Lingshu Yin

First Clinical Investigation of Cone Beam Computed Tomography and Deformable Registration for Adaptive Proton Therapy for Lung Cancer

PURPOSE An adaptive proton therapy workflow using cone beam computed tomography (CBCT) is proposed. It consists of an online evaluation of a fast range-corrected dose distribution based on a virtual CT (vCT) scan. This can be followed by more accurate offline dose recalculation on the vCT scan, which can trigger a rescan CT (rCT) for replanning. METHODS AND MATERIALS The workflow was tested retrospectively for 20 consecutive lung cancer patients. A diffeomorphic Morphon algorithm was used to generate the lung vCT by deforming the average planning CT onto the CBCT scan. An additional correction step was applied to account for anatomic modifications that cannot be modeled by deformation alone. A set of clinical indicators for replanning were generated according to the water equivalent thickness (WET) and dose statistics and compared with those obtained on the rCT scan. The fast dose approximation consisted of warping the initial planned dose onto the vCT scan according to the changes in WET. The potential under- and over-ranges were assessed as a variation in WET at the targets distal surface. RESULTS The range-corrected dose from the vCT scan reproduced clinical indicators similar to those of the rCT scan. The workflow performed well under different clinical scenarios, including atelectasis, lung reinflation, and different types of tumor response. Between the vCT and rCT scans, we found a difference in the measured 95% percentile of the over-range distribution of 3.4 ± 2.7 mm. The limitations of the technique consisted of inherent uncertainties in deformable registration and the drawbacks of CBCT imaging. The correction step was adequate when gross errors occurred but could not recover subtle anatomic or density changes in tumors with complex topology. CONCLUSIONS A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes.

Potential of 3D printing technologies for fabrication of electron bolus and proton compensators

In electron and proton radiotherapy, applications of patient‐specific electron bolus or proton compensators during radiation treatments are often necessary to accommodate patient body surface irregularities, tissue inhomogeneity, and variations in PTV depths to achieve desired dose distributions. Emerging 3D printing technologies provide alternative fabrication methods for these bolus and compensators. This study investigated the potential of utilizing 3D printing technologies for the fabrication of the electron bolus and proton compensators. Two printing technologies, fused deposition modeling (FDM) and selective laser sintering (SLS), and two printing materials, PLA and polyamide, were investigated. Samples were printed and characterized with CT scan and under electron and proton beams. In addition, a software package was developed to convert electron bolus and proton compensator designs to printable Standard Tessellation Language file format. A phantom scalp electron bolus was printed with FDM technology with PLA material. The HU of the printed electron bolus was 106.5±15.2. A prostate patient proton compensator was printed with SLS technology and polyamide material with −70.1±8.1 HU. The profiles of the electron bolus and proton compensator were compared with the original designs. The average over all the CT slices of the largest Euclidean distance between the design and the fabricated bolus on each CT slice was found to be 0.84±0.45 mm and for the compensator to be 0.40±0.42 mm. It is recommended that the properties of specific 3D printed objects are understood before being applied to radiotherapy treatments. PACS number: 81.40

Dynamic simulation of motion effects in IMAT lung SBRT

BackgroundIntensity modulated arc therapy (IMAT) has been widely adopted for Stereotactic Body Radiotherapy (SBRT) for lung cancer. While treatment dose is optimized and calculated on a static Computed Tomography (CT) image, the effect of the interplay between the target and linac multi-leaf collimator (MLC) motion is not well described and may result in deviations between delivered and planned dose. In this study, we investigated the dosimetric consequences of the inter-play effect on target and organs at risk (OAR) by simulating dynamic dose delivery using dynamic CT datasets.MethodsFifteen stage I non-small cell lung cancer (NSCLC) patients with greater than 10 mm tumor motion treated with SBRT in 4 fractions to a dose of 50 Gy were retrospectively analyzed for this study. Each IMAT plan was initially optimized using two arcs. Simulated dynamic delivery was performed by associating the MLC leaf position, gantry angle and delivered beam monitor units (MUs) for each control point with different respiratory phases of the 4D-CT using machine delivery log files containing time stamps of the control points. Dose maps associated with each phase of the 4D-CT dose were calculated in the treatment planning system and accumulated using deformable image registration onto the exhale phase of the 4D-CT. The original IMAT plans were recalculated on the exhale phase of the CT for comparison with the dynamic simulation.ResultsThe dose coverage of the PTV showed negligible variation between the static and dynamic simulation. There was less than 1.5% difference in PTV V95% and V90%. The average inter-fraction and cumulative dosimetric effects among all the patients were less than 0.5% for PTV V95% and V90% coverage and 0.8 Gy for the OARs. However, in patients where target is close to the organs, large variations were observed on great vessels and bronchus for as much as 4.9 Gy and 7.8 Gy.ConclusionsLimited variation in target dose coverage and OAR constraints were seen for each SBRT fraction as well as over all four fractions. Large dose variations were observed on critical organs in patients where these organs were closer to the target.

