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Validating FMEA output against incident learning data: A study in stereotactic body radiation therapy

PURPOSE Though failure mode and effects analysis (FMEA) is becoming more widely adopted for risk assessment in radiation therapy, to our knowledge, its output has never been validated against data on errors that actually occur. The objective of this study was to perform FMEA of a stereotactic body radiation therapy (SBRT) treatment planning process and validate the results against data recorded within an incident learning system. METHODS FMEA on the SBRT treatment planning process was carried out by a multidisciplinary group including radiation oncologists, medical physicists, dosimetrists, and IT technologists. Potential failure modes were identified through a systematic review of the process map. Failure modes were rated for severity, occurrence, and detectability on a scale of one to ten and risk priority number (RPN) was computed. Failure modes were then compared with historical reports identified as relevant to SBRT planning within a departmental incident learning system that has been active for two and a half years. Differences between FMEA anticipated failure modes and existing incidents were identified. RESULTS FMEA identified 63 failure modes. RPN values for the top 25% of failure modes ranged from 60 to 336. Analysis of the incident learning database identified 33 reported near-miss events related to SBRT planning. Combining both methods yielded a total of 76 possible process failures, of which 13 (17%) were missed by FMEA while 43 (57%) identified by FMEA only. When scored for RPN, the 13 events missed by FMEA ranked within the lower half of all failure modes and exhibited significantly lower severity relative to those identified by FMEA (p = 0.02). CONCLUSIONS FMEA, though valuable, is subject to certain limitations. In this study, FMEA failed to identify 17% of actual failure modes, though these were of lower risk. Similarly, an incident learning system alone fails to identify a large number of potentially high-severity process errors. Using FMEA in combination with incident learning may render an improved overview of risks within a process.

Improved accuracy for noncoplanar radiotherapy: an EPID-based method for submillimeter alignment of linear accelerator table rotation with MV isocenter

Accurate alignment of linear accelerator table rotational axis with radiation isocenter is critical for noncoplanar radiotherapy applications. The purpose of the present study is to develop a method to align the table rotation axis and the MV isocenter to submillimeter accuracy. We developed a computerized method using electronic portal imaging device (EPID) and measured alignment stability over time. Mechanical and radiation isocenter coincidence was measured by placing a steel ball bearing at radiation isocenter using existing EPID techniques. Then, EPID images were acquired over the range of table rotation. A MATLAB script was developed to calculate the center of rotation, as well as the necessary adjustment to move the table rotational axis to MV isocenter. Adjustment was applied via torque to screws at the base of the linac table. Stability of rotational alignment was measured with 49 measurements over 363 days on four linacs. Initial rotational misalignment from radiation isocenter ranged from 0.91−2.11 mm on the four tested linacs. Linac‐A had greatest error (>2 mm) and was adjusted with the described method. After adjustment, the error was significantly decreased to 0.40±0.12 mm. The adjustment was stable over the course of 15 measurements over 231 days. Linac‐B was not adjusted, but tracked from time of commissioning with 27 measurements over 363 days. No discernible shift in couch characteristics was observed (mean error 1.40±0.22 mm). The greater variability for Linac‐B may relate to the interchangeable two‐piece couch, which allows more lateral movement than the one‐piece Linac‐A couch. Submillimeter isocenter alignment was achieved by applying a precision correction to the linac table base. Table rotational characteristics were shown to be stable over the course of twelve months. The accuracy and efficiency of this method may make it suitable for acceptance testing, annual quality assurance, or commissioning of highly‐conformal noncoplanar radiotherapy programs. PACS number: 87

An image-guided precision proton radiation platform for preclinical in vivo research

