A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer: Osteopontin, carbonicanhydrase IX and vascular endothelial growth factor

摘要

Background. Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Material and methods. Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. Results. All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p=0.03), VEGF (p=0.02) and CA IX (p=0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/ VEGF/CA IX yielded a 5.9-fold risk of death (p=0.009). The combined assessment of OPN/ VEGF/CA IX correlated independently with prognosis (p=0.03) in a multivariate Cox regression model including N stage, T stage and GTV. Conclusion. This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated.