Carbon ion therapy for laterally located tumors require multiple fixed ports or a rotating gantry.

Mayo Clinic Florida will initially open with the capability to treat with a single horizontal port for carbon ion therapy. Carbon ion therapy is traditionally done using a multi fixed port treatment approach. In this study, for nine treatment sites, clinically approved treatment plan of Osaka Heavy Ion Therapy Center was compared to a treatment plan using only a horizontal port. The treatment sites evaluated in this study were prostate cancer, pancreatic cancer, cervical cancer, recurrent rectal cancer, liver cancer, head and neck cancer, bone cancer (sarcoma and chordoma), and lung cancer. As expected, the prostate plans are identical and are only included for completeness. The DVH results for the pancreas and cervical cancer were very similar. The results for recurrent rectal, head and neck, sarcoma, chordoma, and lung cancer indicate that a single horizontal port with couch roll and yaw will accommodate certain medial targets but will be challenging to treat for laterally located targets without creative mitigations.

Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams.

The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.

Beam delivery characteristics of the Hitachi carbon ion scanning system at Osaka Heavy Ion Medical Accelerator in Kansai (HIMAK).

BACKGROUND: Using the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose between spots (move dose). This technique is also known as Dose-Driven-Continuous-Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or "break points," allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam-off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump. PURPOSE: The influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS. METHOD: We conducted fixed-point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed-point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam-off and beam-on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam-off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model. RESULT: We observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam-off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay ) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay ) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose. CONCLUSION: We conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam-off control.

Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.

BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.

Validation of robust radiobiological optimization algorithms based on the mixed beam model for intensity-modulated carbon-ion therapy.

Currently, treatment planning systems (TPSs) that can compute the intensities of intensity-modulated carbon-ion therapy (IMCT) using scanned carbon-ion beams are limited. In the present study, the computational efficacy of the newly designed IMCT algorithms was analyzed for the first time based on the mixed beam model with respect to the physical and biological doses; moreover, the validity and effectiveness of the robust radiobiological optimization were verified. A dose calculation engine was independently generated to validate a clinical dose determined in the TPS. A biological assay was performed using the HSGc-C5 cell line to validate the calculated surviving fraction (SF). Both spot control (SC) and voxel-wise worst-case scenario (WC) algorithms were employed for robust radiobiological optimization followed by their application in a Radiation Therapy Oncology Group benchmark phantom under homogeneous and heterogeneous conditions and a clinical case for range and position errors. Importantly, for the first time, both SC and WC algorithms were implemented in the integrated TPS platform that can compute the intensities of IMCT using scanned carbon-ion beams for robust radiobiological optimization. For assessing the robustness, the difference between the maximum and minimum values of a dose-volume histogram index in the examined error scenarios was considered as a robustness index. The relative biological effectiveness (RBE) determined by the independent dose calculation engine exhibited a -0.6% difference compared with the RBE defined by the TPS at the isocenter, whereas the measured and the calculated SF were similar. Regardless of the objects, compared with the conventional IMCT, the robust radiobiological optimization enhanced the sensitivity of the examined error scenarios by up to 19% for the robustness index. The computational efficacy of the novel IMCT algorithms was verified according to the mixed beam model with respect to the physical and biological doses. The robust radiobiological optimizations lowered the impact of range and position uncertainties considerably in the examined scenarios. The robustness of the WC algorithm was more enhanced compared with that of the SC algorithm. Nevertheless, the SC algorithm can be used as an alternative to the WC IMCT algorithm with respect to the computational cost.

Treatment planning of carbon ion radiotherapy for prostate cancer based on cellular experiments with PC3 human prostate cancer cells.

