Passive Scattering Proton Therapy Research Articles

Time-resolved diode dosimetry calibration through Monte Carlo modeling for invivo passive scattered proton therapy range verification.

PurposeOur group previously introduced an in vivo proton range verification methodology in which a silicon diode array system is used to correlate the dose rate profile per range modulation wheel cycle of the detector signal to the water‐equivalent path length (WEPL) for passively scattered proton beam delivery. The implementation of this system requires a set of calibration data to establish a beam‐specific response to WEPL fit for the selected ‘scout’ beam (a 1 cm overshoot of the predicted detector depth with a dose of 4 cGy) in water‐equivalent plastic. This necessitates a separate set of measurements for every ‘scout’ beam that may be appropriate to the clinical case. The current study demonstrates the use of Monte Carlo simulations for calibration of the time‐resolved diode dosimetry technique.MethodsMeasurements for three ‘scout’ beams were compared against simulated detector response with Monte Carlo methods using the Tool for Particle Simulation (TOPAS). The ‘scout’ beams were then applied in the simulation environment to simulated water‐equivalent plastic, a CT of water‐equivalent plastic, and a patient CT data set to assess uncertainty.ResultsSimulated detector response in water‐equivalent plastic was validated against measurements for ‘scout’ spread out Bragg peaks of range 10 cm, 15 cm, and 21 cm (168 MeV, 177 MeV, and 210 MeV) to within 3.4 mm for all beams, and to within 1 mm in the region where the detector is expected to lie.ConclusionFeasibility has been shown for performing the calibration of the detector response for three ‘scout’ beams through simulation for the time‐resolved diode dosimetry technique in passive scattered proton delivery.

Diffusion Capacity of the Lungs Following Passive-Scattering Proton Therapy and Intensity-Modulated Photon Radiation Therapy for Locally Advanced Non–small Cell Lung Cancer

Proton therapy exposes smaller volumes of normal lung tissue to radiation dose when compared to photon based therapies and is therefore hypothesized to result in reduced pulmonary toxicity. In this study, we report results of pulmonary function tests (PFTs) in patients with inoperable non-small-cell lung cancer (NSCLC) treated with passively scattered proton therapy (PSPT) vs intensity-modulated (photon) radiotherapy (IMRT). An institutional randomized trial of patients with inoperable NSCLC (stage IIB-IIIB, stage IV with a single brain metastasis, or recurrent lung or mediastinal disease after surgery) randomized to PSPT or IMRT, both with concurrent chemotherapy, has been completed and primary outcomes are in editorial review. Pre and post treatment percent predicted hemoglobin normalized, diffusion capacity of the lungs for carbon monoxide (DLCO) values were obtained up to 12 months after the completion of treatment. Values were grouped in two month intervals up to 1 year. Paired t-test was used to compare baseline to maximum change at any time point. Wilcoxon signed-rank test was used to compare paired pre and post treatment values from baseline to each time point, while two sample t-test was used to compare change in DLCO between the two treatment groups. Pretreatment DLCO did not differ between treatment groups (70.7 IMRT vs 69.2 PSPT; p= .63). There was no difference in the maximum change in DLCO between IMRT and PSPT (-7.0% vs -6.2%; p= .74). At 0-2 months post-treatment, there was a significant reduction in DLCO from baseline for patients treated with IMRT (Mean -5.5%, Median -3%; n=57, p=.002) but not for patients treated with PSPT (Mean -2.5%, Median -2.5%; n=34 p=0.27). At 4-6 months there was a significant drop in DLCO from baseline for both treatment groups (IMRT: Mean -2.5%, Median -5%; n=31, p=0.009; PSPT: Mean -9.1%, Median -7%, n=14, p=0.04), but there was no significant difference in the change in DLCO between treatment groups (p=0.6). While DLCO values significantly decreased following treatment for all patients, there was no significant difference in the maximum change in DLCO between patients treated with PSPT or IMRT. A significant reduction in DLCO was seen for patients treated with IMRT at 0-2 months, while patients treated with PSPT did not experience a significant reduction in DLCO until 4-6 months after treatment.

