Dose Evaluation in 2-Phase Method for Advanced Esophageal Cancer by Hybrid Irradiation Techniques.

Purpose: In concurrent chemoradiotherapy for advanced esophageal cancer, a 2-phase method consisting of initial irradiation of a wide elective nodal region and boost irradiation of the primary lesion is commonly employed. Although dose escalation to the primary lesion may be required to achieve higher local control rates, the radiation dose to critical organs must not exceed dose constraints. To achieve an optimum balance of dose prescription and dose reduction to surrounding organs, such as the lungs and heart, we compared hybrid dose distributions and investigated the best combination of the following recent irradiation techniques: volumetric modulation arc therapy (VMAT), proton broad-beam irradiation, and intensity-modulated proton beam therapy (IMPT). Materials and Methods: Forty-five patients with advanced esophageal cancer whose primary lesions were located in the middle- or lower-thoracic region were studied. Radiotherapy plans for the initial and boost irradiation in the 2-phase method were calculated using VMAT, proton broad-beam irradiation, and IMPT calculation codes, and the dose-volume histogram indices of the lungs and heart for the accumulated plans were compared. Results: In plans using boost proton irradiation with a prescribed dose of 60 Gy(RBE), all dose-volume histogram indices were significantly below the tolerance limits. Initial and boost irradiation with VMAT resulted in the median dose of V30 Gy(RBE)(heart) of 27.4% and an achievement rate below the tolerance limit of 57.8% (26 cases). In simulations of dose escalation up to 70 Gy(RBE), initial and boost IMPT resulted in the highest achievement rate, satisfying all dose constraints in 95.6% (43 cases). Conclusion: Applying VMAT to both initial and boost irradiation is not recommended because of the increased risk of the cardiac dose exceeding the tolerance limit. IMPT may allow dose escalation of up to 70 Gy(RBE) without radiation risks to the lungs and heart in the treatment of advanced esophageal cancer.

[Estimation of Uncertainty of the VMAT Absolute Dose Measurement Due to the Phantom Setup Error Using a Treatment Planning System].

PURPOSE: When performing single-point dose verification in VMAT, it is necessary to avoid the regions with steep dose gradient. We propose a method to obtain the estimated value ( Uplan) of uncertainty of the absolute dose measurement due to the phantom setup error by using dose gradient calculated from treatment planning system (TPS), for evaluating the appropriate measurement points. METHODS: The dose gradient was calculated from the planned dose values in the vicinity of the isocenter point using TPS. The phantom setup error was estimated. The Uplan was calculated using the proposed formula after estimating the phantom setup error. Then, the dose gradient was calculated from the measured dose values in the vicinity of the isocenter point specified by TPS using the Tough water phantom with ionization chamber (IC), and Umeas was calculated as in Uplan. RESULTS: The correlation coefficient between Uplan and Umeas was 0.984, which indicates a high correlation. The average of the difference between Umeas and Uplan was -0.24%. We considered that this result was caused by the influence of volume averaging effect of IC. CONCLUSION: The Uplan obtained from this proposed method reflects the uncertainty of the absolute dose measurement due to the phantom setup error and is useful for evaluating the appropriate measurement points for absolute dose measurement.

Evaluation of Exposure Doses of Elective Nodal Irradiation in Chemoradiotherapy for Advanced Esophageal Cancer.

We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52-80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012-September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy. The median doses were 40.0 and 36.0 Gy in HG and LG, respectively. During the follow-up (median: 36.7 months), no lymph node recurrence was observed in the ENI field in all patients. Lymph node recurrence near the ENI field was observed in six patients. No significant differences were observed between the two groups in median overall survival, progression-free survival, and local control. Grade 3-4 acute and late adverse events were observed in five patients of HG and six patients of LG, respectively. No ulceration or stricture was observed in the ENI field on endoscopy examined with 58 Gy irradiation. In conclusion, an ENI dose of 36 Gy could be considered to control the elective nodes of EC.

Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers.

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan-Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38-90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8-82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient's condition. The median follow-up of surviving patients was 63 months (range, 1-126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications.

A robust optimization method for weighted-layer-stacking proton beam therapy.