[Purpose] Treatment plans for carbon ion radiotherapy (CIRT) in Japan are designed to uniformly deliver the prescribed clinical dose based on the radiosensitivity of human salivary gland (HSG) cells to the planning target volume (PTV). However, sensitivity to carbon beams varies between cell lines, that is, it should be checked that the clinical dose distribution based on the cell radiosensitivity of the treatment site is uniform within the PTV. [Methods] We modeled the linear energy transfer (LET) dependence of the linear-quadratic (LQ) coefficients specific to prostate cancer, which accounts for the majority of CIRT. This was achieved by irradiating prostate cancer cells (PC3) with X-rays from a 4 MV-Linac and carbon beams with different LETs of 11.1-214.3 keV/µm. By using the radiosensitivity of PC3 cells derived from cellular experiments, we reconstructed prostate-cancer-specific clinical dose distributions on patient computed tomography (CT). [Results] The LQ coefficient, α, of PC3 cells was larger than that of HSG cells at low (<50 keV/µm) LET and smaller at high (>50 keV/µm) LET, which was validated by cellular experiments performed on rectangular SOBPs. The reconstructed dose distribution on patient CT was sloped when 1 fraction incident from the one side of the patient was considered, but remained uniform from the sum of 12 fractions of the left-right opposing beams (as is used in clinical practice). [Conclusion] Our study reveals the inhomogeneity of clinical doses in single-field plans calculated using the PC3 radiosensitivity data. However, this inhomogeneity is compensated by using the combination of left-right opposing beams.

Ultra-high Dose-rate Carbon-ion Scanning Beam With a Compact Medical Synchrotron Contributing to Further Development of FLASH Irradiation.

BACKGROUND/AIM: The focus of this report is establishing an irradiation arrangement to realize an ultra-high dose-rate (uHDR; FLASH) of scanned carbon-ion irradiation possible with a compact commonly available medical synchrotron. MATERIALS AND METHODS: Following adjustments to the operation it became possible to extract ≥1.0×109 carbon ions at 208.3 MeV/u (86 mm in range) per 100 ms. The design takes the utmost care to prevent damage to monitors, particularly in the nozzle, achieved by the uHDR beam not passing through this part of the apparatus. Doses were adjusted by extraction times, using a function generator. After one scan by the carbon-ion beam it became possible to create a field within the extraction time. The Advanced Markus chamber (AMC) and Gafchromic film are then able to measure the absolute dose and field size at a plateau depth, with the operating voltage of the chamber at 400 V at the uHDR for the AMC. RESULTS: The beam scanning utilizing this uHDR irradiation could be confirmed at a dose of 6.5±0.08 Gy (±3% homogeneous) at this volume over at least 16×16 mm2 corresponding to a dose-rate of 92.3 Gy/s (±1.3%). The dose was ca. 0.7, 1.5, 2.9, and 5.4 Gy depending on dose-rate and field size, with the rate of killed cells increasing with the irradiation dose. CONCLUSION: The compact medical synchrotron achieved FLASH dose-rates of >40 Gy/s at different dose levels and in useful field sizes for research with the apparatus and arrangement developed here.

Clinical dose assessment for scanned carbon-ion radiotherapy using linear energy transfer measurements and Monte Carlo simulations.

Objective. Dosimetric commissioning of treatment planning systems (TPS) focuses on validating the agreement of the physical dose with experimental data. For carbon-ion radiotherapy, the commissioning of the relative biological effectiveness (RBE) is necessary to predict the clinical outcome based on the radiation quality of the mixed radiation field. In this study, we proposed a approach for RBE commissioning using Monte Carlo (MC) simulations, which was further strengthen by RBE validation based on linear energy transfer (LET) measurements.Approach. First, we tuned the MC simulation based on the results of dosimetric experiments including the beam ranges, beam sizes, and MU calibrations. Furthermore, we compared simulated results to measured depth- and radial-LET distributions of the 430 MeV u-1carbon-ion spot beam with a 1.5 mm2, 36µm thick silicon detector. The measured dose-averaged LET (LETd) and RBE were compared with the simulated results. The RBE was calculated based on the mixed beam model with linear-quadratic parameters depending on the LET. Finally, TPS-calculated clinical dose profiles were validated through the tuned MC-based calculations.Main results. A 10 keVµm-1and 0.15 agreement for LETdand RBE, respectively, were found between simulation and measurement results obtained for a 2σlateral size of 430 MeV u-1carbon-ion spot beam in water. These results suggested that the tuned MC simulation can be used with acceptable precision for the RBE and LET calculations of carbon-ion spot beam within the clinical energy range. For physical and clinical doses, the TPS- and MC-based calculations showed good agreements within 1.0% at the centre of the spread-out Bragg peaks.Significance. The tuned MC simulation can accurately reproduce the actual carbon-ion beams, and it can be used to validate the physical and clinical dose distributions calculated by TPS. Moreover, the MC simulation can be used for dosimetric commissioning, including clinical doses, without LET measurements.

