wencheng, Xu Chuan, Su Chunxia
Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
Department of Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine University of Electronic Science and Technology, Chengdu 610041, China.
Transl Lung Cancer Res. 2020 Apr;9(2):316-324. doi: 10.21037/tlcr.2020.04.15.
Recent studies have suggested obesity could contribute to improved outcomes of immune checkpoint inhibitor (ICI)-based treatment. Non-alcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is also obesity-related, but its association with the efficacy of ICI-based treatment has not yet been reported.
We retrospectively reviewed the medical records of advanced non-small cell lung cancer (NSCLC) patients treated at Shanghai Pulmonary Hospital between June 2015 and June 2019. NAFLD was confirmed by ultrasound examination of the abdomen. The efficacy of ICI-based treatment was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Univariate analysis to compare progression-free survival (PFS) was conducted using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model.
A total of 223 patients with advanced NSCLC who received ICI-based treatment were included in the study, of whom 26.9% (n=60) were confirmed to have NAFLD. Patients with NAFLD were more inclined to to have non-squamous carcinoma and higher body mass index (BMI) compared with those without NAFLD. The median PFS of the entire cohort of patients was 6.6 months. Nno significant difference was found in response [objective response rate (ORR) 43.3% 35.6%, P=0.289, disease control rate (DCR) 83.3% . 75.5%, P=0.211], nor in PFS (7.0 . 6.6 months, P=0.769) between the patients with (n=60) and without NAFLD (n=163). Surprisingly, in the subgroup of patients with liver metastases (LMs), there were dramatically significant differences in ORR (71.4% . 9.1%, P=0.013), DCR (85.7% . 18.2%, P=0.013), and median PFS [5.1 2.1 months, P=0.014, hazard ratio (HR): 0.244] between patients with (n=7) and without (n=11) NAFLD. Multivariate analysis revealed NAFLD to have a significant impact on PFS (P=0.017) in patients with LMs. In addition, the DCR of LMs was significantly higher in patients with NAFLD compared to those who did not have NAFLD (DCR: 42.9% . 0.0%, P=0.038).
In conclusion, NAFLD holds no clinical benefit for advanced NSCLC patients who undergo ICI-based treatment, but it is associated with improved outcomes in patients with LMs.
近期研究表明，肥胖可能有助于改善基于免疫检查点抑制剂（ICI）治疗的疗效。非酒精性脂肪性肝病（NAFLD）是慢性肝病最常见的形式，也与肥胖相关，但其与基于ICI治疗疗效的关联尚未见报道。
我们回顾性分析了2015年6月至2019年6月在上海肺科医院接受治疗的晚期非小细胞肺癌（NSCLC）患者的病历。通过腹部超声检查确诊NAFLD。基于实体瘤疗效评价标准（RECIST，1.1版）评估基于ICI治疗的疗效。采用对数秩检验进行单因素分析以比较无进展生存期（PFS）。使用Cox比例风险模型进行多因素分析。
本研究共纳入223例接受基于ICI治疗的晚期NSCLC患者，其中26.9%（n = 60）确诊患有NAFLD。与无NAFLD的患者相比，患有NAFLD的患者更倾向于患非鳞状癌且体重指数（BMI）更高。整个患者队列的中位PFS为6.6个月。有（n = 60）和无NAFLD（n = 163）的患者在缓解率[客观缓解率（ORR）43.3%对35.6%，P = 0.289，疾病控制率（DCR）83.3%对75.5%，P = 0.211]和PFS（7.0对6.6个月，P = 0.769）方面均未发现显著差异。令人惊讶的是，在有肝转移（LMs）的患者亚组中，有（n = 7）和无（n = 11）NAFLD的患者在ORR（71.4%对9.1%，P = 0.013）、DCR（85.7%对18.2%，P = 0.013）和中位PFS[5.1对2.1个月，P = 0.014，风险比（HR）：0.244]方面存在显著差异。多因素分析显示，NAFLD对有LMs的患者的PFS有显著影响（P = 0.017）。此外，与无NAFLD的患者相比，有NAFLD的患者LMs的DCR显著更高（DCR：42.9%对0.0%，P = 0.038）。
总之，NAFLD对接受基于ICI治疗的晚期NSCLC患者无临床益处，但与有LMs的患者的预后改善相关。
