Specific Examples
The University of Tsukuba started proton clinical studies in 1983 using a synchrotron constructed for physics studies at the High Energy Accelerator Research Organization (KEK) (Figure-1). A total of 700 patients were treated at this facility from 1983 to 2000.
Figure-1
In 2000, a new in-house facility, called Proton Medical Research Center (PMRC), was constructed adjacent to the University Hospital. PMRC is equipped with a synchrotron and two rotating gantries. Clinical treatment was started in September 2001 at this new facility　(Figure-2). The mission of this facility is to prove the clinical utility of proton beam therapy, to develop innovative treatment technologies and techniques, and to train personnel involved in particle radiotherapy.
Figure-2
PMRC focuses mainly on cancers commonly found in Japanese people, such as liver cancer, lung cancer, prostate cancer, esophageal cancer and brain or skull base tumors. Arterio-venous malformation of the brain is one example of the benign conditions treated in our facility. The content of the total approximately 3000 patients treated so far is shown in Figure-3.
Figure-3
Hepatocellular carcinoma
Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic function, and co-existing intercurrent diseases.
Hepatocellular Carcinoma with Portal Vein Tumor Thrombus
Proton radiation therapy is performed for hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombus (PVTT).
Treatment methods for HCC with PVTT are limited and controversial, and prognosis is usually extremely poor. Proton beam therapy for HCC with PVTT is both feasible and effective. Significant improvement in survival and local control for the patient is often shown.
Prostate cancer
There are variety of treatment methods against prostate cancer, including radiotherapy and surgery.
Proton radiation therapy is one of the most effective treatments with few side effects. Patient without metastasis would be a good candidate. One possible side effect is urinary frequency. Another is post-treatment rectal bleeding. Treatment can generally be performed as outpatient setting. In some cases, hormone therapy may be combined with proton radiation therapy.
Early Lung Cancer
Proton therapy is a safe and effective treatment for patients with non-small-cell lung cancer (NSCLC), especially those in the early stages.
Proton beam treatment reduces the burden on the healthy lung and heart compared to conventional radiation therapy, and could concentrate doses to the tumor area.
In one of our reports, the local control rate of early lung cancer was approximately 90%.
Carcinoma of the esophagus
In cases where surgery is not an option due to concomitant illness or elderly, radiotherapy is an effective alternative for this kind of cancer.
Esophageal cancer with no distant metastasis is targeted for treatment. According to the diagnostic results, it can be treated by combination X-ray, combination chemotherapy, and single proton radiotherapy.
Head and Neck cancers
Treatment of head and neck cancers greatly differs depending on the tumor origin, histopathological diagnosis, and the degree of disease progression. Historically, multidisciplinary treatment combined surgery, cytotoxic chemotherapy, and radiotherapy have been carried out for this disease entity. The importance of radiotherapy has been highlighted because it can preserve morphology and function of the organ.
Currently, nasal cancer, paranasal sinus cancer, external auditory canal cancer, parotid gland cancer, and submandibular gland cancer are targeted.
In cases without extensive metastasis, proton radiotherapy can be applicable.
Brain Tumors
Treatment of brain tumors may differ according to tissue types, grade of malignancy and location. Based on precise diagnosis, treatment generally consists of surgery, radiotherapy and chemotherapy. However, as it is sometimes difficult to achieve total surgical removal because of the extent or location of tumors, highly conformal radiotherapy is becoming an alternative treatment option. Especially, proton beam radiotherapy is increasingly drawing attention due to its physical advantage which allows high energy localization on tumors while preserving surrounding critical normal brain tissue. Thus, we have been applying proton beams not only to refractory malignant brain tumors such as glioblastoma but also to unresectable benign tumors such as skull base meningiomas.
So far, our results are favorable compared to those of conventional photon radiotherapy, and we are currently making further optimization of the treatment conditions.
Skull Base Tumors
Skull base tumors develop in the area around the junction of the skull and cervical vertebrae. In most cases, tumors are deep-seated and adjacent to or sometimes involve the cranial nerves, the brain stem and vital blood vessels. Therefore, surgical removal is often very difficult, particularly in cases of chordomas and chondrosarcomas which originate from the bone at the skull base. In these cases, radiotherapy is necessary to kill residual tumors and to prevent recurrence after surgical removal. Especially, proton beam radiotherapy is very efficient, because it is possible to increase the dose to the residual tumors while preserving normal brain tissue. Furthermore, it can be an alternative when surgery is not an option because of a high risk to benefit ratio.