Epigenome-wide association study on methamphetamine dependence.

Repeated abuse of methamphetamine (METH) can cause dependence, repeated relapse of psychotic symptoms, compulsive drug-seeking behaviour, and various neurological symptoms. These long-term biological changes may be associated with epigenetic mechanisms; however, the association between METH use and epigenetic mechanisms has been poorly investigated. Thus, we performed an epigenome-wide association study of METH dependence using genomic DNA extracted from the blood samples of 24 patients with METH dependence and 24 normal controls. All participants were of Japanese descent. We tested the association between METH dependence and DNA methylation using linear regression analysis. We found epigenome-wide significant associations at four CpG sites, one of which occurred in the CNOT1 gene and another in the PUM1 gene. We especially noted the CNOT1 and PUM1 genes as well as several other genes that indicated some degree of association with METH dependence. Among the relatively enriched Gene Ontology terms, we were interested in terms of mRNA metabolism, respirasome, and excitatory extracellular ligand-gated ion channel activity. Among the relatively enriched Kyoto Encyclopedia of Genes and Genome pathways, we noted pathways of several neurological diseases. Our results indicate that genetic changes akin to those in other psychiatric or neurodegenerative disorders may also occur via epigenetic mechanisms in patients with METH dependence.

Carbon-ion radiotherapy for urological cancers.

Carbon-ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon-ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon-ion radiotherapy as a standard cancer therapy, the Japan Carbon-ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon-ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon-ion radiotherapy and our efforts to disseminate the use of this new technology worldwide.

Commissioning of a respiratory gating system involving a pressure sensor in carbon-ion scanning radiotherapy.

This study reports the commissioning methodology and results of a respiratory gating system [AZ - 733 V/733 VI (Anzai Medical Co., Japan)] using a pressure sensor in carbon-ion scanning radiotherapy. Commissioning includes choosing a location and method for pressure sensor installation, delay time measurement of the system, and the final flow test. Additionally, we proposed a methodology for the determination of a threshold level of generating an on/off gate for the beam to the respiratory waveform, which is important for clinical application. Regarding the location and method for installation of the pressure sensor, the actual person's abdomen, back of the body position, and supine/prone positioning were checked. By comparing the motion between the pressure sensor output and the reference LED sensor motion, the chest rear surface was shown to be unsuitable for the sensor installation, due to noise in the signal caused by the cardiac beat. Regarding delay time measurement of the system, measurements were performed for the following four steps: (a). Actual motion to wave signal generation; (b). Wave signal to gate signal generation; (c). Gate signal to beam on/off signal generation; (d). Beam on/off signal to the beam irradiation. The total delay time measured was 46 ms (beam on)/33 ms (beam off); these were within the prescribed tolerance time (<100 ms). Regarding the final flow test, an end-to-end test was performed with a patient verification system using an actual carbon-ion beam; the respiratory gating irradiation was successfully performed, in accordance with the intended timing. Finally, regarding the method for determining the threshold level of the gate generation of the respiration waveform, the target motion obtained from 4D-CT was assumed to be correlated with the waveform obtained from the pressure sensor; it was used to determine the threshold value in amplitude direction.

External dosimetry audit for quality assurance of carbon-ion radiation therapy clinical trials.

PURPOSE: The QA team of the Japan carbon-ion radiation oncology study group (J-CROS) was organized in 2015 to enhance confidence in the accuracy of clinical dosimetry and ensure that the facility QA procedures are adequate. The team conducted onsite dosimetry audits in all the carbon-ion radiation therapy centers in Japan. MATERIALS AND METHODS: A special phantom was fabricated for the onsite dosimetry audit. Target volumes such as the GTV, CTV, and PTV were contoured to the obtained CT images, and two plans with different isocenter depths were created. The dose at the isocenter was measured by an ionization chamber, in the onsite audit and compared with the calculated dose. RESULTS: For all the centers, the average of the percentage ratio between the measured and calculated doses (measured/calculated) was 0.5% (-2.7% to +2.6%) and the standard deviation, 1.7%. In all the centers, the beams were within the set tolerance level of 3%. CONCLUSIONS: The audit demonstrated that the dose at a single point in the water phantom was within tolerance, but it is a big step to say that all doses are correct. In addition, this external dosimetry audit encouraged centers to improve the quality of their dosimetry systems.

