This article originally ran in the February 2008 issue of DOTmed Business News

Proton therapy is an overnight sensation more than 50 years in the making.

It's been known for decades that protons are a better weapon against cancer than the X-ray photons used in conventional radiation therapy. However, the use of protons was strictly limited until recent advances in medical imaging allowed doctors to visualize and target the cancers more clearly to take advantage of the precision delivery of proton radiation.

Now that multi-slice CT scanners, high-powered MRI imaging and PET technologies are in widespread use, the potential for proton therapy efficacy and adoption expands tremendously. Think of protons as cancer-killing "smart bombs" that can be put to use only with effective guidance systems.

"In the early days of proton therapy there was no imaging or very poor imaging so you had a very precise weapon and no way of seeing where you were aiming it," says Bernt Nordin, President, IBA Particle Therapy, Inc., Jacksonville, FL. "Now with better imaging we can define the tumor shape and volume in three dimensions and know exactly where to treat, and more importantly, where not to treat to avoid complications."

What's more, medical imaging advances help spot cancer in the early stages when intervention does the most good.

Why use protons instead of (or in combination with) photons? Conventional photon particles irradiate tumors too, but photons travel right through the tumor, whereas protons can be aimed to remain inside the lesion to deliver their payload.

"Proton therapy allows us to beat the diseases that we couldn't using conventional radiation therapy techniques and equipment," said Susan Michaud, Co-Director of Radiation Therapy Services, Francis H. Burr Proton Therapy Center at Massachusetts General Hospital Cancer Center. "Using conventional treatment, you always end up treating normal tissues and organs. With protons we can provide a true conformal treatment to almost any area of the body and we can do that without treating normal tissues that will leave the patient with side effects," she says, noting the particular importance of that to pediatric patients.

"This is something that over the next couple of decades will be changing the field dramatically because you now have a tool that for the first time puts the radiation where you want it," explains Jerry Slater, M.D, Director of Radiation Oncology at Loma Linda University Medical Center. Slater's father James M. Slater, M.D. is a pioneer in the field who brought the technique into the hospital setting.

The clinical efficacy and promise of protons also portends its business prospects. While five foundational proton therapy centers are operational in the U.S. today (see sidebar), several more are in various stages of planning and development in anticipation of the expanding application for the life-saving power of protons.

An Unlimited Market

Proton therapy is the better mousetrap in radiation oncology. To date about 55,000 patients have received the treatment worldwide, according to the National Association for Proton Therapy, which promotes its use. While the predominant application has been for prostate cancer treatment, proton therapy's tissue-saving advantage is also critical in treating cancers of the brain, eye, lung, kidney and other sites.

Proton therapy can be used for "any localized cancer that radiation is used [for]," Dr. Slater says. "Prostate has been used a lot just because it's such a common disease. There are potentially hundreds of different cancers that will be using protons in the future." The therapy is also used to treat non-malignant conditions.

CIBC estimates that the proton therapy market will exceed $2 billion by 2010. The demand for cancer treatment is projected to be great and, in terms of supply, the U.S. doesn't have nearly enough proton therapy centers.

Let's do the math: About 1.4 million Americans receive a cancer diagnosis each year and about 800,000 receive radiation treatment in some form. A conservative estimate is that 20 percent of those patients or 160,000 would benefit from proton therapy. A four-room proton therapy center could probably treat about 1,500 patients yearly. That suggests a patient population to support more than 100 proton therapy centers.

However, each facility requires expansive physical plant size -- measured in football fields -- and significant investment, along with a partnership of clinical and engineering experts to build it. A proton therapy center today can cost in the range of $150 to $250 million, and that may be an estimate on the low side

The original proton therapy centers were built largely with government dollars. The unit at Loma Linda University Medical Center was funded by the institution, the U.S. Department of Energy, and the Adventist Church. Mass General's unit was funded by the institution and the NIH.