The Majority of United States Citizens With Cancer do not Have Access to Carbon Ion Radiotherapy.

As of December 31, 2020, there were 12 facilities located in Asia and Europe which were treating cancer patients with carbon ion radiotherapy (CIRT). Between June 1994 and December 2020, 37,548 patients were treated with CIRT worldwide. Fifteen of these patients were United States (U.S.) citizens. Using the Surveillance, Epidemiology, and End Results cancer statistics database, the Mayo Clinic in Rochester, MN has conservatively estimated that there are approximately 44,340 people diagnosed each year in the U.S. with malignancies that would benefit from treatment with CIRT. The absence of CIRT facilities in the U.S. not only limits access to CIRT for cancer care but also prevents inclusion of U.S. citizens in phase III clinical trials that will determine the comparative effectiveness and cost effectiveness of CIRT for a variety of malignancies for FDA approval and insurance coverage. Past and present phase III clinical trials have not been able to enroll U.S. citizens due to their unwillingness or inability to travel abroad for CIRT for an extended period. These barriers could be overcome with a limited number of CIRT facilities in the U.S.

Commissioning a newly developed treatment planning system, VQA Plan, for fast-raster scanning of carbon-ion beams.

In this study, we report our experience in commissioning a commercial treatment planning system (TPS) for fast-raster scanning of carbon-ion beams. This TPS uses an analytical dose calculation algorithm, a pencil-beam model with a triple Gaussian form for the lateral-dose distribution, and a beam splitting algorithm to consider lateral heterogeneity in a medium. We adopted the mixed beam model as the relative biological effectiveness (RBE) model for calculating the RBE values of the scanned carbon-ion beam. To validate the modeled physical dose, we compared the calculations with measurements of various relevant quantities as functions of the field size, range and width of the spread-out Bragg peak (SOBP), and depth-dose and lateral-dose profiles for a 6-mm SOBP in water. To model the biological dose, we compared the RBE calculated with the newly developed TPS to the RBE calculated with a previously validated TPS that is in clinical use and uses the same RBE model concept. We also performed patient-specific measurements to validate the dose model in clinical situations. The physical beam model reproduces the measured absolute dose at the center of the SOBP as a function of field size, range, and SOBP width and reproduces the dose profiles for a 6-mm SOBP in water. However, the profiles calculated for a heterogeneous phantom have some limitations in predicting the carbon-ion-beam dose, although the biological doses agreed well with the values calculated by the validated TPS. Using this dose model for fast-raster scanning, we successfully treated more than 900 patients from October 2018 to October 2020, with an acceptable agreement between the TPS-calculated and measured dose distributions. We conclude that the newly developed TPS can be used clinically with the understanding that it has limited accuracies for heterogeneous media.

Commissioning of carbon-ion radiotherapy for moving targets at the Osaka Heavy-Ion Therapy Center.

