Dose distribution estimation toward CT-less adaptive carbon ion radiotherapy for liver tumors using the divided-volume matching technique.

Objective. Dose distribution estimation during the treatment course is essential for carbon ion radiotherapy because beam ranges are highly sensitive to density changes along beam paths, triggering the adaptive re-planning at an appropriate time. This study aims to investigate the feasibility of evaluating daily dose distributions using the divided-volume matching (DVM) technique without additional daily computed tomography (CT) scans for adaptive carbon ion radiotherapy for liver tumors.Approach. Phantom and patient data were included in this study. The developed in-house DVM software generated DVM CTs based on the existing resources, the planning CT, and orthogonal two-dimensional (2D) setup images. Bone matching (BM) and tumor matching (TM) are the two common ways of patient positioning correction to determine the isocenter for the irradiation of the day. We compared the dose distributions between DVM and in-room CTs with different isocenters based on BM or TM to verify whether the DVM CTs sufficiently represent the in-room CTs for daily dose distribution evaluations.Main results. For the phantom study, the clinical target volume coverage (V95%) differences between the in-room and the DVM CTs were <2%, and their dose distribution patterns were similar. For clinical data, the 3%/3 mm gamma passing rates were over 96%, and the planning target volume coverage (V95%) differences were <3% between the in-room and DVM CTs in nine out of ten patients. With different isocenters, the dose coverage of the DVM CT changed consistently with those of the in-room CT.Significance. The DVM technique enabled the evaluation of daily dose distributions without additional CT scans and was shown to be feasible in carbon ion radiotherapy for liver tumors.

Improved Algorithm for Estimation of Linear Energy Transfer in Carbon Ion Radiotherapy Plans.

BACKGROUND/AIM: This study aimed to develop an improved algorithm for linear energy transfer (LET) estimation in carbon ion radiotherapy (CIRT) using relative biological effectiveness (RBE) and to establish a clinical pipeline for LET assessment. MATERIALS AND METHODS: New approximation functions for LET versus RBE were developed for the overkill region. LET estimation performance was examined at two facilities (A and B) using archival- and Monte Carlo simulation-derived LET data, respectively, as a reference. A clinical pipeline for LET assessment was developed using Python and treatment planning systems (TPS). RESULTS: In dataset A, LET estimation accuracy in the overkill region was improved by 80.0%. In dataset B, estimation accuracy was 2.3%±0.67% across 5 data points examined. LET distribution and LET-volume histograms were visualized for multiple CIRT plans. CONCLUSION: The new algorithm showed a greater LET estimation performance at multiple facilities using the same TPS. A clinical pipeline for LET assessment was established.

Assessment of a self-inspection method and reporting measured electrometer correction factors for reference-class electrometers in radiotherapy.

BACKGROUND AND PURPOSE: The standard dosimetry system of medical accelerators in radiotherapy consists of an ionization chamber, an electrometer, and cables. Guidance for TG-51 reference dosimetry reported that the electrometer correction factor (Pelec ) should be checked every few years. Therefore, continuous Pelec measurements have not been reported. The purpose of this study is to measure the Pelec with a charge generator at our institution and to evaluate variations over time. The measurements are compared with calibration data given by an Accredited Dosimetry Calibration Laboratory (ADCL). MATERIALS AND METHODS: We used four reference-class electrometers: RT521R (RTQM system/EMF Japan), Model 35040 (FLUKE), RAMTEC Duo (Toyo medic), and UNIDOS-E (PTW). Each electrometer was connected to the charge generator, and the required charge was applied. The measurement points used were the same as those used for calibration by the ADCL. From the measured charges at each point, the Pelec was obtained from the slope of the linear regression function. The measurements were repeated over a 3-month period to evaluate variations over time for each electrometer. Additionally, error budgets for the Pelec measurements were estimated, and the overall uncertainty was determined. RESULTS: The measured Pelec values were 1.0000, 0.9995, 1.0009/0.9999, and 0.9995/0.9998 for RT521R, Model 35040, the low/medium (L/M) ranges of RAMTEC Duo, and the L/M ranges of UNIDOS-E, respectively. The measured Pelec values agreed within 0.1% with those given by the ADCL. We found a small drift in the measurements for one electrometer. Additionally, the uncertainty considered was 0.26% for k = 2 (k, coverage factor). CONCLUSION: In this study, stable Pelec values were obtained for four electrometers using a charge generator over a three-month period. The measured Pelec values were within the overall uncertainty stated in the electrometer guidelines. However, performing periodic measurements for the Pelec was able to help in detecting small errors.

