Can a gene classifier identify head and neck tumors that may benefit from hypoxic modification?

Details

Hypoxia is common in the microenvironment of solid tumors and is associated with resistance to radiotherapy, reduced treatment response, and poorer clinical outcomes. In head and neck squamous cell carcinoma (HNSCC), adding hypoxic modification to radiotherapy can counteract hypoxia's negative effect on radiotherapy. Clinically applicable ways to evaluate and categorize tumor hypoxia before treatment are needed to predict which patients may benefit from this modification.

The researchers developed a hypoxia classifier based on gene expression. By studying xenograft tumors from human squamous cell carcinoma cell lines, they verified the in vivo relevance of previously identified hypoxia-induced genes derived from in vitro studies. They then evaluated a training set of 58 HNSCC tumors that had been assessed for hypoxia and generated a classifier containing 15 genes. The classifier was validated in 323 patients with HNSCC who were randomized to receive hypoxic modification or placebo in combination with radiotherapy.

Tumors classified as hypoxic were associated with significantly poorer clinical outcomes than nonhypoxic tumors. Adding hypoxic modification improved outcomes for the hypoxic tumors to the level seen in nonhypoxic tumors. The researchers concluded that the classifier had both prognostic and predictive impact and that its use before treatment may help identify patients who will benefit from hypoxic modification of radiotherapy.