Biomedical subjects

Tatsuaki Kanai

Publications and source records attributed to Tatsuaki Kanai.

At least 19 recordsLinked to original sources

PubMed2006

Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: a Phase I/II dose-escalation study.

PURPOSE: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. METHODS AND MATERIALS: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. RESULTS: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. CONCLUSION: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

Adult↗

PubMed2006

Biological dose calculation with Monte Carlo physics simulation for heavy-ion radiotherapy.

Treatment planning of heavy-ion radiotherapy involves predictive calculation of not only the physical dose but also the biological dose in a patient body. The biological dose is defined as the product of the physical dose and the relative biological effectiveness (RBE). In carbon-ion radiotherapy at National Institute of Radiological Sciences, the RBE value has been defined as the ratio of the 10% survival dose of 200 kVp x-rays to that of the radiation of interest for in vitro human salivary gland tumour cells. In this note, the physical and biological dose distributions of a typical therapeutic carbon-ion beam are calculated using the GEANT4 Monte Carlo simulation toolkit in comparison with those with the biological dose estimate system based on the one-dimensional beam model currently used in treatment planning. The results differed between the GEANT4 simulation and the one-dimensional beam model, indicating the physical limitations in the beam model. This study demonstrates that the Monte Carlo physics simulation technique can be applied to improve the accuracy of the biological dose distribution in treatment planning of heavy-ion radiotherapy.

Carbon↗

PubMed2006

Carbon ion radiation therapy for prostate cancer: results of a prospective phase II study.

BACKGROUND AND PURPOSE: To determine the efficacy and feasibility of carbon ion radiotherapy (C-ion RT) for prostate cancer. PATIENTS AND METHODS: Between April 2000 and November 2003, 175 patients received C-ion RT using a recommended dose fractionation (66.0 GyE/20 fractions) established from prior studies. C-ion RT alone was performed for 33 patients constituting a low-risk group (Stage < or =T2a and PSA <20 ng/ml and Gleason score < or =6); the remaining 142 high-risk patients received an additional androgen deprivation therapy (ADT). RESULTS: The 4-year overall survival and bNED rates were 91% and 87%, respectively. Local control was achieved in all but one patient. The 4-year bNED rates were 87% in the low-risk group and 88% in the high-risk group. In very advanced diseases (Stage > or= T3a or PSA > or= 20 ng/ml or Gleason score > or =8), there was significant difference in the bNED rate according to period of ADT administration (ADT > or =24 months: 93%, ADT <24 months: 73%, p<0.01). Grade 2 late toxicities developed in 4 patients (2%) for the rectum and 9 patients (5%) for the genitourinary system but no Grade 3 or higher toxicity was observed. CONCLUSIONS: The effectiveness of C-ion RT for prostate cancer has been well confirmed. Based on these results, new study of a C-ion RT modified for the administration strategy of ADT according to the patient risk has been started by dividing patients into 3 groups, high-risk, intermediate-risk, and low-risk.

Adenocarcinoma↗

PubMed2006

Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an ionization chamber. The good agreement between the derived and the measured distributions implies that the deposited dose distribution in a target can be estimated from the detected annihilation gamma-ray distribution with a positron camera.

Algorithms↗

PubMed2006

Application of heavy-ion CT.

In treatment planning for hadron therapy, information about the relative stopping power in a patient's body is used to calculate the range of incident ions. This information is obtained from computed tomography (CT) images using a conversion table from x-ray CT numbers into stopping powers relative to the stopping power of water. In treatment planning at the National Institute of Radiological Sciences (NIRS), the conversion table has been created based on the polybinary tissue model. However, it has not been fully verified that the model is accurate enough for use in real animal tissues. In order to irradiate heavy ions more precisely in radiotherapy, we have to evaluate the accuracy of the polybinary tissue calibration in animal tissues. We have measured animal tissue samples with a heavy-ion CT (HICT) and an x-ray CT. The x-ray CT image was converted to an image of relative stopping power by using the table derived from the polybinary tissue calibration (polybinary-tissue-model CT (PTCT) image). On the other hand, with HICT, the two-dimensional distribution of relative stopping power can be obtained directly. A comparison between PTCT and HICT images enabled us to verify the accuracy of the conversion table derived from the polybinary tissue calibration. Consequently, it was found that the agreement between the relative stopping powers of PTCT and HICT is 1.6% for fat, muscle and bone.

