Abstract
BackgroundThe aim of this study was to assess the relative prognostic value of biomarkers to measure the systemic inflammatory response (SIR) and improve prognostic modeling in a cohort of patients undergoing potentially curative surgery for gastric adenocarcinoma. The hypothesis was that a single SIR biomarker would be associated with the most prognostic value. MethodsConsecutive 331 patients undergoing surgery for gastric cancer between 2004 and 2016 within a regional UK cancer network were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow Prognostic Score, and differential white cell counts were obtained before surgery, and correlated with histopathological factors (pTNM stage, differentiation, and vascular invasion) and survival. Primary outcome measures were disease-free (DFS) and overall survival (OS). ResultsConsecutive 331 patients were identified and 291 underwent potentially curative gastrectomy for adenocarcinoma. On univariable DFS analysis, female gender (p = 0.027), proximal location (p = 0.018), pT stage (p < 0.001), pN stage (p < 0.001), pTNM stage (p < 0.001), vascular invasion (p < 0.001), poor differentiation (p = 0.001), lymph node ratio (p < 0.001), R1 status (p < 0.001), platelet count (p = 0.038), and mGPS (p = 0.001) were significantly associated with poor survival. The mGPS was associated with advanced pT stage (p = 0.001), pTNM stage (p = 0.013), and poor differentiation (p = 0.030). On multivariable DFS analysis, mGPS [hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.35–4.65, p = 0.011] was the only inflammatory marker to retain independent significance. Multivariable OS analysis revealed similar findings; mGPS (HR 2.75, (95% CI 1.65–4.59), p < 0.001). ConclusionmGPS is an important and only SIR-related prognostic biomarker independently associated with both DFS and OS in gastric cancer.
Highlights
The term biomarker originated in the 1950s and has been defined by the National Institute of Health as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or pharmacological responses to a therapeutic intervention.[1]
Cancer-related inflammation has been termed the 7th hallmark of cancer,[3] and the systemic inflammatory response (SIR) measured using cellular and humoral [C-reactive protein (CRP) and albumin] components
The patient cohort undergoing palliative surgery had a higher proportion of males (p = 0.002), raised serum CRP measurements (p = 0.003), hypoalbuminaemia (p = 0.024), higher mGPS (p = 0.001), and a fewer patients had undergone neoadjuvant chemotherapy (p = 0.024, supplementary table 1)
Summary
Cancer-related inflammation has been termed the 7th hallmark of cancer,[3] and the systemic inflammatory response (SIR) measured using cellular (whole white cell counts, neutrophils, lymphocytes, and platelets) and humoral [C-reactive protein (CRP) and albumin] components. Derivative biomarkers (neutrophil-lymphocyte ratio (NLR),[4] plateletlymphocyte ratio (PLR),[5] neutrophil-platelet score (NPS),[6] and the modified Glasgow prognostic score (mGPS)[7,8] have been described and reported to be associated with poor survival in patients undergoing potentially curative surgery. The aim of this study was to assess the relative prognostic value of biomarkers to measure the systemic inflammatory response (SIR) and improve prognostic modeling in a cohort of patients undergoing potentially curative surgery for gastric adenocarcinoma. Conclusion mGPS is an important and only SIR-related prognostic biomarker independently associated with both DFS and OS in gastric cancer
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