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Pre-treatment inflammatory biomarkers predict early treatment response and favorable survival in patients with metastatic colorectal cancer who underwent first line cetuximab plus chemotherapy

Authors Jiang J, Ma T, Xi W, Yang C, Wu J, Zhou C, Wang N, Zhu Z, Zhang J

Received 3 April 2019

Accepted for publication 29 August 2019

Published 24 September 2019 Volume 2019:11 Pages 8657—8668

DOI https://doi.org/10.2147/CMAR.S211089

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Bilikere Dwarakanath


Jinling Jiang,1 Tao Ma,1 Wenqi Xi,1 Chen Yang,1 Junwei Wu,1 Chenfei Zhou,1 Nan Wang,1 Zhenggang Zhu,1,2 Jun Zhang1,2

1Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 2Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China

Correspondence: Jun Zhang
Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
Tel/Fax +86 216 474 1635
Email junzhang10977@sjtu.edu.cn

Objective: This study was to determine whether peripheral blood biomarkers including neutrophil‑lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) could predict early response to cetuximab; moreover, the prognostic ability of those biomarkers on progression free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) patients with wild-type (WT) RAS was also investigated.
Methods: mCRC patients with WT RAS treated with cetuximab plus chemotherapy were retrospectively analyzed, and early response was evaluated according to RECIST 1.1 after three or four treatment cycles. In prior to chemotherapy, hematologic data and clinic-pathological parameters were collected. The associations between pre-treatment inflammatory biomarkers and early response, and the prognostic value of those biomarkers were analyzed. A total of 102 patients were enrolled and divided into low or high NLR, PLR, and SII groups, respectively.
Results: The early response rate was significantly higher in the low NLR (p<0.001), low PLR (p=0.045), and low SII (p=0.011), respectively. In multivariate analyses, primary tumor resection (hazard ratio (HR) 0.411, p<0.001), carcino-embryonicantigen ≤5 ng/mL (HR 0.406, p<0.001), early treatment response (HR 0.322, p<0.001), and low NLR (HR 0.665, p=0.031) were independent factors of longer PFS. Primary tumor resection (HR 0.488, p=0.003) and early response (HR 0.392, p<0.001) were independent factors of longer OS. Further analysis showed that patients with early response, even in the high groups, can achieve better PFS and OS than non-responders.
Conclusion: Pre-treatment inflammatory biomarkers, especially NLR were predictors of benefit from cetuximab-combined therapy in mCRC patients. They were also predictors of significantly longer PFS and OS of early responders compared to non-responders.

Keywords: inflammatory biomarkers, cetuximab, early treatment response, wild-type RAS, metastatic colorectal cancer


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