Gunma University Heavy Ion Medical Research Articles

Diamond energy-dispersive dosimeter for measuring linear energy deposition distributions in clinical carbon beam therapy

A thin diamond membrane energy-dispersive dosimeter 50 μm thick was fabricated for estimating clinical dose distribution. In contrast to conventional semiconductors, diamond wide-bandgap semiconductors are expected to have excellent radiation tolerance and biological compatibility based on the linear relationship of stopping power ratio for clinical carbon particles. Linear energy transfer (LET) spectra were obtained along with the Bragg curve for a clinical carbon beam generated at Gunma University Heavy Ion Medical Center. The relative biological effectiveness (RBE) distributions were estimated from the LET spectra for both the mono-energy and spread-out Bragg peak irradiation configurations. The diamond detector was also used as a solid ionization chamber to obtain the radiation-induced current (RIC) distribution, which represents the physical dose distribution. The clinical dose distribution was estimated from the RIC and RBE distributions as proof of concept for the clinical carbon beam therapy field with a single-chip diamond energy-dispersive dosimeter.

Measurement of radiation-induced current through a SiC Schottky barrier diode in a clinical carbon beam cancer therapy field

Real-time physical dose evaluation was performed using radiation-tolerant SiC Schottky barrier diodes (SBDs). The radiation-induced current (RIC) generated in the SBD was measured under clinical carbon beam irradiation. A SiC SBD semiconductor detector (epitaxial layer, 69 µm thick; impurity concentration, 9.1 × 1014 cm−3; electrodes, 1 mm2) was used. The SiC SBD was irradiated with carbon ions having energy of 290 MeV/n at a maximum flux of therapeutic intensity (1 × 109 particles per second) at the Gunma University Heavy Ion Medical Center. The transition of the RIC value at any depth point in the Bragg curve was evaluated by changing the thickness of a water tank placed in front of the SiC SBD. The RIC from the SiC SBD was obtained with an applied voltage of up to 100 V for each moderator thickness. The physical dose distribution was also measured using a commercial ionization chamber. The Bragg peak was determined from the RIC distribution, and the transition was similar to that observed using the commercial ionization chamber.

Linear energy transfer (LET) spectroscopy and relative biological effect estimation by SiC-based dosimeter at clinical carbon-beam cancer therapy field

A radiation-tolerant silicon carbide (SiC) based dosimeter was developed for the measurement of linear energy transfer (LET) distributions along the Bragg curve for pristine and spread-out Bragg peak (SOBP) clinical carbon beam. Since the conventional ionized chamber is not suitable and effective for LET measurement, several energy-dispersive dosimeters are being developed and tested in the clinical field. While most of the detector lacks radiation hardness against carbon beam, we have utilized wide-bandgap semiconductors of SiC with different epitaxial layers from 25, 69, and 170 μm as a dosimeter for the clinical carbon field at Gunma University Heavy Ion Medical Center (GHMC). LET spectra were obtained not only for pristine carbon beams with an energy of 290 MeV/n but also SOBP conditions. It was confirmed through the changes in LET distribution, primally carbons and fragments are identified, and those energy depositions are successfully obtained by the fabricated SiC dosimeter. The distribution of relative biological effectiveness (RBE) was estimated from LET through biological estimation models. Results suggested that SiC-based dosimeter is successful in being utilized in the detailed characterization of the clinical carbon therapy field.

Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck in Gunma University

ObjectiveData on the long-term outcomes of carbon-ion radiotherapy for non-squamous cell carcinomas are rare. Gunma University has been utilizing carbon-ion radiotherapy as a treatment for head and neck cancer since 2010. This study aimed to evaluate the long-term efficacy and safety of carbon-ion radiotherapy for the head and neck. MethodsWe prospectively evaluated 35 patients with non-squamous cell carcinoma who underwent carbon-ion radiotherapy at Gunma University Heavy Ion Medical Center between 2010 and 2014. The 5-year local control, overall survival, and progression-free survival rates were evaluated. ResultsThe median age was 59 years (range, 31–77 years), and the median follow-up time was 65 months (range, 6.1–98.8 months). Overall, 32 and 3 patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was the most dominant histopathological type (n = 21 patients, 60 %). The 5-year local control, progression-free survival, and overall survival rates were 74.5 %, 53.2 %, and 81.3 %, respectively. Nine patients had local recurrence, and six patients died. Adverse events included acute grade 3 radiation mucositis (Common Terminology Criteria for Adverse Events version 4.0) in 8 patients; this was improved immediately with conservative therapy. Late grade 4 adverse events were observed, including two cases of visual loss and one case of brain necrosis. No grade 5 adverse events were observed. ConclusionCarbon-ion radiotherapy achieves excellent local control and overall survival rates in non-squamous cell carcinoma patients with expected adverse events.

Safety verification of carbon-ion radiotherapy for patients with cardiac implantable electronic devices (CIEDs)

According to guidelines, carbon-ion beam therapy is considered to carry a high safety risk for patients with cardiac implantable electronic devices (CIEDs), although the actual impacts remain unclear. In this study, we investigated the safety of carbon-ion beam therapy in patients with CIEDs. Patients with CIEDs who underwent carbon-ion therapy at Gunma University Heavy Ion Medical Center between June 2010 and December 2019 were identified and investigated for abnormalities in the operation of their CIEDs, such as oversensing and resetting during irradiation, and abnormalities in operation after treatment. In addition, the risk of irradiation from carbon-ion beam therapy was evaluated by model simulations. Twenty patients (22 sites) with CIEDs were identified, 19 with pacemakers and one with an implantable cardioverter-defibrillator (ICD). Treatments were completed without any problems, except for one case in which the treatment was discontinued because of worsening of the primary disease. Monte Carlo simulation indicated that the carbon beam irradiation produced neutrons at a constant and high level in the irradiation field. Nevertheless, with the distances between the CIEDs and the irradiation fields in the analyzed cases, the quantity of neutrons at the CIEDs was lower than that within the irradiation. Although carbon-ion beam therapy can be safely administered to patients with CIEDs, it is advisable to perform the therapy with sufficient preparation and backup devices because of the risks involved.

Development of wide-bandgap semiconductor-based dosimeter for LET distribution measurement in carbon therapy filed

This paper presents a proof of concept of silicon carbide (SiC), a type of wideband semiconductor, based dosimeter for linear energy transfer (LET) distribution measurement at clinical carbon beam therapy field. SiC Schottky barrier diode (SBD), which has been designed for ionization detector, was utilized for spectroscopy of pristine 290 MeV/u 12C heavy ion therapy beams at Gunma University Heavy Ion Medical Centre (GHMC) facility, Japan. Measurement of LET distribution was successfully demonstrated at different depth with developed SiC SBD dosimeter. Also SiC SBD was exposed with clinical carbon beam with high intensity condition. Through CCE and deep level defect evaluation, sufficient radiation tolerance was examined for SiC SBD for futuristic usage in clinical carbons. Those results suggested that preliminary evaluation of SiC SBD was successful as energy-dispersive dosimeter for heavy ion therapy field.

Estimations of relative biological effectiveness of secondary fragments in carbon ion irradiation of water using CR-39 plastic detector and microdosimetric kinetic model.

