Tumor Hypoxia-Directed De-Escalation of Chemoradiotherapy for Locally Advanced HPV-Related Oropharyngeal Carcinoma

Human papillomavirus (HPV)–related oropharyngeal carcinomas have excellent prognosis when treated with standard chemoradiotherapy, which can cause significant toxicity. De-escalation of standard therapy has been attempted in many clinical trials with various strategies, yet none has demonstrated noninferiority in a phase 3 randomized clinical trial. Tumor hypoxia has been associated with radiation resistance. To assess whether measurement of tumor hypoxia could identify candidates for de-escalation of chemoradiotherapy, investigators enrolled 152 patients with HPV-related oropharyngeal cancer and stage T0-2/N1-2c/M0 disease in a single-arm, single-center, phase 2 study.

Patients underwent primary tumor resection followed by baseline ¹⁸F-fluoromisonidazole (FMISO) positron emission tomography (PET) scan to determine tumor hypoxia. Those with hypoxia had repeat FMISO PET 1 to 2 weeks intratreatment. Patients with no hypoxia at baseline (n=42) or hypoxia resolution during treatment (n=86) received a total of 30 Gy of radiation and 2 cycles of chemotherapy (cisplatin 100 mg/m² or carboplatin AUC=5 and 5-FU 2400 mg/m² over 4 days). Patients with baseline or persistent hypoxia (n=24) received a total of 70 Gy of radiation and 3 cycles of chemotherapy.

Progression-free survival (PFS) at 2 years was similar in the 30-Gy and 70-Gy cohorts (94% and 96%), while the 30-Gy cohort had significantly lower rates of acute and late grade 3 and 4 adverse events (acute, 32% vs. 58.3%; late, 0% vs. 4.5%, respectively).