Boon-Keng Kevin Teo

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.

Effect of Body Mass Index on Magnitude of Setup Errors in Patients Treated With Adjuvant Radiotherapy for Endometrial Cancer With Daily Image Guidance

PURPOSE To determine the impact of body mass index (BMI) on daily setup variations and frequency of imaging necessary for patients with endometrial cancer treated with adjuvant intensity-modulated radiotherapy (IMRT) with daily image guidance. METHODS AND MATERIALS The daily shifts from a total of 782 orthogonal kilovoltage images from 30 patients who received pelvic IMRT between July 2008 and August 2010 were analyzed. The BMI, mean daily shifts, and random and systematic errors in each translational and rotational direction were calculated for each patient. Margin recipes were generated based on BMI. Linear regression and spearman rank correlation analysis were performed. To simulate a less-than-daily IGRT protocol, the average shift of the first five fractions was applied to subsequent setups without IGRT for assessing the impact on setup error and margin requirements. RESULTS Median BMI was 32.9 (range, 23-62). Of the 30 patients, 16.7% (n = 5) were normal weight (BMI <25); 23.3% (n = 7) were overweight (BMI ≥ 25 to <30); 26.7% (n = 8) were mildly obese (BMI ≥ 30 to <35); and 33.3% (n = 10) were moderately to severely obese (BMI ≥ 35). On linear regression, mean absolute vertical, longitudinal, and lateral shifts positively correlated with BMI (p = 0.0127, p = 0.0037, and p < 0.0001, respectively). Systematic errors in the longitudinal and vertical direction were found to be positively correlated with BMI category (p < 0.0001 for both). IGRT for the first five fractions, followed by correction of the mean error for all subsequent fractions, led to a substantial reduction in setup error and resultant margin requirement overall compared with no IGRT. CONCLUSIONS Daily shifts, systematic errors, and margin requirements were greatest in obese patients. For women who are normal or overweight, a planning target margin margin of 7 to 10 mm may be sufficient without IGRT, but for patients who are moderately or severely obese, this is insufficient.

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

Feasibility and limitations of bulk density assignment in MRI for head and neck IMRT treatment planning

Head and neck cancers centered at the base of skull are better visualized on MRI than on CT. The purpose of this investigation was to investigate the accuracy of bulk density assignment in head and neck intensity‐modulated radiation therapy (IMRT) treatment plan optimization. Our study investigates dose calculation differences between density‐assigned MRI and CT, and identifies potential limitations related to dental implants and MRI geometrical distortion in the framework of MRI‐only‐based treatment planning. Bulk density assignment was performed and applied onto MRI to generate three MRI image sets with increasing levels of heterogeneity for seven patients: 1) MRIW: all water‐equivalent; 2) MRIW + B: included bone with density of 1.53 g/cm3; and 3) MRIW + B + A: included bone and air. Using identical planning and optimization parameters, MRI‐based IMRT plans were generated and compared to corresponding, forward‐calculated, CT‐based plans on the basis of target coverage, isodose distributions, and dose‐volume histograms (DVHs). Phantom studies were performed to assess the magnitude and spatial dependence of MRI geometrical distortion. MRIW‐based dose calculations overestimated target coverage by 16.1%. Segmentation of bone reduced differences to within 2% of the coverage area on the CT‐based plan. Further segmentation of air improved conformity near air–tissue interfaces. Dental artifacts caused substantial target coverage overestimation even on MRIW + B + A. Geometrical distortion was less than 1 mm in an imaging volume 20 × 20 × 20 cm3 around scanner isocenter, but up to 4 mm at 17 cm lateral to isocenter. Bulk density assignment in the framework of MRI‐only IMRT head and neck treatment planning is a feasible method with certain limitations. Bone and teeth account for the majority of density heterogeneity effects. While soft tissue is well visualized on MRI compared to CT, dental implants may not be visible on MRI and must be identified by other means and assigned appropriate density for accurate dose calculation. Far off‐center geometrical distortion of the body contour near the shoulder region is a potential source of dose calculation inaccuracy. PACS numbers: 87.61.‐c, 87.55.‐D

The effect of breathing irregularities on quantitative accuracy of respiratory gated PET/CT

PURPOSE 4D positron emission tomography and computed tomography (PET∕CT) can be used to reduce motion artifacts by correlating the raw PET data with the respiratory cycle. The accuracy of each PET phase is dependent on the reproducibility and consistency of the breathing cycle during acquisition. The objective of this study is to evaluate the impact of breathing amplitude and phase irregularities on the quantitative accuracy of 4D PET standardized uptake value (SUV) measurements. In addition, the magnitude of quantitative errors due to respiratory motion and partial volume error are compared. METHODS Phantom studies were performed using spheres filled with (18)F ranging from 9 to 47 mm in diameter with background activity. Motion was simulated using patient breathing data. The authors compared the accuracy of SUVs derived from gated PET (4 bins and 8 bins, phase-based) for ideal, average, and highly irregular breathing patterns. RESULTS Under ideal conditions, gated PET produced SUVs that were within (-5.4 ± 5.3)% of the static phantom measurements averaged across all sphere sizes. With breathing irregularities, the quantitative accuracy of gated PET decreased. Gated PET SUVs (best of 4 bins) were (-9.6 ± 13.0)% of the actual value for an average breather and decreased to (-17.1 ± 10.8)% for a highly irregular breather. Without gating, the differences in the SUV from actual value were (-28.5 ± 18.2)%, (-25.9 ± 14.4)%, and (-27.9 ± 18.2)% for the ideal, average, and highly irregular breather, respectively. CONCLUSIONS Breathing irregularities reduce the quantitative accuracy of gated PET∕CT. Current gated PET techniques may underestimate the actual lesion SUV due to phase assignment errors. Evaluation of respiratory trace is necessary to assess accuracy of data binning and its effect on 4D PET SUVs.

