Unique Duke Trial Recruiting Patients with Certain HPV-related Oropharyngeal Cancers

By Jeni Baker


Study aims to reduce side effects of chemoradiation while maintaining outstanding results

As many cancer patients who have undergone chemoradiation (chemotherapy and radiation treatment at the same time) can attest: the double dose of side effects can be tough.

For adults diagnosed with specific human papillomavirus (HPV)-related cancers of the oropharynx, a Duke clinical trial — currently enrolling eligible patients — aims to change that.

Keep Chemoradiation’s Benefits, Reduce Its Side Effects

The trial, “Radiotherapy Dose De-escalation in HPV-Associated Cancers of the Oropharynx,” arose from the desire to decrease the amount of chemoradiation — and therefore its often severe side effects — whenever possible, without sacrificing its therapeutic benefit.

“Although chemoradiation is often successful, it’s associated with a high level of acute and chronic side effects,” says lead investigator and Leonard Prosnitz Distinguished Professor of Radiation Oncology David M. Brizel, MDalso co-director of Duke Cancer Institute’s Head and Neck Cancer Program and a professor of head and neck surgery and communication sciences.

Begun in April 2021, the trial builds upon the findings of the team’s preliminary study, “Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence,” published in 2020.

“Based on those results, in the current study, a PET scan is performed after the first two weeks of a standard seven-week course of chemoradiation, which typically consists of 35 radiation treatments and seven doses of chemotherapy,” Dr. Brizel explains.

Using PET imaging to better personalize cancer treatments is what distinguishes this Duke trial.

PET Imaging Informs and Personalizes Care

“Most studies being conducted in the U.S. are looking at tumor size at the start of treatment to identify patients for de-escalation,” Dr. Brizel explains. “Our trial is unique in that after two weeks of treatment, we conduct a PET scan to measure the tumor metabolism and to see how much has changed in response to the initial treatment.”

In short, every patient’s unique PET scan influences how the team proceeds with treatment.

“We use that variable to guide our decision to de-escalate treatment for certain patients,” says Dr. Brizel. “If the tumor findings on the PET scan meet the criteria we developed in the preliminary study, we de-intensify treatment to six weeks, or 30 radiation treatments and six chemotherapy doses.”

It’s important to note, he adds, that “a pre-planned safety analysis has not shown any worsening of outcome from less treatment.”

The hope is that de-escalating treatment will result in fewer treatment side effects and faster recovery for patients who meet the criteria. And because fewer chemoradiation doses mean lower overall treatment costs, affected patients may see a financial benefit as well.

The Causes of Many Cases of Oropharynx Cancer Have Changed

Changes to the types of oropharyngeal cancers that people are getting have led to the need for more disease-specific treatments.

“Most of the chemoradiation treatments aimed at non-surgically curing locally advanced oropharynx cancer were developed to treat HPV-negative disease —which is unrelated to human papillomavirus — and has a poor prognosis,” he says.

“The incidence of oropharynx cancers not caused by HPV (‘HPV-negative’) has declined in the last 10 to 15 years,” he says. “Now, nearly 80 percent of these cancers are caused by HPV (‘HPV-positive’), which has a much better prognosis than HPV-negative disease and may not require as much treatment.”

Many groups around the country are investigating less intensive treatment programs that are designed to maintain this excellent prognosis while at the same time reducing treatment-related side effects.

The hope is that the findings of this Duke study and others will improve patient care.

“If the results show that we can de-escalate chemoradiation treatment — based on PET scans after the first two weeks — we will incorporate this process into the routine care of patients with HPV+ oropharynx cancer.”

In the meantime, the trial needs to enroll more eligible patients with HPV-related oropharyngeal cancers.

Participants Needed

Currently, 50 more adults with certain HPV-related squamous-cell oropharyngeal carcinomas are needed for this clinical trial. The enrollment goal is 120 patients, which the team expects will take another year and a half to reach.

The study is enrolling patients at two locations: Duke Cancer Institute in Durham and Duke Raleigh Hospital. Among other participation criteria, eligible trial participants must:

  • Be 18 years old or older
  • Have histologic documentation of squamous cell carcinoma of the oropharynx with p16-positive immunohistochemical staining and/or positive HPV in situ hybridization and/or positive PCR assay for HPV
  • Have stage I-III disease, with a plan for concurrent chemotherapy per the therapeutic standard of care

Learn more about the study and criteria for participation.

It is important to note that patients at both enrollment sites — whether or not they choose to enroll in the study — will receive a thorough multidisciplinary evaluation and treatment personalized to their disease and individual circumstances.

For additional information, contact Heather Franklin, RN, at 919-668-3726 or heather.mccullough@duke.edu.

To schedule an appointment with a Duke Head and Neck Surgery & Communication Sciences expert, call 919-439-1870.

To refer a patient, call 800-633-3853 or use DukeMedLink.