In the next two years, UW Health, the health system associated with the University of Wisconsin, will be the first medical institution worldwide to clinically treat cancer patients sitting upright with proton therapy, using the Marie particle therapy system. Designed by Leo Cancer Care, the solution utilizes a rotating chair to allow the patient to sit in front of the proton beam, instead of lying down, creating a more comfortable body stance.

This naturally positions the heart, lungs, and other organs to reduce unnecessary radiation exposure, while allowing for more precise targeting of tumors. It also creates direct eye-to-eye contact between the patient and care team. Additionally, the scanner requires less space to install and reduces total cost of ownership, compared to other proton therapy systems.

“The significant innovation from Leo Cancer Care is the capacity to have a robotic upright positioning chair with six degrees of freedom that enables the chair to execute the movements that are necessary, rather than swing a big gantry around a patient to deliver the conformal beam,” radiation oncologist Dr. Paul Harari, chair of the department of human oncology at the UW School of Medicine and Public Health, told HCB News.

Several innovations like this are underway to not just improve the efficiency of proton therapy but expand its reach, accessibility, and affordability. HCB News sat down with Harari and other experts in the field to discuss these advancements, and how they are facilitating a greater ability to deliver optimal outcomes to cancer patients.

New innovations out today
About 20 years ago, the cost of setting up a proton therapy system was around $150 million. Today, most centers are paying $40 to $50 million, according to Harari. One reason has been a shift away from more expensive, traditional multiroom systems, to newer, single-room vaults.

The lower prices of these systems make building and the costs of infrastructure for a proton therapy facility more feasible, especially for smaller centers. These healthcare systems also usually have smaller volumes of cancer patients, which may justify investment in a single-room versus a multiroom system.

“The first- and second-generation proton centers were much more expensive. Several ended up going into bankruptcy because they couldn’t manage the business plan initially established. There is not nearly the same concern when dealing with just the single-room centers, which require fewer patients to be successful,” said Dr. Bradford Hoppe, medical director of particle therapy and professor of radiation oncology for Mayo Clinic Florida.

The technology is rapidly emerging with gantries and accelerators being designed in smaller sizes. Rotating chair systems with fixed beams may contribute to further cost savings.

These changes in size decrease infrastructure needs and in turn, expenses, says Dr. Steven Frank, executive director of the Particle Therapy Institute at the University of Texas MD Anderson Cancer Center. “We’re seeing the ability for more access to protons by lowering the cost of the development and the building size. It makes it more accessible not just to academic centers but hospitals in the community.”

Frank also says that as the technology becomes more sophisticated, it closes gaps associated with photon-based radiotherapy, optimizing outcomes and workflows. Advancements include faster and conformal beam delivery; motion management; intensity modulated proton therapy; ARC therapy; real-time tumor tracking; adaptive proton therapy with in-room CT on rails; surface imaging with alignment; and shrinking the spot sizes of beams.

Advanced proton planning techniques using LET optimization, which reduces dose to critical organs, and variable radiation biologic effectiveness (RBE) are being further developed to personalize individual proton treatments.

Matthew Palmer, president and COO of Legion Healthcare Partners, a company in Houston, Texas, that helps providers develop and operate proton therapy centers, says more advanced software developments have improved treatment planning for proton therapy. One example is the incorporation of dual-energy CT scans, which mimic proton characteristics better to allow doctors to reduce the treated volume around the tumor.

"The properties of the dual energy CT scan reduce the total volume that needs to be treated during the treatment planning process. This allows the physician to further reduce the radiation to nearby critical structures and healthy tissue, " he said.

Advanced particle therapies of the future
Progress is also being made with more advanced therapies, especially FLASH, which delivers full proton doses in a fraction of a second, reducing associated side effects even further. Cincinnati Children's/UC Health Proton Therapy Center in Ohio completed enrollment for the first clinical trial involving humans in October 2021. It included 10 patients with bone metastases in their arms and legs, and concluded in April 2022, with follow-up studies now underway to examine potential side effects and outcomes of the treatment.

