Genomic adjusted radiation dose stratifies radiotherapy dosing based on tumor-specific sensitivity in HPV+ oropharyngeal cancer.

Uniform radiation therapy (RT) de-escalation in HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has underperformed in clinical trials, likely due to underlying genomic heterogeneity. In this issue of the JCI, Ho et al. evaluated genomic adjusted radiation dose (GARD), which integrates tumor gene expression with RT dose to estimate biological effect. In 191 locoregionally advanced HPV+ OPSCC patients treated with definitive RT with or without chemotherapy, GARD values varied widely, despite uniform dose delivery, and independently predicted overall survival. These data support a genomically informed framework specific for HPV+ OPSCC patients via GARD for guiding radiation dose de-escalation strategies.