Proton therapy improves outcome in HPV+ oropharyngeal cancer

Most oropharyngeal cancers are caused by the human papilloma virus (HPV). While a diagnosis of HPV in head and neck cancer often has a good prognosis, treatment comes at a cost, according to Alexander Lin, MD. Dr Lin notes that one of the defining features of HPV-positive oropharynx cancers is that they respond very well to treatment. “The challenge, though, is the treatment itself can be quite toxic,” he says.

Dr. Lin is the Executive Vice Chair of the Department of Radiation Oncology at Penn Medicine, and co-author of a study in The Lancet that found proton therapy offers advantages over traditional photon radiation in de-intensification therapy for patients with oropharyngeal cancer. He recently joined the Penn Medicine Physician Interviews Podcast to discuss the results of this influential trial.

“The question is, can proton therapy treat cancer just as effectively as intensity-modulated radiation therapy (IMRT) while reducing side effects? This study is really important because it finally gives us high-quality, head-to-head evidence for this critical question,” Dr. Lin says.

Deintensification for HPV-positive oropharyngeal cancer

Patients with oropharyngeal cancer treated with IMRT often experience long-lasting side effects. These can include dry mouth, taste changes, and difficulty swallowing or speaking—side effects that significantly impair quality of life.

“Because patients do so well from a cancer standpoint, but suffer from the intensity of therapy, there is a strong rationale to explore deintensification—delivering therapy that is just as effective but less toxic,” Dr. Lin says.

Proton therapy offers a potential advantage because it deposits radiation very precisely, delivering the dose into the tumor while minimizing radiation to surrounding healthy tissues. To directly compare proton therapy with standard IRMT, researchers conducted a multicenter Phase III trial of patients with Stage 3 or Stage 4b oropharyngeal cancer.

The study included 440 patients from 21 cancer centers nationwide, including Penn Medicine. All patients received chemotherapy as standard of care, and they were randomized to receive either photon or proton therapy. “Proton therapy matched photon therapy in controlling cancer, but with fewer long-term side effects and better long-term outcomes,” Dr. Lin says.

In fact, proton therapy had a small survival advantage. At five years, 91 percent of patients receiving proton therapy were alive, compared to 81 percent of those treated with photon therapy. Patients who received proton therapy were also less likely to experience severe lymphopenia, swallowing difficulties, dry mouth, and gastrostomy tube dependence.

Compelling evidence for proton therapy

Radiation therapy requires precision, and the study used strict national and multi-institutional quality assurance protocols to ensure that the two therapies were accurately compared. “These steps ensure that the differences in outcomes that we found were purely due to the type of radiation given, proton versus IMRT, and not due to differences in other variables such as plan quality or expertise,” Dr. Lin says.

He adds that given the rigorous methodology and the significant findings, providers should consider proton therapy over IMRT whenever possible for patients with oropharyngeal cancer.

“This is a critical study. The data are clear and compelling given the five-year difference in overall survival and [the improved] side effect profile in favor of proton therapy,” he says. “Patients with this diagnosis are likely to do well from a cancer standpoint, but they’re potentially going to live a long time with side effects from therapy. It’s our obligation to try to minimize those side effects.”

Referral and consultations

The Roberts Proton Therapy Center, part of the Abramson Cancer Center at Penn Medicine, was a first-of-its-kind proton therapy center for the treatment of cancer. For a provider-to-provider consultation with Dr. Lin, please call 877-937-7366, or refer a patient online.

Listen to the Physician Interviews Podcast

Proton Therapy As De-Intensification Strategy For HPV+ Head and Neck Cancers