Dose-volume constraints for head-and-neck cancer in carbon ion radiotherapy: A literature review.

BACKGROUND: Carbon ion radiotherapy (CIRT) has been applied in cancer treatment for over 25 years. However, guidelines for dose-volume constraints have not been established yet. The aim of this review is to summarize the dose-volume constraints in CIRT for head-and-neck (HN) cancer that were determined through previous clinical studies based on the Japanese models for relative biological effectiveness (RBE). METHODS: A literature review was conducted to identify all constraints determined for HN cancer CIRT that are based on the Japanese RBE models. RESULTS: Dose-volume constraints are reported for 17 organs at risk (OARs), including the brainstem, ocular structures, masticatory muscles, and skin. Various treatment planning strategies are also presented for reducing the dose delivered to OARs. CONCLUSIONS: The reported constraints will provide assistance during treatment planning to ensure that radiation to OARs is minimized, and thus adverse effects are reduced. Although the constraints are given based on the Japanese RBE models, applying the necessary conversion factors will potentially enable their application by institutions worldwide that use the local effect model for RBE.

Development and Applications of Compton Camera-A Review.

The history of Compton cameras began with the detection of radiation sources originally for applications in astronomy. A Compton camera is a promising γ-ray detector that operates in the wide energy range of a few tens of keV to MeV. The γ-ray detection method of a Compton camera is based on Compton scattering kinematics, which is used to determine the direction and energy of the γ-rays without using a mechanical collimator. Although the Compton camera was originally designed for astrophysical applications, it was later applied in medical imaging as well. Moreover, its application in environmental radiation measurements is also under study. Although a few review papers regarding Compton cameras have been published, they either focus very specifically on the detectors used in such cameras or the particular applications of Compton cameras. Thus, the aim of this paper is to review the features and types of Compton cameras and introduce their applications, associated imaging algorithms, improvement scopes, and their future aspects.

Linear energy transfer-independent calibration of radiochromic film for carbon-ion beams.

For carbon-ion beams, radiochromic film response depends on the dose and linear energy transfer (LET). For film dosimetry, we developed an LET-independent simple calibration method for a radiochromic film for specific therapeutic carbon-ion beams. The measured film doses were calibrated with a linear function within 5% error. The penumbra positions of the films were consistent with the differences from the planned ones within ~0.4 mm. The results indicated sufficient accuracy for use as a tool for the confirmation of the penumbra position of the fields.

First Human Cell Experiments With FLASH Carbon Ions.

BACKGROUND/AIM: This study aimed to establish a setup for ultra-high-dose-rate (FLASH) carbon-ion irradiation, and to conduct the first human cell experiments using FLASH carbon ions. MATERIALS AND METHODS: A system for FLASH carbon-ion irradiation (1-3 Gy at 13 or 50 keV/µm) was developed. The growth and senescence of HFL1 lung fibroblasts were assessed by crystal violet staining assays and senescence-associated ß-galactosidase staining, respectively. Survival of HSGc-C5 cancer cells was assessed by clonogenic assays. RESULTS: The dose rates of carbon ions ranged from 96-195 Gy/s, meeting the definition of FLASH. With both 13 and 50 keV/µm beams, no FLASH sparing effect was observed on the growth suppression and senescence of HFL1 cells, nor on the survival of HSGc-C5 cells. CONCLUSION: We successfully conducted the first human cell experiments with FLASH carbon ions. No FLASH effect was observed under the conditions examined.

An adaptive planning strategy in carbon ion therapy of pancreatic cancer involving beam angle selection.

