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All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. Methods and Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. Results: For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Conclusions: Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

SU-F-T-154: An Evaluation and Quantification of Secondary Neutron Radiation Dose Due to Double Scatter and Pencil Beam Scanning Proton Therapy

Proton radiation therapy can deliver high radiation doses to tumors while sparing normal tissue. However, protons yield secondary neutron and gamma radiation that is difficult to detect, small in comparison to the prescribed dose, and not accounted for in most treatment planning systems. The risk for secondary malignancies after proton therapy may be dependent on the quality of this dose. Consequently, there is interest in characterizing the secondary radiation. Previously, we used the dual ionization chamber method to measure the separate absorbed dose from gamma-rays and neutrons secondary to the proton beam1, relying on characterization of ionization chamber response in the unknown neutron spectrum from Monte Carlo simulation. We developed a procedure to use Shieldwerx activation foils, with neutron activation energies ranging from 0.025 eV to 13.5 MeV, to measure the neutron energy spectrum from double scattering (DS) and pencil beam scanning (PBS) protons outside of the treatment volume in a water tank. The activated foils are transferred to a NaI well chamber for gamma-ray spectroscopy and activity measurement. Since PBS treats in layers, the switching time between layers is used to correct for the decay of the activated foils and the relative dose per layer is assumed to be proportional to the neutron fluence per layer. MATLAB code was developed to incorporate the layer delivery and switching time into a calculation of foil activity, which is then used to determine the neutron energy fluence from tabulated foil activation energy thresholds.1. Diffenderfer et. al., Med. Phys., 38(11) 2011.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

MO-B-18C-01: Proton Therapy II: Proton Stereotactic Radiotherapy

Proton stereotactic radiotherapy shares fundamental principles with general proton therapy physics, specifically range uncertainties and broad beam measurement techniques. Significant differences emerge when treating with smaller field sizes that suffer lateral disequilibrium and when fractions are reduced. This session will explore the history and scope of proton stereotactic radiotherapy in clinical practice. Uncertainties and treatment planning methods specific to stereotactic treatments will be discussed. The session will include an overview of the physical properties of small proton fields and resulting needs for accurate measurements and modeling of dose distributions for radiosurgery treatment planning. Learning Objectives: Understand the clinical rationale for proton radiosurgery. Understand the similarities and differences from general proton therapy. Understand the similarities and differences from photon stereotactic radiosurgery. Understand the basic physics and clinical physics methods for measuring and commissioning a radiosurgery program.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-28: A Treatment Planning Comparison of Volumetric Modulated Arc Therapy Vs. Proton Therapy for Post-Mastectomy Radiotherapy

Purpose: The delivery of post-mastectomy radiotherapy (PMRT) can be challenging for patients with left-sided breast cancer due to the PTV size and proximity to critical organs. This study investigates the use of protons for PMRT in a clinically-representative cohort of patients, and quantitatively compares volumetric modulated arc therapy (VMAT) to proton therapy to have an evidence-based rationale for selecting a treatment modality for these patients. Methods: Eight left-sided PMRT patients previously treated at our clinic with VMAT were identified for the study. PTVs included the chest wall and regional lymph nodes. Passively scattered (PS) and intensity modulated proton therapy (IMPT) plans were constructed using the Eclipse proton planning system. The resulting plans were compared to the original VMAT plan on the basis of PTV coverage; dose homogeneity index (DHI) and conformity index (CI); dose to organs at risk (OAR); tumor control probability (TCP), normal tissue complication probability (NTCP) and secondary cancer complication probability (SCCP). Differences were tested for significance using the paired Student's t-test (p<0.01). Results: All modalities produced clinically acceptable PMRT plans. The comparison demonstrated proton treatment plans provide significantly lower NTCP values for the heart and the lung while maintaining significantly better CI and DHI. At a prescribed dose of 50.4 Gy (RBE) in the PTV, the calculated mean NTCP value for the patients decreased from 1.3% to 0.05% for the whole heart (cardiac mortality) and from 3.8% to 1.1% for the lungs (radiation pneumonitis) for both proton therapy plans from VMAT plans. Both proton modalities showed a significantly lower SCCP for the contralateral breast compared to VMAT. Conclusion: All three plans (VMAT, PS, and IMPT) provide acceptable treatment plans for PMRT. However, proton therapy shows a significant advantage over VMAT with regards to sparing OARs and may be more advantageous for patients with unfavorable anatomy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

