Nicholas B. Remmes

Optimizing Normal Tissue Sparing in Ion Therapy Using Calculated Isoeffective Dose for Ion Selection

PURPOSE To investigate how the selection of ion type affects the calculated isoeffective dose to the surrounding normal tissue as a function of both normal tissue and target tissue α/β ratios. METHODS AND MATERIALS A microdosimetric biologic dose model was incorporated into a Geant4 simulation of parallel opposed beams of protons, helium, lithium, beryllium, carbon, and neon ions. The beams were constructed to give a homogeneous isoeffective dose to a volume in the center of a water phantom for target tissues covering a range of cobalt equivalent α/β ratios of 1-20 Gy. Concomitant normal tissue isoeffective doses in the plateau of the ion beam were then compared for different ions across the range of normal tissue and target tissue radiosensitivities for a fixed isoeffective dose to the target tissue. RESULTS The ion type yielding the optimal normal tissue sparing was highly dependent on the α/β ratio of both the normal and the target tissue. For carbon ions, the calculated isoeffective dose to normal tissue at a 5-cm depth varied by almost a factor of 5, depending on the α/β ratios of the normal and target tissue. This ranges from a factor of 2 less than the isoeffective dose of a similar proton treatment to a factor of 2 greater. CONCLUSIONS No single ion is optimal for all treatment scenarios. The heavier ions are superior in cases in which the α/β ratio of the target tissue is low and the α/β ratio of normal tissue is high, and protons are superior in the opposite circumstances. Lithium and beryllium appear to offer dose advantages similar to carbon, with a considerably lower normal tissue dose when the α/β ratio in the target tissue is high and the α/β ratio in the normal tissue is low.

Initial clinical experience of postmastectomy intensity modulated proton therapy in patients with breast expanders with metallic ports

PURPOSE The feasibility of proton postmastectomy radiation therapy in patients reconstructed with expanders has not been previously reported, limiting treatment options. We analyzed the dosimetric impact of the metallic port contained within expanders on intensity modulated proton therapy (IMPT) and report our techniques and quality control for treating patients in this setting. METHODS AND MATERIALS Twelve patients with the same expander model underwent 2-field IMPT as part of a prospective registry. All planning dosimetry was checked with an in-house graphic processing unit--based Monte Carlo simulation. Proton ranges through the expander were validated using a sample implant. Dosimetric impact of setup metallic port position uncertainty was evaluated. Pre- and posttreatment photographs were obtained and acute toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS Nine patients had bilateral skin-sparing mastectomy with bilateral tissue expander reconstruction, and 3 patients had unilateral skin-sparing mastectomy and reconstruction. The left side was treated in 10 patients and the right side in 2. Target coverage and normal tissue dose uncertainties resulting from the expander were small and clinically acceptable. The maximum physician-assessed acute radiation dermatitis was grade 3 in 1 patient, grade 2 in 5 patients, and grade 1 in 6 patients. CONCLUSIONS Postmastectomy IMPT in breast cancer patients with expanders is feasible and associated with favorable clinical target volume coverage and normal tissue sparing, even when taking into account treatment uncertainties; therefore, these patients should be eligible to participate in clinical trials studying the potential role of proton therapy in breast cancer. We caution, however, that institutions should carry out similar analyses of the physical properties and dosimetric impact of the particular expanders used in their practice before considering IMPT.

A novel and fast method for proton range verification using a step wedge and 2D scintillator

Purpose To implement and evaluate a novel and fast method for proton range verification by using a planar scintillator and step wedge. Methods A homogenous proton pencil beam plan with 35 energies was designed and delivered to a 2D flat scintillator with a step wedge. The measurement was repeated 15 times (3 different days, 5 times per day). The scintillator image was smoothed, the Bragg peak and distal fall off regions were fitted by an analytical equation, and the proton range was calculated using simple trigonometry. The accuracy of this method was verified by comparing the measured ranges to those obtained using an ionization chamber and a scanning water tank, the gold standard. The reproducibility was evaluated by comparing the ranges over 15 repeated measurements. The sensitivity was evaluated by delivering to same beam to the system with a film inserted under the wedge. Results The range accuracy of all 35 proton energies measured over 3 days was within 0.2 mm. The reproducibility in 15 repeated measurements for all 35 proton ranges was ±0.045 mm. The sensitivity to range variation is 0.1 mm for the worst case. This efficient procedure permits measurement of 35 proton ranges in less than 3 min. The automated data processing produces results immediately. The setup of this system took less than 5 min. The time saving by this new method is about two orders of magnitude when compared with the time for water tank range measurements. Conclusions A novel method using a scintillator with a step wedge to measure the proton range was implemented and evaluated. This novel method is fast and sensitive, and the proton range measured by this method was accurate and highly reproducible.

