Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma

J Clin Oncol. 2019 Aug 1;37(22):1909-1918. doi: 10.1200/JCO.19.00463. Epub 2019 Jun 4.

Abstract

Purpose: The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL).

Patients and methods: MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL.

Results: Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement.

Conclusion: Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

Trial registration: ClinicalTrials.gov NCT01932697.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy, Adjuvant / methods*
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Deglutition / drug effects
  • Deglutition / radiation effects
  • Disease-Free Survival
  • Docetaxel / administration & dosage
  • Dose-Response Relationship, Radiation
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / complications
  • Oropharyngeal Neoplasms / therapy*
  • Papillomaviridae
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / therapy*
  • Postoperative Period
  • Prospective Studies
  • Quality of Life
  • Radiation Dosage
  • Self Report
  • Smoking
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Docetaxel

Associated data

  • ClinicalTrials.gov/NCT01932697