Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study

BMC Cancer

Research Article

Aurélie Chevance¹  Marie-Cecile Le Deley²  Marie-Ange Selva³  Rémy Couderc³  Laurence Brugières⁴  Céline Mahier-Ait Oukhatar⁵  Sophie Piperno-Neumann⁶  Jean-Yves Blay⁷  Nadège Corradini⁸  Marie-Dominique Tabone⁹  Hélène Pacquement^1,10  Natacha Entz-Werle^1,11  Jean-Claude Gentet^1,12  Cyril Lervat^1,13  Perrine Marec-Bérard^1,14 

[1] Biostatistics and Epidemiology unit, Gustave Roussy Cancer Campus, 114 rue E. Vaillant, 94805, Villejuif, France;Biostatistics and Epidemiology unit, Gustave Roussy Cancer Campus, 114 rue E. Vaillant, 94805, Villejuif, France;Paris-Saclay University, Univ. Paris-Sud, CESP, INSERM, Gustave Roussy, Villejuif, France;Department of Biochemistry, Armand Trousseau Hospital, 26 avenue du Dr A. Netter, 75571, Paris cedex12, France;Department of Children and adolescents Oncology, Gustave Roussy Cancer campus, 114 rue E. Vaillant, 94805, Villejuif, France;Department of Clinical Studies, Unicancer, 101 rue de Tolbiac, 75654, 13, Paris cedex, France;Department of Medical Oncology, Curie Institute, 26 rue d’Ulm, 75005, Paris, France;Department of Medical Oncology, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France;Claude Bernard University Lyon 1, 43 boulevard du 11 novembre 1918, 69622, Villeurbanne cedex, France;Department of Paediatric Haemato-Oncology, Mother and Child Hospital, 7 quai Moncousu, 44093, Nantes, France;Department of Paediatric Onco-Haematology, Armand Trousseau Hospital, 26 avenue du Dr A. Netter, 75571, Paris cedex12, France;Department of Paediatric Onco-Haematology AP-HP, GHUEP, Trousseau La Roche-Guyon Hospital, 26 avenue du Dr A. Netter, 75012, Paris, France;Department of Paediatric Oncology, Curie Institute, 26 rue d’Ulm, 75005, Paris, France;Department of Paediatric Oncology, Hautepierre Hospital, 1 avenue Molière, 67100, Strasbourg, France;Department of Paediatric Oncology, La Timone Hospital, 264 rue Saint Pierre, 13385, Marseille cedex 5, France;Department of Paediatric Oncology, Oscar Lambret Cancer Centre, 3 rue Frédéric Combemale, 59020, Lille cedex, France;Institute for Paediatric Haematology and Oncology, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France;

关键词: Osteosarcoma;    Angiogenic factors;    Vascular endothelial growth factor;    Basic fibroblast growth factor;   

DOI  :  10.1186/s12885-017-3409-z

 received in 2016-03-02, accepted in 2017-06-08,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAngiogenesis 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.MethodsPatients 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).ResultsSamples 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.ConclusionsLevels 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 numberclinicaltrials.gov NCT00470223; date of registration: May 3th 2007.

【 授权许可】

CC BY   
© The Author(s). 2017