High-Linear Energy Transfer Irradiation in Clinical Carbon-Ion Beam With the Linear Energy Transfer Painting Technique for Patients With Head and Neck Cancer.

Purpose: Dose-averaged linear energy transfer (LETd) is one of the important factors in determining clinical outcomes for carbon-ion radiation therapy. Innovative LET painting (LP) has been developed as an advanced form of conventional intensity modulated carbon-ion radiation therapy (IMIT) at the QST Hospital. The study had 2 motivations: to increase the minimum LETd (LETdmin) and to improve uniformity of the LETd distribution within the gross tumor volume (GTV) by using LP treatment plans for patients with head and neck cancer while maintaining the relative biologic effectiveness (RBE)-weighted dose coverage within the planning tumor volume (PTV) the same as in the conventional IMIT plan. Methods and Materials: The LP treatment plans were designed with the in-house treatment planning system. For the plans, LETd constraints and LETdmin, goal-LETd, and maximum-LETd (LETdmax) constraints for the GTV were added to the conventional dose constraints in the IMIT prescription. For 13 patients with head and neck cancer, the RBE-weighted dose to 90% (D90) and 50% (D50) of the PTV and the LETdmin, mean (LETdmean), and LETdmax values within the GTV in the LP plans were evaluated by comparing them with those in the conventional IMIT plans. Results: The LP for 13 patients with head and neck cancer could keep D90s and D50s for the PTV within 1.0% of those by the conventional IMIT. Among the 13 patients, the mean LETdmin of the LP plans for the GTV was 59.2 ± 7.9 keV/µm, whereas that of the IMIT plans was 45.9 ± 6.0 keV/µm. The LP increased the LETdmin to 8 to 24 keV/µm for the GTV compared with IMIT. Conclusions: While maintaining the dose coverage to the PTV as comparable to that for IMIT, the LP increased the mean LETdmin to 13.2 keV/µm for the GTV. For a GTV up to 170 cm3, LETd > 44 keV/µm could be achieved using LP, which according to previous studies was associated with lower recurrence. In addition, the LP method delivered more uniform LETd distributions compared with IMIT.

Accelerated epigenetic aging in alcohol dependence.

Alcohol dependence poses a global health threat associated with aging and reduced life expectancy. Recently, aging research through deoxyribonucleic acid (DNA) methylation has gained attention. New epigenetic clocks have been developed; however, no study has investigated GrimAge components, GrimAge2 components and DunedinPACE in patients with alcohol dependence. In this study, we aimed to perform epigenetic clock analysis to evaluate epigenetic age acceleration and DNA methylation-based age-predictive components in patients with alcohol dependence and controls. We utilized publicly available DNA methylation data (GSE98876) for our analysis. Additionally, we compared the values of the same items before and after the patients underwent a treatment program. The dataset comprised 23 controls and 24 patients. We observed that DunedinPACE accelerated more in patients with alcohol dependence. AgeAccelGrim and AgeAccelGrim2 decelerated more after the treatment program than before, and beta-2-microglobulin and Cystatin C decreased after the treatment program than before. These findings are crucial as they affect the cranial nerve area, potentially contributing to cognitive dysfunction and psychiatric symptoms in patients with alcohol dependence.

Association study of a single nucleotide polymorphism in the hypoxia response element of the macrophage migration inhibitory factor gene promoter with suicide completers in the Japanese population.

BACKGROUND: More than 800 000 people die by suicide annually. The heritability of suicide is 30%-50%. We focused on the hypoxia response element (HRE), which promotes the expression of macrophage migration inhibitory factor (MIF) via the hypoxia-inducible factor (HIF) pathway, important in neurogenesis and neuroprotection. We examined a genetic polymorphism of rs17004038, a single-nucleotide polymorphism (SNP), in suicide completers and controls. METHODS: The study population included 1336 suicide completers and 814 unrelated healthy controls. All participants were Japanese. We obtained peripheral blood, extracted DNA, and genotyped the patients for SNP rs17004038 (C > A). RESULTS: No significant differences were observed between the two groups in either the allele or genotype analyses. Subgroup analyses by sex, age (<40 or ≥40), and suicide method (violent or nonviolent suicide) were performed with similar results. CONCLUSION: No association was observed between SNP rs17004038 and suicide completion. Although it is challenging to collect a large number of samples from suicide completers, further MIF-related genetic studies, including those of rs17004038, are necessary with larger sample sizes.

