Since the first patients with cancer were treated with carbon ion particle beam therapy in 1994 in Japan, additional facilities have been built so that as of February 2019, there are 7 carbon therapy and 6 proton and carbon facilities worldwide. Of these, Hitachi has 4 carbon and 1 proton and carbon facility in the installed base. Thus far, Japan has the most (6) carbon capable facilities, followed by China (3), Germany (2), Italy (1) and Austria (1). In the United States, several institutions have expressed interest in developing carbon therapy programs and more carbon facilities are being developed worldwide.
High energy beams of carbon ions have the properties of depositing very little energy in tissues upon entrance into the body and along their path, while forming a very high local dose deposition known as the Bragg Peak inside the defined target volume.
These physical properties result in exquisite dose distributions, similar to those of protons. Carbon-ion radiotherapy is notable for creating more lethal damage to DNA in tumor cells, making it effective in killing tumors that are resistant to traditional therapies. In addition, the reduced dose to non-targeted tissues results in significantly lower normal tissue toxicity and reduced risk of radiation-induced malignancies.
Carbon ions have another physical advantage in comparison to photons and protons in terms of how rapidly the dose falls off at beam edges (penumbra). At tumor depths beyond 7cm the penumbra is larger than 1cm for photons and even larger for protons, while the carbon ion beam fall-off is below a couple of mm even for deep-seated tumors. This allows placing the lateral edge of the carbon ion beam in close proximity to critical organs.
In addition to the physical advantages, carbon ions exhibit a biological advantage over photons and protons. Their relative biological effectiveness (RBE) is relatively low and close to that of photons or protons in the entrance region of the body (where healthy tissue is located) but their RBE is high at the Bragg Peak which is located inside the tumor. RBE is related to linear energy transfer (LET), which is a measure of biological injury in radiotherapy. Carbon ions are high-LET radiation, and their RBE increases as they traverse tissue en route to the tumor.
The physical and biological advantages of carbon ion therapy relative to conventional X-ray therapy have long been of interest to radiation oncologists since more therapeutic dose can be deposited in the target at a reduced integral dose absorbed by uninvolved healthy tissues, while at the same time causing greater biological damage in the target with the same amount of deposited energy.
Some tumors have hypoxic, radioresistant regions that are difficult to treat with low-LET radiotherapy such as conventional X-rays. In these tumors, and in the cases of deep-seated or slow growing tumors, the higher RBE of carbon ions can be exploited for greater tumor control probability and lower risk of side effects.
Because photons associated with conventional X-ray radiotherapy deposit more dose upon entrance into the body and exhibit an exponential decrease of absorbed dose along their path, multiple entry directions are needed in order to spread out the unwanted upstream dose to a large volume of tissue. Carbon ions have a higher peak to plateau RBE ratio, therefore requiring fewer beam ports, which simplifies treatment plan design and shortens treatment duration.
Different types of radiation treatment cause different kinds of damage to the DNA in a tumor cell. X-ray photons (top arrow) cause fairly simple damage (purple area) that cancer cells can sometimes repair between treatments. Charged particles—particularly ions heavier than protons (bottom arrow)—cause more and more complex forms of damage, resulting in less repair and a more lethal effect on the tumor. Image: NASA
Owing to the unique physical and biological advantages of carbon ion beams, it has been demonstrated that higher doses per fraction (than used in conventional radiotherapy) can be administered to a broad spectrum of tumor sites and is well-tolerated by patients. Dose escalation using these highly potent carbon particle beams allows tumor-killing doses to be given in fewer treatments than are normally used in care episodes using photons or protons, known as hypofractionation. Lung and liver tumors have been treated in 1-2 sessions, and prostate/bone/soft tissue tumors have been treated in 16-20 sessions, making treatment courses much shorter and more convenient for patients. The safety and efficacy of hypofractionated carbon ion therapy has shown promising results for almost all tumor types in the first 13 clinical facilities. With another 6 carbon ion facilities under development and scheduled to open within the next 3-4 years, more clinical studies will be undertaken to study the tumor sites, types and conditions under which more patients will benefit from this powerful, localized treatment modality.