Almost every day, a patient steps to the giant wind chime at the center of the UF Health Proton Therapy Institute lobby, grabs the large rope hanging from it and pulls, producing a deep, satisfying tone that echoes through the building.
They’re older men with prostate cancer and children with brain cancer. They have just completed weeks of treatments and can now return home to resume a normal life. Family, doctors, nurses and radiation therapists join in the celebration, which always includes smiles and tears.
In the 20 years since the institute opened on the UF Health campus in Jacksonville, thousands of cancer patients have rung that chime to celebrate the completion of their treatment, and Dr. Nancy Mendenhall, the founding medical director of the institute, says it never fails to inspire her.
“How could it not?” she says. “That’s what it’s all about.”
When UF committed to building the institute in the early 2000s, there was significant risk. Proton facilities were extraordinarily expensive, insurers questioned whether the added cost was justified, and relatively few patients had been treated nationwide. Success would depend on demonstrating that the technology could improve patients’ lives, not simply deliver radiation in a more sophisticated way.
But after treating 13,000 patients from all over the world, leading multiple large-scale clinical trials and publishing nearly 500 papers in the top journals, Mendenhall says the results speak for themselves.
“I think we’ve established beyond a shadow of a doubt that it’s extremely effective and very, very safe, and there is enormous promise that the long-term outcomes for all of these survivors of cancer will be better,” Mendenhall says. “I don’t think we get any insurance rejections now because of the claim that it’s experimental, which we did for the first 10 or 15 years.”
The front entrance to the UF Health Proton Therapy Institute in Jacksonville. This year marks the facility’s 20th anniversary.
Photons or Protons
Almost since the discovery of X-rays, or photons, in 1895, doctors saw the potential of radiation to treat cancers. But for most of the last 130 years, that treatment has come with significant collateral damage to healthy tissue surrounding a tumor.
The dose delivered by traditional X-rays starts high and gradually decreases as the radiation passes through the body, meaning healthy tissue located before and after the tumor is also exposed to enough radiation to increase the risk of short-term side effects like fatigue and skin irritation and longer-term side effects like cognitive deficits, lung scarring and urinary problems.
In the 1970s and ’80s, doctors began exploring the possibility of using a different form of radiation energy, protons, to achieve similar results but with fewer side effects.
Protons are charged atomic particles that have mass, so the distance they travel can be predicted and controlled. Because protons deposit most of their energy when they stop at a specific depth within the body, the area being treated for cancer receives the majority of the radiation dose, and healthy surrounding tissue receives little or no radiation.
Mendenhall had a little experience early in her career with proton therapy for a very select number of brain and eye cancers, but it wasn’t until researchers from Loma Linda University in California, which had opened the first proton treatment facility in the United States in 1994, published a paper in 1998 about their success treating prostate cancer that she fully appreciated the potential.
“When I read that 1998 paper, I thought, ‘Of course you could use protons in prostate cancer, and by the way, anything else that we do with radiation,’” she says. “So I decided I just had to bring it to the attention of our dean.”
Mendenhall says “the stars aligned” because the leadership in the UF College of Medicine immediately grasped the significance of the new technology and committed the college to pursuing a facility. Ultimately, the $125 million facility was funded through state grants, municipal bonds and private donations.
Today, the institute in Jacksonville is one of the world’s leading proton treatment centers and the largest of its kind in the Southeast. Following a $44 million expansion completed in 2023, the 108,000-square-foot facility includes five treatment rooms, treats approximately 100 patients each day and employs more than 125 staff members.
Saving Children
Dr. Daniel Indelicato was completing his residency in radiation oncology at the UF College of Medicine just as the Proton Therapy Institute was rising in Jacksonville.
“I literally got to see this place grow from a hole in the ground up,” Indelicato says. “I knew I wanted to do pediatrics, and I also knew that this proton technology could be very, very important in pediatric radiotherapy, so I got exceptionally lucky that I came out of training at the exact time that there was this new opportunity in our field and at the University of Florida.”
Dr. Danny, as he is known by patients and staff alike, joined the team straight out of residency and today directs UF’s pediatric radiotherapy program.
“At first, when we were the only proton center in the Southeast, when we were one of four in the country, it was very understandable for a lot of pediatric patients to come through the door because there weren’t many other options,” he says.
But as more proton centers opened around the country and internationally, Indelicato expected demand at UF to slow. It hasn’t.
“It turns out that families and patients aren’t just coming for the proton therapy. That’s crystal clear now because they have 45 other places they can go in the United States. They have another 50 places they can go outside of the United States,” he says.
But for patients and families facing one of the most frightening moments of their lives, how the treatment is managed is as important as the technology.
“They’re coming to the University of Florida for something beyond just the technology,” Indelicato says. “They’re coming for the entire comprehensive experience that patients and families have, from the medical expertise in rare tumors to the culture of care that we’ve built over the past two decades.”
A Family Finds Hope
One of those families was the Mulhollands.
