Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002)

J Clin Oncol. 2021 Mar 20;39(9):956-965. doi: 10.1200/JCO.20.03128. Epub 2021 Jan 28.

Abstract

Purpose: Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.

Patients and methods: In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).

Results: Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% (P = .04). For IMRT, 2-year PFS was 87.6% (P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% (P = .56).

Conclusion: The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

Trial registration: ClinicalTrials.gov NCT02254278.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemoradiotherapy / mortality*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / radiotherapy*
  • Oropharyngeal Neoplasms / therapy
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • Prognosis
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / mortality*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Squamous Cell Carcinoma of Head and Neck / radiotherapy*
  • Squamous Cell Carcinoma of Head and Neck / therapy
  • Squamous Cell Carcinoma of Head and Neck / virology
  • Survival Rate

Associated data

  • ClinicalTrials.gov/NCT02254278