FMISO PET hypoxia imaging guides 30Gy chemoradiation with 97% 5-year OS in HPV+ OPC

Integrated analysis of three consecutive Phase II trials tested ^18F-fluoromisonidazole PET (FMISO PET) to stratify definitive chemoradiotherapy intensity in T0–3/N1–2c HPV+ oropharyngeal cancer (n=430; enrollment 10/1/2015–11/30/2023): patients without intratumoral hypoxia received major de-escalation to 30Gy CRT (75%; n=323) while those with intra-treatment hypoxia received standard-dose 70Gy CRT (25%; n=107). At median follow-up 4.05 years, 5-year OS was 97% in both cohorts, with similar 5-year local failure (2.2% vs 1.9%; p=0.7), regional failure (6.2% vs 3.9%; p=0.4), and PFS (91% vs 89%; p=0.5); this appears directionally comparable to contemporary cisplatin-IMRT control outcomes in HPV+ OPC while using far less RT dose in ~75% of patients (historical SOC is ~70Gy with concurrent cisplatin, and cooperative-group de-escalation has generally been “moderate” to ~60Gy rather than 30Gy). Patients with intra-treatment hypoxia still had higher distant failure despite 70Gy (7.5% vs 1.3%; p=0.004), flagging hypoxia as a metastasis-risk marker; toxicity/PRO details were not yet reported here; ongoing Phase III validation noted (NCT06563479) and contributing trials include NCT03323463 and NCT05491512.