Quantitative assessment of anatomical change using a virtual proton depth radiograph for adaptive head and neck proton therapy

The aim of this work is to demonstrate the feasibility of using water‐equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone‐beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray‐tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beams eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy. PACS number(s): 87.55‐x, 87.55.‐D, 87.57.Q‐The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beams eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy. PACS number(s): 87.55-x, 87.55.-D, 87.57.Q.

Ex vivo validation of a stoichiometric dual energy CT proton stopping power ratio calibration

A major source of uncertainty in proton therapy is the conversion of Hounsfield unit (HU) to proton stopping power ratio relative to water (SPR). In this study, we measured and quantified the accuracy of a stoichiometric dual energy CT (DECT) SPR calibration. We applied a stoichiometric DECT calibration method to derive the SPR using CT images acquired sequentially at [Formula: see text] and [Formula: see text]. The dual energy index was derived based on the HUs of the paired spectral images and used to calculate the effective atomic number (Z eff), relative electron density ([Formula: see text]), and SPRs of phantom and biological materials. Two methods were used to verify the derived SPRs. The first method measured the samples water equivalent thicknesses to deduce the SPRs using a multi-layer ion chamber (MLIC) device. The second method utilized Gafchromic EBT3 film to directly compare relative ranges between sample and water after proton pencil beam irradiation. Ex vivo validation was performed using five different types of frozen animal tissues with the MLIC and three types of fresh animal tissues using film. In addition, the residual ranges recorded on the film were used to compare with those from the treatment planning system using both DECT and SECT derived SPRs. Bland-Altman analysis indicates that the differences between DECT and SPR measurement of tissue surrogates, frozen and fresh animal tissues has a mean of 0.07% and standard deviation of 0.58% compared to 0.55% and 1.94% respectively for single energy CT (SECT) and SPR measurement. Our ex vivo study indicates that the stoichiometric DECT SPR calibration method has the potential to be more accurate than SECT calibration under ideal conditions although beam hardening effects and other image artifacts may increase this uncertainty.

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.

Quantification of vaginal motion associated with daily endorectal balloon placement during whole pelvis radiotherapy for gynecologic cancers.

BACKGROUND AND PURPOSE To quantify intra-treatment vaginal motion in women treated with daily endorectal balloon (ERB) placement and external beam radiotherapy for gynecologic cancers. MATERIALS AND METHODS Eighteen post-hysterectomy women with gynecologic cancers underwent computed tomography (CT) simulation scans and daily treatment with ERB. Fiducial markers were placed at the vaginal apex prior to simulation and patients were counseled on a pre-treatment bladder filling protocol. Weekly to biweekly verification CT scans were used to calculate the intra-treatment change in bladder volumes, rectal volumes, and fiducial coordinates along all axes. The planning target volume (PTV) margins required to encompass 95% of intra-treatment fiducial movement were calculated using the van Herk margin recipe. RESULTS The median bladder volume was 223 (range, 29-879)cc for verification CT scans. Mean intra-treatment fiducial displacements were 1.7 (range, 0-9.1)mm, 2.9 (range, 0-15.5)mm, and 2.5 (range, 0-11.8)mm along the left-right (L/R), superior-inferior (S/I), and anterior-posterior (A/P) axes, respectively. The van Herk PTV margins were 3mm (L/R), 10mm (S/I) and 7mm (A/P). CONCLUSION When compared to existing studies, the use of daily ERB with post-hysterectomy radiotherapy reduces vaginal motion along the A/P axis. The impact of variable bladder filling on vaginal motion is most evident along the S/I axis.