Relationship between Local Recurrence and Beam Arrangement of Proton Therapy for NSCLC Patients Treated on a Prospective Randomized Trial

Recent dosimetric tests with the NRG IROC suggested that approximations in analytic dose algorithms on commercial proton planning systems may over predict dose in distal regions of the beams. These findings suggest that the resulting underdosing may lead to recurrences in distal regions of the target. The purpose of this study is to determine if local recurrence is more frequent at the distal region when all beams enter from one side of the chest without an opposing beam. Patients who were treated with proton beam therapy (PBT) on a prospective randomized trial comparing intensity-modulated radiation therapy (IMRT) versus passively scattered proton therapy (PSPT) and developed LR of the tumor (defined as tumor recurring within the PTV) were included in this study. The recurrent tumors were delineated on diagnostic images and registered with the planning CTs and the dose distributions. The locations of the LRs were mapped and divided into two groups based on the hinge beam angle of <=90-degrees versus >90-degrees. We utilized two independent sample Wilcoxon test to compare the LRs in the distal regions between the two groups. A total of 84 patients (41 female and 43 male) underwent PBT, with a median age was 68 years (range, 39-80), mostly white (90.7%). The median radiation dose was 66Gy (range, 60-74Gy). 26 were in <=90-degree-group and 58 patients were in >90-degree-group. There were 5 distal LRs (19.2%) in <=90-degree group and 6 distal LRs (10.3%) in >90-degree group (p <0.001). Our result suggests an association between the beam angle arrangement and distal local recurrence resulting from the limitations of the dose calculation algorithms. The strategy of using opposing beams or wide beam angle in PBT planning should be considered under the existing proton planning system algorithm. Recurrences should be investigated further using more advanced dose calculation techniques (viz. Monte Carlo).

Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy

PurposeTo compare heart and cardiac substructure radiation exposure using intensity-modulated radiotherapy (IMRT) vs. proton beam therapy (PBT) for patients with mid- to distal esophageal cancer who received chemoradiation therapy. Methods and materialsWe identified 727 esophageal cancer patients who received IMRT (n=477) or PBT (n=250) from March 2004 to December 2015. All patients were treated to 50.4Gy with IMRT or to 50.4 cobalt Gray equivalents with PBT. IMRT and PBT dose–volume histograms (DVHs) of the whole heart, atria, ventricles, and four coronary arteries were compared. For PBT patients, passive scattering proton therapy (PSPT; n=237) and intensity-modulated proton therapy (IMPT; n=13) DVHs were compared. ResultsCompared with IMRT, PBT resulted in significantly lower mean heart dose (MHD) and heart V5, V10, V20, V30, and V40as well as lower radiation exposure to the four chambers and four coronary arteries. Compared with PSPT, IMPT resulted in significantly lower heart V20, V30, and V40 but not MHD or heart V5 or V10. IMPT also resulted in significantly lower radiation doses to the left atrium, right atrium, left main coronary artery, and left circumflex artery, but not the left ventricle, right ventricle, left anterior descending artery, or right coronary artery. Factors associated with lower MHD included PBT (P<0.001), smaller planning target volume (PTV; P<0.001), and gastroesophageal junction (GEJ) tumor (P<0.001). Among PBT patients, factors associated with lower MHD included IMPT (P=0.038), beam arrangement other than AP/PA (P<0.001), smaller PTV (P<0.001), and GEJ tumor (P<0.001). ConclusionsIn patients with mid- to distal esophageal cancer, PBT results in significantly lower radiation exposure to the whole heart and cardiac substructures than IMRT. Long-term studies are necessary to determine how this cardiac sparing effect impacts the development of coronary artery disease and other cardiac complications.

Independent dose verification system with Monte Carlo simulations using TOPAS for passive scattering proton therapy at the National Cancer Center in Korea

