H Lu

Relative biological effectiveness (RBE) and out-of-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries

The relative biological effectiveness (RBE) of passive scattered (PS) and pencil beam scanned (PBS) proton beam delivery techniques for uniform beam configurations was determined by clonogenic survival. The radiobiological impact of modulated beam configurations on cell survival occurring in- or out-of-field for both delivery techniques was determined with intercellular communication intact or physically inhibited. Cell survival responses were compared to those observed using a 6 MV photon beam produced with a linear accelerator. DU-145 cells showed no significant difference in survival response to proton beams delivered by PS and PBS or 6 MV photons taking into account a RBE of 1.1 for protons at the centre of the spread out Bragg peak. Significant out-of-field effects similar to those observed for 6 MV photons were observed for both PS and PBS proton deliveries with cell survival decreasing to 50-60% survival for scattered doses of 0.05 and 0.03 Gy for passive scattered and pencil beam scanned beams respectively. The observed out-of-field responses were shown to be dependent on intercellular communication between the in- and out-of-field cell populations. These data demonstrate, for the first time, a similar RBE between passive and actively scanned proton beams and confirm that out-of-field effects may be important determinants of cell survival following exposure to modulated photon and proton fields.

TU‐A‐204B‐02: On the Potential of CBCT for Range Verification in Proton Therapy

Purpose: We have investigated the potential use of cone beam CT(CBCT) for beam range verifications in proton therapy treatment, in addition to its primary role in geometric targeting. Specifically, we studied the intrinsic imaging variability of a CBCT and its effect on the water equivalent path length (WEPL) calculations, in the context of daily beam range verification/correction required for a recently proposed method of treating prostate using anterior fields. The current approach uses only lateral fields due to the lack of precise range control in patient. Materials and Methods: An anthropomorphic pelvic phantom was scanned using CBCT, in eight sessions on eight different days. In each session, the phantom was scanned twice, first at a standard position as determined by the room lasers, and then with a random shift of one centimeter in lateral directions. The Xio treatment planning system was used to perform the analysis. The average Hounsfield unit (HU) numbers for the water column in the rectal balloon was used to perform a linear calibration of the stopping power ratio, independently for each scan, as supported by the planning system. A number of WEPL values vertically from the anterior skin surface to the anterior surface of the water balloon were calculated on slices covering the region of the prostate, in relevance to a prostate treatment using an anterior field. Results: The HU number in the water column varied significantly even within the same CBCT. The average value also varied from day to day for up to 20 units. However, when these average values are used to calibrate the stopping power ratio, the variations in WEPL values along the anterior beam path are mostly within 2 mm. Conclusions: In‐room CBCT can be used in proton therapy to make online verification of protons range in patients with 2mm accuracy.

SU‐E‐T‐447: Methods and Device for Dose Based Proton Radiography

PURPOSE We report on the development of high spatial resolution, large active area proton radiography device that uses the dose measurement method for WEPL determination for both passive scattering (DS) and Pencil Beam Scanning (PBS). METHODS We used on the shelf appropriately CMOS sensor with an active area of 27mm × 22mm and active pixel size of 21.7 μm2. The read out electronics can record images at 2000 fps over 1024 × 1024 pixels. This technology is combined with an on the shelf QA device that uses 900cm2 gadolinium based scintillator and geometric optical system that focus the image on a 45 degree mirror on the above CMOS sensor. When placed behind the patient, the assembled device measures the 2D exit dose distribution. For DS fields, the method utilizes the periodic time dependence of the dose. By measuring the time-dependence of dose at each pixel and comparing it against a library of time-dependence patterns for all depths in water, the radiological path length to the point of measurement can be determined with millimeter accuracy. For PBS fields, the method uses test beam that contains a few scanning layers in depth with properly spaced ranges. Each layer has a known dose profile in water phantom. The ratio between the measured doses from each layer provides the WEPL information through the patient. RESULTS The assembled device achieved high performances as proton radiography device. The WEPL of large objects, up to 900cm2, are imaged, using both passive and active beams, with 0.6mm2 spatial resolutions and mm accuracy. The dose needed to achieve such performance is less than 1cGy for both DS and PBS. CONCLUSION The assembled device proves to be a versatile proton imager. It has the potential for use as in-room tool for pre-treatment QA for patient WEPL verification.

