The power of protons

Lindsay Schoenberger had suffered from headaches since she was a teenager. But in early 2023, when she was 36, things took a turn. She started having intense headaches every day, often accompanied by dizzy spells. "When I had a headache, I felt like I was in a bubble. I couldn't even think of simple words," she says. "It was impacting my entire life." Her doctor prescribed migraine medication, but it didn't help. Then an MRI revealed stage four glioblastoma, a serious brain cancer.

The next few weeks were a blur: travel from her home in Lancaster to Philadelphia for surgery to remove the tumor at the Hospital of the University of Pennsylvania, and meetings with oncologists to discuss a plan for chemotherapy and radiation that she could receive closer to home. In the whirlwind of information coming at her, Schoenberger remembers her radiation oncologist, Pamela Boimel, carefully describing a special kind of radiation that could help protect her brain from radiation side effects.

"When we treat a patient with X-rays, there is an entry dose where the radiation enters the body, and an exit dose where it leaves," explains Boimel, the director of proton therapy at Penn Medicine Lancaster General Health. Protons, by contrast, have no exit dose. That meant the beam could be tailored to stop precisely at the edge of Schoenberger's tumor, limiting the amount of radiation to the normal tissues in her brain. "By stopping the proton beam before it reaches healthy tissue beyond the tumor, we can decrease radiation side effects," Boimel says.

For the better part of a century, proton therapy has occupied a small niche within the field of radiation oncology. But over the last decade or so, demand for proton therapy has grown as evidence for its benefits has piled up. Much of that evidence traces back to Penn Medicine, which has played a leading role in championing proton therapy and moving the field forward.

A central hub for proton therapy

The Roberts Proton Therapy Center at Penn Medicine's Abramson Cancer Center opened in 2010 as the largest and busiest center in the world for proton therapy. That's still true today, with more than 100 patients coming for treatment each day. Over the past two years, Penn Medicine has also expanded access to the specialized therapy by opening proton centers at Penn Medicine Lancaster General Health in Lancaster, where Schoenberger was treated, and at Virtua Health in Voorhees, New Jersey. Collectively across these three centers, Penn Medicine recently surpassed 10,000 patients treated with proton therapy. Meanwhile, research teams across the University of Pennsylvania continue to push the boundaries of these positive particles.

In the early years of the Roberts Proton Therapy Center, the treatment was used in only a small number of cancers, says the center's leader, James Metz, chair and Henry K. Pancoast Professor of Radiation Oncology at the Perelman School of Medicine. "Over the past decade and a half, we've developed new techniques, new technologies, and new imaging modalities that allow us to deliver proton therapy more effectively," Metz says. "Now we can treat virtually every disease site with protons, and it's a very important tool in our toolbox."

Unlike conventional radiation therapy, which uses X-ray photons to kill cancer cells, proton therapy uses a beam of high-energy protons (positively charged particles) accelerated to two-thirds the speed of light. Though the treatments are similarly effective at killing tumors, protons offer some notable benefits. Most significantly, they can cause less damage to tissues surrounding a tumor. That makes protons especially valuable when treating cancers near vital organs like the heart or close to critical structures in the brain.

For her brain cancer, Schoenberger didn't hesitate when she learned she could have proton therapy at Lancaster General Health's Ann B. Barshinger Cancer Institute, just a 10-minute drive from her home. A year later, her headaches have eased and she's able to get back outside for bird-watching hikes, one of her favorite pastimes. "The fact that the proton beam could stop right where it was needed, instead of going straight through my brain, made it the clear way to go," she says. "It was the least invasive of all of my treatments, and I'm extremely grateful it was an option."

The pros in proton

Protons aren't a panacea. Depending on a tumor's location and a patient's anatomy, proton therapy may not offer an advantage over traditional radiation therapy. But for those who are good candidates, the benefits can be significant. "It can be particularly important in situations where we're treating near organs with very high sensitivity to radiation-or when a patient is getting chemotherapy at the same time," Metz says.

Metz and his colleagues demonstrated the benefits of using proton therapy alongside chemotherapy in a 2020 paper published in JAMA Oncology. The study showed that patients with locally advanced cancers had significantly lower risk of severe side effects when chemotherapy was combined with proton therapy versus traditional X-ray radiation. The researchers assessed side effects such as pain, difficulty breathing, trouble swallowing, and nausea, focusing on side effects severe enough that patients had to be hospitalized. They found that proton therapy reduced the relative risk of severe side effects by two-thirds, while cure rates for the two groups remained the same.

Proton therapy can also be helpful for reirradiating patients whose cancer has returned, says Graeme Williams, a Penn Medicine radiation oncologist who treats patients at the Penn Medicine | Virtua Health Proton Therapy Center in Voorhees, New Jersey. "When you treat an area of the body with radiation, it's as if the tissues remember. There's a certain amount of radiation the tissues can tolerate over their lifetime, at which point the risk of side effects increases substantially," he says. "Because protons allow us to spare tissues near the tumor, this treatment gives us an option when we don't have a safe way to offer traditional radiation therapy."