An Athymic Rat Model for Mandibular Osteoradionecrosis Allowing for Direct Translation of Regenerative Treatments

Objective We aim to create a model of mandibular osteoradionecrosis in athymic rats. Athymic rats provide an immunosuppressed environment whereby human stem cells and biomaterials can be used to investigate regenerative solutions for osteoradionecrosis, bridging the gap between in vivo testing and clinical application. Study Design Prospective animal study. Setting Academic otolaryngology department laboratory. Subjects and Methods After Institutional Animal Care and Use Committee approval, 10 athymic nude rats were divided into 2 groups. The experimental group (n = 6) underwent irradiation (20 Gy), while the control group (n = 4) underwent sham irradiation catheter placement only. All 10 rats underwent extraction of the second mandibular molar 7 days later. The rats were sacrificed 28 days after dental extraction, and their mandibles were harvested. The mandibles were examined with histologic analysis and bone volume analysis based on 3-dimensional micro–computed tomography. Results All 10 rats survived the experiment period. Radiographic and histologic analysis revealed decreased bone formation in the experimental group compared with the control group. Jaw region volume ratio was 0.83 for the experimental group versus 0.97 in the control group (P = .003). The region-of-interest volume ratio was 0.75 in the experimental group and 0.97 in the control group (P = .005). Histologically, there were increased osteoclasts (P = .02) and decreased osteoblasts (P = .001) as well as increased fibrosis in the experimental group versus the control group. Conclusion Mandibular osteoradionecrosis can be effectively and reproducibly produced in an athymic rat model. This will allow further research to study regenerative medicine in an athymic rat model.

Human Adipose-Derived Mesenchymal Stem Cells for Osseous Rehabilitation of Induced Osteoradionecrosis: A Rodent Model

Objective Human adipose-derived mesenchymal stem cells (ADSCs) were used to rehabilitate bone damaged by osteoradionecrosis (ORN) in an established animal model. Study Design Prospective animal study. Setting Academic department laboratory. Subjects and Methods After institutional review board and Institutional Animal Care and Use Committee approval, 24 athymic nude rats were divided into 5 groups: 4 groups irradiated (20 Gy) by brachytherapy catheter placed at the left hemimandible and 1 mock irradiation control (n = 4). For all groups, ORN was initiated by extraction of the central molar 1 week later. After 28 days, animals (n = 5/group) received injection at the extraction site with saline (SAL), ADSCs, platelet-rich plasma and collagen (PRP/COL), or ADSCs + PRP/COL. Rats were sacrificed 28 days later and their mandibles harvested for histopathology analysis (osteoblasts, osteoclasts, and fibrosis) and bone volume measurement using 3-dimensional micro–computed tomography. Results All but 1 rat survived the experiment period (23/24). Radiographic and histological analysis revealed 60% bone loss in the SAL group compared with the nonirradiated control. Injection of ADSCs increased jaw region bone volume by up to 36% (P < .01). All experimental groups (ADSC, PRP/COL, and ADSC + PRP/COL) showed dramatically decreased osteoclast counts (P < .001) while injection of PRP/COL with or without ADSCs increased osteoblasts. Increased fibrosis was observed after ADSC injection (P < .05). Conclusion The application of human ADSCs to an induced mandibular osteoradionecrosis model in athymic rats results in increased deposition or preservation of bone, demonstrated both histologically and radiographically. This offers an encouraging possible treatment option for translational research in this difficult disease.