There are many unknowns in the radiobiology of proton beams and other particle beams. We describe the development and testing of an image-guided low-energy proton system optimized for radiobiological research applications. A 50 MeV proton beam from an existing cyclotron was modified to produce collimated beams (as small as 2 mm in diameter). Ionization chamber and radiochromic film measurements were performed and benchmarked with Monte Carlo simulations (TOPAS). The proton beam was aligned with a commercially-available CT image-guided x-ray irradiator device (SARRP, Xstrahl Inc.). To examine the alternative possibility of adapting a clinical proton therapy system, we performed Monte Carlo simulations of a range-shifted 100 MeV clinical beam. The proton beam exhibits a pristine Bragg Peak at a depth of 21 mm in water with a dose rate of 8.4 Gy min-1 (3 mm depth). The energy of the incident beam can be modulated to lower energies while preserving the Bragg peak. The LET was: 2.0 keV µm-1 (water surface), 16 keV µm-1 (Bragg peak), 27 keV µm-1 (10% peak dose). Alignment of the proton beam with the SARRP system isocenter was measured at 0.24 mm agreement. The width of the beam changes very little with depth. Monte Carlo-based calculations of dose using the CT image data set as input demonstrate in vivo use. Monte Carlo simulations of the modulated 100 MeV clinical proton beam show a significantly reduced Bragg peak. We demonstrate the feasibility of a proton beam integrated with a commercial x-ray image-guidance system for preclinical in vivo studies. To our knowledge this is the first description of an experimental image-guided proton beam for preclinical radiobiology research. It will enable in vivo investigations of radiobiological effects in proton beams.

Clinical Commissioning of a Pencil Beam Scanning Treatment Planning System for Proton Therapy

Purpose In this report, we present the commissioning and validation results for a commercial proton pencil beam scanning RayStation treatment planning system. Materials and Methods The commissioning data requirements are (1) integrated depth dose curves, (2) spot profiles, (3) absolute dose/monitor unit calibration, and (4) virtual source position. An 8-cm parallel plate chamber was used to measure the integrated depth dose curves by scanning a beam composed of a single spot in a water phantom. The spot profiles were measured at 5 different planes using a 2-dimensional scintillation detector. The absolute dose/monitor unit calibration was based on dose measurements in single-layer fields of size 10 × 10 cm2. The virtual-source position was calculated from the change in spot spacing with the distance from the isocenter. The beam model validation consisted of a comparison against commissioning data as well as a new set of verification measurements. For end-to-end testing, a series of phantom plans were created. These plans were measured at 1 to 3 depths using a 2-dimensional ion chamber array and evaluated for gamma index using the 3% and 3 mm criteria. Results The maximum deviation for spot sigma measured versus calculated was -0.2 mm. The point-dose measurements for single-layer beams were within ± 3%, except for the largest field size (29 × 29 cm2) and the highest energy (226 MeV). The point doses in the spread-out Bragg peak plans showed a trend in which differences > 3% were seen for ranges > 30 cm, field sizes > 15 × 15 cm2, and depths > 25 cm. For end-to-end testing, 34 planes corresponding to 13 beams were analyzed for gamma index with a minimum pass rate of 92.8%. Conclusion The acceptable verification results and successful end-to-end testing ensured that all components of the treatment planning system were functional and the system was ready for clinical use.

Biological and dosimetric characterisation of spatially fractionated proton minibeams

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator

Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy.

SU-G-TeP1-11: Predictors of Cardiac and Lung Dose Sparing in DIBH for Left Breast Treatment