To estimate relative biological effectiveness (RBE) ascribed to secondary fragments in a lateral distribution of carbon ion irradiation. The RBE was estimated with the microdosimetric kinetic (MK) model and measured linear energy transfer (LET) obtained with CR-39 plastic detectors. A water phantom was irradiated by a 12 C pencil beam with energy of 380MeV/u at the Gunma University Heavy Ion Medical Center (GHMC), and CR-39 detectors were exposed to secondary fragments. Because CR-39 was insensitive to low LET, we conducted Monte Carlo simulations with Geant4 to calculate low LET particles. The spectra of low LET particleswere combined with experimental spectra to calculate RBE. To estimate accuracy of RBE, we calculated RBE by changing yield of low LET particles by±10% and±40%. At a small angle, maximum RBE by secondary fragments was 1.3 for 10% survival fractions. RBE values of fragments gradually decreased as the angle became larger. The shape of the LET spectra in the simulation reproduced the experimental spectra, but there was a discrepancy between the simulation and experiment for the relative yield of fragments. When the yield of low LET particles was changed by±40%, the change in RBE was smaller than 10%. An RBE of 1.3 was expected for secondary fragments emitted at a small angle. Although, we observed a discrepancy in the relative yield of secondary fragments between simulation and experiment, precision of RBE was not so sensitive to the yield of low LET particles.

Scintillator screen for measuring dose distribution in scanned carbon-ion therapy

Precise measurement of the dose distribution of a carbon-ion pencil beam is essential for the safe delivery of treatment in scanned carbon-ion therapy. We developed an easy-to-use and quick dose-measurement tool that employs a silver-activated zinc-sulfide (ZnS) scintillator, which shows a smaller linear energy transfer (LET) dependency than conventional Gd-based scintillator, to measure the dose distribution of a carbon-ion pencil beam with high spatial resolution and small corrections.A ZnS scintillator sheet was set up perpendicular to the beam axis, and scintillation images were recorded using a charge-coupled device camera. We used 290-MeV/nucleon monoenergetic carbon-ion pencil beams at the Gunma University Heavy Ion Medical Center. The thickness of the water tank placed above the scintillator was remotely controlled to adjust the measurement depth. Images were acquired at different water depths, and the depth and lateral profiles were determined from the images. The results were compared with those of conventional Gd-based scintillator.The depth–light intensity profile of the ZnS scintillator matched the depth dose measured using an ionization chamber, which was better than that of a Gd-based scintillator. This result is advantageous for measurements using a carbon-ion pencil beam, which consists of primary carbon ions with a much higher LET than a proton, with smaller corrections. The ZnS scintillator showed good output characteristics, dose linearity (R2 > 0.99), and output reproducibility (deviations below 2%) and good agreement with the lateral-dose profiles measured using a diode down to ~1% of the central dose. The proposed tool can measure lateral profiles at the depth of the Bragg peak and tail in addition to the entrance. Our tool was used to quickly measure the dose distribution of carbon-ion pencil beam with high-spatial resolution and small corrections.

Carbon-Ion Radiotherapy for Bone and Soft Tissue Tumors; Analysis of 92 Patients at Gunma University Heavy Ion Medical Center (GHMC)

To retrospectively evaluate the feasibility and efficacy of carbon-ion radiotherapy (C-ion RT) for unresectable bone and soft tissue tumors treated in Gunma University Heavy Ion Medical Center (GHMC). A total 92 patients with bone or soft tissue tumors treated with C-ion RT between November 2011 and December 2018 in GHMC were retrospectively evaluated. In C-ion RT, 70.4 Gy(RBE) was administrated as the standard total dose for sarcomas; 67.2 Gy(RBE) for sacrococcygeal chordomas; 64.0 Gy(RBE) for spinal bone tumors, in 16 fractions over 4 weeks. Local control rate (LCR), survival outcomes, acute and late adverse events were analyzed. The curves of LCR and overall survival rates (OS) were calculated by Kaplan-Meier method. The median age at the C-ion RT was 68 years (range, 25-90 years). Median follow-up time was 28.5 months (range, 1-97 months). Histologically, 31 patients had chordoma, 13 patients had UPS or MFH, 11 patients had liposarcoma, 8 patients had chondrosarcoma and 7 patients had osteosarcoma. The 3-year LCR and OS in all patients were 85% and 70%, respectively. The 3-year LCR and OS of 50 patients with bone tumor were 95% and 82%, and those of 42 patients with soft tissue tumors were 72% and 51%. The 3-year LCR and OS of 31 patients with chordoma were 96%, 90%; those of 13 patients with UPS or MFH were 45%, 62%; those of 11 patients with liposarcoma were 88%, 36%; those of 8 patients with chondrosarcoma were 86%, 67%; and the 2-year LCR and OS of 7 patients with osteosarcoma were 100%, 46%. The 3-year LCR and OS by volume of clinical target volume (CTV) were 100%, 100% in under 100cc (n=6), 76%, 68% in between 100cc and 500cc (n=29), 76%, 37% in over 500cc (n=24), respectively. There were no patients with Grade 3 or above acute adverse events. The Grade 3 or above late adverse events were shown in 7 patients. The results of this study showed that C-ion RT must be an alternative treatment option for unresectable bone and soft tissue tumors. Both the LCR and OS were influenced by CTV volume.

