Abstract
BackgroundHypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC).Methods and FindingsClinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP) and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA) class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all p<0.05). In multivariate analysis, prealbumin levels (Relative Risk (RR): 0.34 [0.16–0.73], p = 0.0056), CD8+ cell count in tumor tissue (RR = 0.37 [0.16–0.83], p = 0.0162), and disease stage (RR 1.73 [1.03–2.89]; 2.99[1.07–8.37], p = 0.0374- stage I vs II vs III-IV) were independent prognostic markers. When taken together, parameters related to systemic inflammation, nutrition and tumoral immune microenvironment allowed robust prognostic discrimination; indeed patients with undetectable CRP, high (>285 mg/L) prealbumin levels and high (>96/mm2) CD8+ cell count had a 5-year survival rate of 80% [60.9–91.1] as compared to 18% [7.9–35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the prognostic significance of these factors was even more pronounced.ConclusionsOur data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.
Highlights
Lung carcinoma is a leading cause of cancer-related death worldwide [1,2]
The tumoral immune microenvironment has been shown to be an important determinant of long-term outcome in primary and metastatic tumors [9]: in non-small cell lung cancers (NSCLC), high levels of mature dendritic cells and of CD8+ lymphocytes have been both identified as robust prognostic factors [15,16,17]
Factors associated with nutritional status Prealbumin levels were significantly correlated with other parameters related to nutritional status, systemic inflammation and with several histological features, such as histological type, pT parameter, and presence of vascular emboli
Summary
Lung carcinoma is a leading cause of cancer-related death worldwide [1,2]. Despite progresses in chemotherapy and biologically-targeted therapy and refinement in multimodal therapeutic combinations, long-term outcome remains poor, with the exception of stage IA disease, stressing the need for research to better understand the biology of the disease and factors conditioning long-term survival and risk of relapse [3,4,5,6].The interactions between systemic inflammation and tumoral immune microenvironment are increasingly investigated in cancer patients [7,8,9]. It has been shown that slight elevations of inflammatory markers are associated with an increased risk of non-small cell lung carcinoma (NSCLC) occurrence [11,12], and serum C-reactive protein (CRP) has been identified as a prognostic factor in both advanced and resectable NSCLC [13,14]. The tumoral immune microenvironment has been shown to be an important determinant of long-term outcome in primary and metastatic tumors [9]: in NSCLC, high levels of mature dendritic cells (mDC) and of CD8+ lymphocytes have been both identified as robust prognostic factors [15,16,17]. Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC)
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