Dose De-escalation in Adjuvant Chemoradiotherapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma


Key Points

  • The 2-year locoregional tumor control rate was 96.2%.
  • At 2 years, progression-free survival was 91.1% and overall survival was 98.7%.

In a phase II study reported in the Journal of Clinical Oncology, Ma et al found that aggressive radiotherapy dose de-escalation in adjuvant chemoradiotherapy for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma was associated with disease control rates comparable to historical rates with higher radiotherapy doses.

The study aimed to determine differences in outcome with adjuvant radiotherapy dose de-escalation from a standard 60–66 Gy to 30–36 Gy. A total of 80 patients were enrolled between September 2013 and June 2016 at Mayo Clinic Rochester (cohort A = 37) and Mayo Clinic Arizona (cohort B = 43). Cohort A (intermediate-risk) received 30 Gy in 1.5-Gy fractions twice per day over 2 weeks with docetaxel at 15 mg/m2 once per week. Cohort B consisted of 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 endpoint was locoregional tumor control at 2 years.

Locoregional Tumor Control

Median follow-up was 36 months. Locoregional recurrence occurred in none of the patients in cohort A and in four in cohort B, with an overall 2-year locoregional tumor control rate of 96.2% (100% in cohort A; 93.0% in cohort B). At 2 years, progression-free survival was 91.1% and overall survival was 98.7% among all patients.


Grade 2 and grade ≥ 3 toxicity rates preradiotherapy and 1 and 2 years postradiotherapy were 11.4% and 2.5%, 1.4% and 0.0%, and 6.7% and 0.0%, respectively. The most common grade 2 events were dysphagia, xerostomia, and oral mucositis. All Grade ≥ 3 toxicities occurred within 3 months.

Swallowing function improved slightly between preradiotherapy and 12 months postradiotherapy (P = .01), with one patient requiring a temporary feeding tube. Xerostomia worsened in the 1-month posttreatment period (P < .001), but returned to baseline by 1 year posttreatment (P = 0.67). At 1 year posttreatment, quality of life improved slightly vs preradiotherapy on the FACT-HN (P < .001), EORTC-QLQ HN35 (P < .001), and EQ-5D-3L (P < .001) instruments.

The investigators concluded, “Aggressive radiotherapy de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or quality of life.”

Daniel J. Ma, MD, of Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by a National Institutes of Health grant, Braillier Family Research Fund, and Matteson Research Fund. For full disclosures of the study authors, visit

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