SU‐E‐T‐613: A Method to Improve Cone Beam CT Image Quality and Hounsfield Units Accuracy for Prostate Proton Treatment Planning

Purpose: Cone‐beam CT provides 3D anatomical images which could be utilized for adaptive proton therapy. However, CBCTimaging artifacts produces inaccurate Hounsfield Units (HU) that might severely impair its application in proton planning. Specially, the uncertainty of the beam range might increase do to this HU inaccuracies. The goal of this study is to develop a methodology to improve CBCT HU accuracy as it relates to proton planning for prostate cancer patients. Methods: In‐house MATLAB routines were created to correct for HU in CBCT.CT and CBCTimages were acquired at different lateral, longitudinal, and vertical positions for both, a water phantom and Catphan 504 heterogeneous phantom to evaluate uniformity and HU non‐uniformity, respectively. Then, CT and CBCTimages were acquired for a pelvis phantom and for prostate cancer patients. The Matlab routines were used to correct for CBCT global shifts in HU and contrast in these images. Finally, the results were compared and the HU corrections were evaluated Results: Uniformity and contrast in CBCTimages were corrected. For example, the HU values decreased at a rate of 30HU/cm in the raw CBCT vs. 16HU/cm along the lateral direction for the processed CBCTimage for high density objects. The contrast increased around 25% and 30% between fat/soft tissue and soft tissue/bone, respectively, at the periphery of prostate patients. For example, the femoral heads bone goes from 729 in CBCT to 813 in processed CBCT while in the CTimage it is 916HU. This is a 9% increase in accuracy( from 80% to 89%). Conclusions: The potential of CBCT to be used for adaptive protontreatment planning for prostate patient has been investigated. Because inaccuracies of HU are predictable, Cone Beam CTimages can be processed to yield accurate enough dose distribution for proton planning.

SU‐GG‐T‐471: Towards Range Guided Prostate Treatment Using an AP Field

Purpose:Proton treatment of prostate by anterior fields offers potential benefit in rectal sparing. However such treatment requires an accurate control of the beam range. We have recently proposed a method for in‐vivo range determination for prostate treatment by anterior fields, based on time‐resolved dose rate measurement. The method has been successfully tested against range shifting and range mixing of protons due to tissue inhomogeneity using simple geometric configurations in a water tank. In this study, we further evaluate the effectiveness of the method using a human pelvic phantom. Methods: A human pelvic phantom was used to mimic a real prostate treatment. The phantom was first CT scanned with a full bladder and a water balloon in the rectum. A treatment planningsoftware was used to compute the water equivalent path length (WEPL) between the phantom surface and the anterior inner surface of the rectum cavity, along the direction of an anterior beam. The phantom prostate was then irradiated using an anterior proton beam. A pinpoint ionization chamber was used to measure the time‐resolved dose rate function along the wall of the rectal cavity with spatial resolution of 0.25 mm. The obtained dose rate function were used to derive the corresponding WEPL values, and then compared with those calculated by the treatment planning system. Results: The time‐dependence of the measured dose rate functions showed limited deviations from those measured in a water tank, indicating a relatively low level of range mixing. This is consistent with the relatively mild tissue inhomogeneity along the beam path, despite the presence of the pubic bones. The discrepancy between the measured and calculated WEPL values is below 2mm. Conclusions: The time resolved dose rate method can be used, with reasonable accuracy, to control the beam range in prostate patient if treated by anterior fields.