Accelerated epigenetic aging and decreased natural killer cells based on DNA methylation in patients with untreated major depressive disorder.

Major depressive disorder (MDD) is known to cause significant disability. Genome-wide DNA methylation (DNAm) profiles can be used to estimate biological aging and as epigenetic clocks. However, information on epigenetic clocks reported in MDD patients is inconsistent. Since antidepressants are likely confounders, we evaluated biological aging using various DNAm-based predictors in patients with MDD who had never received depression medication. A publicly available dataset consisting of whole blood samples from untreated MDD patients (n = 40) and controls (n = 40) was used. We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAm-based telomere length (DNAmTL), and DNAm-based age-related plasma proteins (GrimAge components), as well as DNAm-based white blood cell composition. The results indicate that patients with untreated MDD were significantly associated with epigenetic aging acceleration in HannumAge and GrimAge. Furthermore, a decrease in natural killer cells, based on DNAm, was observed in patients with untreated MDD.

Epigenetic clock analysis reveals increased plasma cystatin C levels based on DNA methylation in major depressive disorder.

Major depressive disorder (MDD) is a common mental illness and a major public health concern worldwide. Depression is associated with epigenetic changes that regulate gene expression, and analyzing these changes may help elucidate the pathophysiology of MDD. Genome-wide DNA methylation (DNAm) profiles can function as 'epigenetic clocks' that can help estimate biological aging. Here, we assessed biological aging in patients with MDD using various DNAm-based indicators of epigenetic aging. We used a publicly available dataset containing data obtained from the whole blood samples of MDD patients (n = 489) and controls (n = 210). We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and DNAm-based telomere length (DNAmTL). We also investigated seven DNAm-based age-predictive plasma proteins (including cystatin C) and smoking status, which are components of GrimAge. Following adjustment for confounding factors such as age and sex, patients with MDD showed no significant difference in epigenetic clocks and DNAmTL. However, DNAm-based plasma cystatin C levels were significantly higher in patients with MDD than controls. Our findings revealed specific DNAm changes predicting plasma cystatin C levels in MDD. These findings may help elucidate the pathophysiology of MDD, leading to the development of new biomarkers and medications.

Association of two variable number of tandem repeats in the monoamine oxidase A gene promoter with suicide completion: The present study and meta-analysis.

BACKGROUND: One potential cause of suicide is serotonergic dysfunction. Sex differences have been reported to modulate the effects of serotonergic polymorphisms. Monoamine oxidase A (MAOA) is an enzyme that degrades serotonin and is located on the X chromosome. A previous study indicated that the upstream (u) variable number of tandem repeat (VNTR) in the MAOA gene promoter may be associated with suicide. However, a meta-analysis showed that this polymorphism may not be related to suicide. According to a recent study, compared with the uVNTR, the distal (d)VNTR and the haplotypes of the two VNTRs modulate MAOA expression. METHODS: We examined the two VNTRs in the MAOA gene promoter in 1007 subjects who committed suicide and 844 healthy controls. We analyzed the two VNTRs using fluorescence-based polymerase chain reaction assays. We conducted a meta-analysis for the two VNTRs to update it. RESULTS: Our results demonstrated that neither the genotype-based associations nor allele/haplotype frequencies of the two VNTRs were significantly associated with suicide. In the meta-analysis, we did not indicate relationships between uVNTR and suicide nor did we identify articles analyzing dVNTR in suicide. CONCLUSION: Overall, we did not find a relationship between the two VNTRs in the MAOA promoter and suicide completion; thus, warranting further studies are required.

Evaluation of hybrid depth scanning for carbon-ion radiotherapy.

