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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Cancer 1/2017

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

Zeitschrift:
BMC Cancer > Ausgabe 1/2017
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12885-017-3409-z) contains supplementary material, which is available to authorized users.

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.
Zusatzmaterial
Additional file 1: Fig. S1. Participant flow diagram (DOCX 30 kb)
12885_2017_3409_MOESM1_ESM.docx
Additional file 2: Table S1. Characteristics of included and excluded patients (DOCX 18 kb)
12885_2017_3409_MOESM2_ESM.docx
Additional file 3: Table S2. Distribution of plasma VEGF and bFGF levels at diagnosis, according to patient and tumour characteristics (DOCX 16 kb)
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Additional file 4: Fig. S2. Correlation between the different biomarker levels at diagnosis (DOCX 23 kb)
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Additional file 5: Table S3. Association between serum VEGF and bFGF and urinary bFGF levels at diagnosis and the risk of a poor histological response or treatment failure (multivariable analysis) (DOCX 16 kb)
12885_2017_3409_MOESM5_ESM.docx
Additional file 6: Table S4. Sensitivity analysis. Association between serum VEGF and bFGF and urine bFGF variations during pre-operative chemotherapy and the risk of a poor histological response or treatment failure among patients with high biomarker levels at diagnosis (multivariable analysis) (DOCX 16 kb)
12885_2017_3409_MOESM6_ESM.docx
Additional file 7: Table S5. Association between plasma VEGF and bFGF variations during pre-operative chemotherapy and the risk of a poor histological response or treatment failure (multivariable analysis) (DOCX 16 kb)
12885_2017_3409_MOESM7_ESM.docx
Literatur
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