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Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo‐adjuvant cytotoxic chemotherapy and bevacizumab
The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differe...
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| Published in: | International journal of cancer 2016-04, Vol.138 (7), p.1777-1784 |
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| container_end_page | 1784 |
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| container_title | International journal of cancer |
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| creator | Eefsen, Rikke Løvendahl Engelholm, Lars Willemoe, Gro L. Van den Eynden, Gert G. Laerum, Ole Didrik Christensen, Ib Jarle Rolff, Hans Christian Høyer‐Hansen, Gunilla Osterlind, Kell Vainer, Ben Illemann, Martin |
| description | The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p |
| doi_str_mv | 10.1002/ijc.29904 |
| format | article |
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What's new?
A first‐line therapy for colorectal liver metastasis is chemotherapy combined with vascular endothelial growth factor (VEGF) inhibitor bevacizumab. Patient response markers are however lacking. In this first study on the effect of bevacizumab on angiogenesis in colorectal liver metastases, the authors evaluate endothelial cell proliferation and microvessel density in resected liver metastases from patients who were either untreated or received chemotherapy alone or in combination with bevacizumab. Microvessel density is significantly lower and the degree of tumor regression is highest in liver metastases from patients treated with chemotherapy and bevacizumab. These findings may help develop response markers for bevacizumab treatment.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.29904</identifier><identifier>PMID: 26510166</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Aged ; Amputation ; Angiogenesis ; Angiogenesis Inhibitors - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bevacizumab - therapeutic use ; Cancer ; Cell growth ; Cell Proliferation - drug effects ; Chemotherapy ; Chemotherapy, Adjuvant ; colorectal cancer ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Denmark ; Endothelial Cells - drug effects ; Female ; growth pattern ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki67 ; Liver ; liver metastasis ; Liver Neoplasms - drug therapy ; Liver Neoplasms - secondary ; Male ; Medical research ; Metastasis ; microvessel density ; Middle Aged ; Neoadjuvant Therapy ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - pathology ; Proportional Hazards Models</subject><ispartof>International journal of cancer, 2016-04, Vol.138 (7), p.1777-1784</ispartof><rights>2015 UICC</rights><rights>2015 UICC.</rights><rights>2016 UICC</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5244-2c6a1ef4df81723b0f1b25b062048f40e1e6f36ceb52a2a1ce09ceb0289259fa3</citedby><cites>FETCH-LOGICAL-c5244-2c6a1ef4df81723b0f1b25b062048f40e1e6f36ceb52a2a1ce09ceb0289259fa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26510166$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eefsen, Rikke Løvendahl</creatorcontrib><creatorcontrib>Engelholm, Lars</creatorcontrib><creatorcontrib>Willemoe, Gro L.</creatorcontrib><creatorcontrib>Van den Eynden, Gert G.</creatorcontrib><creatorcontrib>Laerum, Ole Didrik</creatorcontrib><creatorcontrib>Christensen, Ib Jarle</creatorcontrib><creatorcontrib>Rolff, Hans Christian</creatorcontrib><creatorcontrib>Høyer‐Hansen, Gunilla</creatorcontrib><creatorcontrib>Osterlind, Kell</creatorcontrib><creatorcontrib>Vainer, Ben</creatorcontrib><creatorcontrib>Illemann, Martin</creatorcontrib><title>Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo‐adjuvant cytotoxic chemotherapy and bevacizumab</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p < 0.0001). Microvessel density was decreased in liver metastases from patients treated with bevacizumab in comparison to those from untreated/chemotherapy‐treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo‐adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect.
What's new?
A first‐line therapy for colorectal liver metastasis is chemotherapy combined with vascular endothelial growth factor (VEGF) inhibitor bevacizumab. Patient response markers are however lacking. In this first study on the effect of bevacizumab on angiogenesis in colorectal liver metastases, the authors evaluate endothelial cell proliferation and microvessel density in resected liver metastases from patients who were either untreated or received chemotherapy alone or in combination with bevacizumab. Microvessel density is significantly lower and the degree of tumor regression is highest in liver metastases from patients treated with chemotherapy and bevacizumab. These findings may help develop response markers for bevacizumab treatment.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Aged</subject><subject>Amputation</subject><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bevacizumab - therapeutic use</subject><subject>Cancer</subject><subject>Cell growth</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotherapy</subject><subject>Chemotherapy, Adjuvant</subject><subject>colorectal cancer</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Denmark</subject><subject>Endothelial Cells - drug effects</subject><subject>Female</subject><subject>growth pattern</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Ki67</subject><subject>Liver</subject><subject>liver metastasis</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - secondary</subject><subject>Male</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>microvessel density</subject><subject>Middle Aged</subject><subject>Neoadjuvant Therapy</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Proportional Hazards Models</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp1kcFu1DAQhi1ERZfCgRdAlriUQ9qx1_FujmhFoagVFzhHjjOmXjn2Yjsp21MfgafgwXgSvKRwQEKyZFnz-Z9_5ifkBYMzBsDP7Vaf8aYB8YgsGDSrCjirH5NFqUG1Ykt5TJ6mtAVgrAbxhBxzWTNgUi7Ij2urY5gwJXS0R59s3lPle4q-D_kGnVWOanSO7mJw1mBU2QZPHU7oErWe6uBCRJ0L5-yEkQ6YVSoHEzUxDHRXfqDPiX4pZU89hp_331W_HSflM9X7HHL4ZjXVNzgcWka1my10OClt78ZBdc_IkVEu4fOH-4R8vnj7afO-uvr47nLz5qrSNRei4loqhkb0Zs1WfNmBYR2vO5AcxNoIQIbSLKXGruaKK6YRmvIAvm543Ri1PCGns26Z9uuIKbeDTYfxVbE9ppatJDS8bE4U9NU_6DaM0Rd3harXhRMAhXo9U2XLKUU07S7aQcV9y6A9hNeW8Nrf4RX25YPi2A3Y_yX_pFWA8xm4tQ73_1dqLz9sZslfMdqo7A</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Eefsen, Rikke Løvendahl</creator><creator>Engelholm, Lars</creator><creator>Willemoe, Gro L.