SU-F-T-169: A Periodic Quality Assurance Program for a Spot-Scanning Proton Treatment Facility

PURPOSE To develop daily and monthly quality assurance (QA) programs in support of a new spot-scanning proton treatment facility using a combination of commercial and custom equipment and software. Emphasis was placed on efficiency and evaluation of key quality parameters. METHODS The daily QA program was developed to test output, spot size and position, proton beam energy, and image guidance using the Sun Nuclear Corporation rf-DQA™3 device and Atlas QA software. The program utilizes standard Atlas linear accelerator tests repurposed for proton measurements and a custom jig for indexing the device to the treatment couch. The monthly QA program was designed to test mechanical performance, image quality, radiation quality, isocenter coincidence, and safety features. Many of these tests are similar to linear accelerator QA counterparts, but many require customized test design and equipment. Coincidence of imaging, laser marker, mechanical, and radiation isocenters, for instance, is verified using a custom film-based device devised and manufactured at our facility. Proton spot size and position as a function of energy are verified using a custom spot pattern incident on film and analysis software developed in-house. More details concerning the equipment and software developed for monthly QA are included in the supporting document. Thresholds for daily and monthly tests were established via perturbation analysis, early experience, and/or proton system specifications and associated acceptance test results. RESULTS The periodic QA program described here has been in effect for approximately 9 months and has proven efficient and sensitive to sub-clinical variations in treatment delivery characteristics. CONCLUSION Tools and professional guidelines for periodic proton system QA are not as well developed as their photon and electron counterparts. The program described here efficiently evaluates key quality parameters and, while specific to the needs of our facility, could be readily adapted to other proton centers.

WE-F-16A-02: Design, Fabrication, and Validation of a 3D-Printed Proton Filter for Range Spreading

PURPOSE To design, fabricate and test a 3D-printed filter for proton range spreading in scanned proton beams. The narrow Bragg peak in lower-energy synchrotron-based scanned proton beams can result in longer treatment times for shallow targets due to energy switching time and plan quality degradation due to minimum monitor unit limitations. A filter with variable thicknesses patterned on the same scale as the beams lateral spot size will widen the Bragg peak. METHODS The filter consists of pyramids dimensioned to have a Gaussian distribution in thickness. The pyramids are 2.5mm wide at the base, 0.6 mm wide at the peak, 5mm tall, and are repeated in a 2.5mm pseudo-hexagonal lattice. Monte Carlo simulations of the filter in a proton beam were run using TOPAS to assess the change in depth profiles and lateral beam profiles. The prototypes were constrained to a 2.5cm diameter disk to allow for micro-CT imaging of promising prototypes. Three different 3D printers were tested. Depth-doses with and without the prototype filter were then measured in a ~70MeV proton beam using a multilayer ion chamber. RESULTS The simulation results were consistent with design expectations. Prototypes printed on one printer were clearly unacceptable on visual inspection. Prototypes on a second printer looked acceptable, but the micro-CT image showed unacceptable voids within the pyramids. Prototypes from the third printer appeared acceptable visually and on micro-CT imaging. Depth dose scans using the prototype from the third printer were consistent with simulation results. Bragg peak width increased by about 3x. CONCLUSIONS A prototype 3D printer pyramid filter for range spreading was successfully designed, fabricated and tested. The filter has greater design flexibility and lower prototyping and production costs compared to traditional ridge filters. Printer and material selection played a large role in the successful development of the filter.

Knowledge of endoscopic ultrasound-delivered fiducial composition and dimension necessary when planning proton beam radiotherapy

Background and study aims  Little consideration has been given to selection of endoscopic ultrasound-guided fiducials for proton radiotherapy and the resulting perturbations in the therapy dose and pattern. Our aim was to assess the impact of perturbations caused by six fiducials of different composition and dimensions in a phantom gel model. Materials and methods  The phantom was submerged in a water bath and irradiated with a uniform 10 cm × 10 cm field of 119.7 MeV monoenergetic spot scanning protons delivered through a 45 mm range shifter. The proton “Bragg Peak” was evaluated. Results  Dose perturbations manifesting as dose reductions up to 30 % were observed. A carbon composite (1 × 5 mm) and gold (0.4 × 10 mm) fiducial with backload potential rather than dedicated EUS pre-loaded gold fiducial needles had the best performance in terms of minimizing the dose perturbation. Conclusions  Our data demonstrate that a carbon composite fiducial has a less untoward effect on proton therapy dose distribution than dedicated EUS pre-loaded gold fiducial needles. Such information is important to consider when selecting fiducials specifically for proton therapy.