Analysis of the Stay Time of Patients in Gunma University Heavy Ion Medical Center (GHMC) Using RFID Technology.

We observed the stay time of patients and staff in Gunma University Heavy Ion Medical Center. The stay time of patients with the prostatic cancer and the facing time with radiotherapy technicians in treatment rooms were significantly reduced as times goes by. This decreasing in time has an implication in scheduling algorithm development: for patients. RFID technology can be a potential method to track both staff and patients and thereby to assess the resource utilization efficiency.

Linear energy transfer (LET) spectra and survival fraction distribution based on the CR-39 plastic charged-particle detector in a spread-out Bragg peak irradiation by a 12C beam

Facilities for heavy ion therapies are steadily increasing in number worldwide. One of the advantages of heavy ions is their high relative biological effect (RBE). In a model used at NIRS (National Institute of Radiological Sciences), linear energy transfer (LET) spectra are required to estimate biological dose (physical dose × RBE). The CR-39 plastic charged-particle detector (CR-39) is suitable for measurement of LET. For the present study, done at the Gunma University Heavy Ion Medical Center (GHMC), we measured LET spectra at 11 depths in spread-out Bragg peak (SOBP) irradiation by a 12C beam of 380 MeV/u. The lower threshold of the CR-39 to measure LET was about 5 keV µm−1 due to poor sensitivity for low LET. Then we calculated biological dose and survival fraction distributions and compared them with treatment planning results at GHMC. We used Monte Carlo simulation (Geant4) to calculate LET spectra. The simulation results were in good agreement with the experimental spectra. Moreover, the biological dose and survival fraction distributions estimated from the CR-39 reproduced the treatment planning. The CR-39 is suitable for estimating biological dose in carbon ion therapy.

The relative biological effectiveness for carbon, nitrogen, and oxygen ion beams using passive and scanning techniques evaluated with fully 3D silicon microdosimeters.

The aim of this study was to measure the microdosimetric distributions of a carbon pencil beam scanning (PBS) and passive scattering system as well as to evaluate the relative biological effectiveness (RBE) of different ions, namely 12 C, 14 N, and 16 O, using a silicon-on-insulator (SOI) microdosimeter with well-defined 3D-sensitive volumes (SV). Geant4 simulations were performed with the same experimental setup and results were compared to the experimental results for benchmarking. Two different silicon microdosimeters with rectangular parallelepiped and cylindrical shaped SVs, both 10 μm in thickness were used in this study. The microdosimeters were connected to low noise electronics which allowed for the detection of lineal energies as low as 0.15 keV/μm in tissue. The silicon microdosimeters provide extremely high spatial resolution and can be used for in-field and out-of-field measurements in both passive scattering and PBS deliveries. The response of the microdosimeters was studied in 290 MeV/u 12 C, 180 MeV/u 14 N, 400 MeV/u 16 O passive ion beams, and 290 MeV/u 12 C scanning carbon therapy beam at heavy ion medical accelerator in Chiba (HIMAC) and Gunma University Heavy Ion Medical Center (GHMC), Japan, respectively. The microdosimeters were placed at various depths in a water phantom along the central axis of the ion beam, and at the distal part of the Spread Out Bragg Peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the microdosimetric lineal energy spectra and the modified microdosimetric kinetic model (MKM), using MKM input parameters corresponding to human salivary gland (HSG) tumor cells. Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results. For a 180 MeV/u 14 N pristine BP, the dose-mean lineal energy yD¯ obtained with two types of silicon microdosimeters started from approximately 29 keV/μm at the entrance to 92 keV/μm at the BP, with a maximum value in the range of 412 to 438 keV/μm at the distal edge. For 400 MeV/u 16 O ions, the dose-mean lineal energy yD¯ started from about 24 keV/μm at the entrance to 106 keV/μm at the BP, with a maximum value of approximately 381 keV/μm at the distal edge. The maximum derived RBE10 values for 14 N and 16 O ions were found to be 3.10 ± 0.47 and 2.93 ± 0.45, respectively. Silicon microdosimetry measurements using pencilbeam scanning 12 C ions were also compared to the passive scattering beam. These SOI microdosimeters with well-defined three-dimensional (3D) SVs have applicability in characterizing heavy ion radiation fields and measuring lineal energy deposition with sub-millimeter spatial resolution. It has been shown that the dose-mean lineal energy increased significantly at the distal part of the BP and SOBP due to very high LET particles. Good agreement was observed for the experimental and simulation results obtained with silicon microdosimeters in 14 N and 16 O ion beams, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in charged particle therapy.