For the independent validation of treatment plans, we developed a fully automated Monte Carlo (MC)-based patient dose calculation system with the tool for particle simulation (TOPAS) and proton therapy machine installed at the National Cancer Center in Korea to enable routine and automatic dose recalculation for each patient. The proton beam nozzle was modeled with TOPAS to simulate the therapeutic beam, and MC commissioning was performed by comparing percent depth dose with the measurement. The beam set-up based on the prescribed beam range and modulation width was automated by modifying the vendor-specific method. The CT phantom was modeled based on the DICOM CT files with TOPAS-built-in function, and an in-house-developed C++ code directly imports the CT files for positioning the CT phantom, RT-plan file for simulating the treatment plan, and RT-structure file for applying the Hounsfield unit (HU) assignment, respectively. The developed system was validated by comparing the dose distributions with those calculated by the treatment planning system (TPS) for a lung phantom and two patient cases of abdomen and internal mammary node. The results of the beam commissioning were in good agreement of up to 0.8 mm2 for B8 option in both of the beam range and the modulation width of the spread-out Bragg peaks. The beam set-up technique can predict the range and modulation width with an accuracy of 0.06% and 0.51%, respectively, with respect to the prescribed range and modulation in arbitrary points of B5 option (128.3, 132.0, and 141.2 mm2 of range). The dose distributions showed higher than 99% passing rate for the 3D gamma index (3 mm distance to agreement and 3% dose difference) between the MC simulations and the clinical TPS in the target volume. However, in the normal tissues, less favorable agreements were obtained for the radiation treatment planning with the lung phantom and internal mammary node cases. The discrepancies might come from the limitations of the clinical TPS, which is the inaccurate dose calculation algorithm for the scattering effect, in the range compensator and inhomogeneous material. Moreover, the steep slope of the compensator, conversion of the HU values to the human phantom, and the dose calculation algorithm for the HU assignment also could be reasons of the discrepancies. The current study could be used for the independent dose validation of treatment plans including high inhomogeneities, the steep compensator, and riskiness such as lung, head & neck cases. According to the treatment policy, the dose discrepancies predicted with MC could be used for the acceptance decision of the original treatment plan.

Feasibility of dynamic adaptive passive scattering proton therapy with computed tomography image guidance in the lung.

Hypo-fractionated proton beam therapy (PBT) is an approach that has been increasingly explored over the past decade. It requires high geometric accuracy for targeting of the PBT beams. However, image-guided PBT is currently commonly performed with kV X-ray images of bony anatomy. A dynamic adaptive passive scattering PBT system using computed tomography-based three-dimensional image guidance was developed, and its effectiveness was then evaluated retrospectively in patients with nonsmall cell lung cancer (NSCLC). The dynamic adaptive PBT system consisted of computed tomography-based image registration and proton dose calculation using a simplified Monte Carlo algorithm, with a range adaptation system that could adjust the range shifter thickness to alter the dose distribution. Three patients were retrospectively analyzed. All plans, which each had a total dose of 60 Gy (relative biological effectiveness; RBE), were generated using two fields (Gantry angles: 270 degree and 180 degree) in a passive scattering method. Three dose distributions were generated for each patient according to the following different registrations: bone registration, tumor registration, and tumor registration with range adaptation. The following dosimetric parameters were compared with the original plan: target dose coverage at D95% for the clinical target volume (CTV), homogeneity of D5% to D95% for the CTV, and dose distributions in normal tissue (Dmax of Spinal cord and V20 Gy of lung). For the bone registration method, the average D95% and D5% to D95% for the CTV showed average differences from the original plan of -3.7 ± 4.1 Gy (mean ± 1SD; RBE) and 3.6 ± 3.9 Gy (RBE) respectively. The tumor registration method achieved better coverage than the bone registration method, although the dosimetric parameters for coverage and homogeneity still showed average differences in -2.0 ± 2.3 Gy (RBE) and 1.9 ± 2.2 Gy (RBE) respectively. The range adaptive plan showed comparable coverage and homogeneity [D95%: -1.0 ± 1.3 Gy (RBE) and D5% to D95%: 0.9 ± 1.0 Gy (RBE) on average] to the original plan, as well as demonstrating similar normal tissue sparing. The approach could be completed in less than 10 min, including CT acquisition, image registration, dose recalculation with range optimization, and the operator's visual verification. The tumor dose coverage in patients with NSCLC may deteriorate as a result of respiratory or body movement if daily proton range adaptation is not performed. Our approach may provide higher geometric accuracy for localization of the tumor, and the dynamic range adaptation enables us to achieve the planned dose distribution for hypo-fractionated PBT in the lung.

