Chie Toramatsu

What is the appropriate size criterion for proton radiotherapy for hepatocellular carcinoma? A dosimetric comparison of spot-scanning proton therapy versus intensity-modulated radiation therapy

BackgroundWe performed a dosimetric comparison of spot-scanning proton therapy (SSPT) and intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma (HCC) to investigate the impact of tumor size on the risk of radiation induced liver disease (RILD).MethodsA number of alternative plans were generated for 10 patients with HCC. The gross tumor volumes (GTV) varied from 20.1 to 2194.5 cm3. Assuming all GTVs were spherical, the nominal diameter was calculated and ranged from 3.4 to 16.1 cm. The prescription dose was 60 Gy for IMRT or 60 cobalt Gy-equivalents for SSPT with 95% planning target volume (PTV) coverage. Using IMRT and SSPT techniques, extensive comparative planning was conducted. All plans were evaluated by the risk of RILD estimated using the Lyman-normal-tissue complication probability model.ResultsFor IMRT the risk of RILD increased drastically between 6.3–7.8 cm nominal diameter of GTV. When the nominal diameter of GTV was more than 6.3 cm, the average risk of RILD was 94.5% for IMRT and 6.2% for SSPT.ConclusionsRegarding the risk of RILD, HCC can be more safely treated with SSPT, especially if its nominal diameter is more than 6.3 cm.

Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study

PURPOSE In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). METHODS A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCP(r)) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, α∕β values of 1.5, 3, and 10 Gy (RBE) were considered. RESULTS It was found that the marker of 1.5 mm diameter does not affect the TCPs with all α∕β values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCP(r) by less than 3%. This is especially true when multiple (two or three) markers are used for alignment of a patient. CONCLUSIONS It is recommended that 1.5-mm markers be used to avoid the reduction of TCP as well as to spare the surrounding critical organs, as long as the markers are visible on x-ray fluoroscopy. When 2-mm markers are implanted, more than two fields should be used and the markers should not be placed close to the distal edge of any of the beams.

NTCP modeling analysis of acute hematologic toxicity in whole pelvic radiation therapy for gynecologic malignancies : A dosimetric comparison of IMRT and spot-scanning proton therapy (SSPT)

PURPOSE This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade ⩾3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). METHODS AND MATERIALS The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45Gy(RBE) in 1.8Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. RESULTS The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP=0.04±0.01 and 0.19±0.03, p=0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI=0.97±0.01 and 0.96±0.02, p=0.3177, and HI=1.24±0.11 and 1.27±0.05, p=0.8473, respectively). CONCLUSION The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT.

A motion-compensated image filter for low-dose fluoroscopy in a real-time tumor-tracking radiotherapy system

In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory-gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low-dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some trajectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within ±2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy

Abstract Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance–covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold.

WE‐D‐17A‐03: Improvement of Accuracy of Spot‐Scanning Proton Beam Delivery for Liver Tumor by Real‐Time Tumor‐Monitoring and Gating System: A Simulation Study

