Yoshinori Hayakawa

Clinical results of fractionated proton therapy

PURPOSE Preliminary results of a multi-site Phase I-II clinical trial investigating the efficacy of high-energy proton beams in a wide variety of human malignancies are reported. METHODS AND MATERIALS Since 1983 proton radiotherapy using 250 MeV proton beams produced by a booster synchrotron of the National Laboratory for High Energy Physics has been carried out at Proton Medical Research Center, University of Tsukuba. As of September 1990, a total of 147 patients received a partial or full treatment with proton beams with curative intent; 92 patients (63%) were treated with proton beams alone and 55 patients (37%) with combined photon and proton beams. There were 91 males and the mean age was 61.8 years old. The follow-up observation period ranged from 10 to 97 months. With regard to a total tumor dose, nearly 80% of patients received 70 Gy or more and 53% received 80 Gy or more. While dose-fractionations used depended upon tumor sites, the large majority of patients received substantially high radiation doses in terms of larger total doses (> 70 Gy) and larger fraction sizes (> 2.5 Gy) than those traditionally used. This fractionation regimen has been used because of limited availability of the accelerator or a shortage of machine time (27-30 weeks/year, 3-3.5 hr/day), and also by the expectation that the superior dose distribution possible with protons will permit administration of high radiation doses without increasing morbidities. In connection with this, we have determined the target volume by setting margins around the tumor boundary as practically small as possible, ranging from 5 to 10 mm. RESULTS AND CONCLUSIONS The current trial has been based on a site and dose searching program, hence a wide variety of tumor sites including the aerodigestive organs has been treated. So far, our judgment is that proton therapy has proven of potential advantage in treatment of the lung, esophageal, liver, uterine cervix, prostate, and head and neck malignancies; and of possible value in treatment of high-grade gliomas, and gastric, urinary bladder, and pediatric tumors.

Multi-layer energy filter for realizing conformal irradiation in charged particle therapy

A new type of filter for charged particle radiotherapy is developed to reduce unwanted dose transfer to the normal tissues around a tumor. The new filter can make a static irradiation field where the width of the spread-out Bragg peak (SOBP) is two-dimensionally adjusted. That makes the field conformal to the tumor three-dimensionally. The filter is made of many layers produced by using stereolithography. The layer has a miniaturized structure that has geometrical similarity to the conventional ridge filter. Shapes of cone and pyramid are also usable for the unit-cell constructing the layer. The spread of the field in the depth direction is decided by the thickness of the filter, or by the number of layers. The experimental result of the irradiation using the ridge-type construction shows a good agreement with an estimate by the Monte Carlo calculation. By combining this technique with intensity modulation that has lateral position dependence, the conformal irradiation can be achieved by a simple procedure.

Waveform simulation based on 3D dose distribution for acoustic wave generated by proton beam irradiation

A pulsed proton beam is capable of generating an acoustic wave when it is absorbed by a medium. This phenomenon suggests that the acoustic waveform produced may well include information on the three-dimensional (3D) dose distribution of the proton beam. We simulated acoustic waveforms by using a transmission model based on the Green function and the 3D dose distribution. There was reasonable agreement between the calculated and measured results. The results obtained confirm that the acoustic waveform includes information on the dose distribution.

Phantom experiments for measuring elasticity of breast cancer by the echo technique

Breast cancer is more stiff compared with benign lesions. The aim of the experiment is to measure the elasticity by pressing the breast with a water bag and measuring the shape change by the echo technique. The ultrasound frequency was 8 MHz. Two kinds of phantoms were created. One is made of silicone rubber 50 mm in thickness and inside is a polymethyl-methacrylate (PMMA) cylinder of diameter 20 mm. The PMMA cylinder is mocking the cancer and is placed with the surface at 10 mm and 20 mm depths from each silicone rubber surface. Another phantom is made of gelatine of 30 weight percent to water instead of silicone rubber. The phantoms were placed between two PMMA plates and pressed by a balloon filled with water, which is connected to a vessel by a rubber tube. The height of the vessel can be adjusted to change the pressure of the balloon. The silicone rubber phantom was too hard to be deformed by water pressure. The gelatine phantom was deformed around the PMMA cylinder by water pressure of up to 3.4 kPa. The gelatine surface was deformed by gravity without water pressure. Apparent differences of gelatine surface deformation depending on different water pressure were confirmed from the echogram thus obtained.

Study on the effect of ultrasound condition upon suppression of cancer cells proliferation: Consideration of ultrasound exposure system with balloon

When an ultrasound wave is irradiated into water, active oxygen is generated together with a shock wave by a cavitation. We studied a method of cancer treatment using the cavitation and active oxygen generated by ultrasound exposure. In this study, an ultrasound exposure system using a balloon with an ultrasound horn was developed taking into clinical applications account. The cancer cells were induced apoptosis. Proliferation of cancer cells was suppressed by the developed ultrasound exposure system.