Animals↗

PubMed2006

Examination of GyE system for HIMAC carbon therapy.

PURPOSE: A retrospective analysis was made to examine appropriateness in the estimation of the biologic effectiveness of carbon-ion radiotherapy using resultant data from clinical trials at the heavy-ion medical accelerator complex (HIMAC) at the National Institute of Radiological Sciences in Chiba, Japan. METHODS AND MATERIALS: At HIMAC, relative biologic effectiveness (RBE) values of therapeutic carbon beams were determined based on experimental results of cell responses, on values expected with the linear-quadratic model, and based on experiences with neutron therapy. We use fixed RBE values independent of dose levels, although this apparently contradicts radiobiologic observations. Our RBE system depends only on LET of the heavy-ion radiation fields. With this RBE system, over 2,000 patients have been treated by carbon beams. With data from these patients, the local control rate of non-small-cell lung cancer was analyzed to verify the clinical RBE of the carbon beam. The local control rate was compared with rates published by groups from Gunma University and Massachusetts General Hospital. Using a simplified tumor control probability (TCP) model, clinical RBE values were obtained for different levels of TCP. RESULTS: For the 50% level of the clinical TCP, the RBE values nearly coincide with those for in vitro human salivary gland cell survival at 10%. For the higher levels of clinical TCP, the RBE values approach closer to those adapted in clinical trials at HIMAC.

Algorithms↗

PubMed2006

Three-dimensional velocity mapping of lung motion using vessel bifurcation pattern matching.

We present a new quantification technique for three-dimensional (3D) lung motion by means of tracking the anatomical features inside the lung using a set of sequential 3D-CT images (a 4D-CT image). The method is based on the conservation of topology, such as connections and junctions of vessels, during the motion. Lung CT images are used to do lung volume modeling, lung vessel extracting and thinning, and coordinates of vessel bifurcations are derived as feature points. Such feature points are tracked in a series of 3D-CT images, i.e., the points are individually tracked between two successive 3D-CT images, in which the lung is deformed. Consequently, 3D displacement vectors are obtained. The feature point tracking is carried out using point pattern matching with a probabilistic relaxation method. We examined this technique using a lung 3D-CT image and artificially deformed one, and separately scanned CT images for a rigid bifurcation phantom. The studies estimated that the error of the vectors is within approximately 1 voxel, i.e., 1 mm or less. Therefore, the accuracy is expected to be high enough for radiation therapy. This technique enables us to quantify realistic 3D organ motion without any fiducial markers. It can be applied to the quantification of tumor (target volume) deformation by gridding interpolation into all voxels. We expect it to be useful for dose estimation in mobile organs and for 4D treatment planning in radiation therapy.

Algorithms↗

PubMed2006

Commissioning of a conformal irradiation system for heavy-ion radiotherapy using a layer-stacking method.

The commissioning of conformal radiotherapy system using heavy-ion beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC) is described in detail. The system at HIMAC was upgraded for a clinical trial using a new technique: large spot uniform scanning with conformal layer stacking. The system was developed to localize the irradiation dose to the target volume more effectively than with the old system. With the present passive irradiation method using a ridge filter, a scatterer, a pair of wobbler magnets, and a multileaf collimator, the width of the spread-out Bragg peak (SOBP) in the radiation field could not be changed. With dynamic control of the beam-modifying devices during irradiation, a more conformal radiotherapy could be achieved. In order to safely perform treatments with this conformal therapy, the moving devices should be watched during irradiation and the synchronousness among the devices should be verified. This system, which has to be safe for patient irradiations, was constructed and tested for safety and for the quality of the dose localization realized. Through these commissioning tests, we were successfully able to prepare the conformal technique using layer stacking for patients. Subsequent to commissioning the technique has been applied to patients in clinical trials.

