Y Matsuzaki

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.

Development and evaluation of a short-range applicator for treating superficial moving tumors with respiratory-gated spot-scanning proton therapy using real-time image guidance.

Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the protons range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial markers trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT.

Optimization and evaluation of multiple gating beam delivery in a synchrotron-based proton beam scanning system using a real-time imaging technique

PURPOSE To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system. METHODS A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase. The gated irradiation efficiency depends on the timer value, Tw. To find the optimum Tw value, gated irradiation efficiency was evaluated for each configurable Tw value. 271 gate signal data sets from 58 patients were used for the simulation. RESULTS The highest mean efficiency 0.52 was obtained in TW=0.2s. The irradiation efficiency was approximately 21% higher than at TW=0s, which corresponds to ordinary synchrotron operation. The irradiation efficiency was improved in 154 (57%) of the 271 cases. The irradiation efficiency was reduced in 117 cases because the TW value was insufficient or the function introduced an unutilized wait time for the next gate-on signal in the flat top phase. In the actual treatment of a patient with a hepatic tumor at Tw=0.2s, 4.48GyE irradiation was completed within 250s. In contrast, the treatment time of ordinary synchrotron operation was estimated to be 420s. CONCLUSIONS The results suggest that the multiple gated-irradiation function has potential to improve the gated irradiation efficiency and to reduce the treatment time.

A simulation study on the dosimetric benefit of real-time motion compensation in spot-scanning proton therapy for prostate

Abstract For proton spot scanning, use of a real-time-image gating technique incorporating an implanted marker and dual fluoroscopy facilitates mitigation of the dose distribution deterioration caused by interplay effects. This study explored the advantages of using a real-time-image gating technique, with a focus on prostate cancer. Two patient-positioning methods using fiducial markers were compared: (i) patient positioning only before beam delivery, and (ii) patient positioning both before and during beam delivery using a real-time-gating technique. For each scenario, dose distributions were simulated using the CT images of nine prostate cancer patients. Treatment plans were generated using a single-field proton beam with 3-mm and 6-mm lateral margins. During beam delivery, the prostate was assumed to move by 5 mm in four directions that were perpendicular to the beam direction at one of three separate timings (i.e. after the completion of the first, second and third quartiles of the total delivery of spot irradiation). Using a 3-mm margin and second quartile motion timing, the averaged values for ΔD99, ΔD95, ΔD5 and D5–95 were 5.1%, 3.3%, 3.6% and 9.0%, respectively, for Scenario (i) and 2.1%, 1.5%, 0.5% and 4.1%, respectively, for Scenario (ii). The margin expansion from 3 mm to 6 mm reduced the size of ΔD99, ΔD95, ΔD5 and D5–95 only with Scenario (i). These results indicate that patient positioning during beam delivery is an effective way to obtain better target coverage and uniformity while reducing the target margin when the prostate moves during irradiation.

TU-FG-BRB-12: Real-Time Visualization of Discrete Spot Scanning Proton Therapy Beam for Quality Assurance.

PURPOSE With the growing adoption of proton beam therapy there is an increasing need for effective and user-friendly tools for performing quality assurance (QA) measurements. The speed and versatility of spot-scanning proton beam (PB) therapy systems present unique challenges for traditional QA tools. To address these challenges a proof-of-concept system was developed to visualize, in real-time, the delivery of individual spots from a spot-scanning PB in order to perform QA measurements. METHODS The PB is directed toward a custom phantom with planar faces coated with a radioluminescent phosphor (Gd2O2s:Tb). As the proton beam passes through the phantom visible light is emitted from the coating and collected by a nearby CMOS camera. The images are processed to determine the locations at which the beam impinges on each face of the phantom. By so doing, the location of each beam can be determined relative to the phantom. The cameras are also used to capture images of the laser alignment system. The phantom contains x-ray fiducials so that it can be easily located with kV imagers. Using this data several quality assurance parameters can be evaluated. RESULTS The proof-of-concept system was able to visualize discrete PB spots with energies ranging from 70 MeV to 220 MeV. Images were obtained with integration times ranging from 20 to 0.019 milliseconds. If not limited by data transmission, this would correspond to a frame rate of 52,000 fps. Such frame rates enabled visualization of individual spots in real time. Spot locations were found to be highly correlated (R2 =0.99) with the nozzle-mounted spot position monitor indicating excellent spot positioning accuracy CONCLUSION: The system was shown to be capable of imaging individual spots for all clinical beam energies. Future development will focus on extending the image processing software to provide automated results for a variety of QA tests.