Effects on the photon beam from an electromagnetic array used for patient localization and tumor tracking

One of the main components in a Calypso 4D localization and tracking system is an electromagnetic array placed above patients that is used for target monitoring during radiation treatment. The beam attenuation and beam spoiling properties of the Calypso electromagnetic array at various beam angles were investigated. Measurements were performed on a Varian Clinac iX linear accelerator with 6 MV and 15 MV photon beams. The narrow beam attenuation properties were measured under a field size of 1 cm×1 cm, with a photon diode placed in a cylindrical graphite buildup cap. The broad beam attenuation properties were measured under a field size of 10 cm×10 cm, with a 0.6 cc cylindrical Farmer chamber placed in a polystyrene buildup cap. Beam spoiling properties of the array were studied by measuring depth‐dose change from the array under a field size of 10 cm×10 cm cm in a water‐equivalent plastic phantom with an embedded Markus parallel plate chamber. Change in depth doses were measured with the array placed at distances of 2, 5, and 10 cm from the phantom surface. Narrow beam attenuation and broad beam attenuation from the array were found to be less than 2%–3% for both 6 MV and 15 MV beams at angles less than 40°, and were more pronounced at more oblique angles. Spoiling effects are appreciable at beam buildup region, but are insignificant at depths beyond dmax. Dose measurements in a QA phantom using patient IMRT and VMAT treatment plans were shown to have less than 2.5% dose difference with the Calypso array. The results indicate that the dose difference due to the placement of Calypso array is clinically insignificant. PACS number: 87.56.‐v

TU-FG-BRB-01: Dual Energy CT Proton Stopping Power Ratio Calibration and Validation with Animal Tissues

PURPOSE The conversion of Hounsfield Unit (HU) to proton stopping power ratio (SPR) is a main source of uncertainty in proton therapy. In this study, the SPRs of animal tissues were measured and compared with prediction from dual energy CT (DECT) and single energy CT (SECT) calibrations. METHODS A stoichiometric calibration method for DECT was applied to predict the SPR using CT images acquired at 80 kVp and 140 kVp. The dual energy index was derived based on the HUs of the paired spectral images and used to calculate the SPRs of the materials. Tissue surrogates with known chemical compositions were used for calibration, and animal tissues (pig brain, liver, kidney; veal shank, muscle) were used for validation. The materials were irradiated with proton pencil beams, and SPRs were deduced from the residual proton range measured using a multi-layer ion chamber device. In addition, Gafchromic EBT3 films were used to measure the distal dose profiles after irradiation through the tissue samples and compared with those calculated by the treatment planning system using both DECT and SECT predicted SPRs. RESULTS The differences in SPR between DECT prediction and measurement were -0.31±0.36% for bone, 0.47±0.42% for brain, 0.67±0.15% for liver, 0.51±0.52% for kidney, and -0.96±0.15% for muscle. The corresponding results using SECT were 3.1±0.12%, 1.90±0.45%, -0.66±0.11%, 2.33±0.21%, and -1.70±0.17%. In the film measurements, average distances between film and calculated distal dose profiles were 0.35±0.12 mm for DECT calibration and -1.22±0.12 mm for SECT calibration for a beam with a range of 15.79 cm. CONCLUSION Our study indicates that DECT is superior to SECT for proton SPR prediction and has the potential to reduce the range uncertainty to less than 2%. DECT may permit the use of tighter distal and proximal range uncertainty margins for treatment, thereby increasing the precision of proton therapy.

WE‐F‐16A‐03: 3D Printer Application in Proton Therapy: A Novel Method to Deliver Passive‐Scattering Proton Beams with a Fixed Range and Modulation for SRS and SRT

PURPOSE To present a novel technique to deliver passive-scattering proton beam with fixed range and modulation using a 3D printed patient-specific bolus for proton stereotactic radiosurgery and radiotherapy. METHODS A CIRS head phantom was used to simulate a patient with a small brain lesion. A custom bolus was created in the Eclipse Treatment Planning System (TPS) to compensate for the different water equivalent depths from the patient surface to the target from multiple beam directions. To simulate arc therapy, a plan was created on the initial CT using three passive-scattering proton beams with a fixed range and modulations irradiating from different angles. The DICOM-RT structure file of the bolus was exported from the TPS and converted to STL format for 3D printing. The phantom was rescanned with the printed custom bolus and head cup to verify the dose distribution comparing to the initial plan. EBT3 films were placed in the sagital plane of the target to verify the delivered dose distribution. The relative stopping power of the printing material(ABSplus-P430) was measured using the Zebra multi-plate ion chamber. RESULTS The relative stopping power of the 3D printing material, ABSplus-P430 was 1.05 which is almost water equivalent. The dose difference between verification CT and Initial CT is almost negligible. Film measurement also confirmed the accuracy for this new proton delivery technique. CONCLUSION Our method using 3D printed range modifiers simplify the treatment delivery of multiple passive-scattering beams in treatment of small lesion in brain. This technique makes delivery of multiple beam more efficient and can be extended to allow arc therapy with proton beams. The ability to create and construct complex patient specific bolus structures provides a new dimension in creating optimized quality treatment plans not only for proton therapy but also for electron and photon therapy.