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.

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.

Inverse planning optimization with lead block effectively suppresses dose to the mandible in high-dose-rate brachytherapy for tongue cancer.

PURPOSE: In this study, we developed in-house software to evaluate the effect of the lead block (LB)-inserted spacer on the mandibular dose in interstitial brachytherapy (ISBT) for tongue cancer. In addition, an inverse planning algorithm for LB attenuation was developed, and its performance in mandibular dose reduction was evaluated. METHODS: Treatment plans of 30 patients with tongue cancer treated with ISBT were evaluated. The prescribed dose was 54 Gy/9 fractions. An in-house software was developed to calculate the dose distribution based on the American Association of Physicists in Medicine (AAPM) Task Group No.43 (TG-43) formalism. The mandibular dose was calculated with consideration of the LB attenuation. The attenuation coefficient of the lead was computed using the PHITS Monte Carlo simulation. The software further optimized the treatment plans using an attraction-repulsion model (ARM) to account for the LB attenuation. RESULTS: Compared to the calculation in water, the D2 cc of the mandible changed by - 2.4 ± 2.3 Gy (range, - 8.6 to - 0.1 Gy) when the LB attenuation was considered. The ARM optimization with consideration of the LB resulted in a - 2.4 ± 2.4 Gy (range, - 8.2 to 0.0 Gy) change in mandibular D2 cc. CONCLUSIONS: This study enabled the evaluation of the dose distribution with consideration of the LB attenuation. The ARM optimization with lead attenuation further reduced the mandibular dose.

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.

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.

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.

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.

Three-dimensional dose prediction and validation with the radiobiological gamma index based on a relative seriality model for head-and-neck IMRT.

This study proposes a quality assurance (QA) method incorporating radiobiological factors based on the QUANTEC-determined tumor control probability and the normal tissue complication probability (NTCP) of head-and-neck intensity-modulated radiation therapy (HN-IMRT). Per-beam measurements were conducted for 20 cases using a 2D detector array. Three-dimensional predicted dose distributions within targets and organs at risk were reconstructed based on the per-beam QA results derived from differences between planned and measured doses. Under the predicted dose distributions, the differences between the physical and radiobiological gamma indices (PGI and RGI, respectively) based on the relative seriality (RS) model were evaluated. The NTCP values in the RS and Niemierko models were compared. The dose covers 98% (D98%) of the clinical target volume (CTV) decreased by 3.2% (P < 0.001), and the mean dose of the ipsilateral parotid increased by 6.3% (P < 0.001) compared with the original dose. RGI passing rates in the CTV and brain stem were greater than PGI ones by 5.8% (P < 0.001) and 2.0% (P < 0.001), respectively. The RS model's average NTCP values for the ipsilateral and contralateral parotids under the original dose were smaller than those of the Niemierko model by 9.0% (P < 0.001) and 7.0% (P < 0.001), respectively. The 3D predicted dose evaluation with RGI based on the RS model was introduced for QA of HN-IMRT, leading to dose evaluation for each organ with consideration of the radiobiological effect. This method constitutes a rational way to perform QA of HN-IMRT in clinical practice.