The Relative Biological Effect of Spread-Out Bragg Peak Protons in Sensitive and Resistant Tumor Cells

Purpose Variations in the radiosensitivity of tumor cells within and between tumors impact tumor response to radiation, including the dose required to achieve permanent local tumor control. The increased expression of DNA-PKcs, a key component of a major DNA damage repair pathway in tumors treated by radiation, suggests that DNA-PKcs-dependent repair is likely a cause of tumor cell radioresistance. This study evaluates the relative biological effect of spread-out Bragg-peak protons in DNA-PKcs-deficient cells and the same cells transfected with a functional DNA-PKcs gene. Materials and Methods A cloned radiation-sensitive DNA-PKcs-deficient tumor line and its DNA-PKcs-transfected resistant counterpart were used in this study. The presence of functional DNA-PKcs was evaluated by DNA-PKcs autophosphorylation. Cells to be proton irradiated or x-irradiated were obtained from the same single cell suspension and dilution series to maximize precision. Cells were concurrently exposed to 6-MV x-rays or mid 137-MeV spread-out Bragg peak protons and cultured for colony formation. Results The surviving fraction data were well fit by the linear-quadratic model for each of 8 survival curves. The results suggest that the relative biological effectiveness of mid spread-out Bragg peak protons is approximately 6% higher in DNA-PKcs-mediated resistant tumor cells than in their DNA-PKcs-deficient and radiation-sensitive counterpart. Conclusion DNA-PKcs-dependent repair of radiation damage is less capable of repairing mid spread-out Bragg peak proton lesions than photon-induced lesions, suggesting protons may be more efficient at sterilizing DNA-PKcs-expressing cells that are enriched in tumors treated by conventional fractionated dose x-irradiation.

SU-F-T-214: Re-Thinking the Useful Clinical Beam Energy in Proton Therapy: An Opportunity for Cost Reduction

PURPOSE We conducted a retrospective study of the useful clinical proton beam energy based on the beam range data of patients treated over the last 10 years at Massachusetts General Hospital Proton Therapy Center. METHODS Treatment field information were collected for all patients treated over the last 10 years (2005-2015) in the two gantry treatment rooms at MGH. The beam ranges for these fields were retrieved and categorized per treatment site. The 10 prostate patients that required the highest beam range (lateral fields) were selected. For these patients, anterior oblique beams (30-40 degrees) were simulated in a planning system to obtain the required beam ranges including the margins for potential range uncertainties. RESULTS There were a total of 4033 patients, treated with combined total of 23603 fields. All treatment indications were considered with the exception of ocular tumors generally treated in a fixed beam room. For all non-prostate treatments (21811 fields), only 5 fields for 4 patients (1-pancreas, 1-lumbar chordoma, 2-spine mets) required beam range greater than 25 cm. There were 446 prostate patients (1792 fields), with the required beam range from 22.3 to 29.0 cm; 386 of them had at least one of their lateral beam range greater than 25 cm. For the 10 prostate patients with highest lateral beam ranges (26 to 29 cm), their treatment with anterior oblique beams would drop the beam ranges below 25 cm (17.3 to 18.5 cm). CONCLUSION if prostate patients are treated with anterior fields only, the useful maximum beam range is reduced to 25 cm. Thus a proton therapy system with maximum beam energy of 196 MeV is sufficient to treat all tumors sites with very rare exceptions (<0.1%). Designing such PT system would reduce the cost of proton therapy for hospitals and patients and increase the accessibility to the treatment.

TU-FG-BRB-02: The Impact of Using Dual-Energy CT for Determining Proton Stopping Powers: Comparison Between Theory and Experiments

PURPOSE To evaluate the clinical performance of dual-energy CT (DECT) in determining proton stopping power ratios (SPR) and demonstrate advantages over conventional single-energy CT (SECT). METHODS SECT and DECT scans of tissue-equivalent plastics as well as animal meat samples are performed with a Siemens SOMATOM Definition Flash. The methods of Schneider et al. (1996) and Bourque et al. (2014) are used to determine proton SPR on SECT and DECT images, respectively. Waterequivalent path length (WEPL) measurements of plastics and tissue samples are performed with a 195 MeV proton beam. WEPL values are determined experimentally using the depth-dose shift and dose extinction methods. RESULTS Comparison between CT-based and experimental WEPL is performed for 12 tissue-equivalent plastic as well as 6 meat boxes containing animal liver, kidney, heart, stomach, muscle and bones. For plastic materials, results show a systematic improvement in determining SPR with DECT, with a mean absolute error of 0.4% compared to 1.7% for SECT. For the meat samples, preliminary results show the ability for DECT to determine WEPL with a mean absolute value of 1.1% over all meat boxes. CONCLUSION This work demonstrates the potential in using DECT for determining proton SPR with plastic materials in a clinical context. Further work is required to show the benefits of DECT for tissue samples. While experimental uncertainties could be a limiting factor to show the benefits of DECT over SECT for the meat samples, further work is required to adapt the DECT formalism in the context of clinical use, where noise and artifacts play an important role.

