Right- vs. left-sided metastatic colorectal cancer: Differences in tumor biology and bevacizumab efficacy

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21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1240
JournalInternational Journal of Molecular Sciences
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 9 2017

Fingerprint

Chemotherapy
chemotherapy
biology
Tumors
Colorectal Neoplasms
tumors
cancer
Drug Therapy
Eph Family Receptors
Neoplasms
Lymphocytes
Nitric Oxide Synthase Type III
lymphocytes
Nitric oxide
nitric oxide
mutations
neutrophils
Hypoxia-Inducible Factor 1
lactates
Mutation

Keywords

  • Bevacizumab
  • Left-sided colon
  • Metastatic colorectal cancer
  • Right-sided colon

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

@article{e158a34a6bcd48b5bb9da8bcbf801ef3,
title = "Right- vs. left-sided metastatic colorectal cancer: Differences in tumor biology and bevacizumab efficacy",
abstract = "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.",
keywords = "Bevacizumab, Left-sided colon, Metastatic colorectal cancer, Right-sided colon",
author = "Paola Ulivi and Emanuela Scarpi and Elisa Chiadini and Giorgia Marisi and Martina Valgiusti and Laura Capelli and {Casadei Gardini}, Andrea and Manlio Monti and Silvia Ruscelli and Frassineti, {Giovanni Luca} and Daniele Calistri and Dino Amadori and Alessandro Passardi",
year = "2017",
month = "6",
day = "9",
doi = "10.3390/ijms18061240",
language = "English",
volume = "18",
journal = "International Journal of Molecular Sciences",
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TY - JOUR

T1 - Right- vs. left-sided metastatic colorectal cancer

T2 - Differences in tumor biology and bevacizumab efficacy

AU - Ulivi, Paola

AU - Scarpi, Emanuela

AU - Chiadini, Elisa

AU - Marisi, Giorgia

AU - Valgiusti, Martina

AU - Capelli, Laura

AU - Casadei Gardini, Andrea

AU - Monti, Manlio

AU - Ruscelli, Silvia

AU - Frassineti, Giovanni Luca

AU - Calistri, Daniele

AU - Amadori, Dino

AU - Passardi, Alessandro

PY - 2017/6/9

Y1 - 2017/6/9

N2 - 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.

AB - 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.

KW - Bevacizumab

KW - Left-sided colon

KW - Metastatic colorectal cancer

KW - Right-sided colon

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U2 - 10.3390/ijms18061240

DO - 10.3390/ijms18061240

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VL - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

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