Cincinnati Children's/UC Health Proton Therapy Center is a member of the FlashForward Consortium, an international group focused on preclinical research and advocacy for FLASH therapy. Formed in 2018 by Cincinnati Children’s, Maryland Proton Treatment Center, and radiation oncology vendor Varian, now a Siemens Healthineers company, the association is composed of nearly 30 members today that are conducting preclinical research and developing and sharing protocols for clinical implementation of the treatment.

Another group, The FLASHKNiFE Consortium, was launched in June by PMB, a subsidiary of industrial company Alcen, around the use of FLASH therapy with the FLASHKNiFE platform, an ultrahigh dose rate LINAC mounted on a mobile base. The solution has been tested in clinical applications for skin cancer treatment and intraoperative radiotherapy, and the FLASHKNiFE Consortium seeks to use it to treat tumors that are resistant to conventional radiotherapy.

“We can consolidate an entire course that goes over a number of weeks into a single or number of treatments. It’s the same tumor control, but with less toxicity compared to conventional radiation courses. It has the potential to really be a disruptor in radiation oncology,” said Dr. James Metz, chair of radiation oncology at Penn Medicine, a clinical and research entity that is made up of the University of Pennsylvania Health System and the Perelman School of Medicine at the University of Pennsylvania.

Another up-and-coming treatment is heavy carbon ion therapy, which uses carbon ions to destroy malignant cells and attack cancers resistant to X-ray radiation. While conformal and similar in effectiveness to protons, carbon ions are expected to cause more biological damage to tumor cells by breaking down their complex DNA double-strands.

In 2022, Mayo Clinic Florida broke ground on what will be the first heavy carbon ion therapy center in the U.S. at its Jacksonville campus. The provider has partnered with Hitachi, one of the few carbon manufacturers, to complete the $233 million building, which is expected to be operational and treating patients by 2025. It also will offer proton therapy treatment, and MR and CT imaging.

“It’s important for us to study the biological and clinical value and define it in terms of when particle therapy like heavy carbon ions should be used and in which patients; when proton therapy should be used; and when conventional X-rays should be used,” said Frank.

Expanding accessibility and affordability
As clinical trials around proton therapy continue to increase and collect more insights, coverage for indications is gradually expanding. Additionally, the American Society for Radiation Oncology (ASTRO) and the National Comprehensive Cancer Network (NCCN) have slowly incorporated more indications into their guidelines based on the growing evidence for proton therapy.

Palmer says payors utilize ASTRO and NCCN as references along with the body of scientific evidence for their coverage policies. As a result, payers are slowly increasing coverage for proton therapy for certain tumors.

"Based on our experience, successful prior authorization results for proton therapy can be achieved with effective techniques, patient specific rationales, supporting evidence, and clinical trial enrollment. Although these efforts help some patients access proton therapy, the pre-authorization process leads to unnecessary delays and creates significant burdens to providers and patients," he said.

Metz says that maintaining strong relationships with insurers, both national and local, as well as associations is important for expanding coverage, and that showing the full benefits that come with reduced toxicity, and how they contribute to better outcomes is essential.

“The data is continuing to mature. By doing that we’re going to continue to push the insurers hard,” he said. “It’s a combination of publishing data and continuing to get the education out there to patients, providers and insurers. Being out there and getting out there is the key.”

Increasing the reach and accessibility for proton therapy also hinges on the cost of the technology and infrastructure. Harari says that as building footprints and infrastructures for these centers continue to shrink, so too will costs associated with them.

“As the cost of construction decreases, the cost that a center has to put forth to bring a proton beam is less and less, and then that cost savings can be passed forward to the consumer,” he said.

Hoppe says that efforts to expand particle therapy research should extend to advanced therapies like FLASH and heavy carbon ions, as well. “Proton therapy is important for delivering FLASH therapy because proton systems can more easily deliver that ultra-high dose rate of radiation compared to photon accelerators. It won’t be prime-time anytime soon, but certainly having cyclotron-based proton therapy makes FLASH a much easier thing to deliver.”

Frank says that understanding the full potential of particle therapy and advanced treatments is necessary for personalizing care and determining who will gain the most from it.

"We want to advance proton and heavy ion therapy to cure patients that are currently
incurable, and reduce the side effects from treatment with existing therapies like conventional X-rays or chemotherapy, or in combination with surgery," he said.