Inflammatory biomarkers in metastatic colorectal cancer: prognostic and predictive role beyond the first line setting

Jakob Michael Riedl; Florian Posch; Florian Moik; Angelika Bezan; Joanna Szkandera; Maria Anna Smolle; Anne-Katrin Kasparek; Martin Pichler; Herbert Stöger; Michael Stotz; Armin Gerger

doi:10.18632/oncotarget.21647

Inflammatory biomarkers in metastatic colorectal cancer: prognostic and predictive role beyond the first line setting

Oncotarget. 2017 Oct 4;8(56):96048-96061. doi: 10.18632/oncotarget.21647. eCollection 2017 Nov 10.

Authors

Affiliations

¹ Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria.
² Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
³ Center for Biomarker Research in Medicine, 8010 Graz, Austria.

Abstract

Introduction: Inflammatory biomarkers are useful prognostic tools in cancer patients. However, the prognostic and predictive value of inflammatory biomarkers beyond the 1^st-line setting in metastatic colorectal cancer (mCRC) is unclear.

Results: In multivariate analysis 1 standard deviation increase in neutrophil-lymphocyte-ratio (NLR) was associated with an 8.5% absolute lower objective-response-rate (ORR) in 1^st-line (p<0.0001), 3% lower ORR in 2^nd-line (p< 0.0001), and 3% lower ORR in 3^rd-line (p=0.24), respectively. Regarding progression free survival (PFS), an increase in the NLR was significantly associated with rising hazard-ratios (HR) over all treatment lines (HR=1.30, p= 0.021 1^st-line); (HR=1.37, p<0.0001 2^nd-line); (HR=1.44, p=0.042 3^rd-line). The platelet-lymphocyte-ratio (PLR) was associated with 6-month PFS over all three treatment lines. Higher C-reactive-protein (CRP) predicted for worse PFS in the first two chemotherapy lines and in best supportive care (BSC). (HR=1.49 (p<0.0001 1^st-line); HR=1.25 (p=0.007 2^nd-line); HR=1.09 (95%CI 0.81-1.48, p=0.552 3^rd-line and HR=1.43 (p= 0.002 in BSC)).

Methods: Two-hundred-fifty-eight patients with mCRC undergoing palliative chemo(immuno-)therapy were retrospectively included. Primary endpoints were 6-month PFS and ORR during 1st-line, 2nd-line, and 3rd-line treatment, and 6-month overall survival during BSC.

Conclusion: This study shows that inflammatory biomarkers are useful predictors of disease outcome and treatment response over several treatment lines in mCRC patients.

Keywords: biomarker; colorectal cancer; inflammation; metastatic; palliative chemotherapy.