The Baseline Serum Lipid Levels and Outcomes of NSCLC Patients Receiving Immunotherapy Combined or Non-Combined with Radiotherapy: A Single Center Retrospective Study

Abstract

In recent years, many studies have shown that lipids and lipid-like substances are key regulatory factors in tumor development and play an important role in immune regulation. However, it remains unclear whether serum lipids influence the outcome of immunotherapy. Therefore, determining the serum lipid levels of the immune treatment-beneficiary population may be valuable. The aim of this study is to evaluate the prognostic value of baseline serum lipid levels in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. We retrospectively included 294 patients with stage III-IV NSCLC who received immunotherapy continuously from December 2018 to November 2021 at our hospital, collecting their pre-treatment lipid levels, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Of these, 160 receiving immunotherapy without combined radiotherapy (ICIs-nRT) and 134 combined with radiotherapy (iRT). The endpoint was the correlation between pre-treatment serum lipid levels and overall survival (OS), as well as progression-free survival (PFS). The X-tile tool was used to determine the optimal cut-off value of the indicators. The Kaplan-Meier survival curves were used to calculate OS and PFS and log rank tests were used for comparison. And the Cox proportional hazard model were used for univariate and multivariate analysis. In all 294 patients, low TG, low TC, and low HDL-C predicted poor OS (P<0.001) and poor PFS (P<0.05). Low LDL-C was associated with poor OS (P = 0.0001). Among 160 patients receiving ICIs-nRT and 134 iRT patients, low levels of TG (P = 0.0134, 0.0024), TC (P = 0.0003, 0.0023), HDL-C (P = 0.0004, 0.0043), and LDL-C (P = 0.0003, 0.0419) were associated with worse OS compared to high levels of them. In the ICIs-nRT patients, low HDL-C predicted poor PFS (P = 0.0011). In 134 iRT patients, low levels of TG (P = 0.0017), TC (P = 0.0028), and LDL-C (P = 0.0330) were poor prognostic factors for PFS. In the univariate and multivariate analysis with OS in all patients, TG and HDL-C were independent risk factors, while TG was an independent risk factor in the analysis with PFS. In ICIs-nRT patients, HDL-C was an independent prognostic factor for patients' OS and PFS. In iRT patients, both TG and HDL-C were prognostic risk factors for OS. These data confirm that higher serum lipid levels are associated with better outcomes in patients with NSCLC undergoing immunotherapy. Serum lipids may identify tumors that are more likely to respond to immunotherapy. Radiation therapy may affect lipid metabolism within the body to enhance the efficacy of immunotherapy.