Faculty Bibliography

Purpose: Recently the Gamma Index of registered CBCT and CT, combining mass density and distance-to-agreement (DTA), has been used as an effective means to evaluate the quality of image guided pretreatment setup, and to identify radiation-induced patient anatomy change. The pass/fail of the Gamma analysis relies heavily on the Gamma criteria. We propose a regression model based on multiple patient data to quantitatively determine the optimal HU and DTA criteria for CBCT Gamma analysis. Methods: We retrospectively analyzed daily setup kV-CBCT (acquired using OBI on True- Beam, Varian Medical) from 10 H&N, 10 thoracic, and 10 abdominal cancer patients. The registration between CBCT and the planning CTwas conducted online by therapists and reviewed by radiation oncologist. Visible region of interests were contoured in the CBCT by experts as the ground truth of CT/ CBCT similarity. Gamma analyses using different levels of criteria, combinations of mass density 0.2 g/cc, 01 g/cc, and 0.05 g/cc, and DTA 3 mm, 2 mm, and 1 mm, were repeated on CBCT using the MobiusCB (by Mobius Medical System) software. The Gamma passing rate of the total irradiated volume and selected region of interests at different levels of gamma criteria were used as training data for multi-variated parametric regression model to determine the optimal gamma criteria. Results: Based on the preliminary data, the optimal Gamma criteria is 0.5 g/cc and 3 mm for head&neck patients, 0.2 g/cc and 2 mm for thoracic cancer patients, and 0.1 g/cc and 2 mm for abdominal cancer patients, depending on clinically used setup margins. Conclusion: Gamma Index of the target volume should be used for CBCT gamma analysis. For different part of the body the optimal CBCT Gamma criteria varies. By using the optimal Gamma criteria, we expect the 90% and 85% Gamma passing rate which are the accepting and warning threshold respectively can be used to accurately guide clinical decisions

Purpose: Air cavity in the digestive tract affects the dose distribution of radiation therapy plans when locates in the beam path. The number, size, and location of air cavity changes during the treatment course and the overall impact to different treatment approaches needs to be evaluated. Methods: We retrospectively picked 30 pancreas cancer patients who received radiation therapy. All patients were setup pretreatment based on daily acquired CBCT (OBI on TrueBeam, Varian Medical). For each patient, one VMAT, one fixed angle IMRT, and one traditional 4 fields 3DCRT plan have been generated. The daily CBCTwere manually registered to the planning CT. In each CBCT set, the air cavity, PTV, and selected OARs were contoured. To remove the impact caused by the uncertainty of CBCT HU calibration, the patient body was assigned with mass density of 1 g/cc except the air cavity, which was assigned to 0 g/cc. All three plans were copied to the CBCT and the dose volumetric histogram of the PTVand OARs were computed. For each type of plan, the cumulative dose from all CBCTs were compared against each other and the planning CT based plan. Results: Preliminary results illustrated that the 3DCRTwas the least vulnerable treatment type to the variation of air cavities. For 3DCRT plans the average variations of the max, min, and mean dose of PTV in the CBCT plans and the planning CTwere 0.8%, 0.3%, and 0.2%, with standard deviation of 1.3%, 0.7%, and 1.1%; for IMRT the average variations were 1.1%, 0.8%, and 0.7%, with standard deviation of 1.2%, 1.1%, and 1.5%; for VMAT the average variations were 2.3%, 2.4%, and 1.5%, with standard deviations 0.5%, 0.4%, and 0.6%. Conclusion: The impact of air cavity maybe significant for certain types of treatment approaches and clinical decisions needs to be made accordingly

