Research Papers:

Outcomes prediction in pre-operative radiotherapy locally advanced rectal cancer: leucocyte assessment as immune biomarker

Alexis Vallard, Max-Adrien Garcia, Peng Diao, Sophie Espenel, Guy de Laroche, Jean-Baptiste Guy, Majed Ben Mrad, Chloé Rancoule, David Kaczmarek, Thierry Muron, Gregoire Pigné, Jack Porcheron, Michel Peoc'h, Jean-Marc Phelip, Julien Langrand-Escure and Nicolas Magné _

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Oncotarget. 2018; 9:22368-22382. https://doi.org/10.18632/oncotarget.25023

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Alexis Vallard1, Max-Adrien Garcia2, Peng Diao3, Sophie Espenel1, Guy de Laroche1, Jean-Baptiste Guy1, Majed Ben Mrad1, Chloé Rancoule1, David Kaczmarek4, Thierry Muron5, Gregoire Pigné1, Jack Porcheron6, Michel Peoc'h7, Jean-Marc Phelip8, Julien Langrand-Escure1 and Nicolas Magné1

1Department of Radiation Oncology, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France

2Public Health Department, Hygée Institute, Saint Priest en Jarez, France

3Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan Province, China

4Department of Thoracic and Digestive Surgery, Private Loire Hospital (HPL), Saint Etienne, France

5Department of Medical Oncology, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France

6Department of Digestive and Oncologic Surgery, North University Hospital, Saint Priest en Jarez, France

7Department of Pathology, North University Hospital, Saint Priest en Jarez, France

8Department of Hepatology and Gastroenterology, North University Hospital, Saint Priest en Jarez, France

Correspondence to:

Nicolas Magné, email: [email protected]

Keywords: rectal cancer; chemoradiation; neutrophil; lymphocyte; ratio

Received: September 01, 2017     Accepted: March 19, 2018     Published: April 27, 2018


Objective: Leukocytes are hypothesized to reflect the inflammatory tumor microenvironment. We aimed to validate their prognostic significance in a large cohort of patients treated with pre-operative radiation for locally advanced rectal cancer (RC).

Results: From 2004 to 2015, 257 RC patients with available biological data underwent a pre-operative radiotherapy, with a median age of 66 years. The median rectal EQD2 was 49.2Gy. Most of patients experienced concurrent chemotherapy (n = 245, 95.4%), mainly with 5-FU (83.3%). Clear surgical margins (i.e. complete resection) were achieved in 234 patients (91.1%). A complete (Mandard TRG1: n = 35, 13.6%) or almost complete pathological response (Mandard TRG2: n = 56, 21.8%) were achieved in 91 patients (35.4%). With a median follow-up of 46.1 months, 8 patients (3.1%) experienced local relapse, 38 (14.8%) experienced metastases and 45 (17.5%) died. Elevated pre-radiation neutrophil to lymphocyte ratio (NLR > 2.8) was identified as an independent predictive factor of increased local relapse, of decreased progression-free survival and overall survival in multivariate analysis. Elevated NLR was marginally associated with incomplete pathological response in multivariate analysis, suggesting a possible value as a biomarker of radio-sensitivity.

Conclusions: Pre-radiation NLR is a simple and robust biomarker for risk stratification in locally advanced RC patients undergoing pre-operative radiotherapy, and might select the subpopulation eligible to treatment intensification or to neoadjuvant chemotherapy.

Material and Methods: Clinical records from consecutive patients treated in a single institution between 2004 and 2015 with curative-intent radiotherapy were retrospectively analyzed. Classical prognosis factors of RC and peripheral immune markers based on lymphocytes and neutrophil counts were studied.

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