Genome-wide variation in cell-free DNA end motif entropy predicts immunotherapy response in head and neck cancer
A blood test measuring DNA fragment patterns could help doctors predict which head-and-neck cancer patients will respond to immunotherapy, independent of current protein markers.
A novel cfDNA fragmentomic metric (regional motif diversity score, rMDS) was developed from whole-genome sequencing of 185 longitudinal plasma samples from 68 HNSCC patients in a prospective phase II trial. rMDS robustly distinguished responders from non-responders to pembrolizumab with AUC 0.89-0.99, independently of PD-L1 expression, offering a non-invasive blood-based biomarker for immunotherapy selection in head and neck cancer.
What the study was
- Study design
- Prospective multi-institutional phase II trial with biomarker analysis
- Population
- Locally advanced surgically resectable HNSCC patients receiving neoadjuvant and adjuvant pembrolizumab
- Sample size
- 68
- Category
- Early Detection
- Maturity
- Validated
- Journal
- J Clin Invest
Why it surfaced
First prospective multi-institutional validation of a fragmentomic cfDNA metric (rMDS) for immunotherapy response prediction in HNSCC, outperforming current standard (PD-L1), with significant DFS improvement in predicted responders. Immediate translational potential for treatment selection.
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