PURPOSE/OBJECTIVE:Through-plane motion introduces uncertainty in 3D motion monitoring when using single slice on board imaging (OBI) modalities such as cine MRI. We propose a principal component analysis (PCA) based framework to determine the optimal imaging plane to minimize the through-plane motion for single slice imaging based motion monitoring METHODS: Four-dimensional computed tomography (4DCT) images of 8 thoracic cancer patients were retrospectively analyzed. The target volumes were manually delineated at different respiratory phases of 4DCT. We performed automated image registration to establish the 4D respiratory target motion trajectories for all patients. PCA was conducted using the motion information to define the three principal components of the respiratory motion trajectories. Two imaging planes were determined perpendicular to the second and third principal component respectively to avoid imaging with the primary principal component of the through-plane motion. Single slice images were reconstructed from 4DCT in the PCA-derived orthogonal imaging planes, and were compared against the traditional AP/Lateral image pairs on through-plane motion, residual error in motion monitoring, absolute motion amplitude error, and the similarity between target segmentations at different phases. We evaluated the significance of the proposed motion monitoring improvement using paired t-test analysis. RESULTS:The PCA-determined imaging planes had overall less through-plane motion compared against the AP/Lateral image pairs. For all patients, the average through-plane motion was 3.6 mm (range: 1.6-5.6 mm) for the AP view, and 1.7 mm (range: 0.6-2.7 mm) for the lateral view. With PCA optimization, the average through-plane motion was 2.5 mm (range: 1.3-3.9 mm) and 0.6 mm (range: 0.2-1.5 mm) for the two imaging planes respectively. The absolute residual error of the reconstructed max-exhale-to-inhale motion averaged 0.7 mm (range: 0.4-1.3 mm, 95% CI: 0.4-1.1 mm) using optimized imaging planes, averaged 0.5 mm (range: 0.3-1.0 mm, 95% CI: 0.2-0.8 mm) using an imaging plane perpendicular to the minimal motion component only, and averaged 1.3 mm (range: 0.4-2.8 mm, 95% CI: 0.4-2.3 mm) in AP/Lat orthogonal image pairs. The root mean square error of reconstructed displacement was 0.8 mm for optimized imaging planes, 0.6 mm for imaging plane perpendicular to the minimal motion component only, and 1.6 mm for AP/Lat orthogonal image pairs. When using the optimized imaging planes for motion monitoring, there was no significant absolute amplitude error of the reconstructed motion (p=0.0988), while AP/Lat images had significant error (p=0.0097) with a paired t-test. The average surface distance (ASD) between overlaid 2D tumor segmentation at end-of-inhale and end-of-exhale for all eight patients was 0.6±0.2 mm in optimized imaging planes and 1.4±0.8 mm in AP/Lat images. The Dice similarity coefficient (DSC) between overlaid 2D tumor segmentation at end-of-inhale and end-of-exhale for all eight patients was 0.96±0.03 in optimized imaging planes and 0.89±0.05 in AP/Lat images. Both ASD (p=0.034) and DSC (p=0.022) were significantly improved in the optimized imaging planes. CONCLUSIONS:Motion monitoring using imaging planes determined by the proposed PCA-based framework had significantly improved performance. Single slice image based motion tracking can be used for clinical implementations such as MR Image Guided Radiation Therapy (MR-IGRT).

The goal of this study was to exam the efficacy of current DVH based clinical guidelines draw from photon experience for lung cancer radiation therapy on proton therapy. Comparison proton plans and IMRT plans were generated for 10 lung patients treated in our proton facility. A gEUD based plan evaluation method was developed for plan evaluation. This evaluation method used normal lung gEUD(a) curve in which the model parameter "a" was sampled from the literature reported value. For all patients, the proton plans delivered lower normal lung V_{5 Gy}with similar V_{20 Gy}and similar target coverage. Based on current clinical guidelines, proton plans were ranked superior to IMRT plans for all 10 patients. However, the proton and IMRT normal lung gEUD(a) curves crossed for 8 patients within the tested range of "a", which means there was a possibility that proton plan would be worse than IMRT plan for lung sparing. A concept of deficiency index (DI) was introduced to quantify the probability of proton plans doing worse than IMRT plans. By applying threshold on DI, four patients' proton plan was ranked inferior to the IMRT plan. Meanwhile if a threshold to the location of curve crossing was applied, 6 patients' proton plan was ranked inferior to the IMRT plan. The contradictory ranking results between the current clinical guidelines and the gEUD(a) curve analysis demonstrated there is potential pitfalls by applying photon experience directly to the proton world. A comprehensive plan evaluation based on radio-biological models should be carried out to decide if a lung patient would really be benefit from proton therapy.