Effect of DIR uncertainty on prostate passive-scattering proton therapy dose accumulation

Deformable image registration (DIR) is important in dose accumulation. Currently, the impact of DIR-algorithm-associated uncertainties in proton therapy is unclear. Here, we quantify the effect of DIR uncertainties on prostate passive-scattering proton therapy (PSPT) dose accumulation. Ten patients with an intermediate risk for prostate cancer formerly treated by PSPT (PTV D95=78GyE) were studied. Dose distributions from all verification CT images (five images per patient) were warped and accumulated in the planning CT geometries with DIR. The dose-volume histogram parameters (Dmean, V40, and V70) for rectum and bladder were calculated. Two commercially available DIR software packages were employed: Velocity AI (Varian Medical Systems) and RayStation (RaySearch Laboratories). The dice similarity coefficient (DSC) and surface distance, which were calculated between planning CT contours and deformed contours, were used for DIR validation, with the relationship between the dose parameter and DIR uncertainty ultimately investigated. On average, when using RayStation, the DSC increased by 0.14 and surface distance decreased by 6.4mm, as compared to Velocity. For Dmean, V40, and V70 to the rectum, the average differences between the RayStation and Velocity were 3.9GyE, 5.5%, and 3.2%, respectively. For the bladder, the differences were 5.2GyE, 5.8%, and 5.4%, respectively. The maximum differences in V40 between RayStation and Velocity were 14.4% and 22.8% for the rectum and bladder, respectively, when the average DSC and surface distance differences were more than 0.14 and 6.4mm, respectively. Such results suggest that DIR uncertainties might significantly affect prostate PSPT dose accumulations.

A Technical Guide for Passive Scattering Proton Radiation Therapy for Breast Cancer.

Most patients treated with proton therapy have had eye tumors, sarcomas, or, more recently, pediatric, or prostate cancers. As more proton centers have developed globally, increased capacity will permit exploration of other potential indications for proton therapy, including for the treatment of breast cancer. The rationale for proton therapy in the treatment of breast cancer is reduced inadvertent radiation dose to the heart and lung, as well as improved target coverage. As with any new technology, multiple technical parameters require optimization to deliver safe and effective radiation therapy and to maximize the benefits of the new technology. The purpose of this report is to provide a technical guide for the treatment of breast cancer with passive-scattering proton therapy and an algorithm for selecting patients with breast cancer who would benefit from proton therapy.

Proton therapy of prostate cancer by anterior-oblique beams: implications of setup and anatomy variations

Proton therapy of prostate by anterior beams could offer an attractive option for treating patients with hip prosthesis and limiting the high-dose exposure to the rectum. We investigated the impact of setup and anatomy variations on the anterior-oblique (AO) proton plan dose, and strategies to manage these effects via range verification and adaptive delivery. Ten patients treated by bilateral (BL) passive-scattering proton therapy (79.2 Gy in 44 fractions) who underwent weekly verification CT scans were selected. Plans with AO beams were additionally created. To isolate the effect of daily variations, initial AO plans did not include range uncertainty margins. The use of fixed planning margins and adaptive range adjustments to manage these effects was investigated. For each case, the planned dose was recalculated on weekly CTs, and accumulated on the simulation CT using deformable registration to approximate the delivered dose. Planned and accumulated doses were compared for each scenario to quantify dose deviations induced by variations. The possibility of estimating the necessary range adjustments before each treatment was explored by simulating the procedure of a diode-based in vivo range verification technique, which would potentially be used clinically. The average planned rectum, penile bulb and femoral heads mean doses were smaller for initial AO compared to BL plans (by 8.3, 16.1 and 25.9 Gy, respectively). After considering interfractional variations in AO plans, the target coverage was substantially reduced. The maximum reduction of V79.2/D95/Dmean/EUD for AO (without distal margins) (25.3%/10.7/1.6/4.9 Gy, respectively) was considerably larger than BL plans. The loss of coverage was mainly related to changes in water equivalent path length of the prostate after fiducial-based setup, caused by discrepancies in patient anterior surface and bony-anatomy alignment. Target coverage was recovered partially when using fixed planning margins, and fully when applying adaptive range adjustments. The accumulated organs-at-risk dose for AO beams after range adjustment demonstrated full sparing of femoral heads and superior sparing of penile bulb and rectum compared to the conventional BL cases. Our study indicates that using AO beams makes prostate treatment more susceptible to target underdose induced by interfractional variations. Adaptive range verification/adjustment may facilitate the use of anterior beam approaches, and ensure adequate target coverage in every fraction of the treatment.

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients

At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children.

