Oncologist Hirohiko Tsujii talks about his work to Carolyn Lee.
Hirohiko Tsujii is director of the Research Center for Charged Particle Therapy, at the National Institute of Radiological Sciences (NIRS), in Chiba, Japan. He is known internationally for his work on treating cancer with carbon ions and is the first doctor to have treated patients using hadron therapy in a clinical environment. Japan is the first country to have a heavy-ion accelerator for medical purposes, built as part of a national 10-year strategy for cancer control. Since the Heavy Ion Medical Accelerator in Chiba (HIMAC) opened in 1994, the facility has provided treatment for more than 3000 patients with various cancers and has resulted in a significant increase in the number of survivors after treatment. Recently, the Committee of Senior Officials for Scientific and Technical Research (COST) and the European Network for Research in Light-Ion Hadron Therapy (ENLIGHT) invited Tsujii as guest of honour at the COST-ENLIGHT workshop on hadron therapy, held at CERN on 3–4 May.
Tsujii has three decades of experience in developing hadron therapy as a novel treatment for cancer. The deposited radiation dose for charged hadrons (protons and heavier ions) rises to a peak near the end of the particle’s range. The aim with hadron therapy is to use this effect to irradiate tumours, while sparing healthy tissue better than with X-rays. “Before working at NIRS, I was involved with proton-beam therapy at Tsukuba University,” he says. Tsujii also worked on research for pion treatment in the US, where the use of pions in cancer therapy was pioneered at Los Alamos in co-operation with New Mexico University. “The biological effect was not as high as expected and it was also claimed that pions could produce a very nice distribution in the human body,” he explains. “However, compared with hadron therapy, such as with protons or carbon ions, the distribution was not that good. Eventually it was decided to stop the study that used pions.”
Japan is a major pioneer of hadron therapy. Each year, 650,000 people in the country are diagnosed with cancer and the number is expected to increase to 840,000 by 2020. Deep-seated tumours are the most challenging type of cancer and Tsujii has developed a special interest in treating them. Tumours found in the lungs, cervix, head and neck, liver, prostate, or bone and soft tissue, for example, are often treated with hadron therapy as they can be difficult to operate on and conventional radiotherapy is not always as effective.
“The reason we at NIRS decided to use carbon ions rather than protons is that it is the most balanced particle. It has the property of providing a constant treatment to the tumour and also has a higher biological effect on the tumour,” explains Tsujii. This means that the carbon-ion beam can be more focused on the tumour, resulting in the greatest cell damage to the tumour with less injury to the surrounding healthy tissue. “Of course, as the mass of the particle increases there is a higher relative biological effectiveness (RBE). But the ratio of RBE between the peak to plateau [before the peak] gets worse when using a particle with a higher mass. Therefore, when considering the biological effect, the carbon ion is the most balanced.”
After treating more than 3000 patients, Tsujii feels that it has been a good decision to use carbon ions in cancer treatment. “There was a lot of discussion in deciding what particle would be best. We decided to choose carbon ions and, for the time being, I am satisfied with this decision.” It took several years before coming to the optimum level of treatment with carbon ions. The local control for almost all types of tumours is 80–90%, and after choosing the optimal level of treatment the local control is expected to be more than 90%.
“Another point that I want to focus on is the use of ‘hypofractionated’ radiotherapy,” says Tsujii. A patient treated with photons – X-ray treatment – will, on average, require about 30–40 fractions (doses) over 6–7 weeks. With carbon ions, the treatment can be given in a single day (just one dose or fraction) for stage I lung cancer while cervical and prostrate cancer or other large tumours require only 16–20 fractions against around 40 fractions using conventional treatment. “It is important to note that there is a minimal toxicity to healthy cells. At the beginning we had some severe toxicity, but we analysed the treatment and techniques, and completely overcame the problem we had when we initially started the studies.”
As chair of the Particle Therapy Co-operative Group, an international group that coordinates all hadron therapy (such as protons and carbon ions), Tsujii sees the future development of carbon-ion therapy as the more popular choice for oncologists. Even the name of this group suggests the changes taking place. Once the Society for Proton Beam Therapy, the name now reflects increased development in high-energy radiation with carbon ions.
“I believe that many parts of radiotherapy will be replaced by carbon therapy – it is just simpler in terms of smaller fractions to apply to the patient, compared with photons. It is a rather complicated procedure with carbon ions, but as each part of the procedure is established, once it is decided, the necessary technique is fixed. This means that we can apply the more reliable technique to the patient’s treatment,” says Tsujii.
For small tumours, the results with carbon ions or photons May be similar, such as in early-stage lung cancer, where the tumour is smaller than 3 cm in diameter. If the tumour is larger, then carbon ions prove to be the better treatment. “We are especially interested in the treatment of tumours in the pelvis or spinal area, which are often difficult to treat with surgery, and we have focused on treating bone and soft-tissue sarcoma – large tumours of 10–15 cm diameter – and we are very satisfied with the improved local control and longer survival rates,” says Tsujii.
Tsujii has not seen a single case of radiation-induced cancer among the patients treated since starting the carbon-ion treatment for cancer 13 years ago. There is a possibility of some cancer being induced by carbon-ion irradiation, but the distribution close to the target area is much better than in traditional treatment. However, the risks of developing radiation-induced cancer are probably similar for both treatments.
The cost of building these kinds of facilities is something that many governments are considering, including Germany and Italy (CERN Courier December 2006 p17). Japan has started a new carbon-ion therapy facility and two proton therapy facilities at a cost of around €100 m, while In Germany and Italy, new facilities with dual capabilities for using carbon ions and protons are expected to open in 2008, at a cost of €90 m each. Tsjuii’s pioneering work seems certain to be expanded to other parts of the world.