Calibration↗

PubMed2006

Microdosimetric measurements and estimation of human cell survival for heavy-ion beams.

The microdosimetric spectra for high-energy beams of photons and proton, helium, carbon, neon, silicon and iron ions (LET = 0.5-880 keV/microm) were measured with a spherical-walled tissue-equivalent proportional counter at various depths in a plastic phantom. Survival curves for human tumor cells were also obtained under the same conditions. Then the survival curves were compared with those estimated by a microdosimetric model based on the spectra and the biological parameters for each cell line. The estimated alpha terms of the liner-quadratic model with a fixed beta value reproduced the experimental results for cell irradiation for ion beams with LETs of less than 450 keV/microm, except in the region near the distal peak.

Cell Line↗

PubMed2005

Enhanced efficiency in cell killing at the penetration depths around the Bragg peak of a radioactive 9C-ion beam.

PURPOSE: To evaluate the potential importance of radioactive 9C-ion beam in cancer radiotherapy. METHODS AND MATERIALS: Human salivary gland (HSG) cells were exposed to a double-radiation-source 9C beam at different depths around the Bragg peak. Cell survival fraction was determined by standard clonogenic assay. For comparison, the same experiment was conducted for a therapeutic 12C beam. To determine relative biologic effectiveness (RBE) values, HSG cells were also irradiated with 60Co gamma-rays of fractionation scheme as the reference. RESULTS: The 9C beam was more efficient in cell killing at the depths around its Bragg peak than was the 12C beam, which corresponded to the 9C-ion stopping region and where delayed low-energy particles were emitted. The RBE value at 50% survival level for the 9C beam varied from 1.38 to 4.23. Compared with the 12C beam, the RBE values for the 9C beam were always higher; an increase in RBE by a factor of up to 1.87 has been observed at the depths distal to the Bragg peak. CONCLUSION: The potential advantage of radioactive 9C-ion beam in cancer therapy has been revealed at low dose rate in comparison with a therapeutic 12C beam. This observation, however, remains to be investigated at therapeutic dose rates in the future.

Carbon↗

PubMed2005

Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions.

We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/microm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to (137)Cs gamma-rays. The mutation frequency increased up to 105 keV/microm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/mum showed all or partial deletions of exons, while among gamma-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not.

Cell Line↗

PubMed2005

Spatial fragment distribution from a therapeutic pencil-like carbon beam in water.

The latest heavy ion therapy tends to require information about the spatial distribution of the quality of radiation in a patient's body in order to make the best use of any potential advantage of swift heavy ions for the therapeutic treatment of a tumour. The deflection of incident particles is described well by Molière's multiple-scattering theory of primary particles; however, the deflection of projectile fragments is not yet thoroughly understood. This paper reports on our investigation of the spatial distribution of fragments produced from a therapeutic carbon beam through nuclear reactions in thick water. A DeltaE-E counter telescope system, composed of a plastic scintillator, a gas-flow proportional counter and a BGO scintillator, was rotated around a water target in order to measure the spatial distribution of the radiation quality. The results revealed that the observed deflection of fragment particles exceeded the multiple scattering effect estimated by Molière's theory. However, the difference can be sufficiently accounted for by considering one term involved in the multiple-scattering formula; this term corresponds to a lateral 'kick' at the point of production of the fragment. This kick is successfully explained as a transfer of the intra-nucleus Fermi momentum of a projectile to the fragment; the extent of the kick obeys the expectation derived from the Goldhaber model.