TH-CD-209-11: Simulation Study of Real-Time-Image Gating On Spot Scanning Proton Therapy for Lung Tumors

PURPOSE To study the impact of a real-time-image gating on spot scanning proton therapy for lung tumors and to examine the suitable size of the gating window (GW). METHODS We investigated a real-time-image gated proton therapy (RGPT), in which two fluoroscopic units monitor a gold sphere fiducial in real-time, and the proton beam is irradiated only when the marker enters within the pre-assigned GW. We designed 5 treatment plans for 7 lung cancer patients: RGPT with a GW of ±1, 2, 5, and 8 mm and free-breathing proton therapy (FBPT) using the end-exhale and average images of 4-dimensional (4D) CT, respectively. 70 Gy(RBE)/10fr was prescribed to 99% of the targets. The time-series data of the three-dimensional marker positions (RTRT data) were grouped into 10 phases to associate with the phases of 4DCT. The 4D dose distributions were calculated using the plan information, RTRT Data, 4DCT, and modeled accelerator pattern. The dose distribution in each respiratory phase was deformed into the end-exhale CT. The D99 and D5-95 of CTV (with a criteria of D99>95% and D5-95<5%), V20 of Lung-GTV, and treatment times were evaluated. RESULTS GWs ≤ ±2 mm satisfied the criteria of CTV in all cases, whereas GWs ≥ ±5 mm did not satisfy the criteria in some cases. The V20 was reduced by more than 18.9% (relative to FBPT) for GW ≤ ±2 mm, but equaled or even surpassed the FBPT for GWs ≥ ±5 mm. The irradiation times for the ±1, 2, 5, and 8 mm GWs and FBPT were 372.4±208.3, 215.2±51.5, 180.9±31.6, 178.4±21.2, and 140.1±15.2 s, respectively. The GW of ±1 mm caused large variation in irradiation time among the patients. CONCLUSION In RGPT for lung cancer, the most suitable GW, in terms of good dose preservation without prolonging the therapeutic beam delivery, is ±2 mm.

SU-F-T-131: No Increase in Biological Effectiveness Through Collimator Scattered Low Energy Protons

PURPOSE To reduce the lateral penumbra of low-energy proton beams, brass collimators are often used in spot-scanning proton therapy (SSPT). This study investigates the increase in biological effectiveness through collimator scattered protons in SSPT. METHODS The SSPT system of the Hokkaido University Hospital Proton Beam Therapy Center, which consists of a scanning nozzle, a 2-cm thick brass collimator, and a 4-cm thick energy absorber, was simulated with our validated Geant4 Monte Carlo code (ver. 9.3). A water phantom was irradiated with proton pencil beams of 76, 110, and 143 MeV. The tested collimator opening areas (COA) were 5×5, 10×10, and 15×15 cm2 . Comparisons were made among the dose-averaged LET values of protons that hit the collimators (LETDColl), protons that did not hit the collimators (LETDNoColl), and all protons (LETDTotal). X-ray equivalent doses (Deq) were calculated using the linear-quadratic model with LETDNoColl and LETDTotal, and their maximum difference was determined over regions where the physical dose was greater than 10% of the peak dose of 2 Gy. RESULTS The ratio of the dose contribution of collimator scattered protons to that of all protons, defined as λ, was large at high proton energies and large COAs. The maximum λ value ranged from 3% (76 MeV, 5×5 cm2 ) to 29% (143 MeV, 15×15 cm2 ). Moreover, a large difference between LETDColl and LETDNoColl was only found in regions where λ was below 20% (ΔLETD > 2 keV/µm) and 8% (ΔLETD > 5 keV/µm). Consequently, the maximum difference between LETDNoColl and LETDTotal was as small as 0.8 keV/µm in all simulated voxels, and the difference of Deq reached a maximum of 1.5% that of the peak dose obtained at the water surface with a 76 MeV beam. CONCLUSION Although collimator scattered protons have high LET, they only increase the physical dose, not the biological effectiveness.

SU-F-T-189: Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

PURPOSE Spot-scanning technique has been utilized to achieve conformal dose distribution to large and complicated tumors. This technique generally does not require patient-specific devices such as aperture and compensator. The commercially available spot-scanning proton therapy (SSPT) systems, however, cannot deliver proton beams to the region shallower than 4 g/cm2. Therefore some range compensation device is required to treat superficial tumors with SSPT. This study shows dosimetric comparison of the following treatment techniques: (i) with a tabletop bolus, (ii) with a nozzle-mounted applicator, and (iii) without any devices and using intensity-modulated proton therapy (IMPT) technique. METHODS The applicator composed of a combination of a mini-ridge filter and a range shifter has been manufactured by Hitachi, Ltd., and the tabletop bolus was made by .decimal, Inc. Both devices have been clinically implemented in our facility. Three patients with liver tumors close to the skin surface were examined in this study. Each treatment plan was optimized so that the prescription dose of 76 Gy(RBE) or 66 Gy(RBE) would be delivered to 99% of the clinical target volume in 20 fractions. Three beams were used for tabletop bolus plan and IMPT plan, whereas two beams were used in the applicator plan because the gantry angle available was limited due to potential collision to patient and couch. The normal liver, colon, and skin were considered as organs at risk (OARs). RESULTS The target heterogeneity index (HI = D5 /D95 ) was 1.03 on average in each planning technique. The mean dose to the normal liver was considerably less than 20 Gy(RBE) in all cases. The dose to the skin could be reduced by 20 Gy(RBE) on average in the IMPT plan compared to the applicator plan. CONCLUSION It has been confirmed that all treatment techniques met the dosimetric criteria for the OARs and could be implemented clinically.

