Dong-Chun Yan

MO‐F‐144‐02: Real‐Time 4D Ultrasound Prostate Gland Motion Tracking During Radiotherapy Fraction Delivery

PURPOSE The intra-fraction variability of target position during the prostate cancer radiotherapy may cause dose discrepancy between planned and delivered dose, especially with longer hypo-fractionated treatments. We report our clinical experience with real-time 4D ultrasound imaging (4D-US) to monitor intrafraction prostate motion. METHODS Three prostate patients were treated on an IRB-approved protocol delivering 51 Gy in 10 fractions using single arc volumetric modulated arc therapy (VMAT). Each patient had three gold markers implanted and had simultaneous CT and 4D-US simulation, followed by an MRI scan. Target and normal organs were delineated on MR images. During setup simultaneous cone-beam CT (CBCT) and continuous 4D-US were acquired, and during VMAT delivery (about 2 min) 4D-US was acquired. The prostate 4D-US position was compared to the CBCT average position, and movement during treatment was characterized. RESULTS The median (range) of mean intra-fraction prostatic motion in the right-left(RL), anterior-posterior(AP) and superior-inferior(SI) directions were 0.1 mm (-1.6 to 0.8 mm), 0 mm (-1.8 to 1.3 mm), and -0.1 mm (-2.2 to 1.4 mm), with respective median (range) of standard deviation were 0.2 mm (0 to 0.8 mm), 0.2 mm (0 to 1.2 mm), and 0.2 mm (0 to 0.7mm). There were 9/27 fractions with shifts >=2 mm in any direction, with an average duration of 23% of treatment time, with a single fraction having a shift greater than 3mm. The discrepancy between 4D-US and CBCT shifts were 0.6±1.6 mm, -0.2±1.4 mm and -0.4±0.7 mm in the RL, AP and SI directions. There was one instance of flatulence during treatment setup where vertical shifts >=3 mm (up to 6.1 mm) persisted for 108 sec. CONCLUSION Real-time imaging is essential for tracking hypo-fractionated prostate motion to reduce dosimetric uncertainty. 4D ultrasound imaging during treatment improves accuracy of dose delivery, and may allow a reduction of treatment margins.

TH-AB-304-06: Investigation of Fractionation Issues in NTCP Modeling of Pneumonitis: An Analysis of Common NTCP Models for Hypo-Fractionated and Standard-Fractionated Data

Purpose: Previous studies showed that NTCP modeling of radiation pneumonitis for hypo-fractionated radiotherapy (HFRT) has resulted in different model parameters, e.g. a much higher MLD5₀, than for standard-fractionated RT (SFRT). This study investigates whether both fractionation schemes can be described by the same NTCP model. Methods: We retrospectively investigated lung DVHs of 487 patients. Of those, 377 were treated with HFRT (3–10 fractions, median Rx=54Gy) at 5 institutions, and 110 were treated with SFRT (23–47 fractions, median Rx=63Gy) at a single institution. NTD₂ was calculated using the LQ-model and the low-dose-hyper-radiosensitivity model (LDHRS). The latter could possibly explain the reduced toxicities observed in HFRT by assuming a threshold dose for induced repair. NTCP was modeled for all patients using the Lyman-MLD and Lyman-EUD model and compared with AICc. Goodness-of-fit was determined using Hosmer-Lemeshow statistics. Results: Within the HFRT group and SFRT group, 7.4% and 10.6% of patients experienced pneumonitis grade>=2 (CTCAE), respectively (median follow-up=2.13 years). Optimal model parameters (Lyman-MLD-LQ: MLD5₀ (NTD)=38.3Gy, m=0.51, AICc=271.0; Lyman-EUD-LQ: EUD5₀ (NTD)=24.3Gy, m=0.55, a=0.6, AICc=271.3; Lyman-MLD-LDHRS: MLD 5₀(NTD)=42.5Gy, m=0.51, AICc=272.0) for all models yielded acceptable fits to the entire dataset and subgroups (pHL>0.05). Differences in log-likelihood and AICc values were not large enough to prefer one model over the other. The low volume-effect parameter (a<1) for the Lyman-EUD-LQ model suggests that lower doses-per-fraction (<0.58Gy) may be an important factor determining NTCP. This is concurrent with the assumptions of the mechanistic LDHRS model. Conclusion: The results indicate that pneumonitis can, theoretically, be described by the same NTCP model for HFRT and SFRT using the investigated models. Furthermore, irradiation with low doses-per-fraction may play a role in causing toxicities. Prior findings of different NTCP model parameters for HFRT and SFRT may be due to extrapolation of the bias introduced by the individual datasets, such as differing volumes receiving low doses-per-fraction. This study was supported by the Elekta Collaborative Lung Research Group grant. Dr. Grills discloses stock ownership and is a member of the Greater Michigan Gamma Knife board of directors.

