A single-armphase II trial treated 20 patients with unresectable and/or metastatic head and neck squamous cell carcinoma with pembrolizumab plus quad-shot radiotherapy (14.8 Gy in 4 twice-daily fractions over 2 days, repeated up to three times). Here quad-shot courses were novelly spaced every 15 weeks (after every five pembrolizumab cycles)–rather than the standard every 3-4 weeks–to function as an immune-modulating intervention more than purely a palliative local therapy. Protocol therapy was completed by 15 patients evaluable for response. Median progression-free survival was 9 months in the treated cohort, and 12 months among evaluable patients, while median overall survival approached 15 months. Notably, disease control extended beyond the irradiated field, with only 1 of 11 non-target lesions progressing. | Hughes, JAMA Otolaryngol Head Neck Surg 2026