The layer-stacking method can provide three-dimensional conformal dose distributions to the target based on a passive scattering method using mini-spread-out Bragg peak (SOBP). The purpose of this work is to demonstrate the effectiveness of a new weight optimization algorithm that can enhance the robustness of dose distributions against layer depth variation in layer-stacking proton beam therapy. In the robustness algorithm, the upper limit of the layer's weight was adapted to the conventional algorithm and varied for 620 weight set evaluations. The optimal weight set was selected by using an analytical objective function based on Gaussian function with σ = 3 mm for WED variation. Then, we evaluated the stabilities of the one-dimensional depth dose distribution against WED variation generated by Gaussian samples. Three-dimensional dose distributions in the water phantom were also evaluated using the Monte-Carlo dose calculation. The variation of dose as well as dose volume histograms for the spherical target and the organ at risk (OAR) were evaluated. The robustness algorithm reduced the change of the dose distribution due to the WED variation by a factor of almost 3/4 compared to those with the conventional procedure. The rate of 91.8% in total samples was maintained within 5% change of the maximum dose, compared with the rate of 64.9% in the conventional algorithm. In the MC calculation, the high dose-volume in the OAR was reduced around the lateral penumbra and distal falloff region by the robustness algorithm. The stability of depth dose distributions was enhanced under the WED variation, compared to the conventional algorithm. This robust algorithm in layer-stacking proton therapy may be useful for treatment in which the sharpness of the distal falloff along the depth distribution needs to be maintained to spare the organ at risk and keep the dose coverage for the target tumor.

Erratum: Shibata S.; et al. Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas. Cancers 2018, 10, 71.

The authors wish to make the following corrections to this paper [...].

Positioning accuracy and daily dose assessment for prostate cancer treatment using in-room CT image guidance at a proton therapy facility.

PURPOSE: To evaluate the effectiveness of CT image-guided proton radiotherapy for prostate cancer by analyzing the positioning uncertainty and assessing daily dose change due to anatomical variations. MATERIALS AND METHODS: Patients with prostate cancer were treated by opposed lateral proton beams based on a passive scattering method using an in-room CT image-guided system. The system employs a single couch for both CT scanning and beam delivery. The patient was positioned by matching the boundary between the prostate and the rectum's anterior region identified in the CT images to the corresponding boundary in the simulator images after bone matching. We acquired orthogonal kV x-ray images after couch movement and confirmed the body position by referring to the bony structure prior to treatment. In offline analyses, we contoured the targeted anatomical structures on 375 sets of daily in-room CT images for 10 patients. The uncertainty of the image-matching procedure was evaluated using the prostate contours and actual couch corrections. We also performed dose calculations using the same set of CT images, and evaluated daily change of dose-volume histograms (DVHs) to compare the effectiveness of the treatment using prostate matching to the bone-matching procedure. RESULTS: The isocenter shifts by prostate matching after bone matching were 0.5 ± 1.8 and -0.8 ± 2.6 mm along the superior-inferior (SI) and anterior-posterior (AP) directions, respectively. The body movement errors (σ) after couch movement were 0.7, 0.5, and 0.3 mm along the lateral, SI and AP direction, respectively, for 30 patients. The estimated errors (σ) in the prostate matching were 1.0 and 1.3 mm, and, in conjunction with the movement errors, the total positioning uncertainty was estimated to be 1.0 and 1.4 mm along the SI and AP directions, respectively. Daily DVH analyses showed that in the prostate matching, 98.7% and 86.1% of the total 375 irradiations maintained a dose condition of V95%  > 95% for the prostate and a dose constraint of V77%  < 18% for the rectum, whereas 90.4% and 66.1% of the total irradiations did so when bone matching was used. The dose constraint of the rectum and dose coverage of the prostate were better maintained by prostate matching than bone matching (P < 0.001). The daily variation in the dose to the seminal vesicles (SVs) was large, and only 40% of the total irradiations maintained the initial planned values of V95% for high-risk treatment. Nevertheless, the deviations from the original value were -4 ± 7% and -5 ± 11% in the prostate and bone matching, respectively, and a better dose coverage of the SV was achieved by the prostate matching. CONCLUSION: The correction of repositioning along the AP and SI direction from conventional bone matching in CT image-guided proton therapy was found to be effective to maintain the dose constraint of the rectum and the dose coverage of the prostate. This work indicated that prostate cancer treatment by prostate matching using CT image guidance may be effective to reduce the rectal complications and achieve better tumor control of the prostate. However, an adaptive approach is desirable to maintain better dose coverage of the SVs.

Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas.

