ICT (carboplatin/paclitaxel/cetuximab) + FMISO-PET Hypoxia Clearance Enables 30Gy De-escalation in T3–T4 HPV+ OPC

In this pilot study (NCT05491512), weekly induction chemotherapy with carboplatin (AUC2) + paclitaxel (90 mg/m²) + cetuximab (after 400 mg/m² load, then 250 mg/m² weekly) for 6 weeks was used to downstage very locally advanced HPV+ oropharyngeal cancer (AJCC v7 T3–T4 and/or bulky N2b–N3) and reduce tumor hypoxia on ¹⁸F-FMISO PET prior to major radiation de-escalation. All 20/20 patients (n=20; accrued 3/2023–12/2023) were hypoxic pre-ICT, all 20/20 downstaged to meet eligibility for the 30-ROC approach, and all 20/20 converted to “no hypoxia,” then received 30Gy definitive chemoradiation; 2-year PFS and 2-year local control were each 90% (95% CI 76.9%–100%) with no distant failures at median 23 months follow-up. While cross-trial comparisons are imperfect, this lands below contemporary SOC definitive chemoradiation control arms (typically ~70Gy + cisplatin; e.g., 2-year PFS ~98% in NRG-HN005’s SOC arm), but importantly extends hypoxia-guided 30Gy feasibility into a group usually excluded from major de-escalation.