Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy.

Abstract

BACKGROUND:

Activation of the insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3) can predict event-free survival (EFS) and overall survival (OS) in Ewing sarcoma patients treated with chemotherapy.

PATIENTS AND METHODS:

Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE) chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t-tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O'Quigley procedure. Survival analyses were performed using Cox regression analysis.

RESULTS:

High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009-0.602 and HR 0.090, 95% CI 0.011-0.712, respectively) in univariate and multivariate analyses (HR 0.063, 95% CI 0.007-0.590 and HR 0.057, 95% CI 0.005-0.585, respectively). OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy (P=0.055 and P=0.023, respectively).

CONCLUSION:

High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated with improved EFS and a trend for improved OS in Ewing sarcoma patients treated with VIDE chemotherapy. These findings suggest the need for further investigation of the IGF-1 pathway as a biomarker of disease progression in patients with Ewing sarcoma.

• Authors: Stefanie de Groot, Hans Gelderblom, Marta Fiocco, Judith Vmg Bovée, Jacobus Jm van der Hoeven, Hanno Pijl, Judith R Kroep
• Journal: OncoTargets and therapy (Onco Targets Ther) Vol. 10 Pg. 2963-2970 ( 2017) ISSN: 1178-6930 [Print] New Zealand
• PMID: 28652778 (Publication Type: Journal Article)