Protons are also an important tool for treating children. Human tissues are particularly sensitive to radiation when they're growing, and radiation can impair bone and muscle growth in kids. Because proton therapy is less damaging to healthy tissues, it's now the go-to choice for children who require radiation, Metz says. Through a partnership with Children's Hospital of Philadelphia (CHOP), specialty-trained pediatric radiation oncologists treat children at the Roberts Proton Therapy Center.

Mapping the future of proton therapy

Proton therapy was first used to treat cancer in the 1950s, but the technique was slow to gain momentum. Now the tide is turning as researchers hone the technology and expand its use. Radiation oncologists at the Roberts Proton Therapy Center were the first to integrate soft-tissue imaging into proton therapy, making the treatment even more precise. Penn Medicine experts were also at the forefront of a new approach known as pencil-beam scanning. With this technique, radiation oncologists use a proton beam a few millimeters wide-about the width of a pencil-to carefully target a tumor layer by layer, almost like painting by numbers. "Over the past 10 years, our ability to shape the proton beams has gotten so much better. We're able to use very sophisticated methods to shape the beam and deliver the treatment very precisely," Boimel says.

Penn Medicine is also one of the world's leading centers for proton research. In addition to its treatment rooms, the Roberts Proton Therapy Center features a dedicated research room outfitted for studying proton therapy in humans and animals. The center is also actively involved in clinical trials, including several national multisite trials currently underway. Many of those trials focus on comparing protons to traditional X-ray radiation for different cancer types, such as esophageal or breast cancer. The ongoing Radiotherapy Comparative Effectiveness (RadComp) Consortium Trial, for example, is the largest clinical trial to date to compare proton and photon therapy for patients with locally advanced breast cancer.

One important aim of RadComp and other proton trials is to follow patients over time to assess long-term outcomes, says Randall Oyer, who retired on June 30 as executive medical director of the Ann B. Barshinger Cancer Institute at Penn Medicine Lancaster General Health. "We can show definitively that proton beams have an advantage in sparing healthy tissue, and we know some treatment side effects are reduced. But proton therapy is new enough that we don't yet have the long-term data to determine whether there are differences in survival," Oyer says. Clinical trials are helping to answer those questions, he adds. "We try to learn from every patient we treat, and treat every patient according to what we've learned."

Meanwhile, experts across Penn Medicine are teaming up to study a promising new form of radiation therapy known as FLASH. A new paradigm for radiotherapy, FLASH delivers an entire course of radiation in just a few ultra-high doses lasting less than a second each. In recent years, Penn Medicine scientists have laid the groundwork for FLASH proton therapy in mouse models and veterinary studies, and they're preparing to launch human trials in the coming year.

Comprehensive training

Thanks in part to research findings from Penn Medicine, patient demand for proton therapy is growing. But specialized training is necessary to administer the treatment, which has limited the growth of proton centers. To meet that need, Penn Medicine has established itself as a proton training ground to prepare professionals worldwide in all aspects of providing patients with proton therapy-not just the medical care, but also operational and infrastructure aspects of running a center.

Through a comprehensive training program, Penn Medicine educates providers including radiation oncologists, medical physicists, medical dosimetrists, and radiation therapists through web-based training and on-site programs in Philadelphia and Lancaster. Since 2014, the Roberts Proton Therapy Center has hosted more than 350 health care professionals for on-site training and provided education to 18 proton centers outside the U.S., in countries such as Poland, Spain, Singapore, China, and India. The curriculum can be customized to meet the needs of visiting trainees, who come from a variety of diverse backgrounds and education levels within the field of radiation oncology. Last year, the center formalized its educational offerings with the launch of the Penn Radiation Medicine Institute, a program to provide training and supportive services to proton centers around the world.

Such training initiatives are helping to grow the reach of proton therapy around the world. Still, few centers match the scale of Penn Medicine's program. Fewer than 50 proton centers are operating in the U.S., and most consist of a single treatment room, says Jeffrey Bradley, vice chair of Proton Therapy & Technology Development at Penn Medicine. The Roberts Proton Therapy Center features five treatment rooms and is one of only a handful of proton programs fully integrated into a National Cancer Institute-designated comprehensive cancer center.

Bradley joined Penn's faculty in 2023, drawn by the size and reputation of the program's clinical and research programs in proton therapy. "So many of the technological advances in proton therapy were first implemented here at Penn, and we continue to be the leader in protons around the world," he says. "We're seeing more and more data to show that protons can offer an advantage, for many types of cancer. Having proton therapy available makes a big difference to the patients we serve."

This story originally ran in Penn Medicine Magazine.