A comprehensive evaluation of the accuracy of CBCT and deformable registration based dose calculation in lung proton therapy

The uncertainties in water equivalent thickness (WET) and accuracy of dose estimation using a virtual CT (vCT), generated from deforming the planning CT (pCT) onto the daily cone-beam CT (CBCT), were comprehensively evaluated in the context of lung malignancies and passive scattering proton therapy. The validation methodology utilized multiple CBCT datasets to generate the vCTs of twenty lung cancer patients. A correction step was applied to the vCTs to account for anatomical modifications that could not be modeled by deformation alone. The CBCT datasets included a regular CBCT (rCBCT) and synthetic CBCTs created from the rCBCT and rescan CT (rCT), which minimized the variation in setup between the vCT and the gold-standard image (i.e., rCT). The uncertainty in WET was defined as the voxelwise difference in WET between vCT and rCT, and calculated in 3D (planning target volume, PTV) and 2D (distal and proximal surfaces). The uncertainty in WET based dose warping was defined as the difference between the warped dose and a forward dose recalculation on the rCT. The overall root mean square (RMS) uncertainty in WET was 3.6 ± 1.8, 2.2 ± 1.4 and 3.3 ± 1.8 mm for the distal surface, proximal surface and PTV, respectively. For the warped dose, the RMS uncertainty of the voxelwise dose difference was 6% ± 2% of the maximum dose (%mD), using a 20% cut-off. The rCBCT resulted in higher uncertainties due to setup variability with the rCT; the uncertainties reported with the two synthetic CBCTs were similar. The vCT followed by a correction step was found to be an accurate alternative to rCT.

An Assessment of the Secondary Neutron Dose in the Passive Scattering Proton Beam Facility of the National Cancer Center

Abstract The purpose of this study is to assess the additional neutron effective dose during passive scattering proton therapy. Monte Carlo code (Monte Carlo N-Particle 6) simulation was conducted based on a precise modeling of the National Cancer Center's proton therapy facility. A three-dimensional neutron effective dose profile of the interior of the treatment room was acquired via a computer simulation of the 217.8-MeV proton beam. Measurements were taken with a 3 He neutron detector to support the simulation results, which were lower than the simulation results by 16% on average. The secondary photon dose was about 0.8% of the neutron dose. The dominant neutron source was deduced based on flux calculation. The secondary neutron effective dose per proton absorbed dose ranged from 4.942 ± 0.031 mSv/Gy at the end of the field to 0.324 ± 0.006 mSv/Gy at 150 cm in axial distance.

Lung Dosimetry, Radiation Pneumonitis, and FDG Uptake in Patients With Stage II-III Non-Small Cell Lung Cancer Treated With Passively Scattered Proton Therapy or Intensity Modulated Pho

Lung Dosimetry, Radiation Pneumonitis, and FDG Uptake in Patients With Stage II-III Non-Small Cell Lung Cancer Treated With Passively Scattered Proton Therapy or Intensity Modulated Pho

Sperm preservation and neutron contamination following proton therapy for prostate cancer study

Background: The present study investigates the impact of scatter dose radiation to the testis on ejaculate and sperm counts from treatment of prostate cancer with passive-scatter proton therapy.Material and methods: From March 2010 to November 2014, 20 men with low- or intermediate-risk prostate cancer enrolled in an IRB-approved protocol and provided a semen sample prior to passive-scatter proton therapy and 6–12 months following treatment. Men were excluded if they had high-risk prostate cancer, received androgen deprivation therapy, were on alpha blockers (due to retrograde ejaculation) prior to treatment, had baseline sperm count <1 million, or were unable to produce a pre-treatment sample or could not provide a follow-up specimen. Sperm counts of 0 were considered azoospermia and <15 million/ml were classified as oligospermia.Results: Four patients were unable to provide a sufficient quantity of semen for analysis. Among the 16 remaining patients, only one was found to have oligospermia (7 million/ml). There was a statistically significant reduction in semen volume (median, 0.5 ml) and increase in pH (median 0.5). Although not statistically significant, there appeared to be a decline in sperm concentration (median, 16 million/ml), total sperm count (median, 98.5 million), normal morphology (median, 9%), and rapid progressive motility (median, 9.5%).Discussion: Men did not have azoospermia 6–12 months following passive-scatter proton therapy indicating minimal scatter radiation to the testis during treatment. Changes in semen quantity and consistency may occur due to prostate irradiation, which could impact future fertility and/or sexual activity.

