Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study
Abstract Background Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors i...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3409-z |
| _version_ | 1831724370331959296 |
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| author | Marie-Dominique Tabone Laurence Brugières Sophie Piperno-Neumann Marie-Ange Selva Perrine Marec-Bérard Hélène Pacquement Cyril Lervat Nadège Corradini Jean-Claude Gentet Rémy Couderc Aurélie Chevance Céline Mahier-Ait Oukhatar Natacha Entz-Werle Jean-Yves Blay Marie-Cecile Le Deley |
| author_facet | Marie-Dominique Tabone Laurence Brugières Sophie Piperno-Neumann Marie-Ange Selva Perrine Marec-Bérard Hélène Pacquement Cyril Lervat Nadège Corradini Jean-Claude Gentet Rémy Couderc Aurélie Chevance Céline Mahier-Ait Oukhatar Natacha Entz-Werle Jean-Yves Blay Marie-Cecile Le Deley |
| author_sort | Marie-Dominique Tabone |
| collection | DOAJ |
| description | Abstract Background Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment. Methods Patients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival). Results Samples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p < 0.0001). No significant correlation was found between this variation and either the histological response, progression-free survival or overall survival (p = 0.26, p = 0.67, and p = 0.87, respectively). No significant association was found between blood or urinary bFGF levels and clinical characteristics, histological response, or survival. Conclusions Levels of VEGF and bFGF angiogenic factors are high in most osteosarcoma patients, but have no significant impact on response to chemotherapy or outcome in this large prospective series. OS 2006 trial registration number clinicaltrials.gov NCT00470223; date of registration: May 3th 2007. |
| first_indexed | 2024-12-21T04:20:41Z |
| format | Article |
| id | doaj.art-1045f74df09a40b1a55af072986c74a6 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-21T04:20:41Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-1045f74df09a40b1a55af072986c74a62022-12-21T19:16:11ZengBMCBMC Cancer1471-24072017-06-0117111010.1186/s12885-017-3409-zPrognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective studyMarie-Dominique Tabone0Laurence Brugières1Sophie Piperno-Neumann2Marie-Ange Selva3Perrine Marec-Bérard4Hélène Pacquement5Cyril Lervat6Nadège Corradini7Jean-Claude Gentet8Rémy Couderc9Aurélie Chevance10Céline Mahier-Ait Oukhatar11Natacha Entz-Werle12Jean-Yves Blay13Marie-Cecile Le Deley14Department of Paediatric Onco-Haematology, Armand Trousseau HospitalDepartment of Children and adolescents Oncology, Gustave Roussy Cancer campusDepartment of Medical Oncology, Curie InstituteDepartment of Biochemistry, Armand Trousseau HospitalInstitute for Paediatric Haematology and Oncology, Léon Bérard Cancer CentreDepartment of Paediatric Oncology, Curie InstituteDepartment of Paediatric Oncology, Oscar Lambret Cancer CentreDepartment of Paediatric Haemato-Oncology, Mother and Child HospitalDepartment of Paediatric Oncology, La Timone HospitalDepartment of Biochemistry, Armand Trousseau HospitalBiostatistics and Epidemiology unit, Gustave Roussy Cancer CampusDepartment of Clinical Studies, UnicancerDepartment of Paediatric Oncology, Hautepierre HospitalDepartment of Medical Oncology, Léon Bérard Cancer CentreBiostatistics and Epidemiology unit, Gustave Roussy Cancer CampusAbstract Background Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment. Methods Patients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival). Results Samples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p < 0.0001). No significant correlation was found between this variation and either the histological response, progression-free survival or overall survival (p = 0.26, p = 0.67, and p = 0.87, respectively). No significant association was found between blood or urinary bFGF levels and clinical characteristics, histological response, or survival. Conclusions Levels of VEGF and bFGF angiogenic factors are high in most osteosarcoma patients, but have no significant impact on response to chemotherapy or outcome in this large prospective series. OS 2006 trial registration number clinicaltrials.gov NCT00470223; date of registration: May 3th 2007.http://link.springer.com/article/10.1186/s12885-017-3409-zOsteosarcomaAngiogenic factorsVascular endothelial growth factorBasic fibroblast growth factor |
| spellingShingle | Marie-Dominique Tabone Laurence Brugières Sophie Piperno-Neumann Marie-Ange Selva Perrine Marec-Bérard Hélène Pacquement Cyril Lervat Nadège Corradini Jean-Claude Gentet Rémy Couderc Aurélie Chevance Céline Mahier-Ait Oukhatar Natacha Entz-Werle Jean-Yves Blay Marie-Cecile Le Deley Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study BMC Cancer Osteosarcoma Angiogenic factors Vascular endothelial growth factor Basic fibroblast growth factor |
| title | Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study |
| title_full | Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study |
| title_fullStr | Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study |
| title_full_unstemmed | Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study |
| title_short | Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study |
| title_sort | prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma a prospective study |
| topic | Osteosarcoma Angiogenic factors Vascular endothelial growth factor Basic fibroblast growth factor |
| url | http://link.springer.com/article/10.1186/s12885-017-3409-z |
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