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ASTRO 2017: De-Escalating Radiation Dose for Throat Cancer

Half the standard dose for HPV-related oropharynx cancer maintains efficacy while lowering toxicity, according to Phase 2 clinical trial.

Jason Socrates Bardi, Editor-in-Chief
Fri, 09/29/2017




SAN DIEGO – The current standard-of-care therapy for HPV-associated oropharyngeal cancer saves lives with a high cure rate but sometimes comes at the cost of serious and life-altering side effects.

Conventional treatment relies on chemoradiation, which has a high toxicity profile. The treatment can affect salivary glands, causing severe and permanent dry mouth, leading to problems swallowing and making patients more prone to dental infections and problems with their jaw. Some people also develop problems swallowing because of fibrosis within their swallowing muscles. Some develop a severely stiff, wood-like neck—also due to fibrosis. Some even need a feeding tube inserted to maintain their daily caloric intake.

"These are patients that are being cured for disease—these are patients that will live a long time with the side effects of their treatment,” said Daniel Ma, an assistant professor of radiation oncology at Mayo Clinic in Rochester, Minnesota. "So I think all the different ways that we can investigate how to reduce the side effects would be very welcome."

Ma was lead author on a study that aimed to do just that, which he presented this week at the American Society for Radiation Oncology (ASTRO) meeting in San Diego. Reporting the two-year results of a phase 2 clinical trial called MC1273, which aimed to "aggressively" de-escalate radiation doses, Ma showed that lowering doses by half can dramatically reduce post-treatment side effects while still maintaining the same cure rates.

A Recent, Growing Problem

Human papilloma virus (HPV)-associated head and neck cancer is relatively new worldwide, but the rates of this type of cancer are among the fastest growing in the United States, doubling between 1988 and 2004, and projected to account for half of all head and neck cancers by 2030.

"It's only in the last 10-12 years that there has been strong recognition that this is, in fact, a distinct tumor type," said Paul Harari, chairman of the department of radiation oncology at the University of Wisconsin-Madison and a 30-year veteran of treating head and neck cancer.

The standard-of-care treatment for this type of cancer is either seven weeks of radiation therapy and chemotherapy or surgery followed by six weeks of radiation. Because of the profound and long-lasting side effects, however, a number of research groups have been exploring ways of lowering radiation doses in recent years.

This week at a press conference, Ma summarized his team's approach through the single-arm, phase 2 MC1273 clinical trial, calling it a "very aggressive course for treatment de-escalation" that halved the radiation dose.

"It is a challenging business, because when you have a high cure rate for a tumor, the last thing you want to do is lower that cure rate," said Harari, who moderated the press conference but was not involved in the research. "If we can maintain equivalent cure rates and diminish the side effect profile, this is a powerful advance for patients and providers."

The clinical trial accrued 80 people from 2013 to 2016 of median age 60.5 years old who all had stage III or stage IV HPV-related oropharyngeal squamous cell carcinoma. Following margin-clearing surgery, they were all treated with 30 gray radiation therapy, reducing by half the standard dose of 60-66 gray. They were assessed using standard quality-of-life scale surveys prior to receiving treatment and again at one, three, 12 and 24 months post-treatment.

The results showed a dramatic reduction of side effects and suggest there may be hope for dramatically lowering the toxicity of treatment for HPV-associated oropharyngeal cancers, although that still needs to be confirmed in further studies.

"Like all phase 2 data, this data will need to be validated in a randomized setting," Ma said, adding that a multi-institutional phase 3 study comparing this regimen compared to the standard of care is currently underway.