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Open AccessArticle

Neutrophil-to-Lymphocyte Ratio in Rectal Cancer—Novel Biomarker of Tumor Immunogenicity During Radiotherapy or Confounding Variable?

1
Department of Radiation Oncology, University Hospital and Medical Faculty Tübingen, Eberhard Karls University Tübingen, 72076 Tübingen, Germany
2
Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, 72076 Tübingen, Germany
3
German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
4
Gastrointestinal Cancer Center, Comprehensive Cancer Center Tübingen-Stuttgart, 72076 Tübingen, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(10), 2448; https://doi.org/10.3390/ijms20102448
Received: 15 April 2019 / Revised: 10 May 2019 / Accepted: 13 May 2019 / Published: 17 May 2019
(This article belongs to the Special Issue Partnership of Radiotherapy and Immunotherapy)
The aim of this study was to investigate the predictive value of blood-derived makers of local and systemic inflammatory responses on early and long-term oncological outcomes. A retrospective analysis of patients with locally advanced rectal cancer treated with preoperative long-course 5-fluorouracil-based radiochemotherapy was performed. Differential blood counts before neoadjuvant treatment were extracted from the patients’ electronic charts. Optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were determined. Potential clinical and hematological prognostic factors for disease-free survival (DFS) were studied using uni- and multivariate analysis. A total of 220 patients were included in the analysis. Median follow-up was 67 months. Five-year DFS and overall survival (OS) were 70% and 85%, respectively. NLR with a cut-off value of 4.06 was identified as optimal to predict DFS events. In multivariate analysis, only tumor volume (HR 0.33, 95% CI (0.14–0.83), p = 0.017) and NLR (HR 0.3, 95% CI (0.11–0.81), p = 0.017) remained significant predictors of DFS. Patients with a good histological response (Dworak 3 and 4) to radiotherapy also had a lower NLR than patients with less pronounced tumor regression (3.0 vs. 4.2, p = 0.015). A strong correlation between primary tumor volume and NLR was seen (Pearson’s r = 0.64, p < 0.001). Moreover, patients with T4 tumors had a significantly higher NLR than patients with T1–T3 tumors (6.6 vs. 3.3, p < 0.001). An elevated pretherapeutic NLR was associated with higher T stage, inferior DFS, and poor pathological response to neoadjuvant radiochemotherapy. A strong correlation between NLR and primary tumor volume was seen. This association is important for the interpretation of study results and for the design of translational studies which are warranted. View Full-Text
Keywords: rectal cancer; inflammation; leukocytosis; neutrophil-to-lymphocyte ratio; pathologic response; neoadjuvant radiotherapy; tumor volume rectal cancer; inflammation; leukocytosis; neutrophil-to-lymphocyte ratio; pathologic response; neoadjuvant radiotherapy; tumor volume
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Braun, L.H.; Baumann, D.; Zwirner, K.; Eipper, E.; Hauth, F.; Peter, A.; Zips, D.; Gani, C. Neutrophil-to-Lymphocyte Ratio in Rectal Cancer—Novel Biomarker of Tumor Immunogenicity During Radiotherapy or Confounding Variable? Int. J. Mol. Sci. 2019, 20, 2448.

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