MO-A-18C-01: Proton Therapy I: Basics of Proton Therapy

The goal of this session is to introduce the audience to the physics, dosimetry and treatment planning procedures used in proton therapy. The course material covers the basic physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for scattered and scanning proton beams. It will include the requirements for dosimetry measurements and present the equipment needed for commissioning of proton beams for clinical use and quality assurance checks as well as methods used for proton beam calibration and dose verification of patient treatment fields. The session covers the treatment planning strategies for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Challenges involved in the motion management in proton therapy will also be discussed. Learning Objectives: Gain knowledge on physics, dosimetry, treatment planning and quality assurance for proton therapy. Understand the uncertainties associated with proton therapy and currently used strategies for their mitigation in treatment planning.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2016

SU-G-TeP2-13: Patient-Specific Reduction of Range Uncertainties in Proton Therapy by Proton Radiography with a Multi-Layer Ionization Chamber

Purpose: The conversion from Hounsfield units (HU) to stopping powers is a major source of range uncertainty in proton therapy (PT). Our contribution shows how proton radiographs (PR) acquired with a multi-layer ionization chamber in a PT center can be used for accurate patient positioning and subsequently for patient-specific optimization of the conversion from HU to stopping powers. Methods: A multi-layer ionization chamber was used to measure the integral depth-dose (IDD) of 220 MeV pencil beam spots passing through several anthropomorphic phantoms. The whole area of interest was imaged by repositioning the couch and by acquiring a 45×45 mm{sup 2} frame for each position. A rigid registration algorithm was implemented to correct the positioning error between the proton radiographs and the planning CT. After registration, the stopping power map obtained from the planning CT with the calibration curve of the treatment planning system was used together with the water equivalent thickness gained from two proton radiographs to generate a phantom-specific stopping power map. Results: Our results show that it is possible to make a registration with submillimeter accuracy from proton radiography obtained by sending beamlets separated by more than 1 mm. This was made possible by the complex shape of the IDD due to the presence of lateral heterogeneities along the path of the beam. Submillimeter positioning was still possible with a 5 mm spot spacing. Phantom specific stopping power maps obtained by minimizing the range error were cross-verified by the acquisition of an additional proton radiography where the phantom was positioned in a random but known manner. Conclusion: Our results indicate that a CT-PR registration algorithm together with range-error based optimization can be used to produce a patient-specific stopping power map. Sylvain Deffet reports financial funding of its PhD thesis by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work. Francois Vander Stappen reports being employed by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-764: Track Repeating Algorithm for Proton Therapy Applied to Intensity Modulated Proton Therapy for Head-And-Neck Patients

Purpose: To determine the suitability of fast Monte Carlo techniques for dose calculation in particle therapy based on track-repeating algorithm for Intensity Modulated Proton Therapy, IMPT. The application of this technique will make possible detailed retrospective studies of large cohort of patients, which may lead to a better determination of Relative Biological Effects from the analysis of patient data. Methods: A cohort of six head-and-neck patients treated at the University of Texas MD Anderson Cancer Center with IMPT were utilized. The dose distributions were calculated with the standard Treatment Plan System, TPS, MCNPX, GEANT4 and FDC, a fast track-repeating algorithm for proton therapy for the verification and the patient plans. FDC is based on a GEANT4 database of trajectories of protons in a water. The obtained dose distributions were compared to each other utilizing the g-index criteria for 3mm-3% and 2mm-2%, for the maximum spatial and dose differences. The γ-index was calculated for voxels with a dose at least 10% of the maximum delivered dose. Dose Volume Histograms are also calculated for the various dose distributions. Results: Good agreement between GEANT4 and FDC is found with less than 1% of the voxels with a γ-index larger than 1 for 2 mm-2%. The agreement between MCNPX with FDC is within the requirements of clinical standards, even though it is slightly worse than the comparison with GEANT4.The comparison with TPS yielded larger differences, what is also to be expected because pencil beam algorithm do not always performed well in highly inhomogeneous areas like head-and-neck. Conclusion: The good agreement between a track-repeating algorithm and a full Monte Carlo for a large cohort of patients and a challenging, site like head-and-neck, opens the path to systematic and detailed studies of large cohorts, which may yield better understanding of biological effects.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

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

Purpose: 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. Methods and Materials: 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, 23.4 Gy (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. Results: 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 V10 Gy(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 V20 Gy(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. Conclusions: 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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Risk of Pneumonitis and Outcomes After Mediastinal Proton Therapy for Relapsed/Refractory Lymphoma: A PTCOG and PCG Collaboration

Despite high response rates, there has been reluctance to use radiation therapy for patients with relapsed/refractory (r/r) Hodgkin (HL) or aggressive non-Hodgkin lymphoma (NHL) given concerns for subacute and late toxicities. Symptomatic pneumonitis, a subacute toxicity, has an incidence of 17% to 24% (≥grade 2) even with intensity modulated radiation therapy. Proton therapy (PT), which has no exit radiation dose, is associated with a lower dose to lung compared with other radiation techniques. As risk of radiation pneumonitis is associated with lung dose, we evaluated whether pneumonitis rates are lower with PT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Optimal Allocation of Proton Therapy Slots in Combined Proton-Photon Radiation Therapy