A carbon CT system: how to obtain accurate stopping power ratio using a Bragg peak reduction technique

In this study, we investigate the performance of the Gunma University Heavy Ion Medical Center’s ion computed tomography (CT) system, which measures the residual range of a carbon-ion beam using a fluoroscopy screen, a charge-coupled-device camera, and a moving wedge absorber and collects CT reconstruction images from each projection angle. Each 2D image was obtained by changing the polymethyl methacrylate (PMMA) thickness, such that all images for one projection could be expressed as the depth distribution in PMMA. The residual range as a function of PMMA depth was related to the range in water through a calibration factor, which was determined by comparing the PMMA-equivalent thickness measured by the ion CT system to the water-equivalent thickness measured by a water column. Aluminium, graphite, PMMA, and five biological phantoms were placed in a sample holder, and the residual range for each was quantified simultaneously. A novel method of CT reconstruction to correct for the angular deflection of incident carbon ions in the heterogeneous region utilising the Bragg peak reduction (BPR) is also introduced in this paper, and its performance is compared with other methods present in the literature such as the decomposition and differential methods. Stopping power ratio values derived with the BPR method from carbon-ion CT images matched closely with the true water-equivalent length values obtained from the validation slab experiment.

Maximum standardized uptake value on FDG-PET predicts survival in stage I non-small cell lung cancer following carbon ion radiotherapy.

The present study (University Hospital Medical Information Network study no. UMIN000003797) aimed to evaluate whether the maximum standardized uptake value (SUVmax) of pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is prognostic factor for stage I non-small cell lung cancer (NSCLC) treated with carbon ion radiotherapy (C-ion RT). Patients treated between June 2010 and June 2013 at Gunma University Heavy Ion Medical Center (Maebashi, Japan) on a prospective protocol were included in the present study. Patients with T1a-b and T2a NSCLC were treated with C-ion RT at a dose of 52.8 Gy [relative biological effectiveness (RBE)] and 60.0 Gy (RBE), respectively, in four fractions. Prior to treatment, all patients underwent FDG-PET, in which the SUVmax of primary tumors was evaluated. Local control, progression-free survival (PFS), and overall survival (OS) were calculated. A total of 45 patients were analyzed and the median follow-up period was 28.9 months. The 2-year local control, PFS and OS rates for all patients were 93, 78 and 89%, respectively. The mean SUVmax of primary tumors was 5.5, and patients were divided into higher (≥5.5) and lower (<5.5) SUVmax groups. The 2-year PFS rates were 61 and 89% for the higher and lower SUVmax groups, respectively (P=0.01), and the 2-year OS rates for the higher and lower SUVmax groups were 76 and 96%, respectively (P=0.01). The higher SUVmax group exhibited a significantly worse PFS and OS compared with the lower SUVmax group; however, the SUVmax was not associated with the local control rate. In total, 2 patients (4%) experienced grade 2 or 3 radiation pneumonitis, with their symptoms improved through conservative treatment. No patients experienced any grade 4 or 5 toxicities. The results of the present study indicate that pretreatment SUVmax is a prognostic indicator for outcomes in patients with stage I NSCLC treated with C-ion RT.