PURPOSE This retrospective study of left sided whole breast radiation therapy (RT) patients investigates possible predictive parameters correlating to cardiac and left lung dose sparing by deep inspiration breath-hold (DIBH) technique compared to free-breathing (FB). METHODS Thirty-one patients having both DIBH and FB CT scans were included in the study. All patients were planned with a standard step-and-shoot tangential technique using MV photons, with prescription of 50Gy or 50.4Gy. The displacement of the breath hold sternal mark during DIBH, the cardiac contact distances of the axial (CCDax) and parasagittal (CCDps) planes, and lateral-heart-to-chest (LHC) distance on FB CT scans were measured. Lung volumes, mean dose and dose-volume histograms (V5, V10 and V20) were analyzed and compared for heart and left lung for both FB and DIBH techniques. Correlation analysis was performed to identify the predictors for heart and left lung dose sparing. Two-tailed Students t-test and linear regression were used for data analysis with significance level of P≤0.05. RESULTS All dosimetric metrics for the heart and left lung were significantly reduced (P<0.01) with DIBH. Breath hold sternal mark displacement ranged from 0.4-1.8 cm and correlated with mean (P=0.05) and V5 (P=0.02) of heart dose reduction by DIBH. FB lung volume showed correlation with mean lung dose reduction by DIBH (P<0.01). The FB-CCDps and FB-LHC distance had strong positive and negative correlation with FB mean heart dose (P<0.01) and mean heart dose reduction by DIBH (P<0.01), respectively. FB-CCDax showed no correlation with dosimetric changes. CONCLUSION DIBH technique has been shown to reduce dose to the heart and left lung. In this patient cohort, FB-CCDps, FB-LHC distance, and FB lung volume served as significant predictors for heart and left lung. These parameters can be further investigated to be used as a tool to better select patients who will benefit from DIBH.

TH-AB-209-05: Validating Hemoglobin Saturation and Dissolved Oxygen in Tumors Using Photoacoustic Computed Tomographic Spectroscopic Imaging

PURPOSE Photoacoustic computed tomographic spectroscopy (PCT-S) provides intra-tumor measurements of oxygenation with high spatial resolution (0.2mm) and temporal fidelity (1-2 minutes) without the need for exogenous agents or ionizing radiation, thus providing a unique in vivo assay to measure SaO2 and investigate acute and chronic forms of hypoxia. The goal of this study is to validate in vivo SaO2 levels within tail artery of mice and the relationship between SaO2 and pO2 within subcutaneous breast tumors using PCT-S imaging, pulse oximetry and an OxyLite probe. METHODS A closed circuit phantom was fabricated to control blood oxygenation levels, where SaO2 was measured using a co-oximeter and pO2 using an Oxylite probe. Next, SaO2 levels within the tail arteries of mice (n=3) were measured using PCT-S and pulse oximetry while breathing high-to-low oxygen levels (6-cycles). Finally, PCT-S was used to measure SaO2 levels in MCF-7, MCF-7-VEGF165, and MDA-MB-231 xenograft breast tumors and compared to Oxylite pO2 levels values. RESULTS SaO2 and pO2 data obtained from the calibration phantom was fit to Hills equation: aO2 levels between 88 and 52% demonstrated a linear relationship (r2=0.96) and a 3.2% uncertainty between PCT-S values relative to pulse oximetry. Scatter plots of localized PCT-S measured SaO2 and Oxylite pO2 levels in MCF-7/MCF-7-VEGF165 and MDA-MD-231 breast tumors were fit to Hills equation: P50=17.2 and 20.7mmHg, and n=1.76 and 1.63. These results are consistent with sigmoidal form of Hills equation, where the lower P50 value is indicative of an acidic tumor microenvironment. CONCLUSION The results demonstrate photoacoustic imaging can be used to measure SaO2 cycling and intra-tumor oxygenation, and provides a powerful in vivo assay to investigate the role of hypoxia in radiation, anti-angiogenic, and immunotherapies.