PURPOSE: In radiotherapy with a scanned carbon-ion beam, its Bragg peak is shifted along the depth direction either by inserting the range shifter plates or by changing the beam-extraction energy of a synchrotron. In the former technique (range shifter scanning: RS), the range shifter plates broaden the beam size and produce secondary fragments through nuclear reactions. In the latter technique (active-energy scanning: ES), it may take several seconds to change the beam energy depending on the synchrotron operation cycle, leading to a long treatment time. The authors propose a hybrid depth scan technique (hybrid scanning: HS), where several beam energies are used in conjunction with the range shifter plates for finer range shift. In this study, HS is evaluated from the viewpoints of dose distribution and treatment time. METHODS: Assuming realistic accelerator and beam-delivery systems, the authors performed computer simulations using GEANT4 Monte Carlo code for beam modeling and a treatment planning system to evaluate HS. Three target volumes with the same dimensions of 60 × 60 × 60 mm(3) were generated at depths of 45, 85, and 125 mm in water phantom, and uniform clinical dose was planned for these targets. The sizes of lateral dose falloff and the peak to plateau ratio defined as the ratio of the clinical dose averaged over the target to the clinical dose at the entrance as well as the treatment time were compared among the three depth scan techniques. RESULTS: The sizes of lateral dose falloffs at the center of SOBP are 11.4, 8.5, and 5.9 mm for the three targets in RS, while they are 5.7, 4.8, and 4.6 mm in ES and 6.6, 5.7, and 5.0 mm in HS, respectively. The peak to plateau ratios are 1.39, 1.96, and 2.15 in RS, while they are 1.48, 2.04, and 2.19 in ES and 1.47, 2.03, and 2.18 in HS, respectively. The treatment times are 128.7, 128.6, and 128.6 s in ES, while they are 61.2, 54.6, and 47.8 s in RS and 43.2, 44.1, and 44.7 s in HS, respectively. The multiple scattering and the nuclear reaction by range shifter degraded the beam qualities such as lateral dose falloff and peak to plateau ratio, which was especially pronounced for the shallow target in RS. The depth scan timing was limited by accelerator cycle in ES. That increased the treatment time by a few times. CONCLUSIONS: This study revealed that HS can provide dose distributions with steeper lateral dose falloffs and higher peak to plateau ratio comparing to RS and comparable to ES. In addition, the treatment time can be considerably reduced in HS compared to ES.

Patient handling system for carbon ion beam scanning therapy.

Our institution established a new treatment facility for carbon ion beam scanning therapy in 2010. The major advantages of scanning beam treatment compared to the passive beam treatment are the following: high dose conformation with less excessive dose to the normal tissues, no bolus compensator and patient collimator/multi-leaf collimator, better dose efficiency by reducing the number of scatters. The new facility was designed to solve several problems encountered in the existing facility, at which several thousand patients were treated over more than 15 years. Here, we introduce the patient handling system in the new treatment facility. The new facility incorporates three main systems, a scanning irradiation system (S-IR), treatment planning system (TPS), and patient handling system (PTH). The PTH covers a wide range of functions including imaging, geometrical/position accuracy including motion management (immobilization, robotic arm treatment bed), layout of the treatment room, treatment workflow, software, and others. The first clinical trials without respiratory gating have been successfully started. The PTH allows a reduction in patient stay in the treatment room to as few as 7 min. The PTH plays an important role in carbon ion beam scanning therapy at the new institution, particularly in the management of patient handling, application of image-guided therapy, and improvement of treatment workflow, and thereby allows substantially better treatment at minimum cost.

Development of digital reconstructed radiography software at new treatment facility for carbon-ion beam scanning of National Institute of Radiological Sciences.

To increase the accuracy of carbon ion beam scanning therapy, we have developed a graphical user interface-based digitally-reconstructed radiograph (DRR) software system for use in routine clinical practice at our center. The DRR software is used in particular scenarios in the new treatment facility to achieve the same level of geometrical accuracy at the treatment as at the imaging session. DRR calculation is implemented simply as the summation of CT image voxel values along the X-ray projection ray. Since we implemented graphics processing unit-based computation, the DRR images are calculated with a speed sufficient for the particular clinical practice requirements. Since high spatial resolution flat panel detector (FPD) images should be registered to the reference DRR images in patient setup process in any scenarios, the DRR images also needs higher spatial resolution close to that of FPD images. To overcome the limitation of the CT spatial resolution imposed by the CT voxel size, we applied image processing to improve the calculated DRR spatial resolution. The DRR software introduced here enabled patient positioning with sufficient accuracy for the implementation of carbon-ion beam scanning therapy at our center.

Epigenetic clock analysis in methamphetamine dependence.