Carbon↗

PubMed2005

Hypofractionated radiotherapy with carbon ion beams for prostate cancer.

PURPOSE: Analysis of the results of hypofractionated conformal carbon ion radiotherapy for localized prostate cancer was performed, with special regard to normal tissue morbidity and biochemical relapse-free rate (bNED). METHODS AND MATERIALS: Analysis was performed for 201 patients treated with the dose fractionation regimen established during three clinical trials performed between June 1995 and February 2004. Outcomes were measured in terms of toxicity, survival, freedom from local recurrence, and bNED. RESULTS: No Grade 3 or higher toxicities were observed in either the rectum or genitourinary system, and the incidences of Grade 2 rectum or genitourinary morbidity were only 1.0% and 6.0%, respectively. The overall 5-year biochemical relapse-free survival was 83.2% without any local recurrence. Gleason score, initial PSA, and T stage were all significant prognostic factors for bNED, which was 97.1% in patients with Gleason score < or =7 and initial PSA <20 ng/mL. CONCLUSION: Hypofractionated carbon ion radiotherapy with the established dose fractionation regimen yielded satisfactory bNED without local recurrence and with minimal morbidity. Long-term results are necessary to confirm the utility of carbon ion radiotherapy in the treatment of localized prostate cancer.

Adenocarcinoma↗

PubMed2005

Responses of a diamond detector to high-LET charged particles.

The responses of a commercial diamond detector (type 60003, PTW-Freiburg) to several heavy ions were examined. The responses to heavy-ion beams reached stable levels with relatively small pre-irradiation doses compared to photon-beam irradiations. The responses also reached stable levels with a smaller pre-irradiation dose when the dose rate of the He beams was increased. A total accumulated dose of about 5 Gy was required for the pre-irradiation dose of heavy-ion beams. No angular dependence of the detector responses was observed within a deviation of 5%. The dose-rate dependence of the detector responses to heavy-ion beams was far smaller than that to gamma rays. The decrease in the response was within 0.9%, with a variation from 0.88 to 18.2 Gy min(-1) in the carbon beam. We examined the LET dependence of the diamond detector responses using various kinds of heavy-ion beams. The responses had particle dependence in addition to LET dependence. The responses decreased more with higher LET particles and decreased less with large-Z particles. We proposed a gradual-saturation model based on the track structure under several simple assumptions to explain the LET and particle dependences of the response.

Diamond↗

PubMed2005

Quantitative comparison of suitability of various beams for range monitoring with induced beta+ activity in hadron therapy.

In radiation therapy with hadron beams, it is important to evaluate the range of incident ions and the deposited dose distribution in a patient body for the effective utilization of such properties as the dose concentration and the biological effect around the Bragg peak. However, there is some ambiguity in determining this range because of a conversion error from the x-ray CT number to the charged particle range. This is because the CT number is related to x-ray absorption coefficients, while the ion range is determined by the electron density of the substance. Using positron emitters produced in the patient body through fragmentation reactions during the irradiation has been proposed to overcome this problem. The activity distribution in the patient body can be deduced by detecting pairs of annihilation gamma rays emitted from the positron emitters, and information about the range of incident ions can be obtained. In this paper, we propose a quantitative comparison method to evaluate the mean range of incident ions and monitor the activity distribution related to the deposited dose distribution. The effectiveness of the method was demonstrated by evaluating the range of incident ions using the maximum likelihood estimation (MLE) method and Fisher's information was calculated under realistic conditions for irradiations with several kinds of ions. From the calculated Fisher's information, we compared the relative advantages of initial beams to determine the range of incident ions. The (16)O irradiation gave the most information among the stable heavy ions when we measured the induced activity for 500 s and 60 s just after the irradiation. Therefore, under these conditions, we concluded that the (16)O beam was the optimum beam to monitor the activity distribution and to evaluate the range. On the other hand, if the positron emitters were injected directly as a therapeutic beam, the (15)O irradiation gave the most information. Although the relative advantages of initial beams as well as the measured activity distributions slightly varied according to the measurement conditions, comparisons could be made for different conditions by using Fisher's information.