M.D. Anderson's proton therapy center is a for-profit model with many investors including Sanders Morris Harris (SMH), a Houston-based investment bank. Hitachi provided the equipment, debt financing and equity investment in their center. Other investors include local police and firefighter pension funds, and GE.

The University of Pennsylvania's center, under construction, was paid for by the institution. The University of Florida used tax-exempt bonds. Financing options vary widely and are tailored to the project from outright purchase to debt equity financing, leasing, fee-per-use rental, special purpose tax-exempt bonds, and other arrangements.

"Every transaction is different with the magnitude of the expense varying widely," said Jon W. Slater (also James' son), President and CEO, Optivus Proton Therapy Inc., San Bernadino, CA. "The preferred financing for most of the academic centers and a lot of smaller non-profits is to work with large financial firms to put together a bond financing device to limit the liability exposure of the hospital yet have them maintain full control of clinical operations." Optivus, the engineering firm that maintains and upgrades Loma Linda's center, is working on more than a half-dozen prospects for new proton therapy centers at U.S. sites.

The reality for health care organizations that want to offer proton therapy is that many years of planning and approvals, along with institutional, state and federal aid, plus private investment, may all be needed to bring a center to fruition.

But some new ideas are springing up in the private sector. A few innovators offer turnkey solutions so that physician groups or hospitals can get into the segment. One such business model comes from ProCure Treatment Centers, Inc.

"A proton project is a very capital intensive, very complex process. It is going to be beyond the wherewithal -- the staffing and financial capabilities--of larger doctor groups or community hospitals," says ProCure's CEO Hadley Ford. The company, staffed by technical experts in this esoteric field and backed by venture capital, builds the centers for its partners including radiation oncology groups and hospitals. ProCure has two centers in the works. Partners in their first site in Oklahoma City include two radiation oncology physician groups, and INTEGRIS Health, the state's largest non-profit health system. IBA, the leading proton therapy particle accelerator manufacturer, is providing its cyclotron for the project. Another ProCure site is planned in the western Chicago suburbs at Central DuPage Hospital.

ProCure handles the business end of gaining investment and running the entire project and facility, while partner physicians handle the clinical end. "It's a typical outsource model," Ford says. "It's not dissimilar from EDS or IBM installing a large computer system into your company. They own it and run it and man the help desks so that you can focus on what your business does best. We figure hospitals and doctors treat patients best. We build proton centers best so it's a good match."

Nordin says, "When a new technology comes, it's usually the large universities that are the early adopters and it takes time before this comes into community health care settings. ProCure is going to accelerate that spread of the benefits of proton therapy to more patients in more places.

A Few Specialized Players

Only a handful of companies provide major equipment for proton therapy, although more OEMs are getting involved with some supporting technologies and works in progress.

The main piece of equipment used in proton therapy is the sub-atomic particle accelerator, which comes in two designs: either a cyclotron or a synchrotron. Both use magnetic fields to accelerate the particles and focus the beam, although there are technical differences in the accelerator path and beam output. Synchrotrons are installed at Loma Linda and M.D. Anderson. Nearly all other U.S. sites have IBA cyclotrons including Mass General and the University of Florida; and at the forthcoming locations at the University of Pennsylvania and Hampton University, as well as Oklahoma.

IBA, headquartered in Belgium, offers its own scalable approach, working with ProCure and other equipment makers including Elekta, a market leader in linear accelerators, who brings IBA its know-how in workflow and information systems, patient immobilization, and other techniques and devices. Another IBA partner is CMS, experts in treatment and dose planning.

"The equipment is turnkey in the sense that we build it, ship, install, but we also service it so that for the hospital it's basically a push-button operation," said Nordin. "They never have to worry about all the complex technology behind the thick wall. They can bring in their patients and treat them as they would in conventional radiation therapy and not really notice much of a difference."

Varian Medical Systems, Palo Alto, California, is poised to become a major player. The company acquired ACCEL Instruments GmbH, which made cyclotrons in service in Switzerland and Germany. Varian is known for its treatment planning system and patient information management systems, and for its installed base of 5,000 linear accelerators used in photon therapy.

