Predictive Biomarkers and Personalized Medicine A 26-Gene Hypoxia Signature Predicts Benefit fromHypoxia- Modifying Therapy in Laryngeal Cancer but Not Bladder Cancer

Purpose: Tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome, andhypoxic status predicts benefit from treatment. Yet, there is nouniversalmeasureof clinical hypoxia. The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxiamodifying treatment in both cancer types. ExperimentalDesign: Sampleswere available from157T2–T4 laryngeal cancer and185 T1–T4a bladder cancer patients enrolled on the accelerated radiotherapy with carbogen and nicotinamide (ARCON) and bladder carbogennicotinamide (BCON)phase III randomized trials of radiotherapy alone orwith carbogen and nicotinamide (CON) respectively. Customized TaqMan low density arrays (TLDA) were used to assess expression of the 26-gene signature using quantitative real-time PCR. Themedian expression of the 26 genes was used to derive a hypoxia score (HS). Patients were categorized as TLDA-HS low ( median) or TLDA-HS high (>median). The primary outcome measures were regional control (RC; ARCON) and overall survival