Algorithms↗

PubMed2005

Measurements of neutron effective doses and attenuation lengths for shielding materials at the heavy-ion medical accelerator in Chiba.

The effective doses and attenuation lengths for concrete and iron were measured for the design of heavy ion facilities. Neutrons were produced through the reaction of copper, carbon, and lead bombarded by carbon ions at 230 and 400 MeV.A, neon ions at 400 and 600 MeV.A, and silicon ions at 600 and 800 MeV.A. The detectors used were a Linus and a Andersson-Braun-type rem counter and a detector based on the activation of a plastic scintillator. Representative effective dose rates (in units of 10(-8) microSv h(-1) pps(-1) at 1 m from the incident target surface, where pps means particles per second) and the attenuation lengths (in units of m) were 9.4 x 10(4), 0.46 for carbon ions at 230 MeV.A; 8.9 x 10(5), 0.48 for carbon ions at 400 MeV.A; 9.3 x 10(5), 0.48 for neon ions at 400 MeV.A; 3.8 x 10(6), 0.50 for neon ions at 600 MeV.A; 3.9 x 10(6), 0.50 for silicon ions at 600 MeV.A; and 1.1 x 10(7), 0.51 for silicon ions at 800 MeV.A. The attenuation provided by an iron plate approximately 20 cm thick (nearly equal to the attenuation length) corresponded to that of a 50-cm block of concrete in the present energy range. Miscellaneous results, such as the angular distributions of the neutron effective dose, narrow beam attenuation experiments, decay of gamma-ray doses after the bombardment of targets, doses around an irradiation room, order effects in the multi-layer (concrete and iron) shielding, the doses from different targets, the doses measured with a scintillator activation detector, the gamma-ray doses out of walls and the ratio of the response between the Andersson-Braun-type and the Linus rem counters are also reported.

Construction Materials↗

PubMed2005

Exploration of "over kill effect" of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death.

The reason why RBE for cell killing fell to less than unity (1.0) with very high-LET heavy-ions ((40)Ar: 1,640 keV/microm; (56)Fe: 780, 1,200, 2,000 keV/microm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). CHO cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/microm) or Fe-ions (2,000 keV/microm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/microm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/microm) was not particularly high (approximately 15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/microm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by "cellular over kill effect". Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (sigma[R]) began to increase when LET exceeded 100 keV/microm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/microm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and sigma[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage which lowers the energy efficiency for producing damage and RBE.

Animals↗

PubMed2005

LET and ion species dependence for cell killing in normal human skin fibroblasts.

We studied the LET and ion species dependence of the RBE for cell killing to clarify the differences in the biological effects caused by the differences in the track structure that result from the different energy depositions for different ions. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon, neon, silicon and iron ions that were generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS) in Japan. Cell killing was measured as reproductive cell death using a colony formation assay. The RBE-LET curves were different for carbon ions and for the other ions. The curve for carbon ions increased steeply up to around 98 keV/microm. The RBE of carbon ions at 98 keV/microm was 4.07. In contrast, the curves for neon, silicon and iron ions had maximum peaks around 180 keV/microm, and the RBEs at the peak position ranged from 3.03 to 3.39. When the RBEs were plotted as a function of Z*2/beta2 (where Z* is the effective charge and beta is the relative velocity of the ion) instead of LET, the discrepancies between the RBE-LET curves for the different ion beams were reduced, but branching of the RBE-Z*2/beta2 curves still remained. When the inactivation cross section was plotted as a function of either LET or Z*2/beta2, it increased with increasing LET. However, the inactivation cross section was always smaller than the geometrical cross section. These results suggest that the differences in the energy deposition track structures of the different ion sources have an effect on cell killing.

Cell Survival↗