BACKGROUND AND PURPOSE: In carbon-ion radiotherapy for pancreatic cancer, altered dose distributions due to changes in the gastrointestinal gas volume and anatomy during irradiation are an unresolved therapeutic issue. We developed and investigated an adaptive strategy involving beam angle selection to improve dose distributions in pancreatic cancer. MATERIALS AND METHODS: In the adaptive strategy, multiple beams were prepared with angles similar to those of the conventional strategy, and the beam that best reproduces the dose distribution of the treatment plan was used. The dose distributions of the adaptive strategy were compared with those of the conventional strategy for five patients. Patients underwent computed tomography (CT) before every irradiation. The adaptive strategy was evaluated using the same irradiation schedule as that of the conventional method and an adjusted method based on anatomical changes per fraction. Dose distributions on the pre-treatment CT and accumulated dose distributions on the treatment planning CT were evaluated using the volume receiving ≥95% of the prescription dose (V95) from the clinical target volume (CTV) between strategies. RESULTS: There were significant differences in the CTV V95 values for the pre-treatment CT between all strategies. The median (range) CTV V95 for the conventional strategy was 92.7% (87.1-96.1%), for the proposed adaptive strategy without adjusted schedules was 96.9% (95.1-97.8%), and for the proposed strategy with adjusted schedules was 97.8% (96.5-99.2%). CONCLUSIONS: The adaptive strategy can improve target coverage for the pre-treatment CT and accumulated dose distributions for the treatment planning CT without increasing the dose to critical organs.

Carbon range verification with 718 keV Compton imaging.

Carbon ion radiotherapy is a sophisticated radiation treatment modality because of its superiority in achieving precise dosage distribution and high biological effectiveness. However, there exist beam range uncertainties that affect treatment efficiency. This problem can be resolved if the clinical beam could be monitored precisely in real-time, such as by imaging the prompt gamma emission from the target. In this study, we performed real-time detection and imaging of 718 keV prompt gamma emissions using a Si/CdTe Compton camera. We conducted experiments on graphite phantoms using clinical carbon ion beams of 290 MeV/u energy. Compton images were reconstructed using simple back-projection methods from the energy events of 718 keV prompt gamma emissions. The peak intensity position in reconstructed 718 keV prompt gamma images was few millimeters below the Bragg peak position. Moreover, the dual- and triple-energy window images for all positions of phantoms were not affected by scattered gammas, and their peak intensity positions were approximately similar to those observed in the reconstructed 718 keV prompt gamma images. In conclusion, the findings of the current study demonstrate the feasibility of using our Compton camera for real-time beam monitoring of carbon ion beams under clinical beam intensity.

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.

Adaptive planning based on single beam optimization in passive scattering carbon ion radiotherapy for patients with pancreatic cancer.

BACKGROUND: Daily anatomical deviations may distort the dose distribution in carbon ion radiotherapy (CIRT), which may cause treatment failure. Therefore, this study aimed to perform re-planning to maintain the dose coverage in patients with pancreatic cancer with passive scattering CIRT. METHODS: Eight patients with pancreatic cancer and 95 daily computed tomography (CT) sets were examined. Two types of adaptive plans based on new range compensators (RCs) (AP-1) and initial RCs (AP-2) were generated. In AP-2, each beam was optimized by manually adjusting the range shifter thickness and spread-out Bragg peak size to make dose reduction by < 3% of the original plan. Doses of the original plan with bone matching (BM) and tumor matching (TM) were examined for comparison. We calculated the accumulated dose using the contour and intensity-based deformable image registration algorithm. The dosimetric differences in respect to the original plan were compared between methods. RESULTS: Using TM and BM, mean ± standard deviations of daily CTV V95 (%) difference from the original plan was - 5.1 ± 6.2 and - 8.8 ± 8.8, respectively, but 1.2 ± 3.4 in AP-1 and - 0.5 ± 2.1 in AP-2 (P < 0.001). AP-1 and AP-2 enabled to maintain a satisfactory accumulated dose in all patients. The dose difference was 1.2 ± 2.8, - 2,1 ± 1.7, - 7.1 ± 5.2, and - 16.5 ± 15.0 for AP-1, AP-2, TM, and BM, respectively. However, AP-2 caused a dose increase in the duodenum, especially in the left-right beam. CONCLUSIONS: The possible dose deterioration should be considered when performing the BM, even TM. Re-planning based on single beam optimization in passive scattering CIRT seems an effective and safe method of ensuring the treatment robustness in pancreatic cancer. Further study is necessary to spare healthy tissues, especially the duodenum.

Rectal dose-sparing effect with bioabsorbable spacer placement in carbon ion radiotherapy for sacral chordoma: dosimetric comparison of a simulation study.