Conformal irradiation by proton beam scanning and multilayer energy filter

Using a new energy filter, three-dimensional conformal irradiation for proton therapy can be realized by monoenergetic beam scanning. It is a big advantage that the method does not necessitate energy scanning from the viewpoint of shortening the scanning time for cancer treatment of a moving organ. The new filter can yield an irradiation field where the width of the spread-out Bragg peak is adjusted to the target. Present work shows evidence of three-dimensional conformal irradiation by the new filter. Instead of the intensity modulation necessary for conformal irradiation by beam scanning, irradiation-time modulation is performed in scanning using constant beam current. As the result, a conformal field around a step-shaped virtual target in a solid phantom is realized by the filter.

Three-dimensional conformal irradiation with a multilayer energy filter for proton therapy

The first experimental evidence of three-dimensional conformal irradiation is performed by using a new type of filter developed for charged particle radiotherapy. The new filter can yield a static irradiation field where the width of the spread-out Bragg peak is adjusted to the target as a two-dimensional continuous function in the transverse plane. The filter is made of many layers produced by using stereolithography. In the filter, a structure with two regions with different shaped miniaturized ridges is adopted to get a flat dose profile on the spread-out peak. A conformal field around a spherical target is realized by a filter that has a shape corresponding to the outward form of the target.

Phantom and Human Experiments for Breast Cancer Detection by Ultrasound Transmission Technique

A new technique named the ultrasound transmission technique has been proposed by the authors. The idea was developed from the clinical findings that sound velocity in breast cancer is higher than in normal tissue by 49-90 m/s. Phantom experiments were conducted. Plexiglas (PMMA) plates 3 mm, 2 mm, or 1 mm thick were put into a cubic container (86 × 86 × 86 mm) filled with degassed water. In the echogram, the apparent distance between the back wall of the container and transducer was shortened because of the higher velocity of sound waves in plexiglas (2700 m/s) than degassed water (1500 m/s). This result showed the validity of the method. A breast to be examined can be sandwiched between a planar ultrasound transducer and reflector plate. Similar experiments were performed using a slice of pork (42 mm thick) instead of degassed water. The shortening of the reflector was apparent. The forearm of a human volunteer was also examined with plexiglas 2mm or 1 mm thick with similar results, suggesting the validity of the method.

HYPOTHESIS OF PIEZOELECTRICITY OF INNER CORE AS THE ORIGIN OF GEOMAGNETISM

A novel hypothesis is proposed that assumes piezoelectricity of the inner core as the origin of geomagnetism. By high pressure, an electric charge is created on the surface and at the center of the earth. Inner core rotation yields a magnetic field. From the intensity and direction of geomagnetism at the present time, the surface charge density of the inner core is assumed to be –2x10 -5 C/m 2 . The rotation axis of the inner core is inclined by 10.4 degrees from that of the mantle. The inner core rotates with the mantle rotation. The reason for this is thought to be the eddy currents induced in the outer core of electrically conductive fluid that rotates with the mantle.

Basic experiments of elastograpy for breast cancer by water bag pressing for obtaining elastic modulus

Measurement of elastic modulus by water bag pressing is under development in our laboratories. Basic experiments were performed by pressing breast cancer phantom by water bag. The phantom is made of 10 weight percent gelatin of the thickness of 40mm, in which Plexiglas cylinder of the diameter of 10mm, mimicking the cancer, was placed in 10mm and 20mm depth from each surface. Phantoms was placed on the desk and pressed by a balloon filled with water with the pressure. The height of the vessel of water was adjusted to change the pressure in the balloon. Deformation of the phantom was detected by ultrasound echo technique. Ultrasound frequency was 11MHz. The gelatin phantom (density of 1.03) was deformed around Plexiglas cylinder by water pressure of 1.1 to 2.4kPa. Apparent differences of gelatin surface deformation depending on different water pressure was confirmed from echogram thus obtained. The experimental results were simulated by computer using Finite Element Method (ANSYS 9.0) to confirm the experimental findings. The elastic modulus of gelatin phantom was compared to computer simulation using Finite Element Method (ANSYS 9.0) assuming Poisson ratio of gelatin of 0.49 and/or 0.45 to give the elastic modulus of gelatin to be 6kPa to 9kPa The apparent difference of elastic modulus seems to be due to stretching force of rubber of balloon containing water. Computer simulation by Finite Element Method were achieved for future experiments, showing simpler geometry is beneficial.