</creator><creator>Van den Eynden, Gert G.</creator><creator>Laerum, Ole Didrik</creator><creator>Christensen, Ib Jarle</creator><creator>Rolff, Hans Christian</creator><creator>Høyer‐Hansen, Gunilla</creator><creator>Osterlind, Kell</creator><creator>Vainer, Ben</creator><creator>Illemann, Martin</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20160401</creationdate><title>Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo‐adjuvant cytotoxic chemotherapy and bevacizumab</title><author>Eefsen, Rikke Løvendahl ; Engelholm, Lars ; Willemoe, Gro L. ; Van den Eynden, Gert G. ; Laerum, Ole Didrik ; Christensen, Ib Jarle ; Rolff, Hans Christian ; Høyer‐Hansen, Gunilla ; Osterlind, Kell ; Vainer, Ben ; Illemann, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5244-2c6a1ef4df81723b0f1b25b062048f40e1e6f36ceb52a2a1ce09ceb0289259fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Aged</topic><topic>Amputation</topic><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bevacizumab - therapeutic use</topic><topic>Cancer</topic><topic>Cell growth</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemotherapy</topic><topic>Chemotherapy, Adjuvant</topic><topic>colorectal cancer</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Denmark</topic><topic>Endothelial Cells - drug effects</topic><topic>Female</topic><topic>growth pattern</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Ki67</topic><topic>Liver</topic><topic>liver metastasis</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - secondary</topic><topic>Male</topic><topic>Medical research</topic><topic>Metastasis</topic><topic>microvessel density</topic><topic>Middle Aged</topic><topic>Neoadjuvant Therapy</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Proportional Hazards Models</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eefsen, Rikke Løvendahl</creatorcontrib><creatorcontrib>Engelholm, Lars</creatorcontrib><creatorcontrib>Willemoe, Gro L.</creatorcontrib><creatorcontrib>Van den Eynden, Gert G.</creatorcontrib><creatorcontrib>Laerum, Ole Didrik</creatorcontrib><creatorcontrib>Christensen, Ib Jarle</creatorcontrib><creatorcontrib>Rolff, Hans Christian</creatorcontrib><creatorcontrib>Høyer‐Hansen, Gunilla</creatorcontrib><creatorcontrib>Osterlind, Kell</creatorcontrib><creatorcontrib>Vainer, Ben</creatorcontrib><creatorcontrib>Illemann, Martin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eefsen, Rikke Løvendahl</au><au>Engelholm, Lars</au><au>Willemoe, Gro L.</au><au>Van den Eynden, Gert G.</au><au>Laerum, Ole Didrik</au><au>Christensen, Ib Jarle</au><au>Rolff, Hans Christian</au><au>Høyer‐Hansen, Gunilla</au><au>Osterlind, Kell</au><au>Vainer, Ben</au><au>Illemann, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo‐adjuvant cytotoxic chemotherapy and bevacizumab</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>138</volume><issue>7</issue><spage>1777</spage><epage>1784</epage><pages>1777-1784</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p < 0.0001). Microvessel density was decreased in liver metastases from patients treated with bevacizumab in comparison to those from untreated/chemotherapy‐treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo‐adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect.
What's new?
A first‐line therapy for colorectal liver metastasis is chemotherapy combined with vascular endothelial growth factor (VEGF) inhibitor bevacizumab. Patient response markers are however lacking. In this first study on the effect of bevacizumab on angiogenesis in colorectal liver metastases, the authors evaluate endothelial cell proliferation and microvessel density in resected liver metastases from patients who were either untreated or received chemotherapy alone or in combination with bevacizumab. Microvessel density is significantly lower and the degree of tumor regression is highest in liver metastases from patients treated with chemotherapy and bevacizumab. These findings may help develop response markers for bevacizumab treatment.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>26510166</pmid><doi>10.1002/ijc.29904</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | Wiley |
| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - mortality Adenocarcinoma - pathology Aged Amputation Angiogenesis Angiogenesis Inhibitors - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab - therapeutic use Cancer Cell growth Cell Proliferation - drug effects Chemotherapy Chemotherapy, Adjuvant colorectal cancer Colorectal Neoplasms - drug therapy Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Denmark Endothelial Cells - drug effects Female growth pattern Humans Immunohistochemistry Kaplan-Meier Estimate Ki67 Liver liver metastasis Liver Neoplasms - drug therapy Liver Neoplasms - secondary Male Medical research Metastasis microvessel density Middle Aged Neoadjuvant Therapy Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology Proportional Hazards Models |
| title | Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo‐adjuvant cytotoxic chemotherapy and bevacizumab |
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