Methamphetamine (MA) is used worldwide and causes serious public health and social problems. MA affects the central nervous, cardiac, and immune systems, which causes neuropsychiatric and cardiovascular diseases and infection. Epigenetic changes, including DNA methylation (DNAm), are associated with various clinical phenotypes of MA abuse. DNAm is related to biological aging and health risks; hence, we aimed to assess the changes in biological aging in MA dependence using the DNAm age and DNA methylation-based telomere length (DNAmTL). We used five measures of DNAm age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAmTL, and DNAm-based age-predictive factors (plasma proteins and blood cell composition). We compared patients with MA dependence and healthy controls (n = 24 each) using the DNAm profiles obtained from whole-blood samples. Patients with MA dependence showed significant acceleration in PhenoAge and GrimAge, as well as a trend for significant acceleration in DNAmTL. Following adjustment for confounding factors, MA dependence was significantly associated with accelerations in PhenoAge, GrimAge, and DNAmTL, as well as alterations in DNAm-based age-predictive factors (beta-2-microglobulin, granulocytes, and naive cluster of differentiation 4+ T cells). Our results suggested an acceleration of biological aging and specific changes in the DNAm of age- predictive factors in MA dependence.

Prognostic significance of acute pain preceding out-of-hospital cardiac arrest.

BACKGROUND: Sudden loss of consciousness (LOC) and chest pain are common manifestations of out-of-hospital cardiac arrest (OHCA). History of acute pain may be helpful in estimating aetiology and prognosis of OHCA victims. The objective of this study was to evaluate the relationship between acute pain at various locations preceding collapse and outcome. METHODS: Clinical data of 250 witnessed, non-traumatic OHCA victims were reviewed, and the incidence of pain based on anatomical distribution was documented. The focus was on identifying the difference between those collapsing with LOC alone and those collapsing with chest pain (CP). Clinical variables predictive of survival were identified using a logistic regression model. RESULTS: Among the 250 victims, 55.2% collapsed with LOC alone. The incidence of acute pain was: 28.0% for CP, 3.2% for headache, 2.8% for abdominal pain and 2.4% for back pain. The overall 6-month survival rate was 7.2%. The LOC group had a significantly higher return of spontaneous circulation (ROSC) rate compared with the CP group (48.6% vs 31.4%, p<0.05). The rate was elevated in the LOC group; however, only when the initial rhythm was non-shockable. There was no significant intergroup difference in the survival rate. Initial shockable rhythm positively and history of cardiovascular diseases negatively predicted survival. None of the victims in the headache, abdominal pain or back pain groups survived. CONCLUSION: The LOC group's seemingly higher ROSC rate may be due to its aetiological heterogeneity. Complaint of a headache, abdominal pain or back pain in OHCA victims carries a poor prognosis.

[Charged Particle Therapy Technologies Originated in Japan].

A charged particle therapy was proposed by Robert R. Wilson in 1946 and a clinical study of proton radiotherapy had been started at Lawrence Berkeley National Laboratory in 1954. Clinical studies have been promoted mainly in the United States and Europe. However, in Japan as well, the University of Tsukuba (KEK Campus) and the National Institute of Radiological Sciences (NIRS) started proton radiotherapy around 1980, and NIRS started carbon-ion radiotherapy in 1994. Following pioneering clinical studies, now in Japan, many proton and carbon-ion radiotherapy facilities are in operation, and some vendors are supplying equipment. Among them, charged particle therapy technologies originating in Japan have been developed, such as a respiratory-gated irradiation technology, a spot scanning irradiation technology, and a clinical dose design for ion radiotherapy. I look back on them and discuss the future direction of research and development of the charged particle therapy.

The Emerging Potential of Multi-Ion Radiotherapy.

Research into high linear energy transfer (LET) radiotherapy now spans over half a century, beginning with helium and deuteron treatment in 1952 and today ranging from fast neutrons to carbon-ions. Owing to pioneering work initially in the United States and thereafter in Germany and Japan, increasing focus is on the carbon-ion beam: 12 centers are in operation, with five under construction and three in planning. While the carbon-ion beam has demonstrated unique and promising suitability in laboratory and clinical trials toward the hypofractionated treatment of hypoxic and/or radioresistant cancer, substantial developmental potential remains. Perhaps most notable is the ability to paint LET in a tumor, theoretically better focusing damage delivery within the most resistant areas. However, the technique may be limited in practice by the physical properties of the beams themselves. A heavy-ion synchrotron may provide irradiation with multiple heavy-ions: carbon, helium, and oxygen are prime candidates. Each ion varies in LET distribution, and so a methodology combining the use of multiple ions into a uniform LET distribution within a tumor may allow for even greater treatment potential in radioresistant cancer.