SU-F-T-128: Dose-Volume Constraints for Particle Therapy Treatment Planning

PURPOSE Determine equivalent Organ at Risk (OAR) tolerance dose (TD) constraints for MV x-rays and particle therapy. METHODS Equivalent TD estimates for MV x-rays are determined from an isoeffect, regression-analysis of published and in-house constraints for various fractionation schedules (n fractions). The analysis yields an estimate of (α/β) for an OAR. To determine equivalent particle therapy constraints, the MV x-ray TD(n) values are divided by the RBE for DSB induction (RBEDSB ) or cell survival (RBES ). Estimates of (RBEDSB ) are computed using the Monte Carlo Damage Simulation, and estimates of RBES are computed using the Repair-Misrepair-Fixation (RMF) model. A research build of the RayStation™ treatment planning system implementing the above model is used to estimate (RBEDSB ) for OARs of interest in 16 proton therapy patient plans (head and neck, thorax, prostate and brain). RESULTS The analysis gives an (α/β) estimate of about 20 Gy for the trachea and heart and 2-4 Gy for the esophagus, spine, and brachial plexus. Extrapolation of MV x-ray constraints (n = 1) to fast neutrons using RBEDSB = 2.7 are in excellent agreement with clinical experience (n = 10 to 20). When conventional (n > 30) x-ray treatments are used as the reference radiation, fast neutron RBE increased to a maximum of 6. For comparison to a constant RBE of 1.1, the RayStation™ analysis gave estimates of proton RBEDSB from 1.03 to 1.33 for OARs of interest. CONCLUSION The presented system of models is a convenient formalism to synthesize from multiple sources of information a set of self-consistent plan constraints for MV x-ray and hadron therapy treatments. Estimates of RBEDSB from the RayStation™ analysis differ substantially from 1.1 and vary among patients and treatment sites. A treatment planning system that incorporates patient and anatomy-specific corrections in proton RBE would create opportunities to increase the therapeutic ratio. The research build of the RayStation used in the study was made available to the University of Washington free of charge. RaySearch Laboratories did not provide any monetary support for the reported studies.

Electron beam energy QA — a note on measurement tolerances

Monthly QA is recommended to verify the constancy of high‐energy electron beams generated for clinical use by linear accelerators. The tolerances are defined as 2%/2 mm in beam penetration according to AAPM task group report 142. The practical implementation is typically achieved by measuring the ratio of readings at two different depths, preferably near the depth of maximum dose and at the depth corresponding to half the dose maximum. Based on beam commissioning data, we show that the relationship between the ranges of energy ratios for different electron energies is highly nonlinear. We provide a formalism that translates measurement deviations in the reference ratios into change in beam penetration for electron energies for six Elekta (6‐18 MeV) and eight Varian (6‐22 MeV) electron beams. Experimental checks were conducted for each Elekta energy to compare calculated values with measurements, and it was shown that they are in agreement. For example, for a 6 MeV beam a deviation in the measured ionization ratio of ±15% might still be acceptable (i.e., be within ±2 mm), whereas for an 18 MeV beam the corresponding tolerance might be ±6%. These values strongly depend on the initial ratio chosen. In summary, the relationship between differences of the ionization ratio and the corresponding beam energy are derived. The findings can be translated into acceptable tolerance values for monthly QA of electron beam energies. PACS number(s): 87.55, 87.56Monthly QA is recommended to verify the constancy of high-energy electron beams generated for clinical use by linear accelerators. The tolerances are defined as 2%/2 mm in beam penetration according to AAPM task group report 142. The practical implementation is typically achieved by measuring the ratio of readings at two different depths, preferably near the depth of maximum dose and at the depth corresponding to half the dose maximum. Based on beam commissioning data, we show that the relationship between the ranges of energy ratios for different electron energies is highly nonlinear. We provide a formalism that translates measurement deviations in the reference ratios into change in beam penetration for electron energies for six Elekta (6-18 MeV) and eight Varian (6-22 MeV) electron beams. Experimental checks were conducted for each Elekta energy to compare calculated values with measurements, and it was shown that they are in agreement. For example, for a 6 MeV beam a deviation in the measured ionization ratio of ±15% might still be acceptable (i.e., be within ±2 mm), whereas for an 18 MeV beam the corresponding tolerance might be ±6%. These values strongly depend on the initial ratio chosen. In summary, the relationship between differences of the ionization ratio and the corresponding beam energy are derived. The findings can be translated into acceptable tolerance values for monthly QA of electron beam energies. PACS number(s): 87.55, 87.56.