PURPOSE: Hypoxia adversely relates with prognosis in human tumours. Five hypoxia specific predictive marker assays were compared and correlated with definitive radiotherapy. PATIENTS AND METHODS: Sixty-seven patients with advanced head and neck carcinomas were studied for pre-treatment plasma osteopontin measured by ELISA, tumour oxygenation status using pO(2) needle electrodes and tumour osteopontin, hypoxia inducible factor 1alpha (HIF-1alpha) and carboxyanhydrase 9 (CA9) by immunohistochemistry. The primary treatment was radiotherapy and the hypoxic radiosensitizer nimorazole. Loco-regional tumour control was evaluated at 5 years. RESULTS: All five markers showed inter-tumour variability. Inter-marker correlations were inconsistent. Only plasma osteopontin inversely correlated with median tumour pO(2), (p=0.02, r=0.28) and CA9 correlated with HIF-1alpha (p<0.01, r=0.45). In Kaplan-Meier analysis high plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9 and tumour osteopontin failed to predict loco-regional control in this set dataset. When analyzing Hb, stage, and the five markers by competing risks HP(2.5) was the strongest variable to predict for loco-regional tumour control. CONCLUSION: There was diversity and lack of correlation among five different hypoxia assays within individual tumours. High plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9 and tumour OPN failed to predict local control.
PURPOSE:Hypoxia adversely relates with prognosis in humantumours. Five hypoxia specific predictive marker assays were compared and correlated with definitive radiotherapy. PATIENTS AND METHODS: Sixty-seven patients with advanced head and neck carcinomas were studied for pre-treatment plasma osteopontin measured by ELISA, tumour oxygenation status using pO(2) needle electrodes and tumourosteopontin, hypoxia inducible factor 1alpha (HIF-1alpha) and carboxyanhydrase 9 (CA9) by immunohistochemistry. The primary treatment was radiotherapy and the hypoxic radiosensitizer nimorazole. Loco-regional tumour control was evaluated at 5 years. RESULTS: All five markers showed inter-tumour variability. Inter-marker correlations were inconsistent. Only plasma osteopontin inversely correlated with median tumour pO(2), (p=0.02, r=0.28) and CA9 correlated with HIF-1alpha (p<0.01, r=0.45). In Kaplan-Meier analysis high plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9 and tumourosteopontin failed to predict loco-regional control in this set dataset. When analyzing Hb, stage, and the five markers by competing risks HP(2.5) was the strongest variable to predict for loco-regional tumour control. CONCLUSION: There was diversity and lack of correlation among five different hypoxia assays within individual tumours. High plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9 and tumour OPN failed to predict local control.