PURPOSE: Herein, we report the methods and results of the Hitachi carbon-ion therapy facility commissioning to determine the optimum values of the magnitude of movement and repaint number in respiratory-gated irradiation. METHODS: A virtual-cylinder target was created using the treatment-planning system (VQA Plan), and measurements were performed to study the effects of respiratory movements using a two-dimensional ionization-chamber array detector and a phantom with movable wedge and stage. For simulations, we selected a 10 × 10 × 10 cm3 cubic irradiation pattern with a uniform physical dose and two actual cases of liver-cancer treatments, whose prescribed doses were 60 Gy(RBE)/4 fraction (Case 1) and 60 Gy(RBE)/12 fraction (Case 2). We employed two types of repainting methods, one produced by the algorithm of VQA Plan (VQA algorithm) and the other by ideal repainting. The latter completely repeats all spots with set number of repaintings. We performed flatness calculations and gamma analysis to evaluate the effects of each condition. RESULTS: From the measurements, the gamma passing rates for which the criteria were 3%/3 mm exceeded 95% for displacements in the head-to-tail direction if the repaint number was greater than 3 and the magnitude of the residual motions was less than 5.0 mm. In simulations with the cubic irradiation pattern, the gamma passing rates (with criteria of 2%/2 mm) exceeded 95% when the magnitude of the residual motions was 3.0 mm and the repaint number was greater than 3. When the repaint number was set to 4 in the VQA with the actual liver cases, the flatness results for Case 2 was minimal. For ideal repainting, the flatness results for all ports fell within ∼3.0% even when the magnitude of the residual motions was 5.0 mm if the repaint number was 6. However, the flatness was less than 3.0% for almost all ports if the magnitude of the residual motions was less than 3.0 mm with a repaint number of 4 in case of both types of repaint methods. CONCLUSIONS: At our facility, carbon-ion radiotherapy can be provided safely to a moving target with residual motions of 3.0 mm magnitude and with a repaint number of 4.

Retrospective comparison of rectal toxicity between carbon-ion radiotherapy and intensity-modulated radiation therapy based on treatment plan, normal tissue complication probability model, and clinical outcomes in prostate cancer.

This retrospective study assessed the treatment planning data and clinical outcomes for 152 prostate cancer patients: 76 consecutive patients treated by carbon-ion radiation therapy and 76 consequtive patients treated by moderate hypo-fractionated intensity-modulated photon radiation therapy. These two modalities were compared using linear quadratic model equivalent doses in 2 Gy per fraction for rectal or rectal wall dose-volume histogram, 3.6 Gy per fraction-converted rectal dose-volume histogram, normal tissue complication probability model, and actual clinical outcomes. Carbon-ion radiation therapy was predicted to have a lower probability of rectal adverse events than intensity-modulated photon radiation therapy based on dose-volume histograms and normal tissue complication probability model. There was no difference in the clinical outcome of rectal adverse events between the two modalities compared in this study.

Carbon ion radiotherapy using fiducial markers for prostate cancer in Osaka HIMAK: Treatment planning.

PURPOSE: Carbon ion radiotherapy for prostate cancer was performed using two fine needle Gold Anchor (GA) markers for patient position verification in Osaka Heavy Ion Medical Accelerator in Kansai (Osaka HIMAK). The present study examined treatment plans for prostate cases using beam-specific planning target volume (bsPTV) based on the effect of the markers on dose distribution and analysis of target movements. MATERIALS AND METHODS: Gafchromic EBT3 film was used to measure dose perturbations caused by markers. First, the relationships between the irradiated film density and absolute dose with different linear energy transfer distributions within a spread-out Bragg peak (SOBP) were confirmed. Then, to derive the effect of markers, two types of markers, including GA, were placed at the proximal, center, and distal depths within the same SOBP, and dose distributions behind the markers were measured using the films. The amount of internal motion of prostate was derived from irradiation results and analyzed to determine the margins of the bsPTV. RESULTS: The linearity of the film densities against absolute doses was constant within the SOBP and the amount of dose perturbations caused by the markers was quantitatively estimated from the film densities. The dose perturbation close behind the markers was smallest (<10% among depths within the SOBP regardless of types of markers) and increased with depth. The effect of two types of GAs on dose distributions was small and could be ignored in the treatment planning. Based on the analysis results of internal motions of prostate, required margins of the bsPTV were found to be 8, 7, and 7 mm in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. CONCLUSION: We evaluated the dose reductions caused by markers and determined the margins of the bsPTV, which was applied to the treatment using fiducial markers, using the analysis results of prostate movements.

Three-dimensional dose-distribution measurement of therapeutic carbon-ion beams using a ZnS scintillator sheet.