It is difficult to treat patients with an inoperable sarcoma adjacent to the gastrointestinal (GI) tract using carbon ion radiotherapy (C-ion RT), owing to the possible development of serious GI toxicities. In such cases, spacer placement may be useful in physically separating the tumor and the GI tract. We aimed to evaluate the usefulness of spacer placement by conducting a simulation study of dosimetric comparison in a patient with sacral chordoma adjacent to the rectum treated with C-ion RT. The sacral chordoma was located in the third to fourth sacral spinal segments, in extensive contact with and compressing the rectum. Conventional C-ion RT was not indicated because the rectal dose would exceed the tolerance dose. Because we chose spacer placement surgery to physically separate the tumor and the rectum before C-ion RT, bioabsorbable spacer sheets were inserted by open surgery. After spacer placement, 67.2 Gy [relative biological effectiveness (RBE)] of C-ion RT was administered. The thickness of the spacer was stable at 13-14 mm during C-ion RT. Comparing the dose-volume histogram (DVH) parameters, Dmax for the rectum was reduced from 67 Gy (RBE) in the no spacer plan (simulation plan) to 45 Gy (RBE) in the spacer placement plan (actual plan) when a prescribed dose was administered to the tumor. Spacer placement was advantageous for irradiating the tumor and the rectum, demonstrated using the DVH parameter analysis.

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.

Combined Environment Simulator for Low-Dose-Rate Radiation and Partial Gravity of Moon and Mars.

Deep space exploration by humans has become more realistic, with planned returns to the Moon, travel to Mars, and beyond. Space radiation with a low dose rate would be a constant risk for space travelers. The combined effects of space radiation and partial gravity such as on the Moon and Mars are unknown. The difficulty for such research is that there are no good simulating systems on the ground to investigate these combined effects. To address this knowledge gap, we developed the Simulator of the environments on the Moon and Mars with Neutron irradiation and Gravity change (SwiNG) for in vitro experiments using disposable closed cell culture chambers. The device simulates partial gravity using a centrifuge in a three-dimensional clinostat. Six samples are exposed at once to neutrons at a low dose rate (1 mGy/day) using Californium-252 in the center of the centrifuge. The system is compact including two SwiNG devices in the incubator, one with and one without radiation source, with a cooling function. This simulator is highly convenient for ground-based biological experiments because of limited access to spaceflight experiments. SwiNG can contribute significantly to research on the combined effects of space radiation and partial gravity.

Reconstruction of dose distributions for fine carbon-ion beams using iterative approximation toward carbon-knife.

For the practical application of carbon-knife with fine carbon-ion beams, the quantification of the dose distribution is essential and requires a high spatial resolution. We propose a novel method to quantify dose distributions with a spatial resolution smaller than the dosimeter size. The proposed method innovates the iterative reconstruction technique. Using a diode dosimeter with a sensitive area of 1 mm2, two-dimensional dose-area-product (DAP) distributions were measured at a 0.1 mm step at the surface and near the Bragg peak depths for fine carbon-ion beams of ∼1 mm size at the full width at half maximum (FWHM). Then, the dose distributions were reconstructed with a spatial resolution of 0.1 × 0.1 mm2 from the measured DAP distributions. However, an unnaturally high noise was observed in the reconstructed dose distributions, which were considered to originate from the measurement reproducibility errors of the DAP distributions estimated to be 2.5%-3%. Therefore, a low-pass filtering process was implemented to reduce the errors on the reconstructed dose distributions. The optimum cut-off frequencies of the low-pass filter were estimated depending on the amplitude of the induced noise. Using the filtering process with the obtained optimum cut-off frequency, the dose distribution was quantified with an average error of approximately 3% or less with respect to the peak value, when the actual measurement had an error of 3%. In the reconstructed dose rate distributions, a steep penumbra P80-20 ∼ 0.2 mm was observed at the surface, and a dose rate at the center axis of ∼90 Gy s-1 and a beam size of ∼1.1 mm at FWHM near the Bragg peak were obtained. The proposed method is expected to be useful for the measurement-based determination of microbeam models for commissioning and dose distribution calculations toward carbon-knife applications.

Crosstalk Reduction Using a Dual Energy Window Scatter Correction in Compton Imaging.

Compton cameras can simultaneously detect multi-isotopes; however, when simultaneous imaging is performed, crosstalk artifacts appear on the images obtained using a low-energy window. In conventional single-photon emission computed tomography, a dual energy window (DEW) subtraction method is used to reduce crosstalk. This study aimed to evaluate the effectiveness of employing the DEW technique to reduce crosstalk artifacts in Compton images obtained using low-energy windows. To this end, in this study, we compared reconstructed images obtained using either a photo-peak window or a scatter window by performing image subtraction based on the differences between the two images. Simulation calculations were performed to obtain the list data for the Compton camera using a 171 and a 511 keV point source. In the images reconstructed using these data, crosstalk artifacts were clearly observed in the images obtained using a 171 keV photo-peak energy window. In the images obtained using a scatter window (176-186 keV), only crosstalk artifacts were visible. The DEW method could eliminate the influence of high-energy sources on the images obtained with a photo-peak window, thereby improving quantitative capability. This was also observed when the DEW method was used on experimentally obtained images.