Proton therapy is a limited resource that is not available to all patients who may benefit from it. We investigated combined proton-photon treatments, in which some fractions are delivered with protons and the remaining fractions with photons, as an approach to maximize the benefit of limited proton therapy resources at a population level.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

SU-E-T-369: Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in CSI of Pediatric Patients

Purpose: To investigate the trade-off between vertebral column sparing and thecal-sac target coverage in craniospinal irradiation (CSI) of pediatric patients treated with passive-scattering (PS) and intensity modulated (IMPT) proton therapy. Methods: We selected 2 pediatric patients treated with PS CSI for medulloblastoma. Spinal irradiation was re-planned with IMPT. For all cases, we assumed prescription dose of 23.4 Gy(RBE), with the spinal canal receiving at least 95% of 23.4 Gy(RBE). PS planning was performed using the commercial system XiO. IMPT planning was done using the Astroid planning system. Beam arrangements consisted of (a) PS posterior-anterior (PA) field, PS-PA, (b) IMPT PA field, IMPT-PA, and (c) two posterior oblique IMPT fields, IMPT2 (-35°, 35°). Dose distributions were re-calculated using TOPAS Monte Carlo, along with LET distributions, to investigate LET variations within the target and vertebra anatomy. Variable RBE-weighed dose distributions were also calculated based on a dose and LET-dependent biophysical model. Dosimetric data were compared among the plans for the target volume, spinal cord and adjacent critical organs (thecal-sac and cauda equina). Results: IMPT2 resulted in better sparing of the posterior vertebral column (entrance region posterior to thecal-sac), where planned dose was approximately 6–8Gy(RBE). For IMPT-PA and PS-PA the MC-calculated dose to the posterior vertebral column was, on average, 20Gy and 18Gy respectively. For IMPT2 higher mean-LET (5keV/µm/(g/cm3)) values were observed in anterior vertebral column (beyond the thecal-sac) relative to IMPT-PA and PS-PA, where mean-LET was 3.5keV/µm/(g/cm3) and 2.5keV/µm/(g/cm3) respectively. The higher LET region observed for both IMPT plans was in the distal end of treatment fields, where dose delivered was less 5Gy(RBE). Conclusion: The two-oblique proton beams IMPT2 best spared the spinal column, while reducing the dose to the posterior spinal column from 18–20 to 6–8 Gy(RBE). The best LET distribution was obtained with the PS-PA fields.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Experimental validation of the TOPAS Monte Carlo system for passive scattering proton therapy

Purpose: TOPAS (TOol for PArticle Simulation) is a particle simulation code recently developed with the specific aim of making Monte Carlo simulations user-friendly for research and clinical physicists in the particle therapy community. The authors present a thorough and extensive experimental validation of Monte Carlo simulations performed with TOPAS in a variety of setups relevant for proton therapy applications. The set of validation measurements performed in this work represents an overall end-to-end testing strategy recommended for all clinical centers planning to rely on TOPAS for quality assurance or patient dose calculation and, more generally, for all the institutions using passive-scattering proton therapy systems. Methods: The authors systematically compared TOPAS simulations with measurements that are performed routinely within the quality assurance (QA) program in our institution as well as experiments specifically designed for this validation study. First, the authors compared TOPAS simulations with measurements of depth-dose curves for spread-out Bragg peak (SOBP) fields. Second, absolute dosimetry simulations were benchmarked against measured machine output factors (OFs). Third, the authors simulated and measured 2D dose profiles and analyzed the differences in terms of field flatness and symmetry and usable field size. Fourth, the authors designed a simple experiment using a half-beam shifter to assess the effects of multiple Coulomb scattering, beam divergence, and inverse square attenuation on lateral and longitudinal dose profiles measured and simulated in a water phantom. Fifth, TOPAS’ capabilities to simulate time dependent beam delivery was benchmarked against dose rate functions (i.e., dose per unit time vs time) measured at different depths inside an SOBP field. Sixth, simulations of the charge deposited by protons fully stopping in two different types of multilayer Faraday cups (MLFCs) were compared with measurements to benchmark the nuclear interaction models used in the simulations. Results: SOBPs’ range and modulation width were reproduced, on average, with an accuracy of +1, −2 and ±3 mm, respectively. OF simulations reproduced measured data within ±3%. Simulated 2D dose-profiles show field flatness and average field radius within ±3% of measured profiles. The field symmetry resulted, on average in ±3% agreement with commissioned profiles. TOPAS accuracy in reproducing measured dose profiles downstream the half beam shifter is better than 2%. Dose rate function simulation reproduced the measurements within ∼2% showing that the four-dimensional modeling of the passively modulation system was implement correctly and millimeter accuracy can be achieved in reproducing measured data. For MLFCs simulations, 2% agreement was found between TOPAS and both sets of experimental measurements. The overall results show that TOPAS simulations are within the clinical accepted tolerances for all QA measurements performed at our institution. Conclusions: Our Monte Carlo simulations reproduced accurately the experimental data acquired through all the measurements performed in this study. Thus, TOPAS can reliably be applied to quality assurance for proton therapy and also as an input for commissioning of commercial treatment planning systems. This work also provides the basis for routine clinical dose calculations in patients for all passive scattering proton therapy centers using TOPAS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

