Junichiro Tada

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.

Time resolved properties of acoustic pulses generated in water and in soft tissue by pulsed proton beam irradiation—A possibility of doses distribution monitoring in proton radiation therapy

Time-resolved acoustic pulses generated in water and in soft tissue by pulsed proton beam irradiation were observed. The spatial resolution of depth dose distribution in the clinically applied beam intensity is estimated about 3 mm by means of TOF measurement. The dependence of the acoustic signal intensity on the temperature of medium was examined. Proportionality of acoustic pulse intensity to absorbed dose per pulse was confirmed as well. These results suggest the possibility of clinical application to monitor dose distribution in the patients body during irradiation of pulsed proton beam.

Application of an imaging plate to dose distribution measurement of proton beam

Abstract The linearity between proton dose to photostimulated luminescence was maintained between 0.0 to 1.3 cGy. Proton depth dose distributions measured by photostimulated luminescence and by Si diode in water were proportional.

Acoustic Pulse Generation in Water by Pulsed Proton Beam Irradiation and its Possible Application to Radiation Therapy

Acoustic pulse generation in water irradiated by pulsed proton beam was observed. The dose rate of the beam was 0.05 Gy/pulse and 0.0025 Gy/pulse. A hydrophone sensitive to the acoustic frequency band between 0 to 300 kHz was used for detection. The detected acoustic pulse in water was qualitatively the same shape as the depth dose distribution of the proton beam, when the depth scale is divided by the sound velocity. The intensity of the generated acoustic pulse is believed to allow monitoring of the radiation dose distribution in patients irradiated by pulsed heavy charged particle beam.

Compensation for beam intensity fluctuation in determination of Pion, the ion‐recombination correction factor for ionization chambers, by the two‐voltage technique

We have developed a method of compensation for fluctuations in beam intensity that may occur during measurement of Pion, the ion-recombination correction factor, by the two-voltage technique. The method requires signals proportional to beam intensity during measurement. We used a parallel-plate ionization chamber, whose Pion was known, and a vacuum chamber to obtain signals that were proportional to the beam intensity. Experiments were conducted using pulsed proton beam providing doses that ranged from 0.16 to 0.01 cGy/pulse. The value of Pion of a thimble ionization chamber was measured. With these measurements, the validity of the method which we proposed for pulsed beam was verified experimentally.

Characteristics of proton beams after field shaping at PMRC.

The proton irradiation control system was developed for cancer radiotherapy at the Proton Medical Research Center, with the extension of a beam line connected to a synchrotron at the High Energy Physics Laboratory. The initial energy of the 500 MeV proton beam supplied by the accelerator is degraded down to 243 MeV after passing through a graphited rod. In the control system, a proton beam is scattered to form a large field, its Bragg peak width is spread out, and its energy is degraded to the optimum value with a range covering tumour depth. The characteristics of the devices required for these procedures have been investigated from the viewpoint of the relationship between dose rate and field flatness, taking the setting-up geometry of these devices into consideration.

Characteristics of neutron beam generated by 500 MeV proton beam

A neutron irradiation facility was constructed at PARMS, University of Tsukuba to produce an ultrahigh energy neutron beam with a depth dose distribution superior to an x-ray beam generated by a modern linac. This neutron beam was produced from the reaction on a thick uranium target struck by a 500 MeV proton beam from the booster synchrotron of the High Energy Physics Laboratory. The percentage depth dose of this neutron beam was nearly equivalent to that of x-rays around 20 MV and the dose rate was 15 cGy per minute. The relative biological effectiveness (RBE) of this neutron beam has been estimated using the cell inactivation effect and the HMV-I cell line. The survival curve of cells after neutron irradiation has a shoulder with n and Dq of 8 and 2.3 Gy, respectively. The RBE value at the 10(-2) survival level for the present neutron beam as compared with 137Cs gamma rays was 1.24. The results suggest that the biological effects of ultrahigh energy neutrons are not large enough to be useful, although the depth dose distribution of neutrons can be superior to that of high energy linac x-rays.

Validity of the Concept of Absorbed Dose as a Physical Quantity

The concept of the \lq\lqabsorbed dose” of ionizing radiation is scrutinized from physical point of view. It is shown that the concept and definition of the quantity in the ICRU system is disqualified as a physical quantity and the absorbed dose can not always be a \lq\lqmeasure of cause” in describing causality relation between radiation and effects on matter. The current absorbed dose depends even on the energy that have already been brought out from the matter, contrary to the intention of introducing the quantity. Trials to remove these difficulties are made. However, it is also shown there still exists an essential problem that cannot be solved by improving the formulation.

Computer Simulation of Measurement of Ultrasound Attenuation Coefficient by Broad Band Continuous-Echo Technique (Gamma Variate Method)

Computer simulation experiments were made using the gamma variate method. The method is one proposed by the authors and uses a broad band interrogating wave. The interrogating wave was assumed to be delta function in time scale. Five random scatterers at distances of 90 and 100 mm from the transducer were assumed. An attenuation coefficient proportional to the frequency (0.01 Np/mm/MHz) was also assumed. Frequencies between 0.2 and 3.2 MHz were used for the analysis. The averaged spectrum of 300 simulation experiments gave 0.00996 Np/mm/MHz which was approximately equal to the assumed value.

The Oligomeric Model of the Excitable Membrane with the Asymmetrical Behaviour of the Inner and the Outer Sides of the Membrane with Respect to Adsorption of Permeants

The properties of the oligomeric transport model of the excitable membrane are investigated analytically in the case of the extreme asymmetrical behaviour of the inner and the outer sides of the membrane based on the model proposed and discussed numerically by Blumenthal (J. Theor. Biol. 49 (1975) 219). The dependence of behaviours of the model on the overall concentration gradient and diffusion rate constants is discussed. In the model which takes into account lateral diffusion over the membrane surface, the possibility of spatial pattern formation over the membrane surface is also discussed.