Photon therapy offers strong outcomes in treating oropharyngeal cancers; however, some radiation can reach and damage nearby healthy tissue. The damage can lead to side effects that may be severe for some patients. In a new nationwide study published in The Lancet that included Mayo Clinic, investigators found that patients with oropharyngeal cancer can live longer with fewer side effects if treated with proton beam radiation therapy.
Photon radiation therapy, which uses X-rays to cure cancers, is a standard treatment for a type of throat cancer called oropharyngeal cancer. Rates of oropharyngeal cancers are increasing in the U.S., mainly driven by HPV infection.
Reducing the toll of treatment
Proton beam therapy has been used for years in children, where research shows it lowers both short- and long-term treatment-related side effects. "Protons have been studied extensively in pediatric populations and consistently demonstrate reduced short- and long-term toxicity," says Nadia Laack, M.D., chair of the Department of Radiation Oncology at Mayo Clinic in Rochester. "It has been more difficult to prove the benefits in adult cancer because many adult studies have not measured side effects as carefully or as long."
To explore whether the same advantages apply to adults, investigators directly compared proton beam therapy with modern photon radiation called intensity-modulated radiation therapy (IMRT), which precisely targets tumors while limiting exposure to nearby healthy tissue. "It is effective as an oropharyngeal cancer treatment, but there's always some incidental dose to surrounding tissues because of the physical nature of X-rays," says Daniel Ma, M.D., radiation oncologist at Mayo Clinic and the Mayo site primary investigator of the study. This incidental dose of radiation can sometimes cause long-term complications, including pain, problems with swallowing and a weakened jawbone.
To alleviate these unwanted side effects, investigators studied proton beam radiation therapy as a treatment option. "Protons are charged particles that can stop at a certain depth, so the delivery is more focused," says Dr. Ma. "If you set up your proton fields thoughtfully, you can avoid irradiating critical structures like the mouth, voice box and swallowing muscles. That's the advantage of proton therapy and why we decided to investigate it within a clinical trial."
Mayo Clinic was one of 18 participating institutions around the U.S. that enrolled patients in the first-ever phase 3 randomized trial comparing the two types of radiation for oropharyngeal cancer. Dr. Ma collaborated with Robert Foote, M.D., emeritus professor of radiation oncology at Mayo Clinic and senior author of the study, and Samir Patel, M.D., radiation oncologist at Mayo Clinic, to help lead Mayo Clinic's involvement in the study.
Study results found that proton beam therapy weakened the immune system by 15% less than photon therapy. It also lowered the risk of severe swallowing problems by 13% and reduced the need for feeding tubes by more than 13%.
An unexpected outcome
The treatments were similar in effectiveness in controlling cancer growth and spread, so Dr. Ma expected survival to be approximately the same, but the survival results were surprising.
"Unexpectedly, we found that the overall survival at five years was 91% with proton therapy and 81% with photon therapy," he says.
These results weren't immediately apparent. "The survival benefit in our study didn't start separating out until three years and wasn't apparent until five years, so longer follow-up with patients was key," he says.
Dr. Ma says this result is likely due to a variety of factors, including less toxicity and immune suppression. He adds, "Because of this, we feel strongly that proton therapy should be a standard treatment for oropharyngeal cancer patients who can tolerate and receive it."
"This study is important because it confirms what we believe to be true in many adult cancer cases: reducing toxicity has a meaningful impact on quality of life and long-term outcomes," says Dr. Laack. "As our treatments improve and our patients live longer, reducing toxicity and improving quality of life is more important than ever."
The study was led by The University of Texas MD Anderson Cancer Center. Review the study for a complete list of authors, disclosures and funding.
