Differential risk assessments from five hypoxia specific assays: The basis for biologically adapted individualized radiotherapy in advanced head and neck cancer patients

PurposeHypoxia adversely relates with prognosis in human tumours. Five hypoxia specific predictive marker assays were compared and correlated with definitive radiotherapy.Patients and methodsSixty-seven patients with advanced head and neck carcinomas were studied for pre-treatment plasma osteopontin measured by ELISA, tumour oxygenation status using pO2 needle electrodes and tumour osteopontin, hypoxia inducible factor 1α (HIF-1α) 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.ResultsAll five markers showed inter-tumour variability. Inter-marker correlations were inconsistent. Only plasma osteopontin inversely correlated with median tumour pO2, (p = 0.02, r = 0.28) and CA9 correlated with HIF-1α (p < 0.01, r = 0.45). In Kaplan–Meier analysis high plasma osteopontin, high HIF-1α and high proportion of tumour pO2 ⩽ 2.5 mm Hg (HP2.5) 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 HP2.5 was the strongest variable to predict for loco-regional tumour control.ConclusionThere was diversity and lack of correlation among five different hypoxia assays within individual tumours. High plasma osteopontin, high HIF-1α and high proportion of tumour pO2 ⩽ 2.5 mm Hg (HP2.5) related significantly with poorer loco-regional control, whereas CA9 and tumour OPN failed to predict local control.