Simultaneous determination of the dose and linear energy transfer (LET) of carbon-ion beams using radiochromic films.

Radiochromic films are useful as dosimeters in high-precision radiotherapy owing to their high spatial resolution. However, when a particle beam is measured using a radiochromic film, the dose cannot be estimated accurately because the film darkness varies with variations in linear energy transfer (LET). This paper proposes a novel method for estimating the LET and the dose based on the film darkness. In this method, after a high-LET particle beam, such as a carbon-ion beam, was incident on the film, the film was digitized and its net optical density was determined. Further, the non-linearity of the film response curve between the dose and the darkness, depending on LET, was used. Then, calibration curves were created using 290 MeV u-1 mono energetic carbon-ion beams. We used LETs of 20, 50, 100, and 150 keV µm-1 and a physical dose of 2-14 Gy. The calibration curves were approximated for each LET using a quadratic function. The correlations between the coefficients of the quadratic function and the LET were also obtained. To verify the proposed method, the films were irradiated under 12 different conditions corresponding to various depths and doses. Four depths of -2, -5, -10, and -20 mm with respect to the Bragg peak, and three different preset values were used for the film measurements. The films were analyzed in four groups, where each group comprised films irradiated at the same depth. The LETs obtained from the film analysis, ordered from the upstream of the beam, were 20, 41, 56, and 97 keV µm-1, and the doses for the lowest preset value were 3.95, 4.07, 4.03, and 3.99 Gy for the four groups. The LETs obtained from the film analysis increased toward the Bragg peak, and the doses measured in the ionization chamber were almost equal to 4 Gy.

Divided-volume matching technique for volume displacement estimation of patient positioning in radiation therapy.

PURPOSE: We propose the Divided-Volume Matching (DVM) technique to visualize and estimate three-dimensional (3D) displacements of internal structures to enable more accurate patient positioning for radiation therapy. METHODS: A CT volume is divided into a volume of interest (VOI) and a base volume (BV); 2D-3D matching is achieved using digital radiography (DR) images and digitally reconstructed radiographs (DRRs), where the DRRs are iteratively generated by changing the 3D positions and rotation angles of the separate volumes independently to identify the best match with the DR images. We demonstrate this technique with two phantom and two clinical cases. RESULTS: 3D displacements of the VOIs could be estimated independently and simultaneously with those of the BVs, with accuracies comparable to those of the conventional 2D-3D matching. The proposed technique yielded more suitable matching results when internal displacements occurred in the regions of interest (ROIs). The best matches were found when the ROI was confined to the focused structure, initial displacement values were coarsely adjusted, one volume was matched while the other was fixed, or any combination thereof. CONCLUSIONS: The proposed technique can be used effectively for independent displacement estimations of VOIs and BVs for patient positioning in radiation therapy.

Development of a Vaginal Immobilization Device: A Treatment-planning Study of Carbon-ion Radiotherapy and Intensity-modulated Radiation Therapy for Uterine Cervical Cancer.

AIM: We developed a vaginal immobilization device for external radiotherapy in gynaecological malignancies and evaluated its bowel dose-reduction effect during carbon-ion radiotherapy (CIRT) and intensity-modulated radiation therapy (IMRT) in patients with cervical cancer. PATIENTS AND METHODS: Computed tomographic images obtained with and without the device in seven patients with cervical cancer were assessed. Treatment plans for CIRT and IMRT were generated, and dose-volume parameters (V20, V25, V35, and D2cc) of the rectum, sigmoidal colon, and bladder were evaluated. RESULTS: The mean±standard deviation of the rectal volume in CIRT for V35 with and without the device were 2.1±2.1 and 13.6±4.4 ml, respectively, and those in IMRT were 2.0±2.2 and 13.7±3.8 ml, respectively; these values were significantly lower in CIRT and IMRT using this device. CONCLUSION: Using our novel vaginal immobilization device, high rectal doses were largely reduced in CIRT and IMRT.