A large clinical study recently published in The Lancet showed that patients treated with proton therapy for oropharyngeal cancers (cancers of the upper throat including the tonsils and back of the tongue) experienced less toxicity than those treated with conventional X-ray radiation.
Radiation therapy combined with chemotherapy is a key treatment approach for head and neck cancers; cancers related to human papilloma virus (HPV) are especially responsive to this approach.
Radiation is also often preferred when tumors are inoperable or if physicians want to avoid invasive surgeries. Radiation can also be a successful tactic following surgery. Adding chemotherapy can improve cancer control and survival by treating the body systemically.
Jay J. Liao, MD, who treats head-and-neck cancer patients at Fred Hutch – Proton Therapy, said this combination has been the standard of care in many patients for about 25 years.
“Many patients are successfully cured; however, these treatments are very intensive and often associated with significant short and long-term toxicities,” Liao said. “Many current efforts are focused on strategies to reduce the side effects of treatment, including the potential for proton beam radiation to lessen treatment intensity by further reducing radiation exposure to normal tissues.”
The landmark study published in The Lancet — a multicenter randomized trial comparing radiation modalities — included researchers from both Fred Hutch and the University of Washington. It was the largest trial completed to date to compare conventional X-ray-based treatment to proton radiation in patients with oropharynx cancers.
The trial, which enrolled Stage 3 and Stage 4 head-and-neck cancer patients from 21 sites, showed very high rates of cancer control and low risk of recurrence with proton beam radiation, which was comparable to X-ray based therapy.
Notably, proton therapy significantly reduced the rates of severe side effects including dry mouth, immune suppression, swallowing problems and feeding tube dependence. This reduction in toxicity in patients treated with protons may also contribute to improved long-term survival five years post treatment.
“Side effects from head and neck radiation can be quite significant both in the short and long term,” Liao said. “This can be influenced by the exact location and extent of the cancer. Many patients are cured of cancer but may deal with major long-term consequences on their voice, swallowing, eating and oral health from these intensive treatments. In this study, proton therapy was shown to maintain high rates of cancer cure, while reducing the toxicity of treatment. It is an important step toward improving the quality of life of our patients after treatment and returning patients closer to their pre-treatment baseline.”
Further analyses from this study will be released in the future with more details on long-term survival outcomes as well as patient-reported health outcomes during and after treatment.
Physicians, including Liao, also plan to evaluate whether additional side effect measures may be improved with proton therapy.
Given that providers can better direct proton radiation to a solid tumor, Liao and colleagues, Neil Panjwani, MD and Paul Riviere, MD, are using proton radiation to treat a number of different types of head-and-neck cancer beyond oropharynx, such as some cancers of the nasopharynx, nasal cavity and sinuses, salivary glands, base of skull and recurrent cancers.
Many critical organs — the brain, eyes and optic nerves, inner ear, salivary glands, swallowing muscles, jaw and mouth — are all close to each other and can be impacted by any cancer found in the area. The precision of protons can better limit radiation to surrounding healthy tissue.
Another recent study published in the New England Journal of Medicine looked at adding immunotherapy — which uses the body’s own immune system to find and destroy cancer cells — before and after surgery in patients with operable, locally-advanced head and neck cancer. Fred Hutch physicians and researchers are leaders in discovering new ways to harness the immune system to treat cancer.
“This study showed that adding immunotherapy to the standard of treatment — surgery followed by radiation or chemoradiation — has led to a significant improvement in disease-free survival and has ushered in a paradigm shift in the treatment of some patients with surgically-managed head-and-neck cancer,” Liao said. “It’s one of the largest positive trials we’ve seen in a while. Bringing this effectively into clinical practice requires significant multispecialty care coordination.”
Because head-and-neck cancer treatment involves so many steps and careful collaboration among multiple physicians, Fred Hutch recently expanded its head-and-neck cancer multidisciplinary clinic to three full days a week. This allows patients to be seen by the various experts in their care, including the head and neck surgeon, medical oncologist and radiation oncologist, in addition to key support services like speech and swallow therapy and nutrition, all on the same day.
“It’s very patient-centric,” Liao said. “The care team can communicate and work closely together to make complex decisions and deliver multidisciplinary care plans, which may include leading-edge therapies, clinical trials and advanced technologies such as proton beam radiation. This team approach is focused on optimizing the care of our patients in order to provide the best outcomes.”
To learn more about proton therapy for head-and-neck cancers, check out our webpage.
Read more about our other head-and-neck cancer radiation specialists, Neil Panjwani, MD and Paul Riviere, MD.
Despite an incomplete understanding of how and why it works, Fred Hutch researchers are increasingly excited about the promise of a new type of radiation therapy (FLASH-RT) currently in pre-clinical trials that protects healthy tissue from the effects of radiation while destroying cancerous cells.
FLASH-RT refers to radiation that is administered extremely quickly to the site of a tumor, called ultra-high dose rate, or UHDR. Researchers discovered that by delivering radiation at very high dose rates — more than 40 Gy per second compared to the average rate of 0.5 to 5 Gy per minute — ‘the FLASH effect’ occurs: healthy tissues surrounding a tumor are protected from the toxic effects of radiation.
Radiation harms all cells, but healthy tissue recovers while cancerous tissue dies. That’s why radiation has remained a mainstay in cancer care, especially when radiation to healthy tissue can be minimized, such as with proton therapy and other treatments.
With FLASH-RT, the difference between the normal tissue’s response to radiation (healing) and cancerous tissue’s response (dying) is even larger.
