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Is Less More When Treating Patients with Radiation Therapy?


Unlike other types of cancer treatments, less may be more when it comes to managing certain types of head and neck cancer with radiation and chemotherapy. At the Sentara EVMS Comprehensive Head and Neck Center, patients and providers are at the forefront of medical research designed to improve outcomes. At the same time, we are limiting toxicity for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC).


HPV-associated head and neck cancer research aims to improve outcomes

Together with clinical trial participants, Sentara’s radiation oncology providers, including Edwin Crandley, M.D., explore different methods to de-intensify treatment for patients with HPV-associated OPSCC.

“Research has focused on how we can decrease the intensity of treatment while maintaining the excellent cancer control outcomes we expect in HPV-associated OPSCC,” says Dr. Crandley. “In some cases, that may involve decreasing the amount of radiation therapy delivered or combining it with different systemic therapies.”


Prevalence of HPV-associated oropharyngeal cancers

According to the Centers for Disease Control and Prevention, HPV contributes to approximately 70 percent of all oropharyngeal squamous cell carcinomas diagnosed in the United States. The oropharynx is composed of the:

  • Base of the tongue
  • Tonsils
  • Soft palate
  • Posterior pharyngeal wall

Most HPV-associated OPSCC occurs in the tongue base or tonsils. Traditional treatment regimens for these types of cancers typically include intense daily radiation therapy over seven weeks along with chemotherapy delivered either weekly or every three weeks.


Transoral surgery may decrease need for radiation therapy in HPV-associated OPSCC 

Recent research suggests it may be possible to use less radiation for certain individuals with HPV-associated oropharyngeal cancers. The ECOG-E3311 clinical trial, which is currently closed and results pending, explored using surgery in this patient population as a way to decrease the overall dose of radiation therapy.

This trial accrued 511 participants across several study sites, including Sentara Healthcare.  After undergoing transoral robotic surgery, patients were classified as low risk, intermediate risk, and high risk based on pathologic findings. In the study:

  • Low-risk patients underwent surgery alone.
  • Intermediate-risk patients were randomized to five versus six weeks of radiation alone. Our experimental question was whether patients at intermediate risk for recurrence experience the same cancer-control outcomes with decreased toxicity when receiving a lower dose of radiation therapy over five weeks. The typical course of post-operative radiation therapy for head and neck cancer spans six weeks.
  • High-risk patients received intensive treatment with six and a half weeks of radiation therapy and chemotherapy. The purpose of this study was not to explore de-intensification of therapy in this patient population.


Other studies look at potential for de-intensifying radiation therapy for HPV-associated head and neck cancers

Other research indicates lower doses of radiation may provide excellent control of disease in patients with HPV-associated OPSCC who are treated without surgery. Data from one study by University of North Carolina at Chapel Hill researchers demonstrated outcomes similar to what is observed with conventional higher-intensity treatment when:

  • Radiation therapy is delivered over six weeks
  • The chemotherapy dose is decreased

Outcomes with this approach are exciting, but this treatment method will require validation in randomized trials before it becomes the standard of care.

“With these types of cancers, the stakes are high. But we’re learning that for HPV-mediated head and neck cancers, these higher doses of radiation may not be necessary,” says Dr. Crandley. “While these results are not yet standard practice, the data may one day change how patients affected by HPV-associated head and neck cancers receive treatment.”


Combining chemotherapeutic agents with radiation therapy to improve outcomes

Beyond de-intensifying radiation doses, some current clinical trials investigate using newer drugs together with radiation therapy to promote better outcomes for patients. Cetuximab, an anti-neoplastic drug, is often prescribed to individuals with head and neck cancers who cannot receive conventional chemotherapy. While cetuximab does promote positive results along with radiation therapy, it is not as effective as other chemotherapeutic agents, such as cisplatin.

Cisplatin has an excellent track record of increasing the effectiveness of radiation therapy, but it also increases the likelihood of toxicity. This drug, given intravenously, can be tremendously hard on patients, causing side effects ranging from nausea and vomiting to kidney toxicity and ototoxicity.

“Radiation therapy with concurrent chemotherapy provides the best outcomes in patients with locally advanced head and neck cancer,” says Dr. Crandley. “But not all patients will be candidates for this intense treatment due to advanced age or medical co-morbidities. Cetuximab is often used instead of cisplatin in this patient population.”


Durvalumab may offer benefits where cetuximab and cisplatin fall short

One clinical trial taking place at Sentara Healthcare is looking at whether using an immune checkpoint inhibitor drug in combination with radiation therapy—instead of cetuximab—could promote better outcomes.

The NRG HN004 clinical trial examines the use of durvalumab, a monoclonal antibody that may promote the body’s immune response against cancer cells. The study population consists of patients with locally advanced head and neck cancer receiving radiation therapy who are not candidates for conventional chemotherapy. They are randomized to receive either cetuximab or durvalumab with radiation therapy.

Sentara physicians, along with other researchers, seek to understand whether immunotherapy drugs like durvalumab have activity along with radiation therapy for head and neck cancers. It may be especially beneficial for patients with locally advanced disease who aren’t candidates for cisplatin.

The trial is open at Sentara Norfolk General Hospital, but accrual is currently on hold while preliminary data on the safety and toxicity of durvalumab in this patient population is evaluated.