Mollie Mulholland was 2 years old when doctors diagnosed her with rhabdomyosarcoma, a rare tumor located near her eye. The recommended treatment combined chemotherapy and radiation. Because of the tumor’s location, proton therapy offered the possibility of delivering an effective dose while reducing the severity of side effects to nearby healthy tissue.
In 2018, Mollie’s parents, Fiona and Declan Mulholland, temporarily relocated their family from Northern Ireland to Jacksonville for nine weeks. Mollie underwent 5 1/2 weeks of proton therapy while also receiving chemotherapy.
“It’s hard to have hope in the middle of a storm like the cancer diagnosis of your child. However, proton therapy was the key to Mollie’s survival. We got the best treatment available to her,” her parents said during a follow-up visit to Jacksonville in 2023.
The family’s experience also illustrated what Indelicato means by a comprehensive culture of care. Radiation therapists greeted Mollie in the treatment room with her favorite song from Disney’s Frozen to help calm her anxious thoughts and feelings. While Mollie was in treatment, her sister Grace did arts and crafts in the lobby with the artist-in-residence.
“They took an experience that was traumatic for all of us and delivered it in a fun way,” Declan says. “The team truly made this a family-friendly experience.”
Indelicato is a passionate advocate for this comprehensive approach, which includes not just doctors, nurses and radiation therapists, but child life specialists and social workers. It’s not just new technology, but pediatric-themed spaces and a wide range of programming matched to each patient’s developmental stage.
“Although these efforts are more abstract than a new cyclotron or medical device, I have come to believe the care environment is every bit as important to our mission in caring for children with cancer,” Indelicato says.
Because doctors are aiming for millimeter accuracy, patients must stay extremely still during treatments, which can be hard for a child.
“If a child can’t stay still, we have to put them to sleep with anesthesia each day for six weeks. And there’s some kids where that’s absolutely necessary, and that’s what we do because it’s that important,” Indelicato says. “But if we can avoid it, it makes a major difference for that patient’s treatment course: They don’t need the anesthesia drugs each day, they can wake up and have breakfast, we have flexibility in the scheduling of their treatment, etc.
“But it also is a cost issue,” he continues. “By hiring a child life specialist who can help get a 6-year-old through treatment without needing anesthesia, not only do you have all those quality-of-life benefits that I’ve just described, but you also save the healthcare system hundreds of thousands of dollars a year.”
In fact, a UF medical student recently published a paper estimating that for a center with 100 patients under treatment per year, a full-time child life specialist in pediatric radiation who works with young patients to teach them how to relax and keep still, can save the healthcare system more than $700,000.
“It’s a win-win,” Indelicato says. “It’s better for the patients, and it’s better for the economics.”
Prostate Power
From the beginning, Mendenhall knew that treating prostate cancer was going to be a major part of the institute’s mission, as it had been at Loma Linda.
“We expected maybe 15 or 20% of our population would be prostate patients, but the men who had been treated at Loma Linda knew fundamentally that their quality of life was better, and they told all their friends,” she says. “From day one, we had enormous demand from prostate cancer patients from all over the country, and now we’ve treated over 7,000 prostate cancer patients.”
Mendenhall says the high volume of prostate cancer patients at UF, and now at other proton facilities around the country, has enabled more statistically valid clinical trials comparing the efficacy of photon and proton treatment and the development of new approaches that protect adjacent organs and reduce side effects.
In 2017, Mendenhall received an $11.9 million grant from the Patient-Centered Outcomes Research Institute to lead a national study designed to directly compare proton therapy and conventional radiation therapy for prostate cancer. The COMPPARE study has enrolled more than 2,500 men at 51 centers nationwide and continues to collect data on treatment decisions, cure rates, quality of life and side effects.
Initial results reported earlier this year found no significant differences between proton and photon radiation therapy in cure rates and quality of life, reaffirming Mendenhall’s belief that proton can become the “standard of care” for most prostate cancers. But Mendenhall also says the risk of radiation-induced secondary cancers and other late-onset side effects may not become evident until five years or more after treatment.
“These are three-year outcomes that we’re reporting,” she says. “I suspect that as we get more data at five years, the differences will start to appear.”
The Next 20 Years
Both Mendenhall and Indelicato say artificial intelligence is already having a significant impact on their field, and they welcome UF’s new AI-focused Jacksonville campus just down the road from the institute as a place to develop new partnerships.
“UF investing in a new campus right down the street from us is such a great opportunity,” Indelicato says. “It’s fantastic for the city of Jacksonville and it’s fantastic for the Proton Therapy Institute.”
As a specialty built on advanced technology and sophisticated treatment planning, radiation oncology is particularly well positioned to benefit from new computational capabilities, Indelicato says.
“I use it in my job probably every day, already,” he says. “It really helps with decision-making when you have large volumes of data to sort through.”
Mendenhall says that while AI is not yet used to define cancer targets for treatment, it is helping physicians complete some of the most time-consuming aspects of treatment planning, like mapping surrounding organs on hundreds of CT scans.