SU‐F‐T‐150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

Purpose:The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial.Methods:Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion‐incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter‐compared as were the selected dose‐volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched‐paired signed‐rank test to determine the dose regions where the statistically significant differences existed.Results:As expected, the average 5, 20 and 50% IRVNT's for PSPT was found to be significantly smaller than for IMRT (p &lt; 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224).Conclusion:PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

WE-FG-202-09: Voxel-Level Analysis of Adverse Treatment Response in Pediatric Patients Treated for Ependymoma with Passive Scattering Proton Therapy

Purpose: We identified patients treated for ependymoma with passive scattering proton therapy who subsequently developed treatment-related imaging changes on MRI. We sought to determine if there is any spatial correlation between imaged response, dose, and LET. Methods: A group of 14 patients treated for ependymoma were identified as having post-treatment MR imaging changes observable as T2-FLAIR hyperintensity with or without enhancement on T1 post-contrast sequences. MR images were registered with treatment planning CT images and regions of treatment-related change contoured by a practicing radiation oncologist. The contoured regions were identified as response with voxels represented as 1 while voxels within the brain outside of the response region were represented as 0. An in-house Monte Carlo system was used to recalculate treatment plans to obtain dose and LET information. Voxels were binned according to LET values in 0.3 keV µm−1 bins. Dose and corresponding response value (0 or 1) for each voxel for a given LET bin were then plotted and fit with the Lyman-Kutcher-Burman dose response model to determine TD50 and m parameters for each LET value. Response parameters from all patients were then collated, and linear fits of the data were performed. Results: The response parameters TD50 and m both show trends with LET. Outliers were observed due to low numbers of response voxels in some cases. TD50 values decreased with LET while m increased with LET. The former result would indicate that for higher LET values, the dose is more effective, which is consistent with relative biological effectiveness (RBE) models for proton therapy. Conclusion: A novel method of voxel-level analysis of image biomarker-based adverse patient treatment response in proton therapy according to dose and LET has been presented. Fitted TD50 values show a decreasing trend with LET supporting the typical models of proton RBE. Funding provided by NIH Program Project Grant 2U19CA021239-35.

Novel Hybrid Scattering- and Scanning-Beam Proton Therapy Approach

To determine whether a hybrid intensity-modulated proton therapy (IMPT) and passive scattered proton therapy (PSPT) technique, termed HimpsPT, could be adopted as an alternative delivery method for patients demanding scanning beam proton therapy. We identified 3 representative clinical cases-an oropharyngeal cancer, skull base chordoma, and stage III non-small-cell lung cancer-that had been treated with IMPT at our center. We retrospectively redesigned these cases using HimpsPT. The PSPT plans for all three cases were designed with the same prescriptions as those used in the IMPT plans. In this way, the whole treatment was delivered using alternating or sequential PSPT and IMPT. All HimpsPT plans met the clinical dose criteria and were of similar quality as the IMPT plans. In the skull base case, the mixed plan was more effective at sparing the brain stem because the sharp penumbra of the aperture in the PSPT plans was not present in the IMPT plans. The HimpsPT plans were more robust than the clinical IMPT plans generated without robust optimization. The HimpsPT delivery technique can achieve a treatment-plan quality similar to that of IMPT, even in the most challenging clinical cases. In addition, at centers equipped with both scattering and scanning beam capabilities, the HimpsPT technique may allow more patients to benefit from scanning beam technology.

SU‐F‐J‐57: Effectiveness of Daily CT‐Based Three‐Dimensional Image Guided and Adaptive Proton Therapy

Purpose:Daily CT‐based three‐dimensional image‐guided and adaptive (CTIGRT‐ART) proton therapy system was designed and developed. We also evaluated the effectiveness of the CTIGRT‐ART.Methods:Retrospective analysis was performed in three lung cancer patients: Proton treatment planning was performed using CT image datasets acquired by Toshiba Aquilion ONE. Planning target volume and surrounding organs were contoured by a well‐trained radiation oncologist. Dose distribution was optimized using 180‐deg. and 270‐deg. two fields in passive scattering proton therapy. Well commissioned Simplified Monte Carlo algorithm was used as dose calculation engine. Daily consecutive CT image datasets was acquired by an in‐room CT (Toshiba Aquilion LB). In our in‐house program, two image registrations for bone and tumor were performed to shift the isocenter using treatment CT image dataset. Subsequently, dose recalculation was performed after the shift of the isocenter. When the dose distribution after the tumor registration exhibits change of dosimetric parameter of CTV D90% compared to the initial plan, an additional process of was performed that the range shifter thickness was optimized. Dose distribution with CTV D90% for the bone registration, the tumor registration only and adaptive plan with the tumor registration was compared to the initial plan.Results:In the bone registration, tumor dose coverage was decreased by 16% on average (Maximum: 56%). The tumor registration shows better coverage than the bone registration, however the coverage was also decreased by 9% (Maximum: 22%) The adaptive plan shows similar dose coverage of the tumor (Average: 2%, Maximum: 7%).Conclusion:There is a high possibility that only image registration for bone and tumor may reduce tumor coverage. Thus, our proposed methodology of image guidance and adaptive planning using the range adaptation after tumor registration would be effective for proton therapy.This research is partially supported by Japan Agency for Medical Research and Development (AMED).