Dosimetric impact of interfraction catheter movement and organ motion on MRI/CT guided HDR interstitial brachytherapy for gynecologic cancer.

PURPOSE To determine the dosimetric impact of catheter movement for MRI/CT image guided high dose rate (HDR) interstitial brachytherapy (ISBT) for gynecologic cancers. MATERIALS AND METHODS Ten patients were treated with HDR ISBT. The CTV and organs at risk were contoured using a postimplant MRI and CT. 5 fractions were delivered twice daily on 3 consecutive days. The first fraction was delivered on day 1 (d1), fraction 2-3 on d2 and fraction 4-5 on d3. MRI/CT was acquired prior to the second and fourth fractions. Four scenarios were modeled. (1) The d1 plan was applied to the d2 and d3 CT, using the updated catheter positions. (2) Replanning was performed for d2 and d3. (3) We applied the dwell positions/times from the d2 replan over the d3 CT and compared with a d3 CT replan. (4) Based on daily MRI, target volumes were recontoured and replanned. Dosimetry was analyzed for each plan and compared to the d1 dose distribution. RESULTS (1) When using the d1 plan on the d2 and d3 CT with the updated catheter positions, the mean CTV D90 was reduced from 93.4% on d1 to 89.3% (p=0.08) on d2 and to 87.7% (p=0.005) on d3. (2) Replanning on d2 and d3 compensated for catheter movement, mean CTV D90 of 95.4% on d2 and 94.6% (p=0.36) on d3. (3) When compared to the replan of d2 applied on the d3 CT vs the d3 replan, there was no significant difference in coverage, mean CTV D90 of 90.9% (p=0.09). (4) Reoptimization based on daily MRI, significantly improved the CTV coverage for each day. The mean D2cc for the rectum was significantly higher with model 1 vs model 3 59.1±4.7 vs 60.9±4.8 (p=0.04) Gy EQD2. There were no significant differences in D2cc of bladder and sigmoid between models. CONCLUSIONS Interfraction dosimetric changes significantly decreased the CTV coverage of the third day. Rather than replanning on each day, replanning on the day 2 CT before the second or third fraction would give an optimal solution that would compensate for interfraction catheter displacement.

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.

Clinical utility of integrated positron emission tomography/computed tomography imaging in the clinical management and radiation treatment planning of locally advanced rectal cancer

PURPOSE The role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in the staging and radiation treatment planning of locally advanced rectal cancer is ill defined. We studied the role of integrated PET/CT in the staging, radiation treatment planning, and use as an imaging biomarker in rectal cancer patients undergoing multimodality treatment. METHODS AND MATERIALS Thirty-four consecutive patients with T3-4N0-2M0-1 rectal adenocarcinoma underwent FDG-PET/CT scanning for staging and radiation treatment planning. Planned clinical management was compared before and after the addition of PET/CT information. Three radiation oncologists independently delineated CT-based gross tumor volumes (GTVCT) using clinical information and CT imaging data, as well as gradient autosegmented PET/CT-based GTVs (GTVPETCT). The mean GTV, interobserver concordance index (CCI), and proximal and distal margins were compared. The maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), and dual-time point PET parameters were correlated with clinicopathologic endpoints. RESULTS Clinical management was altered by PET/CT in 18% (n = 6) of patients with clinical upstaging in 6 patients and radiation treatment planning altered in 5 patients. Of the 30 evaluable preoperative patients, the mean GTVPETCT was significantly smaller than the mean GTVCT volumes: 88.1 versus 102.8 cc (P = .03). PET/CT significantly increased interobserver CCI in contouring GTV compared with CT only-based contouring: 0.56 versus 0.38 (P < .001). The proximal and distal margins were altered by a mean of 0.4 ± 0.24 cm and -0.25 ± 0.18 cm, respectively. MTV was inversely associated with 2-year progression-free survival (PFS) and overall survival (OS): smaller MTVs (<33 cc) had superior 2-year PFS (86% vs 60%, P = .04) and OS (100% vs 45%, P < .01) compared with larger MTVs (>33 cc). SUVmax and dual-time point PET parameters did not correlate with any endpoints. CONCLUSIONS FDG-PET/CT imaging impacts overall clinical management and is useful in the radiation treatment planning of rectal cancer patients by decreasing interobserver variability in contouring target boost volumes. Pretreatment MTV may provide useful prognostic information and requires further study.

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.