Heavy ion therapy — the most potent form of radiotherapy — may finally become available in the United States.
The irony is that it was first investigated in the United States, but decades later, it has still not reached the clinic. In contrast, it is being used elsewhere in the world. Clinics using this modality have sprung up in Japan, Germany, Italy and China, with more being planned or under construction in both Europe and Asia.
But initiatives are now under way to bring heavy ion therapy back home, as the National Cancer Institute (NCI) has already awarded two planning grants to establish the research components of a future facility based in the United States. Funding is also coming from the Department of Energy to research technology to develop accelerator and delivery systems related to heavy ion therapy.
The case for heavy ion radiation is outlined in a Viewpoint published in JAMA Oncology, coauthored by Arnold Pompos, PhD, and Hak Choy, MD, both from the University of Texas Southwestern Medical Center, Dallas, which has just received one of the two NCI planning grants. Coauthor on the article is Marco Durante, PhD, from the Trento Institute for Fundamental Physics and Applications, National Institute of Nuclear Physics, University of Trento, Italy.
Heavy ion beams are the most powerful form of radiotherapy and offer clinical, physical, and biological advantages over conventional photon and proton therapies, they write.
Charged particle therapy in general has advantages over conventional radiotherapy, the authors note, because it delivers energy far more selectively than x-rays do. This in turn allows for greater local control of the tumor and a lower probability of damage to surrounding healthy tissue.
The use of protons has made some headway, although its use lags far behind that of standard photon radiotherapy. Because protons carry an electrical charge, their physical properties are superior to x-rays, but the "scatter of protons in a lateral direction and the uncertainty in their physical range in tissue limit their precise delivery to a tumor target," the authors write.
However, ions that are heavier than protons, especially carbon ions, offer additional physical advantages over protons. Because of their increased mass, they have more limited scattering and are able to maintain their direction when aimed at a tumor.
Demonstrated Efficacy
Heavy ion therapy was originally pioneered between 1975 and 1992 at the Lawrence Berkeley National Laboratory, write Dr Pompos and colleagues. "However, oncologists and clinical scientists in the United States have not had access to this cancer care tool for nearly a quarter century," they note, whereas elsewhere — in Asia and Europe — this technology has been developed with national government support.
The most serious impediment to developing heavy ion therapy centers in the United States is the high cost involved in setting up new treatment centers, Dr Pompos and colleagues comment.
Another issue is that no comparative trials have demonstrated the efficacy of heavy ions compared with other modalities.
"There have been no randomized clinical trials to date that compare conventional or proton irradiation with carbon ion irradiation," Dr Pompos told Medscape Medical News.
Heavy ion radiation has been used the most extensively in Japan, where more than 8000 patients with cancer have been treated with carbon ions since 1994.
Ethics has also been a concern, as far as conducting comparative research. "The Japanese are very convinced about its benefits and they would find it unethical to offer proton or photon to patients where they believe carbon ions can offer more benefit," said Dr Pompos.
Clinical data from Japan have demonstrated that carbon ions are effective in treating various solid tumor types, including adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, and various types of sarcomas.
And as previously reported by Medscape Medical News, Japanese researchers have also reported that the modality is promising for patients with inoperable spinal tumors, who have not had access to this cancer care.
All of these malignancies are frequently resistant to conventional radiation therapy, Dr Pompos and colleagues comment.
"There are quite a few results from various disease sites the Japanese produced where they show the results, such as survival, local control, or toxicity, are better than other modalities," Dr Pompos explained. "One of the most prominent is for unresectable, locally advanced pancreatic cancer. But again, [there has been] no randomization, so it is difficult to interpret the results."
High Cost and Lack of Comparative Data
Proton beam therapy has been attacked as being too expensive, and except for a few specific indications, there is controversy over whether outcomes are better than with standard radiation therapy. High cost will also be an issue for heavy ions.
Dr Pompos and colleagues note that the cost of building a state-of-the-art heavy ion system that has the capacity to treat 1000 patients per year will be about twice as high as for a similarly sized proton center. But that cost, they emphasize, is lower than the development cost for a chemotherapeutic or biological agent.
The high cost is primarily due to the complexity of the system needed to reach deeply seated tumors, requiring a particle accelerator that measures approximately 20 m in diameter. "The circular beam with a diameter of approximately 5 mm needs to be magnetically steered both vertically and horizontally with submillimeter precision from a distance of approximately 2500 mm to 'paint' the tumor in 3 dimensions with the prescribed therapeutic radiation dose," they write.
Dr Pompos pointed out that the proponents of proton therapy made a mistake in that they didn't conduct comparative trials right from the beginning. "This has had huge consequences for today, and only now are a few trials starting to emerge," he said.
Speaking about his own institution, which is the recipient of one of the NCI planning grants to develop research proposals for a heavy ion center, Dr Pompos emphasized that "we would like to avoid this kind of start if we build the first heavy ion center in the US. Our philosophy is to put every patient on a trial and gather extremely solid clinical data."
But they do need support on the state and federal level to get the first one or two systems in place. "So we need to show the benefit, and then the market will take care of further spread and price reduction," he said.
Time for Access
Approached by Medscape Medical News for an independent comment, Nina Mayr, MD, professor and chair of the Department of Radiation Oncology at the University of Washington, Seattle, reiterated that the technology was developed in the United States but did not lead to accessible clinical care.
"We have seen several carbon ion centers being developed around the world. There was a large-scale effort in the US about 10 years ago at Ohio State University (OSU), and we saw this urgent need when I was at OSU," Dr Mayr said.
"I believe this recent effort was ultimately unsuccessful in the US, in part because government support was lacking, as particle therapy is a very expensive investment," she said. "Other particle therapy centers around the world frequently have large-scale state or federal support, while they are developed in conjunction with a major academic center."
Dr Mayr noted that there is a renewed interest in the technology and that there is an urgent need for the United States to develop a clinical particle therapy center. "This is needed for our cancer patients, and we have already fallen behind worldwide," she said. "I have seen patients treated with particle therapy, and it is an exceptional modality, where indicated. Similar in the protection of normal tissues to proton therapy, particle therapy, such as carbon ion therapy, is about three times more powerful against the cancer.
"Particle therapy should become part of our armamentarium against cancer here in the US," Dr Mayr added. "We are the leader and we developed it, so now our patients should have access to it."
The authors have disclosed no relevant financial relationships.
JAMA Oncol. 2016;2:1539-1540. Abstract
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Cite this: Time for 'Heavy Ion' Therapy to Come Home to the US? - Medscape - Feb 06, 2017.
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