“I recall a pediatric cancer case in which a resident spent 21 hours creating an initial set of contours for a single treatment plan,” Mendenhall says. “AI programs trained to recognize the bladder, rectum, femurs, lung tissue, heart and numerous normal tissues are helping to eliminate much of that burden, allowing clinicians to focus more attention on care decisions and patient outcomes.”
Researchers are also exploring AI’s potential to analyze millions of data points across thousands of cases to predict how certain patients will respond to treatment. Mendenhall and her colleagues are developing studies that use data from prostate cancer patients, genetic profiles and radiation dose information to identify which patients may need more aggressive therapies or alternative approaches.
“We’re all interested in predictive outcomes because if we can identify in advance which patients may not do well and need another approach or more aggressive therapy, that will be very helpful,” she says.
Indelicato believes UF holds a unique advantage in developing future AI applications because of the depth of its clinical data. The radiation oncology department has tracked patient outcomes for decades and built research infrastructure that links treatment information with long-term results. Pediatric proton therapy is a relatively rare field, and many institutions lack the patient volume and follow-up data necessary to create reliable AI models.
“The quality of an AI model depends on inputs,” Indelicato says. “We’ve treated 2,500 patients. I think we at the University of Florida are better positioned than anybody else for the inputs.”
He adds that all that patient outcomes data, including information from both proton therapy and conventional radiation treatments, gives UF an exceptional foundation for building AI tools that can improve care for future patients.
“It will never be a totally automated procedure, but there is the expectation that it will help us with treatment planning, which is really a manual, iterative, laborious part of the work, requiring human oversight to assure safety and quality,” Mendenhall says.
The Next Generation
Patient care and research are two pillars of the institute’s mission. Education is the third.
Over the past two decades, faculty and staff have educated physicians, physicists, dosimetrists and radiation therapists who now lead programs across the United States and around the world. As proton therapy expanded nationally, many of the institute’s most experienced professionals were recruited to help launch new centers, extending UF’s influence far beyond Jacksonville.
“We’ve trained the medical directors, physics directors and physician directors for half the centers in the country,” Mendenhall says. “We’ve been able to have an impact that goes beyond the walls of this building and the patients we’ve treated directly here.”
Mendenhall notes that education has always been a core part of the institute’s academic mission. Residents from the University of Florida, Moffitt Cancer Center and Mayo Clinic rotate through the program each year, while one of the nation’s earliest pediatric proton therapy fellowships has trained specialists who now practice in Canada, Japan, England, Singapore and other countries.
“The impact of this place from an educational standpoint is global,” she says.
For Indelicato, one of the most rewarding aspects of the institute’s legacy is seeing former trainees take what they learned at UF and build programs of their own.
“When I go to these professional meetings and I see these radiation oncologists and physicists who trained here now running their own programs at other centers, it fulfills me,” he says. “The next generation, we’ve got to bring them up. We’ve got to let them see the value of the technology and then keep it growing.”
The institute’s training environment offers students and residents exposure to an unusually broad range of technologies and patient populations. Rather than learning a single treatment platform, trainees gain experience with proton therapy, conventional radiation treatments, brachytherapy and specialized pediatric care, all within one integrated program.
“These student radiation therapists, when they graduate and they’ve done a year of clinical rotations here, they are head and shoulders above their classmates,” says Bradlee Robbert, the institute’s director of operations.
Through partnerships with schools across the nation, Robbert says the institute helps prepare the next generation of radiation professionals while providing hands-on experience that few centers can match. The institute’s impact is measured not only by the patients it treats today, but also by the clinicians and scientists it prepares for tomorrow.
Going Home
When the Mulhollands returned to Jacksonville in April 2023, the news for then 7-year-old Mollie was good. Indelicato, one of the most experienced pediatric radiation oncologists in the treatment of rhabdomyosarcoma, told them her scans showed the residual tumor was stable.
The visit also allowed the family to reflect on the relationships they had formed with institute staff and the Jacksonville community.
“Jacksonville felt like home back in 2018,” Declan says. “But coming back, we realized that it was not just the city, but the people who cared for us that made it feel like home. Coming back felt like we were coming home because of the people.”
This writer understands what he means.
In 2019, after completing my own course of proton therapy at the institute, I walked to the center of the lobby and rang the chime, my wife by my side.
At the time, I wasn’t thinking about clinical trials, publication counts or the future of artificial intelligence. I wasn’t thinking about 20 years of research or the hundreds of people who helped transform proton therapy from a promising technology into a proven tool against cancer.
I was thinking about getting on with my life.
Over the past two decades, thousands of patients have pulled that rope. The Proton Therapy Institute has given them the opportunity to get on with their lives.
From left: Fiona, Mollie, Grace and Declan Mulholland
Sources
Nancy Mendenhall, M.D.
Medical Director and Professor
Department of Radiation Oncology
menden@shands.ufl.edu
Daniel J. Indelicato, M.D.
Professor and Associate Vice Chair
Department of Radiation Oncology
dindelic@ufl.edu
Bradlee Robbert
Director of Operations
brobbert@floridaproton.org
Related website:
https://www.floridaproton.org