Primary Transoral Surgery and Reduced-Dose Adjuvant Radiation Therapy for HPV-Positive Locally Advanced Oropharyngeal Cancer

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As reported in the Journal of Clinical Oncology by Robert L. Ferris, MD, PhD, and colleagues, the phase II ECOG-ACRIN E3311 trial has shown high progression-free survival rates and good functional outcomes in patients with intermediate-risk human papillomavirus (HPV; p16)-positive locally advanced oropharyngeal cancer who underwent transoral surgery followed by reduced-dose radiotherapy.

As stated by the investigators, “Definitive or postoperative chemoradiation is curative for HPV-associated oropharyngeal cancer but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery and reduced postoperative radiation therapy in intermediate-risk HPV-positive oropharyngeal cancer.”

Primary transoral surgery and reduced postoperative radiotherapy result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV-positive oropharyngeal cancer.
— Robert L. Ferris, MD, PhD, and colleagues

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Study Details

The multicenter study included 359 patients, enrolled between December 2013 and July 2017, who underwent transoral surgery and were categorized based on pathology findings as low-risk (n = 38), intermediate-risk (n = 208), or high-risk (n = 113). Following transoral surgery, low-risk patients (group A) underwent observation and high-risk patients (group D) received radiotherapy at 66 Gy with concurrent weekly cisplatin at 40 mg/m2. Intermediate-risk patients were randomly assigned to receive radiotherapy at 50 Gy (group B, n = 100) or 60 Gy (group C, n = 108). The primary efficacy outcome measure was 2-year progression-free survival among intermediate-risk patients. Quality of life and swallowing were measured by the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) and MD Anderson Dysphagia Index.

Key Findings

Median follow-up was 35.2 months.

Kaplan-Meier estimated 2-year progression-free survival rates were 96.9% (90% confidence interval [CI] = 91.9%–100%) in group A (observation), 94.9% (90% CI = 91.3%–98.6%) in group B (radiotherapy at 50 Gy), 96.0% (90% CI = 92.8%–99.3%) in group C (radiotherapy at 60 Gy), and 90.7% (90% CI = 86.2%–95.4%) in group D (radiotherapy at 66 Gy plus weekly cisplatin). Exploratory comparisons between groups suggested no significant differences between groups B vs C (P = .90), B vs D (P = .30) or C vs D (P = .30).

Estimated progression-free survival rates at 3 years were 96.9% in group A, 94.9% in group B, 93.4% in group C, and 90.7% in group D. Estimated overall survival rates at 2 years were 100% in group A, 99.0% in group B, 98.1% in group C, and 96.3% in group D.

During adjuvant treatment, grade 3, 4, and 5 treatment-related toxicity occurred in 13%, 2%, and 0% of group B patients; 24%, 0%, and 0% of group C patients; and 49%, 11%, and 1% of group D patients. The most common grade 3 toxicities were oral mucositis (5% in group B, 11% in group C, and 19% in group D) and dysphagia (3% in group B, 5% in group C, and 16% in group D). Significant differences in grade 3 to 5 toxicity rates were observed between group B vs group C (14% vs 24%, P = .030), group B vs group D (60% in group D, P < .0001), and group C vs group D (P < .0001).

Consistent declines in quality-of-life and swallowing scores were observed during treatment in all groups, but recovered to baseline levels in groups A, B, and C, with slightly poorer scores in group D. Stable or improved FACT-HN total scores from baseline to 6 months post-treatment were observed in 56% of patients in groups B and C combined vs 38% of group D (P = .009) and in 63% of group B vs 49% of group C (P = .066).

The investigators concluded, “Primary transoral surgery and reduced postoperative radiotherapy result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV-positive oropharyngeal cancer.”

Dr. Ferris, of the University of Pittsburgh Medical Center Hillman Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.