Impact of hypoxia in head and neck cancer radiotherapy

Abstract

Background

Radiotherapy plays an important role in the treatment of pharyngo-laryngeal and oral cavity head and neck squamous cell carcinoma (HNSCC) either as single modality, in combination with concomitant chemotherapy or epithermal growth factor inhibitor, or as adjuvant treatment after curative surgery. Various biological factors have been shown to impact on tumour response to radiotherapy, and among them tumour hypoxia.

Aim

This article reviews the clinical data on measurement of tumour hypoxia and summarizes the various options to counteract it, with a special emphasis on the use of hypoxic cell radiosensitizers, radiation dose escalation, and the proper selection of patients who may benefit from such therapeutic interventions.

Results

It has been shown that up to 25% of HNSCC express pO₂ value below 2.5 mm Hg, and modification of tumour hypoxia has been demonstrated to improve loco-regional control and overall survival. In particular, the concomitant use of nimorazole, a hypoxic cell radiosensitizer, has been demonstrated in a seminal DAHANCA trial to significantly improve outcome in patients with head and neck SCC. More recently, among the patients included into this trial, a 15-gene hypoxia classifier indicated that only those patients with hypoxic tumours benefited from the combined radiotherapy and nimorazole treatment.

Conclusions

An ongoing trial is validating both the use of nimorazole and the gene classifier for patients treated with concomitant chemo-radiotherapy.