Three-Dimensional Dosimetry of Carbon Ion Beams by Gel Dosimeters

A three-dimensional dosimetry method is strongly required in the dose distribution measurement of a patient QA of a heavy ion therapy. Nanocomposite Fricke gel dosimeters are the most possible candidate for this purpose. Experimental dose distribution measurements were carried out using a scanning irradiation port of Gunma University Heavy Ion Medical Center. The result showed no significant LET dependence and indicated a possibility for a precise dosimetry of a heavy ion therapy. It also indicated the importance of three-dimensional dosimetry in the commissioning process of the treatment accelerator.

A multi-institutional analysis of prospective studies of carbon ion radiotherapy for prostate cancer: A report from the Japan Carbon ion Radiation Oncology Study Group (J-CROS)

Background and purposeA multi-institutional observational study (J-CROS1501PR) has been carried out to analyze outcomes of carbon-ion radiotherapy (CIRT) for patients with prostate cancer. Patients and methodsData of the patients enrolled in prospective studies of following 3 CIRT institutions were analyzed: National Institute of Radiological Sciences (NIRS; Chiba, Japan), Gunma University Heavy Ion Medical Center (GHMC; Gunma, Japan), and Ion Beam Therapy Center, SAGA HIMAT Foundation (HIMAT; Saga, Japan). Endpoints of the clinical trial are biochemical recurrence-free survival (bRFS), overall survival (OS), cause-specific survival (CSS), local control rate (LCR), and acute/late adverse effects. ResultsA total of 2157 patients’ data were collected from NIRS (n=1432), GHMC (n=515), and HIMAT (n=210). The number of patients in low-risk, intermediate-risk, and high-risk groups was 263 (12%), 679 (31%), and 1215 (56%), respectively. The five-year bRFS in low-risk, intermediate-risk, and high-risk patients was 92%, 89%, and 92%, respectively. The five-year CSS in low-risk, intermediate-risk, and high-risk patients was 100%, 100%, and 99%, respectively. The incidence of grade 2 late GU/GI toxicities was 4.6% and 0.4%, respectively, and the incidence of ⩾G3 toxicities were 0%. ConclusionsFavorable overall outcomes of CIRT for prostate cancer were suggested by the analysis of the first multi-institutional data.

Translational Research to Improve the Efficacy of Carbon Ion Radiotherapy: Experience of Gunma University.

Carbon ion radiotherapy holds great promise for cancer therapy. Clinical data show that carbon ion radiotherapy is an effective treatment for tumors that are resistant to X-ray radiotherapy. Since 1994 in Japan, the National Institute of Radiological Sciences has been heading the development of carbon ion radiotherapy using the Heavy Ion Medical Accelerator in Chiba. The Gunma University Heavy Ion Medical Center (GHMC) was established in the year 2006 as a proof-of-principle institute for carbon ion radiotherapy with a view to facilitating the worldwide spread of compact accelerator systems. Along with the management of more than 1900 cancer patients to date, GHMC engages in translational research to improve the treatment efficacy of carbon ion radiotherapy. Research aimed at guiding patient selection is of utmost importance for making the most of carbon ion radiotherapy, which is an extremely limited medical resource. Intratumoral oxygen levels, radiation-induced cellular apoptosis, the capacity to repair DNA double-strand breaks, and the mutational status of tumor protein p53 and epidermal growth factor receptor genes are all associated with X-ray sensitivity. Assays for these factors are useful in the identification of X-ray-resistant tumors for which carbon ion radiotherapy would be beneficial. Research aimed at optimizing treatments based on carbon ion radiotherapy is also important. This includes assessment of dose fractionation, normal tissue toxicity, tumor cell motility, and bystander effects. Furthermore, the efficacy of carbon ion radiotherapy will likely be enhanced by research into combined treatment with other modalities such as chemotherapy. Several clinically available chemotherapeutic drugs (carboplatin, paclitaxel, and etoposide) and drugs at the developmental stage (Wee-1 and heat shock protein 90 inhibitors) show a sensitizing effect on tumor cells treated with carbon ions. Additionally, the efficacy of carbon ion radiotherapy can be improved by combining it with cancer immunotherapy. Clinical validation of preclinical findings is necessary to further improve the treatment efficacy of carbon ion radiotherapy.