Estimating the biological effects of helium, carbon, oxygen, and neon ion beams using 3D silicon microdosimeters.

In this study, the survival fraction (SF) and relative biological effectiveness (RBE) of pancreatic cancer cells exposed to spread-out Bragg peak helium, carbon, oxygen, and neon ion beams are estimated from the measured microdosimetric spectra using a microdosimeter and the application of the microdosimetric kinetic (MK) model. To measure the microdosimetric spectra, a 3D mushroom silicon-on-insulator microdosimeter connected to low noise readout electronics (MicroPlus probe) was used. The parameters of the MK model were determined for pancreatic cancer cells such that the calculated SFs reproduced previously reported in vitro SF data. For a cuboid target of 10 × 10 × 6 cm3, treatment plans of helium, carbon, oxygen, and neon ion beams were designed using in-house treatment planning software (TPS) to achieve a 10% SF of pancreatic cancer cells throughout the target. The physical doses and microdosimetric spectra of the planned fields were measured at different depths in polymethyl methacrylate phantoms. The biological effects, such as SF, RBE, and RBE-weighted dose at different depths along the fields were predicted from the measurements. The predicted SFs at the target region were generally in good agreement with the planned SF from the TPS in most cases.

Application of lung substitute material as ripple filter for multi-ion therapy with helium-, carbon-, oxygen-, and neon-ion beams.

A development project for hypo-fractionated multi-ion therapy has been initiated at the National Institute of Radiological Sciences in Japan. In the treatment, helium, carbon, oxygen, and neon ions will be used as primary beams with pencil beam scanning. A ripple filter (RiFi), consisting of a thin plastic or aluminum plate with a fine periodic ridge and groove structure, has been used to broaden the Bragg peak of heavy-ion beams in the beam direction. To sufficiently broaden the Bragg peak of helium-, carbon-, oxygen-, and neon-ion beams with suppressed lateral scattering and surface dose inhomogeneity, in this study, we tested a plate made of a lung substitute material, Gammex LN300, as the RiFi. The planar integrated dose distribution of a 183.5 MeV u-1neon-ion beam was measured behind a 3 cm thick LN300 plate in water. The Bragg peak of the pristine beam was broadened following the normal distribution with the standard deviationσvalue of 1.29 mm, while the range of the beam was reduced by 8.8 mm by the plate. To verify the LN300 performance as the RiFi in multi-ion therapy, we measured the pencil beam data of helium-, carbon-, oxygen- and neon-ion beams penetrating the 3 cm thick LN300 plate. The data were then modeled and used in a treatment planning system to achieve a uniform 10% survival of human undifferentiated carcinoma cells within a cuboid target by the beam for each of the different ion species. The measured survival fractions were reasonably reproduced by the planned ones for all the ion species. No surface dose inhomogeneity was observed for any ion species even when the plate was placed close to the phantom surface. The plate made of lung substitute material, Gammex LN300, is applicable as the RiFi in multi-ion therapy with helium-, carbon-, oxygen- and neon-ion beams.

Moving target irradiation with fast rescanning and gating in particle therapy.

PURPOSE: In moving target irradiation with pencil beam scanning, the interplay effect between the target motion and the scanned beam is a problem because this effect causes over or under dosage in the target volume. To overcome this, we have studied rescanning using a gating technique. METHODS: A simulation and experimental study was carried out. In the experiment, we used the fast scanning system developed at the HIMAC to verify the validity of phase controlled rescanning method, in which the time for rescanning irradiation of each slice is matched to the gating duration. RESULTS: Simulation and experimental results showed that controlling the scan speed to match the respiration cycle with rescans can deliver the blurred dose distribution. In the comparison between the static measurements and the moving measurements with the phase controlled rescanning method, the dose difference was less than 2% for pinpoint chambers in the target volume. CONCLUSIONS: The simulation and experimental results demonstrated that the phase controlled rescanning method makes it possible to deliver the dose distribution close to the expected one. As an experimental result for 3D irradiation, it was estimated that blurring by the probability density function was not only for a lateral distribution, but also for a distal distribution, even in the lateral rescanning.