Patients
This study was approved by the Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University.We retrospectively identified 138 patients with advanced (stage IIIB–IV) or recurrent SqCLC who were treated with PD-1 inhibitors (pembrolizumab, camrelizumab, sintilimab, nivolumab, tislelizumab, or toripalimab) between November 2017 and January 2021 at our institution, with the final follow-up occurring on January 31, 2022. All patients were at least 70 years of age and received 200mg of PD-1inhibitors intravenously every 3 weeks. The clinical and auxiliary examination data were integrated.
The key exclusion criteria included history of autoimmune disease, primary or secondary immunodeficiency, chronic active viral hepatitis, or uncontrolled central nervous system metastasis. Because SqCLC has a male predominance, we also excluded women and included only men.
Definition of sarcopenia
Dual-energy X-ray absorptiometry and bioelectric impedance analysis are the gold standards for diagnosing sarcopenia. However, this technology is not widely used in all departments of our hospital; therefore, pre-treatment(within one month) computed tomography (CT) was used to evaluate body composition to determine sarcopenia. Two observers read and analyzed the CT images. We used the third lumbar vertebra (L3) skeletal muscle mass index (SMI) as an estimator of sarcopenia. The cross-sectional area of the skeletal muscle at the L3 level was measured using ImageJ software(National Institutes of Health, Bethesda, MD, USA). The skeletal muscle area included the psoas, erector spinae, quadratus lumborum, transversus abdominis, external and internal oblique, and rectus abdominis muscles. The CT HU thresholds were − 29 to + 150 for quantifying muscle. The SMI was calculated as follows: SMI (cm2/m2) = cross-sectional area (cm2)/height2 (m2). Sarcopenia was defined as an SMI < 52.4 cm2/m2 for men, according to previous studies[15, 18].
Data collection
Baseline demographics, Eastern Cooperative Oncology Group performance status (ECOG PS), previous treatment history, laboratory results, and PD-L1 positivity were collected. PD-L1 expression in the tumor samples was assessed by immunohistochemistry (IHC) using a PD-L1 IHC kit (22C3; Dako,Denmark) and characterized according to the tumor proportion score(TPS).
Response evaluation was performed using a CT scan of the target lesions and classified according to the immune-related Response Evaluation Criteria in Solid Tumors[19]. Evaluations were performed every 8 weeks. The co-primary endpoints were PFS, defined as the time from initial treatment to clinical or radiographic progression or death, and OS, defined as the time from initial treatment to death due to any cause. Secondary endpoints included the objective response rate (ORR, defined as the proportion of patients whose best overall response was complete or partial response[CR,PR]) and the disease control rate (DCR, defined as the proportion of patients whose best overall response was CR, PR, or stable disease[SD]).
Statistics
Quantitative data were presented as mean ± standard deviation. The Kolmogorov-Smirnov test was performed to test for normality. Quantitative variables were compared using Student’s t-test for independent samples or the nonparametric Mann-Whitney test. Differences between categorical variables were compared using the chi-square test. Survival curves were constructed using the Kaplan-Meier method, and differences in survival were calculated using the log-rank test. Cox proportional hazards regression analysis was used to estimate the HRs for risk factors using the backward elimination method. P < 0.05 was considered to denote significance. Statistical analyses were performed using the SPSS software (version 22.0; SPSS, Chicago, IL, USA) and Prism (GraphPad, Software,La Jolla,CA,USA).