Omar Mian, MD, PhD, who heads one of Fred Hutch’s research labs in the Human Biology Division, studies the mechanisms of radiation sensitivity of cells. He is excited about FLASH-RT.
“We are trying to understand the widened gap in response between healthy and cancerous tissue at the molecular level,” he said. “We see this astonishing effect, and we want to understand the underlying causes. We’re asking how FLASH radiation affects certain tissues and cells differently, at the level of proteins and DNA, for example. This will help us determine which cancers would benefit most from this treatment and what doses are optimal.”
FLASH-RT in itself does not kill cancer better than non-FLASH radiation, Mian said, but it is better at protecting healthy tissue. No one is exactly sure why it works, he said, but it may allow providers to escalate the dose for more effective tumor control, which is not currently feasible due to potential side effects.
Fred Hutch researchers are currently in a pre-clinical phase with the goal of human trials in the future.
Fred Hutch is also one of only a few cancer centers studying FLASH-RT using protons, which have a long track record of safety and can reach the UHDR necessary to achieve the FLASH effect. As heavy, subatomic particles, protons can be sped up to nearly the speed of light. Pencil beam scanning using protons also allows physicians to even more narrowly target the tumor when delivering radiation.
Radiation oncology resident Felicia Lew, MD, DVM, is currently studying FLASH-RT with Mian. A veterinary medical oncologist before she earned her medical degree, Lew is now designing a pre-clinical trial that will study how dogs with cancer respond when treated with FLASH-RT.
“We believe that FLASH-RT can address an unmet medical need in the vet community,” Lew said. “This trial would be therapeutic in nature, meaning pets with cancer would be treated with the intent to cure and also be evaluated and treated for side effects. Any advances we make will help future pets and findings will help us learn for trials on humans and larger mammals.”
Owners of dogs with aggressive tumors enroll them in the trial, much as humans enroll in cancer clinical trials; Fred Hutch does not use research dogs.
Fred Hutch researchers are also separately studying higher doses of FLASH-RT in mice with brain cancers, and the potential for more than one dose.
“There are limitations,” said Mian. “The technologies that shape radiation to match irregular tumors also slow the delivery rate of radiationm so for now we can’t use these technologies with FLASH-RT. Also, FLASH-RT field sizes are relatively small, so very large tumors are also not ideal. Radiation therapy is often split into smaller doses delivered over days and weeks, but to get the tissue-sparing effect of FLASH, delivery must be extremely quick. That’s why we want to study whether we can deliver FLASH with multiple doses over a period of days, or if this will negate the positive response.”
In the long term, Mian hopes that FLASH-RT can be an option to treat tumors resistant to radiation or cases of reirradiation, as well as tumors near sensitive organs that FLASH might spare.
“Our goal is to ensure FLASH-RT is both practical and safe,” Mian said. “While we are moving in the right direction, achieving clinical breakthroughs requires research and patience.”
Radiation oncologist Ben Li, MD, MBA, treats breast cancer as well as brain tumors at Fred Hutch Cancer Center.
The eldest son of two primary care physicians, he grew up wanting to help others and hoped that his life’s work would have a global impact. He first pursued a degree in Physics and Chemistry from Harvard but discovered he missed the human element in his studies.
While undergoing treatment for anemia, Li had a realization: if he went into medicine, he could help people individually and create a chain reaction of positive influence.
“If you are going to be in a career for your entire life, what’s not going to get old is the people,” he said. “Everyone is unique. In radiation oncology you can make a big difference in their lives, and you also get to know each one of them.”
Li moved to Seattle in 2023 to join UW Medicine and Fred Hutch. It was the culture of collaboration that drew him here, as well as the global oncology programs in hematology and medical oncology, which the two organizations were looking to expand. Li was excited to be able to add radiation oncology to the global program and help underserved populations.
“The properties of radiation — photons, electrons, protons, et cetera — are the same no matter where you are, and so is their potential for treating cancer,” Li said. “Once you have the equipment, radiation oncology is often a great way to treat cancer, so empowering practices and making sure each radiation center works to the best of its capabilities can make a huge difference.”
To that end, Li leads an outreach and education program for radiation oncologists around the world to share new research, best practices and insights with each other. He has gathered support from more than 300 volunteer professionals to help improve radiotherapy practices for thousands of clinics around the world through a non-profit organization, Rayos Contra Cancer, making a global difference just as he’d hoped.
Li said his local perspective shapes his global efforts.
“We are lucky to have access to many of the best treatment modalities here at Fred Hutch, including proton therapy,” said Li. “As a physician, having options to best treat your patient is a privilege. If you have a patient who can benefit but they don’t have access, it’s heartbreaking.”
Outside of work, Li is a long-distance runner. He began running in high school, and continued through undergraduate and medical school, despite a period of profound iron deficiency anemia. Li is a member of Club Northwest, an elite running club in Seattle, which recently placed third in the national championships.
“You become what you practice, and you achieve what you prioritize,” said Li. “I tried to run every day even during my residency, which is the most insane time during medical schooling. I run races ranging from a half mile up to marathon distances, and my next goal is to qualify for the 2028 Olympic trials. To do that, I have to run a marathon in 2 hours and 16 minutes. I just need to shave off four minutes!”
Li recently ran 2:20:02 at the 2025 California International Marathon, placing first in his age group.
Running, he said, has helped him become the best version of himself, while giving him the stamina to help others. Setting and achieving goals allows him to be a positive coach for patients, and to motivate them through treatment.
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