We evaluated the effectiveness and toxicity of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) >5 cm without fiducial markers using four-dimensional CT (4D-CT) planning. The subjects were 29 patients treated at our hospital between March 2011 and March 2015. The median total dose was 76 Cobalt Gray Equivalents (CGE) in 20 fractions (range; 66-80.5 CGE in 10-32 fractions). Therapy was delivered with end-expiratory phase gating. An internal target volume (ITV) margin was added through the analysis of respiratory movement with 4D-CT. Patient age ranged from 38 to 87 years (median, 71 years). Twenty-four patients were Child-Pugh class A and five patients were class B. Tumor size ranged from 5.0 to 13.9 cm (median, 6.9 cm). The follow-up period ranged from 2 to 72 months (median; 27 months). All patients completed PBT according to the treatment protocol without grade 4 (CTCAE v4.03 (draft v5.0)) or higher adverse effects. The two-year local tumor control (LTC), progression-free survival (PFS), and overall survival (OS) rates were 95%, 22%, and 61%, respectively. The LTC was not inferior to that of previous reports using fiducial markers. Respiratory-gated PBT with 4D-CT planning without fiducial markers is a less invasive and equally effective treatment for large HCCs as PBT with fiducial markers.

Effects of organ motion on proton prostate treatments, as determined from analysis of daily CT imaging for patient positioning.

PURPOSE: We quantified interfractional movements of the prostate, seminal vesicles (SVs), and rectum during computed tomography (CT) image-guided proton therapy for prostate cancer and studied the range variation in opposed lateral proton beams. MATERIALS/METHODS: We analyzed 375 sets of daily CT images acquired throughout the proton therapy treatment of ten patients. We analyzed daily movements of the prostate, SVs, and rectum by simulating three image-matching strategies: bone matching, prostate center (PC) matching, and prostate-rectum boundary (PRB) matching. In the PC matching, translational movements of the prostate center were corrected after bone matching. In the PRB matching, we performed PC matching and correction along the anterior-posterior direction to match the boundary between the prostate and the rectum's anterior region. In each strategy, we evaluated systematic errors (Σ) and random errors (σ) by measuring the daily movements of certain points on each anatomic structure. The average positional deviations in millimeter of each point were determined by the Van Herk formula of 2.5Σ + 0.7σ. Using these positional deviations, we created planning target volumes of the prostate and SVs and analyzed the daily variation in the water equivalent length (WEL) from the skin surface to the target along the lateral beam directions using the density converted from the daily CT number. Based on this analysis, we designed prostate cancer treatment planning and evaluated the dose volume histograms (DVHs) for these strategies. RESULTS: The SVs' daily movements showed large variations over the superior-inferior direction, as did the rectum's anterior region. The average positional deviations of the prostate in the anterior, posterior, superior, inferior, and lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9, 9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9) (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5, 11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB matching showed the smallest positional deviations at all portions except for the anterior portion of the prostate and was able to markedly reduce the positional deviations at the posterior portion. The averaged WEL variations at the distal and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm, respectively, and showed the increasing of a few millimeters in PC and PRB matching compared to bone matching. In the treatment planning simulation, the DVH values of the rectum in PRB matching were reduced compared to those obtained with other matching strategies. CONCLUSION: The positional deviations for the prostate on the posterior side and the SVs were smaller by PRB matching than the other strategies and effectively reduced the rectal dose. 3D dose calculations indicate that PRB matching with CT image guidance may do a better job relative to other positioning methods to effectively reduce the rectal complications. The WEL variation was quite large, and the appropriate margin (approx. 10 mm) must be adapted to the proton range in an initial planning to maintain the coverage of target volumes throughout entire treatment.

Respiratory-gated Proton Beam Therapy for Hepatocellular Carcinoma Adjacent to the Gastrointestinal Tract without Fiducial Markers.

The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has been reported, but insertion of fiducial markers in the liver is usually required. We evaluated the efficacy and toxicity of respiratory-gated PBT without fiducial markers for HCC located within 2 cm of the gastrointestinal tract. From March 2011 to December 2015 at our institution, 40 patients were evaluated (median age, 72 years; range, 38-87 years). All patients underwent PBT at a dose of 60 to 80 cobalt gray equivalents (CGE) in 20 to 38 fractions. The median follow-up period was 19.9 months (range, 1.2-72.3 months). The median tumor size was 36.5 mm (range, 11-124 mm). Kaplan-Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 76%, 60%, and 94%, respectively. One patient (2.5%) developed a grade 3 gastric ulcer and one (2.5%) developed grade 3 ascites retention; none of the remaining patients developed grade >3 toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.0.). This study indicates that PBT without fiducial markers achieves good local control without severe treatment-related toxicity of the gastrointestinal tract for HCC located within 2 cm of the gastrointestinal tract.

Development of the breast immobilization system in prone setup: The effect of bra in prone position to improve the breast setup error.