The accurate measurement of the 3D dose distribution of carbon-ion beams is essential for safe carbon-ion therapy. Although ionization chambers scanned in a water tank or air are conventionally used for this purpose, these measurement methods are time-consuming. We thus developed a rapid 3D dose-measurement tool that employs a silver-activated zinc sulfide (ZnS) scintillator with lower linear energy transfer (LET) dependence than gadolinium-based (Gd) scintillators; this tool enables the measurement of carbon-ion beams with small corrections. A ZnS scintillator sheet was placed vertical to the beam axis and installed in a shaded box. Scintillation images produced by incident carbon-ions were reflected with a mirror and captured with a charge-coupled device (CCD) camera. A 290 MeV/nucleon mono-energetic beam and spread-out Bragg peak (SOBP) carbon-ion passive beams were delivered at the Gunma University Heavy Ion Medical Center. A water tank was installed above the scintillator with the water level remotely adjusted to the measurement depth. Images were recorded at various water depths and stacked in the depth direction to create 3D scintillation images. Depth and lateral profiles were analyzed from the images. The ZnS-scintillator-measured depth profile agreed with the depth dose measured using an ionization chamber, outperforming the conventional Gd-based scintillator. Measurements were realized with smaller corrections for a carbon-ion beam with a higher LET than a proton. Lateral profiles at the entrance and the Bragg peak depths could be measured with this tool. The proposed method would make it possible to rapidly perform 3D dose-distribution measurements of carbon-ion beams with smaller quenching corrections.

Physical and biological beam modeling for carbon beam scanning at Osaka Heavy Ion Therapy Center.

We have developed physical and biological beam modeling for carbon scanning therapy at the Osaka Heavy Ion Therapy Center (Osaka HIMAK). Carbon beam scanning irradiation is based on continuous carbon beam scanning, which adopts hybrid energy changes using both accelerator energy changes and binary range shifters in the nozzles. The physical dose calculation is based on a triple Gaussian pencil-beam algorithm, and we thus developed a beam modeling method using dose measurements and Monte Carlo simulation for the triple Gaussian. We exploited a biological model based on a conventional linear-quadratic (LQ) model and the photon equivalent dose, without considering the dose dependency of the relative biological effectiveness (RBE), to fully comply with the carbon passive dose distribution using a ridge filter. We extended a passive ridge-filter design method, in which carbon and helium LQ parameters are applied to carbon and fragment isotopes, respectively, to carbon scanning treatment. We then obtained radiation quality data, such as the linear energy transfer (LET) and LQ parameters, by Monte Carlo simulation. The physical dose was verified to agree with measurements to within ±2% for various patterns of volume irradiation. Furthermore, the RBE in the middle of a spread-out Bragg peak (SOBP) reproduced that from passive dose distribution results to within ±1.5%. The developed carbon beam modeling and dose calculation program was successfully applied in clinical use at Osaka HIMAK.

Calculation of Stopping-Power Ratio from Multiple CT Numbers Using Photon-Counting CT System: Two- and Three-Parameter-Fitting Method.

The two-parameter-fitting method (PFM) is commonly used to calculate the stopping-power ratio (SPR). This study proposes a new formalism: a three-PFM, which can be used in multiple spectral computed tomography (CT). Using a photon-counting CT system, seven rod-shaped samples of aluminium, graphite, and poly(methyl methacrylate) (PMMA), and four types of biological phantom materials were placed in a water-filled sample holder. The X-ray tube voltage and current were set at 150 kV and 40 µA, respectively, and four CT images were obtained at four threshold settings. A semi-empirical correction method that corrects the difference between the CT values from the photon-counting CT images and theoretical values in each spectral region was also introduced. Both the two- and three-PFMs were used to calculate the effective atomic number and electron density from multiple CT numbers. The mean excitation energy was calculated via parameterisation with the effective atomic number, and the SPR was then calculated from the calculated electron density and mean excitation energy. Then, the SPRs from both methods were compared with the theoretical values. To estimate the noise level of the CT numbers obtained from the photon-counting CT, CT numbers, including noise, were simulated to evaluate the robustness of the aforementioned PFMs. For the aluminium and graphite, the maximum relative errors for the SPRs calculated using the two-PFM and three-PFM were 17.1% and 7.1%, respectively. For the PMMA and biological phantom materials, the maximum relative errors for the SPRs calculated using the two-PFM and three-PFM were 5.5% and 2.0%, respectively. It was concluded that the three-PFM, compared with the two-PFM, can yield SPRs that are closer to the theoretical values and is less affected by noise.