Evaluation of an empirical monitor output estimation in carbon ion radiotherapy

A conventional broad beam method is applied to carbon ion radiotherapy at Gunma University Heavy Ion Medical Center. According to this method, accelerated carbon ions are scattered by various beam line devices to form 3D dose distribution. The physical dose per monitor unit (d/MU) at the isocenter, therefore, depends on beam line parameters and should be calibrated by a measurement in clinical practice. This study aims to develop a calculation algorithm for d/MU using beam line parameters. Two major factors, the range shifter dependence and the field aperture effect, are measured via PinPoint chamber in a water phantom, which is an identical setup as that used for monitor calibration in clinical practice. An empirical monitor calibration method based on measurement results is developed using a simple algorithm utilizing a linear function and a double Gaussian pencil beam distribution to express the range shifter dependence and the field aperture effect. The range shifter dependence and the field aperture effect are evaluated to have errors of 0.2% and 0.5%, respectively. The proposed method has successfully estimated d/MU with a difference of less than 1% with respect to the measurement results. Taking the measurement deviation of about 0.3% into account, this result is sufficiently accurate for clinical applications. An empirical procedure to estimate d/MU with a simple algorithm is established in this research. This procedure allows them to use the beam time for more treatments, quality assurances, and other research endeavors.

Effects of Carbon Ion Beam Alone or in Combination With Gemcitabine and/or Cisplatin on Cholangiocarcinoma Stem-Like Cells

In Vitro Determination of the Relative Biological Effectiveness of Carbon Ion Beam Irradiation in Cells Derived From Human Normal Lung Tissues N. Okano, T. Oike, J. Saitoh, K. Shirai, T. Kiyono, M. Enari, M. Isono, K. Torikai, T. Ohno, and T. Nakano; Gunma University, Maebashi, Gunma, Japan, Gunma University Heavy Ion Medical Center, Gunma University, Maebashi, Gunma, Japan, National Cancer Center Research Institute, Tokyo, Japan

Operation status of the electron cyclotron resonance ion source at Gunma University

An ECR ion source of Gunma University Heavy Ion Medical Center, so-called KeiGM [M. Muramatsu, A. Kitagawa, Y. Sakamoto, S. Sato, Y. Sato, H. Ogawa, S. Yamada, H. Ogawa, Y. Yoshida, and A. G. Drentje, Rev. Sci. Instrum. 76, 113304 (2005)], has been operated for cancer therapy and physical/biological experiment since 2010. KeiGM produces typically 230 μA of 10keV/u C(4+) ions from CH4 gases. The vacuum pressure is kept between 1.2 × 10(-4) and 1.7 × 10(-4)Pa so as to suppress the pulse-to-pulse current fluctuation within ±10%. The extraction electrode is cleaned every 6-8 months in order to remove deposited carbon, which increases the leak current and discharge. In order to investigate the possibility of long-term operation without such maintenances, oxygen aging for the cleaning of the extraction electrode has been tested in the test bench. The same-designed ion sources at National Institute of Radiological Sciences and SAGA Heavy Ion Medical Accelerator in Tosu (SAGA-HIMAT) are also operated with stable C(4+) current, which are suitable for the continuous operation for cancer therapy.