SU-C-207A-05: Feature Based Water Equivalent Path Length (WEPL) Determination for Proton Radiography by the Technique of Time Resolved Dose Measurement

PURPOSE Studies show that WEPL can be determined from modulated dose rate functions (DRF). However, the previous calibration method based on statistics of the DRF is sensitive to energy mixing of protons due to scattering through different materials (termed as range mixing here), causing inaccuracies in the determination of WEPL. This study intends to explore time-domain features of the DRF to reduce the effect of range mixing in proton radiography (pRG) by this technique. METHODS An amorphous silicon flat panel (PaxScan™ 4030CB, Varian Medical Systems, Inc., Palo Alto, CA) was placed behind phantoms to measure DRFs from a proton beam modulated by a specially designed modulator wheel. The performance of two methods, the previously used method based on the root mean square (RMS) and the new approach based on time-domain features of the DRF, are compared for retrieving WEPL and RSP from pRG of a Gammex phantom. RESULTS Calibration by T80 (the time point for 80% of the major peak) was more robust to range mixing and produced WEPL with improved accuracy. The error of RSP was reduced from 8.2% to 1.7% for lung equivalent material, with the mean error for all other materials reduced from 1.2% to 0.7%. The mean error of the full width at half maximum (FWHM) of retrieved inserts was decreased from 25.85% to 5.89% for the RMS and T80 method respectively. Monte Carlo simulations in simplified cases also demonstrated that the T80 method is less sensitive to range mixing than the RMS method. CONCLUSION WEPL images have been retrieved based on single flat panel measured DRFs, with inaccuracies reduced by exploiting time-domain features as the calibration parameter. The T80 method is validated to be less sensitive to range mixing and can thus retrieve the WEPL values in proximity of interfaces with improved numerical and spatial accuracy for proton radiography.

TU‐FG‐BRB‐10: A New Approach to Proton Radiography Using the Beamline X‐Ray Flat Panel

PURPOSE Proton radiography, which images the patients with the same type of particles that they are to be treated with, is a promising approach for image guidance and range uncertainties reduction. This study aimed to realize quality proton radiography by measuring dose rate functions (DRF) in time domain using a single flat panel and retrieve water equivalent path length (WEPL) from them. METHODS An amorphous silicon flat panel (PaxScan™ 4030CB, Varian Medical Systems, Inc., Palo Alto, CA) was placed behind phantoms to measure DRFs from a proton beam modulated by the modulator wheel. To retrieve WEPL and RSP, calibration models based on the intensity of DRFs only, root mean square (RMS) of DRFs only and the intensity weighted RMS were tested. The quality of obtained WEPL images (in terms of spatial resolution and level of details) and the accuracy of WEPL were compared. RESULTS RSPs for most of the Gammex phantom inserts were retrieved within ± 1% errors by calibration models based on the RMS and intensity weighted RMS. The mean percentage error for all inserts was reduced from 1.08% to 0.75% by matching intensity in the calibration model. In specific cases such as the insert with a titanium rod, the calibration model based on RMS only fails while the that based on intensity weighted RMS is still valid. The quality of retrieved WEPL images were significantly improved for calibration models including intensity matching. CONCLUSION For the first time, a flat panel, which is readily available in the beamline for image guidance, was tested to acquire quality proton radiography with WEPL accurately retrieved from it. This technique is promising to be applied for image-guided proton therapy as well as patient specific RSP determination to reduce uncertainties of beam ranges.