Predictive clinical model of tumor response after chemoradiation in rectal cancer
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Marisa D. Santos1,2, Cristina Silva1,2, Anabela Rocha1,2, Carlos Nogueira1,2, Fernando Castro-Poças2,3, António Araujo2,4, Eduarda Matos5, Carina Pereira2,6,7, Rui Medeiros2,6,7,8 and Carlos Lopes2,9,10
1 Department of Surgery, Digestive Surgery Service, Hospital Center of Porto, Porto, Portugal
2 Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
3 Gastroenterology Service, Hospital Center of Porto, Porto, Portugal
4 Service of Medical Oncology, Hospital Center of Porto, Porto, Portugal
5 Department of Health Community, Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
6 Molecular Oncology and Viral Pathology Group, IPO Research Center, Portuguese Oncologic Institute, Porto, Portugal
7 Research Department, Portuguese League Against Cancer, Porto, Portugal
8 CEBIMED, Faculty of Health Sciences of Fernando Pessoa, University of Porto, Porto, Portugal
9 Department of Pathology, Pathological Anatomy Service, Hospital Center of Porto, Porto, Portugal
10 Department of Pathology and Molecular Immunology, Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal
Marisa D. Santos, email:
Keywords: neutrophil lymphocyte ratio, molecular marker, neoadjuvant chemoradiation, prediction, rectal cancer
Received: March 12, 2017 Accepted: July 18, 2017 Published: July 28, 2017
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.
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