SU‐F‐T‐143: Implementation of a Correction‐Based Output Model for a Compact Passively Scattered Proton Therapy System

Purpose:To commission and investigate the accuracy of an output (cGy/MU) prediction model for a compact passively scattered proton therapy system.Methods:A previously published output prediction model (Sahoo et al, Med Phys, 35, 5088–5097, 2008) was commissioned for our Mevion S250 proton therapy system. This model is a correction‐based model that multiplies correction factors (d/MUwnc=ROFxSOBPF xRSFxSOBPOCFxOCRxFSFxISF). These factors accounted for changes in output due to options (12 large, 5 deep, and 7 small), modulation width M, range R, off‐center, off‐axis, field‐size, and off‐isocenter. In this study, the model was modified to ROFxSOBPFxRSFxOCRxFSFxISF_OCFxGACF by merging SOBPOCF and ISF for simplicity and introducing a gantry angle correction factor (GACF). To commission the model, outputs over 1,000 data points were taken at the time of the system commissioning. The output was predicted by interpolation (1D for SOBPF, FSF, and GACF; 2D for RSF and OCR) with inverse‐square calculation (ISF_OCR). The outputs of 273 combinations of R and M covering total 24 options were measured to test the model. To minimize fluence perturbation, scattered dose from range compensator and patient was not considered. The percent differences between the predicted (P) and measured (M) outputs were calculated to test the prediction accuracy ([P‐M]/Mx100%).Results:GACF was required because of up to 3.5% output variation dependence on the gantry angle. A 2D interpolation was required for OCR because the dose distribution was not radially symmetric especially for the deep options. The average percent differences were −0.03±0.98% (mean±SD) and the differences of all the measurements fell within ±3%.Conclusion:It is concluded that the model can be clinically used for the compact passively scattered proton therapy system. However, great care should be taken when the field‐size is less than 5×5 cm2 where a direct output measurement is required due to substantial output change by irregular block shape.

Reirradiation of Head and Neck Cancers With Proton Therapy: Outcomes and Analyses

Reirradiation of head and neck (H&N) cancer is a clinical challenge. Proton radiation therapy (PRT) offers dosimetric advantages for normal tissue sparing and may benefit previously irradiated patients. Here, we report our initial experience with the use of PRT for H&N reirradiation, with focus on clinical outcomes and toxicity. We retrospectively reviewed the records of patients who received H&N reirradiation with PRT from April 2011 through June 2015. Patients reirradiated with palliative intent or without prior documentation of H&N radiation therapy were excluded. Radiation-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events Version 4.0. The conditions of 60 patients were evaluated, with a median follow-up time of 13.6months. Fifteen patients (25%) received passive scatter proton therapy (PSPT), and 45 (75%) received intensity modulated proton therapy (IMPT). Thirty-five patients (58%) received upfront surgery, and 44 (73%) received concurrent chemotherapy. The 1-year rates of locoregional failure-free survival, overall survival, progression-free survival, and distant metastasis-free survival were 68.4%, 83.8%, 60.1%, and 74.9%, respectively. Eighteen patients (30%) experienced acute grade 3 (G3) toxicity, and 13 (22%) required a feeding tube at the end of PRT. The 1-year rates of late G3 toxicity and feeding tube independence were 16.7% and 2.0%, respectively. Three patients may have died of reirradiation-related effects (1 acute and 2 late). Proton beam therapy can be a safe and effective curative reirradiation strategy, with acceptable rates of toxicity and durable disease control.