Cutting Radiation Exposure by 50% Appears Safe and Effective in HPV-Positive Head and Neck Cancer

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“This is the first clinical trial in head and neck cancer to demonstrate no injury to swallowing function after radiation. These are exciting data.”
— Daniel Ma, MD

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AGGRESSIVE REDUCTION in radiation therapy appears to be a potential win-win situation for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, according to the results of a phase II trial presented at the 2017 Annual Meeting of the American Society for Radiation Oncology (ASTRO).1 Cutting the dose of radiation by 50% achieved similar locoregional control rates compared with historical controls at 2 years, with low toxicity and no decrement in swallowing function or quality of life. Experts noted that this approach, if validated, could spare patients from the potentially severe side effects of more aggressive radiation and be cost-effective. 

“This is the first clinical trial in head and neck cancer to demonstrate no injury to swallowing function after radiation. These are exciting data,” said lead author Daniel Ma, MD, of the Mayo Clinic, Rochester, Minnesota. 

A phase III study called the De-Escalated Adjuvant Radiation Therapy (DART)-HPV trial is underway to compare de-escalated radiation therapy against the standard of care. 

HPV-associated oropharyngeal cancer is on the rise and is expected to comprise an estimated 50% of head and neck cancers by the year 2030. HPV-associated oropharyngeal cancer typically afflicts younger patients, and with contemporary treatments, it has a much better prognosis than other head and neck cancers. 

“Good cure rates are achieved with standard therapy, which includes 7 weeks of radiation and chemotherapy. Many of these patients will live another 30 or 40 years, and standard treatment has serious and potentially life-altering side effects, such as dry mouth, loss of taste, and pain, with up to 50% of patients experiencing difficulty swallowing,” Dr. Ma explained. 

Several studies are looking at incremental reductions in the dose of radiation for HPV-associated oropharyngeal squamous cell carcinoma. Dr. Ma and his colleagues at the Mayo Clinic in Rochester and Phoenix, wanted to study a more aggressive strategy. In the phase II MC1273 trial, “we sought to lessen the side effects by cutting total radiotherapy dose in half, from between 60 and 66 Gy to 30 to 36 Gy,” he told listeners. 

Study Details 

THE STUDY INCLUDED 80 patients with stage III or IV HPV-associated oropharyngeal squamous cell carcinoma, negative surgical margins, and a minimal smoking history (less than 10 packs per year). The median age was 60.5 years; 73 patients were male, and 7 were female. “There was a broad distribution of patients concerning T stage and N stage,” Dr. Ma noted. 

Cohort A (n = 37 patients) received 30 Gy in (1.5 Gy twice daily) over 10 days plus 2 courses of docetaxel at 15 mg/m2 on days 1 and 8; cohort B (n = 43 patients) included high-risk patients with extracapsular extension who received a total dose of 36 Gy (1.8 Gy twice daily for 10 days) plus the same dose of weekly docetaxel. 

Survival, Recurrence, and Toxicity 

AT A MEDIAN FOLLOW-UP of 2 years, 2-year progression-free survival was 91.3%; four patients had distant recurrence and three had locoregional recurrence. The locoregional control rate at 2 years was 96.3%, with two local recurrences and one nodal recurrence. 

Dr. Ma said these rates compared favorably with the results of the Radiation Therapy Oncology Group (RTOG) 0234 trial of high-dose radiation therapy, which reported a 2-year disease-free survival rate of 86.4% in HPV-associated cancers.2 


  • De-escalating the dose of radiation in patients with HPV-associated head and neck cancer resulted in disease control rates similar to historical controls treated with standard-dose radiation.
  • This strategy reduced the incidence and severity of side effects compared with historical controls.
  • These results require validation in an ongoing phase III trial.

Grade 2 toxicity was reported in 10% of patients, which compares favorably with 55% reported in RTOG 0234 in patients treated with standard-of-care radiation therapy, Dr. Ma announced. All grade 3 or higher toxicity occurred during the first 3 months (14 patients, 18%) and resolved by 6 months. No patient required a feeding tube for swallowing difficulty, and swallowing function was unchanged on formal swallowing evaluation after de-escalated radiation therapy. 

“Side effects with dose-reduced treatment were dramatically less than what we usually see in the treatment of adjuvant radiation therapy for oropharyngeal cancer. For example, no patient in this trial needed a feeding tube placed, whereas close to one-third of patients had feeding tubes placed with traditional doses in other recent clinical trials,” Dr. Ma observed. 

According to three validated quality-of-life instruments, quality of life remained unchanged (ie, Functional Assessment of Cancer Therapy–Head and Neck version, the EuroQol [EQ-5D], and the European Organisation for Research and Treatment of Cancer instrument for head and neck. The only side effect that worsened at 1 year was dry mouth, he added. 

“Halving the dose of radiation achieves similar disease control at 2 years compared with historical controls and significantly reduces posttreatment side effects,” Dr. Ma told listeners. ■

DISCLOSURE: Dr. Ma reported no conflicts of interest. 


1. Ma DJ, Price K, Moore EJ, et al: Two-year results for MC1273, a phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiation in HPV+ oropharynx squamous cell carcinoma. 2017 ASTRO Annual Meeting. Abstract LBA-14. Presented September 25, 2017. 

2. Kies MS, Harris J, Rotman MZ, et al: Phase II randomized trial of postoperative chemoradiation plus cetuximab for high-risk squamous cell carcinoma of the head and neck (RTOG 0234). 2009 ASTRO Annual Meeting. Abstract 29. 

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