Proton therapy used to be the next-generation cancer treatment that was larger than life and too expensive for any institution other than the most cutting-edge research hospital. Not anymore. This technology is still large and comes with a big price tag, but proton systems are becoming increasingly scalable and more affordable for most metropolitan cancer centers.

Following the 2014 American Society for Radiation Oncology (ASTRO) Annual Meeting held Sept. 14-17 at the Moscone Center in San Francisco, Molecular Imaging Insight caught up with two experts in proton therapy technology and policy, David Beyer, MD, ASTRO president-elect, and Sameer Keole, MD, vice chair of ASTRO’s government relations council and a radiation oncologist at the Mayo Clinic in Phoenix, to talk about how this state-of-the-art technology is changing. Some of the topics we covered include advancement of clinical trials, scalability, innovative image guidance and the emergence of an appropriate use model for proton therapy. 

Proton nation

There are currently 14 proton centers in operation in the U.S. alone. Average cost of a new center is about $235 million and profits can be as high as $50 million a year, according to a July 2014 review published in The Lancet Oncology.

Proton therapy was originally approved for use as a treatment of cancer in the late 1980s and was shortly thereafter covered by CMS for select applications in so-called eloquent areas of anatomy. What is different today is the sheer enormity of data that have been amassed and that continues to develop, and specifically comparison data between X-ray based therapy and protons that show how proton systems are as effective, if not superior to X-ray technologies for treating certain cancers.

One of these studies, published in the August 2014 The Lancet Oncology, revealed how treatment with charged particles such as proton therapy was superior than treatment with photons such as intensity-modulated radiation therapy (IMRT) for certain head and neck cancers. 

“I don’t practice in a center that does not have protons,” Beyer insists. The most common application of proton systems is for the treatment of prostate cancer, but just a few of the applications gaining support across the industry include pediatric cancers, melanoma of the eye and some blood cancers. “Those are things that we believe have some potential, either because we are able to give more radiation and cure more patients or able to give less radiation,” says Beyer. “We believe that these should be covered.”

Other clinical applications that have already made a lot of strides include lung cancers, head and neck cancers and sarcomas.

“We now have some very impressive clinical data,” says Keole. “Up until this point a lot of the data have been theoretical, but now we are starting to see the difference between X-rays and protons.”

Scaling things down in both size and price

Another major improvement in proton therapy is a reduction in cost and scalability of design. Where a full-blown proton center serving several treatment rooms might cost a couple hundred million to build, today there are single-room strategies that can cut those costs by three quarters to $25 million. This option could be the optimal choice for mid-range radiation oncology institutions in metropolitan cities.

“Proton therapy is to becoming attainable in medium sized markets,” comments Keole. “Not everybody can travel to Harvard or MD Anderson.”

The first installation of these junior proton centers went to Washington University in St. Louis. Another single room center with on-board CT guidance and pencil-beam scanning has been installed at the Willis-Knighton Cancer Center in Shreveport, La. Other systems have been in the works just over the past year, including a single room system in Japan.

“Before one was installed at Washington University it was something that everyone thought was unimaginable,” explains Beyer. “Now they are up and running and treating patients.”

For larger clinics, multi-room designs are still the desired design. Such centers are in the process of installation at the Mayo Clinics in both Rochester, Minn., and in Pheonix. Even so, careful study of health outcomes must precede any proliferation of technology, especially for such a large ticket item.

“We want to give proton therapy a fair shake,” adds Keole. “We have a window and it is very important that we all work together and provide proof of the benefits of proton therapy from institutions that deliver care, the national research institutions and the insurers to continue to support clinical trials that are testing the value of proton therapy.”

Some of the perks of the systems being installed in the past few years are state-of-the-art detectors and cone-beam CT volumetric imaging like the one in the Willis-Knighton Cancer Center in Louisiana. Keole estimated that this will become industry standard within 5 to 10 years.

Appropriate use of protons

ASTRO just recently put out a model policy on proton therapy to guide appropriate use across institutions. Areas where proton therapy has absolute reign and should be supported 100 percent by not just CMS but private insurers is in the case of ocular tumors and melanomas and tumors that are wrapped around the spinal cord and other eloquent areas of anatomy. But the clinical benefit is scattered far and wide beyond these conventional applications. What is needed, both Beyer and Keole agree, is coverage with evidence development across the board.

“We want more science to study what’s going to be better for our patients,” says Keole.

More phase III clinical trials are necessary in order to pull together an anthology of comprehensive data. A lot of phase II and some phase III data exists, but researchers need more to drive it home for better reimbursement across private insurers. An October 2014 analysis published in the Journal of the American College of Radiology figured a dismal 60 percent of pediatric patients were treated at a net loss to the treating institution (DOI: 10.1016/j.jacr.2014.04.004).

A phase II/III study that compares IMRT to proton therapy in the case of oropharyngeal cancer is currently underway at the MD Anderson Cancer Center in Houston, according to yet another review of proton therapy from the June 2014 issue of the International Journal of Radiation Oncology Biology Physics. Authors Emma B. Holiday, MD, and Steven J. Frank, MD, from the MD Anderson Center assert that such multi-center international trials may be impractical due in part to the types of cancers that proton centers treat and the difficulty in enrolling enough patients across multiple sites. An alternative means of validating proton therapy could be found in dose-volume histogram findings for head and neck cancer, dosimetric comparative planning studies and normal tissue complication probability (NTCP) models, all of which could be used to assess the real benefit of proton therapy by the numbers (DOI: 10.1016/j.ijrobp.2014.02.029).

“So much of what we do is driven by reimbursement,” says Beyer. “If treatment X is not covered, we have to rethink what we do.”

Struggling for reimbursement in the private sector

The U.S. Centers for Medicare & Medicaid Services (CMS) covers proton therapy rather liberally for those who are eligible. The problem is with private insurers that often deem proton therapy as an experimental therapy. But a therapy that was approved in the 1980s and reimbursed by CMS by the 1990s is well established, notes Keole. This is more a semantic game that insurers can play—a loophole that keeps them from being obligated to proton centers and patients. Even those insurers who do reimburse for proton therapy may stagger coverage levels between several plans.

“There are incredible variations between companies,” says Beyer. “And even within companies. You can get the top of the line plans and the bare-bones plans. There is pretty wide variation. Some may even cover in-patient care but not out-patient care. We have a messy system and some people like it that way.”

This is why compiling solid health outcomes for proton therapy is so important. It is also getting cheaper, which will provide added incentive to insurers to reimburse proton procedures more in line with linear accelerators, Beyer suggests. Proton therapy still accounts for a small portion of all radiation treatments and the most expensive per procedure, but they are becoming a more integrated instrument in radiological practice.

“Proton technology is big and complex and involves advanced physics and qualified people to operate these systems. It will always be a higher-end type of treatment at higher-end value.”