A comparison of inflammation markers for predicting oncological outcomes after surgical resection of non-small-cell lung cancer: a validated analysis of 2,066 patients

Abstract

Clinical and pathological predictors have proved to be insufficient in identifying high-risk patients who develop cancer recurrence after tumour resection. We aimed to compare the prognostic ability of various inflammation markers in patients undergoing surgical resection of lung cancer. We consecutively included 2,066 patients with stage I–III non-small-cell lung cancer undergoing surgical resection at the center between 2005 and 2015. We evaluated prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative changes. We conducted stepwise backward variable elimination and internal validation to compare the selected markers’ predictive performance for postoperative recurrence-free survival and overall survival. Preoperative neutrophil-to-lymphocyte ratio independently predicts recurrence-free survival (HR: 1.267, 95% CI 1.064–1.509, p = 0.0079, on base-2 logarithmic scale) and overall survival (HR: 1.357, 95% CI 1.070–1.721, p = 0.0117, on base-2 logarithmic scale). The cut-off value is 2.3 for predicting both recurrence (sensitivity: 46.1% and specificity: 66.7%) and mortality (sensitivity: 84.2% and specificity: 40.4%). Advanced cancer stage, poor tumour differentiation, and presence of perineural infiltration were significantly correlated with higher preoperative neutrophil-to-lymphocyte ratio. We concluded that preoperative neutrophil-to-lymphocyte ratio is superior to prognostic nutritional index and platelet-to-lymphocyte ratio in predicting postoperative recurrence and mortality of patients undergoing surgical resection of non-small-cell lung cancer.

Elevations of monocyte and neutrophils, and higher levels of granulocyte colony‐stimulating factor in peripheral blood in lung cancer patients

“…G‐CSF and GM‐CSF are cytokines that stimulate bone marrow to produce myeloid cells, such as monocytes and neutrophils. Preliminary studies reported that high serum levels of G‐CSF or GM‐CSF may be useful for lung cancer diagnosis 20–22 . In the present study, increases in both myeloid cells and myeloid cell‐specific CSFs were detected using several types of cell subsets and CSFs.…”

“…Preliminary studies reported that high serum levels of G‐CSF or GM‐CSF may be useful for lung cancer diagnosis. 20 , 21 , 22 In the present study, increases in both myeloid cells and myeloid cell‐specific CSFs were detected using several types of cell subsets and CSFs. These findings indicate the important role of G‐CSF/GM‐CSF‐induced myeloid cell mobilization in the pathogenesis of lung cancer.…”

“…Colony‐stimulating factor promotes tumor progression via either an autocrine or paracrine mechanism. Various solid, advanced malignancies simultaneously produce G‐CSF and express its receptor, thus enabling the autocrine proliferation of tumor cells 21 . CSF1 has been previously shown to increase A549 proliferation and invasion.…”

“…Mechanistic studies proposed that G‐CSF triggers the G‐CSFR/JAK/STAT3 signaling pathway, leading to the epithelial‐mesenchymal transition in NSCLCs 20 . Moreover, tumor‐secreted G‐CSF and GM‐CSF may act as paracrine factors in the tumor microenvironment, thereby promoting mobilization into tumor sites via the recruitment of immature and mature neutrophils that function as MDSCs, in turn intensifying the immunosuppressive milieu of the tumor microenvironment 20,21,24 . G‐CSF‐triggered increases in immature myeloid cells in bone marrow, blood, and the spleen have been found to be predictive of poor disease prognosis 21 …”

Epidural analgesia does not impact recurrence or mortality in patients after rectal cancer resection

“…Third, we did not consider the medical conditions which were intrinsically linked to cancer recurrence and mortality, such as inflammatory bowel disease and concurrent malignancy. Fourth, we did not routinely measure inflammation-related markers (such as lymphocyte count and c-reactive protein) in this cohort and therefore could not adjust for them in the analyses 37 . Fifth, the follow-up period of this study is limited to August 2016.…”