Predictive clinical model of tumor response after chemoradiation in rectal cancer.

Marisa D Santos,Cristina Silva,Rui Medeiros,Carina Pereira,Anabela Rocha,António Araujo,Carlos Lopes,Eduarda Matos,Carlos Nogueira,Fernando Castro-Poças

doi:10.18632/oncotarget.19651

Marisa D Santos, Cristina Silva + Show 8 more

Open Access

https://doi.org/10.18632/oncotarget.19651

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Abstract

Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard TRG. The patients were divided as: “good responders” (Mandard TRG1-2) and “poor responders” (Mandard TGR3-5). We examined predictive factors for Mandard response and performed statistical analysis. In univariate analysis, distance from anal verge, neutrophil lymphocyte ratio (NLR), cyclin D1, VEGF, EGFR, protein 21 and rs1810871 interleukin 10 (IL10) gene polymorphism are the pretreatment variables with predictive value for Mandard response. In multivariable analysis, NLR, cyclin D1, protein 21 and rs1800871 in IL10 gene maintain predictive value, allowing a clinical model design. Conclusion: It seems possible to use pretreatment expression of blood and tissue biomarkers, and build a model of tumor response prediction to neoadjuvant chemoradiation in rectal cancer.

Highlights

Colorectal cancer is still one of the most common malignancy in Western Countries and the second in mortality, despite all improvements in therapeutic approach [1]
Our objective was to assess whether neutrophil lymphocyte ratio (NLR) in pretreatment blood sample, pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and p21, and 61 tagSNPs could be used to predict pathologic response in the setting of rectal cancer treated in a single tertiary center with Neoadjuvant chemoradiotherapy (nCRT) followed by surgery
Description of study population and clinical parameters. This cohort study gathered 186 consecutive patients with locally advanced rectal cancer (LARC) treated with nCRT follow by curative surgery with total mesorectal excision at one single University Hospital

Summary

Introduction

Colorectal cancer is still one of the most common malignancy in Western Countries and the second in mortality, despite all improvements in therapeutic approach [1]. Treatment in locally advanced rectal cancer (LARC) is paradigmatic for this issue. The accuracy of the current available imaging modalities, including diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET) on restaging tumor after nCRT seems to be less effective than was expected to be [8,9,10]. For this reason, the search for biomarkers predictors of rectal cancer response to chemoradiation, retains all relevance and great interest [11, 12]

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