Study on the RBE estimation for carbon beam scanning irradiation using a solid-state microdosimeter.

PURPOSE: The purpose of this study was to study the field size effect on the estimated Relative Biological Effectiveness (RBE) for carbon scanning beam irradiation. METHODS: A silicon-on-insulator (SOI) microdosimeter system developed by the Centre for Medical Radiation Physics, University of Wollongong, Australia, was used for lineal-energy measurements (microdosimetric quantity). The RBE values were derived based on the modified microdosimetric kinetic model (MKM) at different depths in a water phantom in the scanning carbon beam for various scanned areas. RESULTS: Our study shows that the difference in RBE values derived from the SOI microdosimeter measurements with the MKM model and from the Treatment Planning System (TPS). The difference of the RBE values is within 6.5 % at the peak point of the spread-out Bragg Peak (SOBP) region. Compared to the spot-beam, RBE values obtained in the scanned-beam with a larger scanned area of 1.0 × 1.0 cm2 have better agreement with which estimated by the TPS. CONCLUSIONS: This study shows the possibility of using the SOI microdosimeter system as a quality assurance (QA) tool for RBE evaluation in carbon-pencil beam scanning radiotherapy.

ESTIMATION OF RBE VALUES FOR CARBON-ION BEAMS IN THE WIDE DOSE RANGE USING MULTICELLULAR SPHEROIDS.

Hypofractionated carbon-ion therapy has been applied to treatment of several tumours. In this case, relative biological effectiveness (RBE) at high dose region must be considered, however, the RBE calculated physically has been not verified biologically. In this study, spheroid technique was adopted to estimate RBE in wide dose range. Cells were irradiated with X-rays and heavy-ions with LET of 13, 35, 100 and 300 keV/µm with monolayer and spheroid condition. Surviving fractions in wide dose range (0-15 Gy) were obtained to combined monolayer with spheroid survival data. The linear-quadratic and multi-target single-hit equation fitted well in survival data at low dose, and high dose region, respectively. A multi-process equation showed best fitting for survival data in wide dose range. RBE values of heavy-ions could be estimated by combination of monolayer and spheroid data. The values converged at 1.1-1.4 and varied by LET values at high and low dose region, respectively.

MRI response of obturator internus muscle to carbon-ion dose in prostate cancer treatment.

It is important to confirm the dose distribution and its biophysiological response in patients subjected to carbon-ion radiotherapy (CIRT) by using medical imaging methods. In this study, the correlation between the signal intensity changes of muscles observed in magnetic resonance imaging (MRI) after CIRT and planned dose distribution was evaluated. Seven patients were arbitrarily selected from among localized prostate cancer patients on whom CIRT was performed in our facilities in 2010. All subjects received the same dose of CIRT, namely, 57.6 Gy relative biological effectiveness (RBE) in 16 fractions. The following two types of images were acquired for each subject: planning computed tomography (CT) images overlaying the dose distribution of CIRT and MRI T2-weighted images (T2WI) taken 1 year after CIRT. The fusion image of the planning CT and MRI images was registered by using a treatment-planning system, and the CIRT dose distribution was compared with changes observed in the MRI of the obturator internus muscles located near the prostate. The signal changes in the axial image passing through the isocenter of the planning target volume were digitized, and a scatter diagram was created showing the relationship between the radiation dose and digitized signal changes. A strong correlation between the radiation dose and the MRI signal intensity changes was observed, and a quadratic function was found to have the best fit. However, estimating the dose distribution from the normalized MRI signal intensity is difficult at this point, owing to the wide variation. Therefore, further investigation is required.

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.