SU‐E‐T‐266: Development of Evaluation System of Optimal Synchrotron Controlling Parameter for Spot Scanning Proton Therapy with Multiple Gate Irradiations in One Operation Cycle

Purpose: We have developed a gated spot scanning proton beam therapy system with real-time tumor-tracking. This system has the ability of multiple-gated irradiation in a single synchrotron operation cycle controlling the wait-time for consecutive gate signals during a flat-top phase so that the decrease in irradiation efficiency induced by irregular variation of gate signal is reduced. Our previous studies have shown that a 200 ms wait-time is appropriate to increase the average irradiation efficiency, but the optimal wait-time can vary patient by patient and day by day. In this research, we have developed an evaluation system of the optimal wait-time in each irradiation based on the log data of the real-time-image gated proton beam therapy (RGPT) system. Methods: The developed system consists of logger for operation of RGPT system and software for evaluation of optimal wait-time. The logger records timing of gate on/off, timing and the dose of delivered beam spots, beam energy and timing of X-ray irradiation. The evaluation software calculates irradiation time in the case of different wait-time by simulating the multiple-gated irradiation operation using several timing information. Actual data preserved in the log data are used for gate on and off time, spot irradiation time, and time moving to the next spot. Design values are used for the acceleration and deceleration times. We applied this system to a patient treated with the RGPT system. Results: The evaluation system found the optimal wait-time of 390 ms that reduced the irradiation time by about 10 %. The irradiation time with actual wait-time used in treatment was reproduced with accuracy of 0.2 ms. Conclusion: For spot scanning proton therapy system with multiple-gated irradiation in one synchrotron operation cycle, an evaluation system of the optimal wait-time in each irradiation based on log data has been developed. Funding Support: Japan Society for the Promotion of Science (JSPS) through the FIRST Program.

WE-EF-303-05: Development and Commissioning of Real-Time Imaging Function for Respiratory-Gated Spot-Scanning Proton Beam Therapy

Purpose: To realize real-time-image gated proton beam therapy (RGPT) for treating mobile tumors. Methods: The rotating gantry of spot scanning proton beam therapy has been designed to equip two x-ray fluoroscopy devices that enable real-time imaging of the internal fiducial markers during respiration. Three-dimensional position of the fiducial marker located near the tumor can be calculated from the fluoroscopic images obtained from orthogonal directions and therapeutic beam is gated only when the fiducial marker is within the predefined gating window. Image acquisition rate can be selected from discrete value ranging from 0.1 Hz to 30 Hz. In order to confirm the effectiveness of RGPT and apply it clinically, clinical commissioning was conducted. Commissioning tests were categorized to main three parts including geometric accuracy, temporal accuracy and dosimetric evaluation. Results: Developed real-time imaging function has been installed and its basic performances have been confirmed. In the evaluation of geometric accuracy, coincidence of three-dimensional treatment room coordinate system and imaging coordinate system was confirmed to be less than 1 mm. Fiducial markers (gold sphere and coil) were able to be tracked in simulated clinical condition using an anthropomorphic chest phantom. In the evaluation of temporal accuracy, latency from image acquisition to gate on/off signal was about 60 msec in typical case. In dosimetric evaluation, treatment beam characteristics including beam irradiation position and dose output were stable in gated irradiation. Homogeneity indices to the mobile target were 0.99 (static), 0.89 (w/o gating, motion is parallel to direction of scan), 0.75 (w/o gating, perpendicular), 0.98 (w/ gating, parallel) and 0.93 (w/ gating, perpendicular). Dose homogeneity to the mobile target can be maintained in RGPT. Conclusion: Real-time imaging function utilizing x-ray fluoroscopy has been developed and commissioned successfully in order to realize RGPT. Funding Support: This research was partially supported by Japan Society for the Promotion of Science (JSPS) through the FIRST Program. Conflict of Interest: Prof. Shirato has research fund from Hitachi Ltd, Mitsubishi Heavy Industries Ltd and Shimadzu Corporation.