PURPOSE/OBJECTIVE(S): Accurate and reproducible positioning of the breast is difficult due to its deformability and softness; thus, targeting a breast tumor or tumor bed with fractionated radiotherapy using external beam radiation is difficult. The aim of this study was to develop a novel bra to aid in breast immobilization in the prone position. MATERIALS & METHODS: To assess the accuracy of prone position fixation of breast tumors, 33 breast cancer patients with 34 lesions were recruited. The bra used in this verification was customized from a commercially available bra. Duplicate MRI were acquired in the prone position, alternating with and without the bra, and for each series, patients were asked to step off the MRI table and re-set up in the prone position. Patients were also asked to remove and re-fit the bra for the second MRI. Each pair of images were superimposed to match the shape of the skin surface, and the maximum difference in tumor geometric center in three axes was measured. The required set up margin was calculated as: required margin = mean difference in geometric center + 2.5 standard deviation. The volumetric overlap of the tumor, as well as contouring uncertainties, was evaluated using contour analysis software. RESULTS: The median breast size was 498 cc. The required margins for the lateral, vertical, and longitudinal directions were estimated to be 4.1, 4.1, and 5.0 mm, respectively, with the bra, and 5.1, 6.9, and 6.7 mm, respectively, without the bra. These margins covered the dislocation of more than 33 lesions in total. With the bra, 33 lesions had achieved an objective overlap of 95% and 99% with 2 and 4 mm margins, respectively, whereas 4 and 8 mm, respectively, were needed without the bra. CONCLUSION: The use of an immobilizing bra reduced the setup margin for prone position fixation of breast tumors.

Evaluation of Focal Liver Reaction after Proton Beam Therapy for Hepatocellular Carcinoma Examined Using Gd-EOB-DTPA Enhanced Hepatic Magnetic Resonance Imaging.

BACKGROUND: Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC. MATERIAL AND METHODS: Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area. RESULTS: FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/ß = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months. CONCLUSION: This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

Semi-analytical model for output factor calculations in proton beam therapy with consideration for the collimator aperture edge.

In the development of an external radiotherapy treatment planning system, the output factor (OPF) is an important value for the monitor unit calculations. We developed a proton OPF calculation model with consideration for the collimator aperture edge to account for the dependence of the OPF on the collimator aperture and distance in proton beam therapy. Five parameters in the model were obtained by fitting with OPFs measured by a pinpoint chamber with the circular radiation fields of various field radii and collimator distances. The OPF model calculation using the fitted model parameters could explain the measurement results to within 1.6% error in typical proton treatment beams with 6- and 12 cm SOBP widths through a range shifter and a circular aperture more than 10.6 mm in radius. The calibration depth dependences of the model parameters were approximated by linear or quadratic functions. The semi-analytical OPF model calculation was tested with various MLC aperture shapes that included circles of various sizes as well as a rectangle, parallelogram, and L-shape for an intermediate proton treatment beam condition. The pre-calculated OPFs agreed well with the measured values, to within 2.7% error up to 620 mm in the collimator distance, though the maximum difference was 5.1% in the case of the largest collimator distance of 740 mm. The OPF calculation model would allow more accurate monitor unit calculations for therapeutic proton beams within the expected range of collimator conditions in clinical use.

A model-based analysis of a simplified beam-specific dose output in proton therapy with a single-ring wobbling system.

In radiation therapy, it is necessary to preset a monitor unit in an irradiation control system to deliver a prescribed absolute dose to a reference point in the planning target volume. The purpose of this study was to develop a model-based monitor unit calculation method for proton-beam therapy with a single-ring wobbling system. The absorbed dose at a calibration point per monitor unit had been measured for each beam-specific measurement condition without a patient-specific collimator or range compensator before proton therapeutic irradiation at Shizuoka Cancer Center. In this paper, we propose a simplified dose output model to obtain the output ratio between a beam-specific dose and a reference field dose, from which a monitor unit for the proton treatment could be derived without beam-specific measurements. The model parameters were determined to fit some typical data measured in a proton treatment room, called a Gantry 1 course. Then, the model calculation was compared with 5456 dose output ratios that had been measured for 150-, 190- and 220 MeV therapeutic proton beams in two treatment rooms over the past decade. The mean value and standard deviation of the difference between the measurement and the model calculation were respectively 0.00% and 0.27% for the Gantry 1 course, and -0.25% and 0.35% for the Gantry 2 course. The model calculation was in good agreement with the measured beam-specific doses, within 1%, except for conditions less frequently used for treatment. The small variation for the various beam conditions shows the high long-term reproducibility of the measurement and high degree of compatibility of the two treatment rooms. Therefore, the model was expected to assure the setting value of the dose monitor for treatment, to save the effort required for beam-specific measurement, and to predict the dose output for new beam conditions in the future.