PURPOSE To improve the accuracy of spot-scanning proton beam delivery for target in motion, a real-time tumor-monitoring and gating system using fluoroscopy images was developed. This study investigates the efficacy of this method for treatment of liver tumors using simulation. METHODS Three-dimensional position of a fiducial marker inserted close to the tumor is calculated in real time and proton beam is gated according to the markers distance from the planned position (Shirato, 2012). The efficient beam delivery is realized even for the irregular and sporadic motion signals, by employing the multiple-gated irradiations per operation cycle (Umezawa, 2012). For each of two breath-hold CTs (CTV=14.6cc, 63.1cc), dose distributions were calculated with internal margins corresponding to freebreathing (FB) and real-time gating (RG) with a 2-mm gating window. We applied 8 trajectories of liver tumor recorded during the treatment of RTRT in X-ray therapy and 6 initial timings. Dmax/Dmin in CTV, mean liver dose (MLD), and irradiation time to administer 3 Gy (RBE) dose were estimated assuming rigid motion of targets by using in-house simulation tools and VQA treatment planning system (Hitachi, Ltd., Tokyo). RESULTS Dmax/Dmin was degraded by less than 5% compared to the prescribed dose with all motion parameters for smaller CTV and less than 7% for larger CTV with one exception. Irradiation time showed only a modest increase if RG was used instead of FB; the average value over motion parameters was 113 (FB) and 138 s (RG) for smaller CTV and 120 (FB) and 207 s (RG) for larger CTV. In RG, it was within 5 min for all but one trajectory. MLD was markedly decreased by 14% and 5-6% for smaller and larger CTVs respectively, if RG was applied. CONCLUSIONS Spot-scanning proton beam was shown to be delivered successfully to liver tumor without much lengthening of treatment time. This research was supported by the Cabinet Office, Government of Japan and the Japan Society for the Promotion of Science (JSPS) through the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program), initiated by the Council for Science and Technology Policy (CSTP).

SU-E-CAMPUS-J-03: Commissioning of the On-Board Cone-Beam CT System Equipped On the Rotating Gantry of a Proton Therapy System

PURPOSE Proton therapy requires highly-precise image guidance in patient setup to ensure accurate dose delivery. Cone-beam CT (CBCT) is expected to play an important role to reduce uncertainties in patient setup. Hokkaido University has developed a new proton therapy system dedicated to spot-scanning under a collaborative work with Hitachi Ltd. In our system, an orthogonal X-ray imaging system is mounted on a full-rotating gantry. On-board CBCT imaging is therefore available. We have conducted commissioning of the CBCT system for clinical use in proton therapy. METHODS The orthogonal X-ray imaging system, which consists of two sets of X-ray tubes and flat panel detectors (FPDs), are equipped on the rotating gantry. The FPDs are mounted on the proton beam nozzle and can be retracted when not in use. The distance between the X-ray source and the FPD is about 2.1 m. The maximum rotation speed of the gantry is 1 rpm, so CBCT images can be acquired in approximately 1 minute. The maximum reconstruction volume is nearly 40 cm in diameter and 20 cm in axial length. For commissioning of the CBCT system, mechanical accuracy of the rotating gantry first was evaluated. Imaging performance was examined via quantitative evaluation of image quality. RESULTS Through the mechanical test, the isocentricity of the gantry was confirmed to be less than 1 mm. Moreover, it was improved to 0.5 mm with an appropriate correction. The accurate rotation of the gantry contributes to the CBCT image quality. In the image quality test, objects with 7 line-pairs per cm, which corresponds to a line spacing of 0.071 cm, could be discerned. Spatial linearity and uniformity were also sufficient. CONCLUSION Clinical commissioning of the on-board CBCT system for proton therapy was conducted, and CBCT images with sufficient quality were successfully obtained. This research was supported by the Cabinet Office, Government of Japan and the Japan Society for the Promotion of Science (JSPS) through the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program), initiated by the Council for Science and Technology Policy (CSTP).

SU-E-T-346: Validation of Beam Accuracy of a Gated Spot-Scanning Proton Therapy System with Real-Time Tumor-Tracking at Hokkaido University