WE-G-BRE-07: Proton Therapy Enhanced by Tumor-Targeting Gold Nanoparticles: A Pilot in Vivo Experiment at The Proton Therapy Center at MD Anderson Cancer Center

Purpose: Assess tumor-growth delay and survival in a mouse model of prostate cancer treated with tumor-targeting gold nanoparticles (AuNPs) and proton therapy. Methods: We first examined the accumulation of targeting nanoparticles within prostate tumors by imaging AuNPs with ultrasound-guided photoacoustics at 24h after the intravenous administration of goserelin-conjugated AuNPs (gAuNP) in three mice. Nanoparticles were also imaged at the cellular level with TEM in PC3 cells incubated with gAuNP for 24h. Pegylated AuNPs (pAuNP) were also imaged in vivo and in vitro for comparison. PC3 cells were then implanted subcutaneously in nude mice; 51mice with 8–10mm tumors were included. AuNPs were injected intravenously at 0.2%w/w final gold concentration 24h before irradiation. A special jig was designed to facilitate tumor irradiation perpendicular to the proton beam. Proton energy was set to 180MeV, the radiation field was 18×18cm{sup 2}, and 9cm or 13.5cm thick solid-water compensators were used to position the tumors at either the beam entrance (BE) or the SOBP. Physical doses of 5Gy were delivered to all tumors on a patient beam line at MD Anderson's Proton Therapy Center. Results: The photoacoustic experiment reveled that our nanoparticles leak from the tumor-feeding vasculature and accumulate within the tumor volume over time. Additionally, TEM images showed gAuNP are internalized in cancer cells, accumulating within the cytoplasm, whereas pAuNP are not. Tumor-growth was delayed by 11 or 32days in mice receiving gAuNP irradiated at the BE or the SOBP, relative to proton radiation alone. Survival curves (ongoing experiment) reveal that gAuNPs improved survival by 36% or 74% for tumors irradiated at the BE or SOBP. Conclusion: These important, albeit preliminary, in vivo findings reveal nanoparticles to be potent sensitizers to proton therapy. Further, conjugation of AuNPs to tumor-specific antigens that promote enhanced cellular internalization improved both tumor-growth delay and survival of mice after proton therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

High resolution Cerenkov light imaging of induced positron distribution in proton therapy

Purpose: In proton therapy, imaging of the positron distribution produced by fragmentation during or soon after proton irradiation is a useful method to monitor the proton range. Although positron emission tomography (PET) is typically used for this imaging, its spatial resolution is limited. Cerenkov light imaging is a new molecular imaging technology that detects the visible photons that are produced from high-speed electrons using a high sensitivity optical camera. Because its inherent spatial resolution is much higher than PET, the authors can measure more precise information of the proton-induced positron distribution with Cerenkov light imaging technology. For this purpose, they conducted Cerenkov light imaging of induced positron distribution in proton therapy. Methods: First, the authors evaluated the spatial resolution of our Cerenkov light imaging system with a {sup 22}Na point source for the actual imaging setup. Then the transparent acrylic phantoms (100 × 100 × 100 mm{sup 3}) were irradiated with two different proton energies using a spot scanning proton therapy system. Cerenkov light imaging of each phantom was conducted using a high sensitivity electron multiplied charge coupled device (EM-CCD) camera. Results: The Cerenkov light’s spatial resolution for the setup was 0.76 ± 0.6 mm FWHM. They obtained high resolution Cerenkov light images of the positron distributions in the phantoms for two different proton energies and made fused images of the reference images and the Cerenkov light images. The depths of the positron distribution in the phantoms from the Cerenkov light images were almost identical to the simulation results. The decay curves derived from the region-of-interests (ROIs) set on the Cerenkov light images revealed that Cerenkov light images can be used for estimating the half-life of the radionuclide components of positrons. Conclusions: High resolution Cerenkov light imaging of proton-induced positron distribution was possible. The authors conclude that Cerenkov light imaging of proton-induced positron is promising for proton therapy.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