ASCO Conference Coverage

Phase 2 FMISO PET-Guided CRT De-Escalation Shows 97% 5-Year OS in HPV+ Oropharyngeal Cancer

Edited by:
Anthony Calabro, MA

Key Highlights

  • FMISO PET was used to stratify patients with HPV-associated oropharyngeal carcinoma by intratumoral hypoxia.
  • Patients without hypoxia received de-escalated chemoradiotherapy to 30 Gy, while patients with intratreatment hypoxia received standard chemoradiotherapy to 70 Gy.
  • 5-year overall survival was 97% in both the 30-Gy and 70-Gy cohorts.
  • Patients with intratreatment hypoxia had a higher distant failure rate than patients without hypoxia.

FMISO PET-guided radiation dose de-escalation was associated with durable long-term outcomes in patients with human papillomavirus–associated oropharyngeal carcinoma (HPV+ OPC), according to findings that will be presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, IL.

Researchers conducted a prespecified integrated analysis of 3 consecutive phase 2 trials that used the same therapeutic strategy with progressive refinements. Patients with T0-3/N1-2c HPV+ OPC were enrolled from October 1, 2015, through November 30, 2023. FMISO PET was used to assess intratumoral hypoxia and guide treatment selection: patients without hypoxia received de-escalated chemoradiotherapy (CRT) to 30 Gy, while those with intratreatment hypoxia received standard CRT to 70 Gy.

The primary end point was 5-year overall survival (OS); secondary end points included local, regional, and distant failure, progression-free survival (PFS), treatment-related toxicities, and patient-reported outcomes.

Study Findings

A total of 430 patients were enrolled and treated. Tumor stages were T0/TX in 51 patients, T1 in 198, T2 in 173, and T3 in 8. Nodal stages were N1 in 62 patients, N2a in 48, N2b in 252, and N2c in 68. Ninety-six patients had more than 10 pack-years of smoking history.

Overall, 323 patients, or 75%, had no hypoxia on FMISO PET and received 30 Gy, while 107 patients, or 25%, had evidence of intratreatment tumor hypoxia and received 70 Gy. At a median follow-up of 4.05 years, 5-year OS was 97% in both cohorts. Five-year local failure was 2.2% in the 30-Gy cohort vs 1.9% in the 70-Gy cohort (P = .7), regional failure was 6.2% vs 3.9% (P = .4), and PFS was 91% vs 89% (P = .5). Distant failure was higher among patients with intratreatment hypoxia who received 70 Gy than among those without hypoxia who received 30 Gy, at 7.5% vs 1.3% (P = .004).

Clinical Implications

According to the study authors, FMISO PET-guided biological and personalized major radiation dose de-escalation resulted in durable long-term outcomes and benefited approximately 75% of patients. The authors stated that this precision-based approach is being validated in an ongoing randomized phase 3 trial.

The abstract did not include detailed toxicity or patient-reported outcome data, noting that detailed acute and late toxicities and patient-reported outcomes would be presented at the meeting. The authors also stated that patients with intratreatment hypoxia had a higher rate of distant metastasis and that additional therapy could be considered in future trials.

Expert Commentary

“FMISO PET–guided biological and personalized major radiation dose de-escalation results in durable long-term outcomes, benefiting approximately 75% of patients,” the researchers concluded.

Reference
Lee NY, Sherman EJ, Schöder H, et al. Long-term outcomes of 18F-fluoromisonidazole positron emission tomography (FMISO PET)–guided major radiation dose de-escalation in HPV-associated oropharyngeal cancer: the 30 ROC approach. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; abstract 103.