PURPOSE At Hokkaido University, we have developed a gated spot scanning proton beam therapy system with real-time tumor-tracking under collaborative work with Hitachi Ltd. This system has the ability to gate proton beams from the synchrotron, turning the beam on only when the actual positions of inserted fiducial markers monitored by two fluoroscopic X-ray systems are within the planned positions [Shirato, 2012]. In this research, we validated the accuracy of the proton beams while utilizing external gating signals. METHODS The accuracy of spot positions, spot dose, absolute dose at the center of the SOBP, and range were measured while utilizing external gating signals. The following external gating signals were generated by an arbitrary waveform generator: (1) ON at all times (without gating), (2) an OFF period of 4 s followed by an ON period of 1 s, (3) two ON periods of 0.5 s with a 0.15 s OFF interval, (4) signals recorded during the treatment of real-time tumor-tracking X-ray therapy in Hokkaido University. The spot positions and spot dose were measured by beam monitors in the nozzle. The ranges were measured with a multi-layer ion chamber made by Hitachi Ltd. The absolute dose was measured with a Farmer ionization chamber and a RFA300 water phantom system. RESULTS The maximum error of the beam position in the isocenter plane was 0.8 mm without the gating signal and 1.0 mm with the gating signal. The maximum error of the spot dose was 0.0029 MU, below the criterion of 0.0032 MU. The maximum error of the absolute dose was 0.4% and the maximum variation of the range was 0.1 mm. CONCLUSION It was confirmed with measurements of the beam that the accuracy of the proton beam met the criteria with external gating signals. This research was supported by the Cabinet Office, Government of Japan and the Japan Society for the Promotion of Science (JSPS) through the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program), initiated by the Council for Science and Technology Policy (CSTP).

Improvement of tracking accuracy and stability by recursive image processing in real-time tumor-tracking radiotherapy system

In the real-time tumor-tracking radiotherapy (RTRT) system, the fiducial markers are inserted in or near the target tumor in order monitor the respiratory-induced motion of tumors. During radiation treatment, the markers are detected by continuous fluoroscopy operated at 30 frames/sec. The marker position is determined by means of a template pattern matching technique which is based on the normalized cross correlation. With high tube voltage, large current and long exposure, the fiducial marker will be recognized accurately, however, the radiation dose due to X-ray fluoroscopy increases. On the other hand, by decreasing the fluoroscopy parameter settings, the fiducial marker could be lost because the effect of statistical noise is increased. In the respiratory-gated radiotherapy, the error of the image guidance will induce the reduction of the irradiation efficiency and accuracy. In order to track the marker stably and accurately in low dose fluoroscopy, we propose the application of a recursive filter. The effectiveness of the image processing is investigated by tracking the static marker and the dynamic marker. The results suggest that the stability and the accuracy of the marker tracking can be improved by applying the recursive image filter in low dose imaging.

SU‐E‐T‐506: Dosimetric Study for Shallow‐Seated Tumor Using Passive/active Scanning Proton Beam

PURPOSE To investigate the possibility of using a single spot scanning proton beam to treat superficial lesions. METHODS A cylindrical phantom with a simulated superficial target (it seated 0.5-4cm depth from the surface, volume: 270cm3 ) was created in Eclipse treatment planning system. Three proton plans were generated: (a) a single AP uniform scanning beam with aperture and range compensator; (b) a single AP spot scanning beam with a pre-absorber. The location and thickness of the pre-absorber were calculated using Geant4 to Monte Carlo code to make use of the available spot scanning beams to get a conformal plan. (c) a five-beam spot scanning beam plan using multi-field optimization. The prescription is 54 cobalt grey equivalent (CGE) which covers 95% of the target. The target coverage, lateral penumbra at 2 and 4cm depth in water, the doses to normal tissue (phantom-target) and skin (2mm from the surface) were evaluated and compared for three plans. RESULTS The mean doses to the target are comparable within 2.4% for all three plans. The conformity indices (at 95%) are 1.36, 1.04 and 0.98 for plan (a), (b) and (c) respectively. The lateral penumbra (80% to 20%) for plan (a), (b) are both 0.73 cm, while it is 3.75 cm for plan (c). The skin dose which received more than 40 (CGE) from plan (a) is 10% higher than that of other two plans. Plan (c) has 70% higher mean doses to normal tissue than that of plan (a) and (b). CONCLUSIONS Each plan provides good coverage of target. And in this study, it showed that, with a properly designed pre-absorber, it is possible to use a single spot scanning beam to treat superficial lesion. The plan provides good target coverage and maintains normal tissue sparing in the mean time.