PURPOSE/OBJECTIVE(S)/OBJECTIVE:To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. METHODS AND MATERIALS/METHODS:We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. RESULTS:During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. CONCLUSIONS:Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

PURPOSE/OBJECTIVE:We propose a methodology to evaluate the stoichiometric calibration method on MVCT against the corresponding kVCT calibration using patient data. METHODS:Stoichiometric calibrations were conducted for a MVCT and a kVCT scanner, respectively. We retrospectively analyzed kVCT and MVCT images of 21 patients by picking small tissue volumes in kVCT images and performing image registration to locate the tissue volumes in corresponding MVCT images. We computed the difference between the mean proton stopping power derived through kVCT and MVCT calibration, taking into account the uncertainties in calibration, imaging, and image registration. RESULTS:kVCT and MVCT calibration curves were in good agreement for soft tissues such as muscle and brain, but showed statistically significant difference (p < 0.05) in stopping power of adipose (2.4 ± 1.7%) and bony structures such as spongiosa, and cranium (-3.2 ± 1.4 and -3.1 ± 2.1%, respectively). CONCLUSION/CONCLUSIONS:The MVCT calibration might not agree with the corresponding kVCT calibration for some tissues.

PURPOSE/OBJECTIVE:To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). METHODS AND MATERIALS/METHODS:We included 52 patients with NSCLC treated with definitive concurrent carboplatin-paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding x radiation dose. RESULTS:Grade ≥ 3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥ 3 leukopenia across multiple DVH parameters, including TV V20 (TVV) (odds ratio [OR] 1.06; P=.025), TVV30 (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV30 (β = -0.004; P=.018) and TVV20 (β = -0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥ 3 leukopenia was associated with a MVD of 13.5 Gy and a TTV30 of 28%. Cutoff values to avoid grade ≥ 3 leukopenia were MVD ≤ 23.9 Gy, TVV20 ≤ 56.0%, and TVV30 ≤ 52.1%. CONCLUSIONS:Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

Magnetic resonance (MR) imaging of Gafchromic film causes perturbation to absolute dosimetry measurements; the purpose of this work was to characterize the perturbation and develop a correction method for it. Three sets of Gafchromic EBT2 film were compared: radiation (control), radiation followed by MR imaging (RAD + B), and MR imaging followed by radiation (B + RAD). The T1-weighted and T2-weighted MR imaging was performed using a 1.5T scanner with the films wedged between two chicken legs. Doses from 0 to 800 cGy were delivered with a 6MV linac. The time interval between radiation and MR imaging was less than 10 min. Film calibration was generated from the red channel. Microscopic imaging was performed on two pieces of film. The effect of specific absorption rate (SAR) was determined by exposing another three sets of films to low, medium, and high levels of SAR through a series of pulse sequences. No discernible preferential alignment was detected on the microscopic images of the irradiated film exposed to MRI. No imaging artifacts were introduced by Gafchromic film on any MR images. On average, 4% dose difference was observed between B + RAD or RAD + B and the control, using the same calibration curve. The pixel values between the B + RAD or RAD + B and the control films were found to follow a linear relationship pixel(Control) = 1.02 × pixel(B + RAD or RAD + B). By applying this correction, the average dose error was reduced to approximately 2%. The SAR experiment revealed a dose overestimation with increasing SAR even when the correction was applied. It was concluded that MR imaging introduces perturbation on Gafchromic film dose measurements by 4% on average, compared to calibrating the film without the presence of MRI. This perturbation can be corrected by applying a linear correction to the pixel values. Additionally, Gafchromic film did not introduce any imaging artifacts in any of the MR images acquired.

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.