Cargando…

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy

There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 3...

Descripción completa

Detalles Bibliográficos
Autores principales: Ulivi, Paola, Scarpi, Emanuela, Chiadini, Elisa, Marisi, Giorgia, Valgiusti, Martina, Capelli, Laura, Casadei Gardini, Andrea, Monti, Manlio, Ruscelli, Silvia, Frassineti, Giovanni Luca, Calistri, Daniele, Amadori, Dino, Passardi, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486063/
https://www.ncbi.nlm.nih.gov/pubmed/28598398
http://dx.doi.org/10.3390/ijms18061240
_version_ 1783246192451256320
author Ulivi, Paola
Scarpi, Emanuela
Chiadini, Elisa
Marisi, Giorgia
Valgiusti, Martina
Capelli, Laura
Casadei Gardini, Andrea
Monti, Manlio
Ruscelli, Silvia
Frassineti, Giovanni Luca
Calistri, Daniele
Amadori, Dino
Passardi, Alessandro
author_facet Ulivi, Paola
Scarpi, Emanuela
Chiadini, Elisa
Marisi, Giorgia
Valgiusti, Martina
Capelli, Laura
Casadei Gardini, Andrea
Monti, Manlio
Ruscelli, Silvia
Frassineti, Giovanni Luca
Calistri, Daniele
Amadori, Dino
Passardi, Alessandro
author_sort Ulivi, Paola
collection PubMed
description There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa)”, randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1α), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017). Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.
format Online
Article
Text
id pubmed-5486063
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-54860632017-06-29 Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy Ulivi, Paola Scarpi, Emanuela Chiadini, Elisa Marisi, Giorgia Valgiusti, Martina Capelli, Laura Casadei Gardini, Andrea Monti, Manlio Ruscelli, Silvia Frassineti, Giovanni Luca Calistri, Daniele Amadori, Dino Passardi, Alessandro Int J Mol Sci Article There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa)”, randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1α), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017). Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors. MDPI 2017-06-09 /pmc/articles/PMC5486063/ /pubmed/28598398 http://dx.doi.org/10.3390/ijms18061240 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ulivi, Paola
Scarpi, Emanuela
Chiadini, Elisa
Marisi, Giorgia
Valgiusti, Martina
Capelli, Laura
Casadei Gardini, Andrea
Monti, Manlio
Ruscelli, Silvia
Frassineti, Giovanni Luca
Calistri, Daniele
Amadori, Dino
Passardi, Alessandro
Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy
title Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy
title_full Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy
title_fullStr Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy
title_full_unstemmed Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy
title_short Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy
title_sort right- vs. left-sided metastatic colorectal cancer: differences in tumor biology and bevacizumab efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486063/
https://www.ncbi.nlm.nih.gov/pubmed/28598398
http://dx.doi.org/10.3390/ijms18061240
work_keys_str_mv AT ulivipaola rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT scarpiemanuela rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT chiadinielisa rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT marisigiorgia rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT valgiustimartina rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT capellilaura rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT casadeigardiniandrea rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT montimanlio rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT ruscellisilvia rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT frassinetigiovanniluca rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT calistridaniele rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT amadoridino rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy
AT passardialessandro rightvsleftsidedmetastaticcolorectalcancerdifferencesintumorbiologyandbevacizumabefficacy