The usefulness of vinyl polysiloxane dental impression material as a proton beam stopper to save normal tissue during irradiation of the oral cavity: basic and clinical verifications.

PURPOSE: To evaluate the feasibility and usefulness of vinyl polysiloxane (VPS) dental impression material as a proton beam stopper for oral cavity irradiation. METHODS: VPS compounds with different base-catalyst mixture ratios were created, and the relative linear stopping power (RLSP) of each VPS compound was measured to compare with the RLSPs obtained from converted CT data. Then, a model plan was created to simulate oral cancer, and depth-dose distributions that were calculated using radiation treatment planning (RTP) were investigated by comparing the distribution with the measurements. The radioactivation of the VPS material was also measured after 2-Gy proton beam irradiations. For clinical use, a T4 gingival squamous cell carcinoma was treated using proton beam therapy with a VPS bite block. Treatment plans with and without the VPS bite block were created, and the dose-volume histograms (DVH) of the tongues were compared. RESULTS: Both the RLSPs and the CT numbers were constant of the ratio of VPS mixtures. The measured RLSP of the VPS was 1.51±0.01, which was approximately 4% greater than the CT-converted RLSP. In a model simulation, the measured depth-dose distribution inside the VPS dropped steeply compared to the RTP calculation, and the dose behind the VPS bite block was less than 0.1% of the prescribed dose. The equivalent dose rates for VPS immediately after irradiation were below 1 µSv∕h and reached background levels within 30 min. In clinical use, VPS reduced a 10 cc local overdose region as well as the mean dose in the tongue compared to the plan without VPS, while the DVH of the planning target volume was maintained. The onset of severe mucositis was not observed behind the VPS bite block. CONCLUSIONS: VPS is easy to shape and reproducible. The authors succeeded in demonstrating its safety and accuracy as a proton beam stopper.

Preliminary calculation of RBE-weighted dose distribution for cerebral radionecrosis in carbon-ion treatment planning.

Cerebral radionecrosis is a significant side effect in radiotherapy for brain cancer. The purpose of this study is to calculate the relative biological effectiveness (RBE) of carbon-ion beams on brain cells and to show RBE-weighted dose distributions for cerebral radionecrosis speculation in a carbon-ion treatment planning system. The RBE value of the radionecrosis for the carbon-ion beam is calculated by the modified microdosimetric kinetic model on the assumption of a typical clinical α/ß ratio of 2 Gy for cerebral radionecrosis in X-rays. This calculation method for the RBE-weighted dose is built into the treatment planning system for the carbon-ion radiotherapy. The RBE-weighted dose distributions are calculated on computed tomography (CT) images of four patients who had been treated by carbon-ion radiotherapy for astrocytoma (WHO grade 2) and who suffered from necrosis around the target areas. The necrotic areas were detected by brain scans via magnetic resonance imaging (MRI) after the treatment irradiation. The detected necrotic areas are easily found near high RBE-weighted dose regions. The visual comparison between the RBE-weighted dose distribution and the necrosis region indicates that the RBE-weighted dose distribution will be helpful information for the prediction of radionecrosis areas after carbon-ion radiotherapy.

Microdosimetric approach to NIRS-defined biological dose measurement for carbon-ion treatment beam.

The RBE-weighted absorbed dose, called "biological dose," has been routinely used for carbon-ion treatment planning in Japan to formulate dose prescriptions for treatment protocols. This paper presents a microdosimetric approach to measuring the biological dose, which was redefined to be derived from microdosimetric quantities measured by a tissue-equivalent proportional counter (TEPC). The TEPC was calibrated in (60)Co gamma rays to assure a traceability of the TEPC measurement to Japanese standards and to eliminate the discrepancies among matching counters. The absorbed doses measured by the TEPC were reasonably coincident with those measured by a reference ionization chamber. The RBE value was calculated from the microdosimetric spectrum on the basis of the microdosimetric kinetic model. The biological doses obtained by the TEPC were compared with those prescribed in the carbon-ion treatment planning system. We found that it was reasonable for the measured biological doses to decrease with depth around the rear SOBP region because of beam divergence, scattering effect, and fragmentation reaction. These results demonstrate that the TEPC can be an effective tool to assure the radiation quality in carbon-ion radiotherapy.