"The technologies are very complementary.... Our role isn't favoring one particular technology or another, our role is as a tool maker, to make all the clinical tools clinicians need because all cancer patients aren't the same," says Lester Boeh, Vice President of Emerging Technologies at Varian. "We have operations all over the world that we can leverage in terms of design, manufacturing, productization, installation, customer support, spare parts distribution, marketing... all that infrastructure already exists around the world."

The company's expertise in clinical workflow will prove useful as proton therapy continues to move from research environments to mainstream clinical settings. "We see a big opportunity to bring all of our skills and expertise in clinical workflow to proton therapy as we have been doing so successful in photon therapy-or radiation therapy-all these decades," Boeh says. Note that Varian also teams with GE on a position management system as part of GE's proton package for its CT scanners.

An interesting niche company in proton therapy is Still River Systems, Littleton, MA, which, in partnership with MIT, is developing a compact proton therapy system one-third the size of current systems. The design is driven by practical necessity rather than theory.

"We took a different approach. Why start with a physics experiment? Why not start with what people are doing today in radiation oncology?" says Lionel Bouchet, Director of Customer Service and Support for Still River Systems. "Although the particles are small you will always need large systems to accelerate [protons]-bigger than regular linear accelerators [used in photon therapy].... But cyclotrons (unlike synchrotrons) can be reduced in size by increasing the magnetic field." The first installation for the company will be at Barnes Jewish Hospital in St. Louis, MO, which reported its center will cost $20 million -- significantly less than others--and have a patient capacity of about 250 per year. Note that Accuray has partnered with Still River Systems to supply a robotic patient positioning system.

Other OEMs include Hitachi's Power and Industrial Division. The company acquired AccSys Technology, Inc., a world leader in the commercial supply of ion linear accelerator systems. TomoTherapy is the other equipment maker for this specialty, partnering with Lawrence Livermore National Laboratory on a prototype for a smaller, lower-cost system than now available. Siemens has works in progress and is exploring the next generation carbon ion approach to particle therapy.

Rounding out the manufacturers is Mitsubishi, which built two synchrotron systems in Japan.

A Promising Future

A New York Times article (12/26/07) put proton therapy in the public eye but raised concerns over costs. The fact that Medicare and aligned insurers pay for the treatment supports its value, although published research is scant since randomized clinical trials that withhold proton therapy would be unethical.

Most experts conclude that the technology in the past was limited only by the imaging equipment used in conjunction with treatment planning.

"As the imaging improves, we're now able to focus [protons therapy] better and better. We're just still on the very frontier of what it is potentially going to do," Dr. Slater says.

With the imaging problem solved only the issue of money stands in the way of more widespread adoption of proton therapy. New cyclotron designs and creative business models are providing more manageable and affordable options that may soon bring proton beam therapy to the masses, so to speak.

"It is going to be a big change for radiation oncology. I hope that places can get up and running and that many more centers open. I really think this is going to replace portions of conventional therapy in the next ten years," Michaud predicted. "As the public becomes more aware of proton therapy and the demand continues to grow, we as health care providers need to provide this latest technology. People count on us for that."

U.S. Proton Therapy Centers:
-James M. Slater, M.D. Proton Treatment and Research Center at Loma
Linda University Medical Center
-Francis H. Burr Proton Therapy Center at Massachusetts General Hospital Cancer Center
-The Proton Therapy Center at M. D. Anderson Cancer Center
-Midwest Proton Therapy Institute, Bloomington, IN
-University of Florida Proton Therapy Institute
Proton Therapy Centers Planned or Under Construction:
-Hampton University (VA)
-University of Pennsylvania Medical Center
-Northern Illinois University Proton Treatment and Research Center (DuPage National Technology Park in West Chicago)
-Central DuPage Hospital/ProCure Treatment Center
-Oklahoma ProCure Treatment Center, Oklahoma City
-Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO

Patients with questions about proton therapy should call 1-800-PROTONS