SU‐E‐T‐400: Evaluation of Shielding and Activation at Two Pencil Beam Scanning Proton Facilities

Purpose: To verify acceptably low dose levels around two newly constructed identical pencil beam scanning proton therapy facilities and to evaluate accuracy of pre-construction shielding calculations. Methods: Dose measurements were taken at select points of interest using a WENDI-2 style wide-energy neutron detector. Measurements were compared to pre-construction shielding calculations. Radiation badges with neutron dose measurement capabilities were worn by personnel and also placed at points throughout the facilities. Seven neutron and gamma detectors were permanently installed throughout the facility, continuously logging data. Potential activation hazards have also been investigated. Dose rates near water tanks immediately after prolonged irradiation have been measured. Equipment inside the treatment room and accelerator vault has been surveyed and/or wipe tested. Air filters from air handling units, sticky mats placed outside of the accelerator vault, and water samples from the magnet cooling water loops have also been tested. Results: All radiation badges have been returned with readings below the reporting minimum. Measurements of mats, air filters, cooling water, wipe tests and surveys of equipment that has not been placed in the beam have all come back at background levels. All survey measurements show the analytical shielding calculations to be conservative by at least a factor of 2. No anomalous events have been identified by the building radiation monitoring system. Measurements of dose rates close to scanning water tanks have shown dose rates of approximately 10 mrem/hr with a half-life less than 5 minutes. Measurements around the accelerator show some areas with dose rates slightly higher than 10 mrem/hr. Conclusion: The shielding design is shown to be adequate. Measured dose rates are below those predicted by shielding calculations. Activation hazards are minimal except in certain very well defined areas within the accelerator vault and for objects placed directly in the path of the beam.

SU‐C‐19A‐04: Evaluation of Patient Positioning Reproducibility with Three Supine Breast Boards

PURPOSE To evaluate positioning reproducibility using three commercially available breast board immobilization systems for whole breast radiation therapy. METHODS Weekly pre-treatment cone beam CT images from 18 free-breathing breast radiotherapy patients, each immobilized with one of three breast boards, were retrospectively registered to the planning CT. Relative shifts between breast tissue and sternum/chest wall (CW), and breast tissue and spine compared to planning CT were obtained for each board. Positioning reproducibility, inter-patient variation and intra-patient variation were evaluated by group mean (M), standard deviation of group mean (Σ) and standard deviation of random shift (σ). Margins to account for setup uncertainties were calculated based on shift uncertainties in x, y, and z directions. RESULTS For breast positioning relative to sternum/CW, the average shift from planned positioning was 4.5mm (95% CI: 3.5 - 5.3), 3.3mm (CI: 2.9 - 3.8) and 2.6mm (CI: 1.8 - 3.5) for Breast Boards I, II, and III, respectively. The respective numbers for breast positioning relative to spine were 7.2 mm (CI: 4.1 - 10.3), 6.4 mm (CI: 4.3 - 8.3) and 4.3 mm (CI: 2.5 - 6.2). Localizing to the sternum/CW as a surrogate for the breast tissue, margins for setup uncertainties were 5.7mm, 5.5mm, and 6.0mm for Breast Board I, 5.0mm, 4.0mm and 4.3mm for Breast Board II, and 3.8mm, 3.5mm and 4.8mm for Breast Board III, in the lateral, anterior/posterior, and superior/inferior directions, respectively. CONCLUSION Better patient positioning reproducibility was observed with Boards II and III compared to Board I. Inter- and intra-patient set-up uncertainties were also improved with Boards II and III, which requires smaller PTV margins. Independent of breast board, breast cancer patient positioning to the sternum/CW is a better surrogate than the spine. Our findings have potential dosimetric consequences from set-up uncertainties when employing IMRT or proton treatments, and further analyses are on-going.