Systemic Inflammation and Lung Cancer: Is It a Real Paradigm? Prognostic Value of Inflammatory Indexes in Patients with Resected Non-Small-Cell Lung Cancer

Abstract

Background (1): Our goal was to investigate if and how pre-operative inflammatory status can influence the long-term prognosis of patients undergoing lung surgery for cancer. Materials and Methods (2): This prospective observational study includes the agreement of all operable patients to the study, who were referred to our department between 1 January 2017 and 30 December 2018. The inflammatory pre-operative status of the patients was investigated by calculating albumin, CPR (c-protein reactive), complete blood count (neutrophils, lymphocytes, platelets, hemoglobin), and some other indexes referring to inflammatory status, namely the HALP amalgamated index, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes ratio (NLR), systemic immune-inflammation index (SII), and advanced lung cancer inflammation Index (ALI). The follow-up ended in November 2021. Patient overall survival was assessed using the Kaplan-Meier method. The log-rank test was used to compare survival rates. Variables significantly associated with survival at univariate analysis were entered int Cox multivariate analysis (stepwise mode) to assess their independent character. Hazard ratios and their 95% confidence intervals were calculated. Variables associated with p < 0.05 were considered significative. Results (3): We enrolled 257 patients in our study. The overall survival of the cohort was as follows: 1 year, 96.1%; 3 year, 81.3%; and 4 year, 74.2%. Univariate analysis showed risk factors for overall survival as follows: Thoracoscore ≥ 2 (p = 0.002); histology (p = 0.002); HALP < 32.2 (p = 0.0002); SII ≥ 808.9 (p = 0.0004); ALI < 34.86 (p = 0.0005); NLr ≥ 2.29 (p = 0.01); hemoglobin < 13 g/dl (p = 0.01); PLR ≥ 196.1 (p = 0.005); pN+ (p < 0.0001); pleural invasion (p = 0.0002); and presence of vascular or lymphatic tumor emboli (p = 0.0002). Multivariate Cox analysis (stepwise model) identified Thoracoscore ≥ 2 (p = 0.02); histology, HALP < 32.2 (p = 0.004), and pN (p < 0.0001) as independent predictors of death. Conclusion (4): Pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery.

Keywords: HALP; NSCLC; inflammation; inflammatory status; lung cancer.

Figure 1

Flow chart of the study. In this study, we analyzed the long-term outcomes of the first part (257 patients) of a 1077 patient series (January 2017–August 2021) [21], undergoing anatomical surgical resection for non-small-cell Lung Cancer. We included all patients undergoing anatomic lung resection in the period January 2017–December 2018, with pre-operative available biological panels performed in our departmental laboratory.

Figure 2

Receiver operating characteristic (ROC) curves for 3-year mortality of the Thoracoscore and of selected inflammatory parameters. HALP: hemoglobin, albumin, lymphocyte, and platelet score; NLR: derived neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio; SI: systemic immune-inflammation index; ALI: advanced lung cancer inflammation index. Best cut-off values (Youden index): HALP (32.2); NLR (2.29); PLR (196); SII (809); ALI (34.9); Thoracoscore (2.3).

Figure 3

Overall survival of 257 patients who underwent lung cancer surgery overall (A), according to Thoracoscore (B), HALP (C), and pN (D).