New developments in hypoxia-directed patient selection and stratification in radiotherapy

Tumor hypoxia is a negative prognostic factor that causes radiotherapy resistance. Decades of clinical trials employing various hypoxia intervention strategies have had limited impact on daily clinical practise. This is largely due to modest benefits of hypoxia modification in unselected patient populations, combined with higher toxicity and increases in cost and time. However, numerous studies have employed post-hoc analysis to demonstrate a benefit of hypoxia intervention in patients with the most hypoxic tumors, and these benefits are of sufficient magnitude to warrant further pursuit. For the first time, we have recently seen the emergence of interventional trials with patient selection or stratification based on tumor hypoxia biomarkers. The purpose of this mini-review is to present the design and results from these recent trials, and highlight their impact in propelling this field forward.

Recent trials employing patient selection based on hypoxia biomarkers have investigated the effects of dose (distribution) modifications, and drug-induced tumor reoxygenation or radiosensitization. Encouraging results from some approaches have laid the foundation for larger follow-up studies that have the potential to change clinical practice. These clinical trials set an important precedent for future trial design and help guide the path for the future of hypoxia-directed radiotherapy.