SU‐E‐T‐164: Comparing Measurement Derived (3DVH) and Machine Log File Derived Dose Reconstruction Methods for VMAT QA in Heterogeneous Patient Geometries

PURPOSE To extend the 3DVH analysis to heterogeneous patient geometries for VMAT delivery and comparing its accuracy using machine log file derived dose reconstruction method Methods: A total of 10 patient plans were selected from a regular fractionation plan to complex SBRT plans. Treatment sites in the lung and abdomen were chosen to explore the effects of tissue heterogeneity on the respective dose reconstruction algorithms. Delivered plan in the patient geometry was reconstructed by using ArcCheck Planned Dose Perturbation (ACPDP) within 3DVH software, and by converting the machine logfile to Pinnacle3 9.0 treatment plan format. In addition, delivered gantry angles between machine logfile and 3DVH 4D measurement was also compared to evaluate the accuracy of the virtual inclinometer within the 3DVH. RESULTS Measured ion chamber and 3DVH derived isocenter dose agreed with planned dose within 0.3±0.7 Gy and -0.5±0.8 Gy respectively. Machine log file reconstructed doses and TPS dose agreed to within 2 Gy in PTV and OARs over the entire treatment course. 3DVH reconstructed dose showed a difference of up to 3.2 Gy in maximum PTV doses compared to planned dose in hypo lung patients due to plan heterogeneity. For majority of normal structures, dose differences were within 1 Gy except for few cases, where a maximum point dose difference of up to 2.2 Gy in proximal bronchial tree dose for a hypo lung patient was seen. The average Virtual Inclinometer Error (VIE) was - 0.65±1.6° for all patients, with a maximum error of -5.16±4.54° for an SRS case. CONCLUSION Both methods are capable of taking into account the plan delivery errors. 3DVH is more sensitive to these errors compared to machine log file.

SU‐D‐213AB‐01: Dosimetry Improvement and Needle Number Reduction in Prostate Brachytherapy Using Electromagnetically Guided Needle Placement

PURPOSE To investigate dosimetry improvement in prostate brachytherapy by conforming needles to urethral and prostate shape using an electromagnetic tracking device. METHODS We have reported a needle tracking system using an electromagnetic sensor embedded inside the tip of the needle to improve needle reconstruction accuracy and efficiency in conventional prostate HDR brachytherapy. Utilizing the same system, we propose to guide needle insertion following pre-optimized tracks based onthe target shape. In this study, we investigate possible dosimetry improvement and needle number reduction by comparing plans using the conventional implant method and the proposed method. Twelve prostate brachytherapy patients were selected and studied retrospectively. New virtual plans were created using the proposed method and conforming needle tracks to the urethral and prostate shapes. Same optimization constraints were applied to both the conventional and the new plans. DVH parameters and total needles used have been analyzed to quantify dosimetry improvement and potential toxicity sparing due to reduction in implant needles. RESULTS Prostate volumes are 41.16±13.27 cc. Number of needles used for the conventional plan is 16.6±1.2, vs. 13 for all the new plans. The prostate volume receiving 100% (V100), 125% (V125), and 150% (V150) of the prescription dose in conventional plans vs. those in the new plans are 99.48%±0.21% vs. 99.53%±0.20%, 53.90%±5.61% vs. 50.30%±5.23%, and 25.37%±4.91% vs. 20.96%±3.41%, respectively. The corresponding urethra V100 and V110 are 90.96%±3.10% vs. 85.78%±7.76% and 2.06%±1.23 vs. 0.46%±0.28%. CONCLUSIONS The needle numbers and the urethral V110 in the new plans are significantly lower than those in conventional plans(p<0.001 and p=0.004, respectively), with no significant changes in doses tothe prostate. Conformai needle implant following pre-optimized tracks with electromagnetic guidance may significantly reduce acute and late toxicities in prostate brachytherapy by reducing the number of needles and theurethral doses.

SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor

PURPOSE To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. METHODS FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function of pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. RESULTS Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. CONCLUSION Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.

SU-E-J-144: MRI Visualization of a Metallic Fiducial Marker Used for Image Guided Prostate Radiotherapy

PURPOSE Unlike on the daily CBCT used for the image-guided radiation therapy, the visualization of an implantable metallic fiducial marker on the planning MRI images has been a challenge due to the inherent insensitivity of metal in MRI, and very thin (∼ 1 mm or less) diameter. Here, an MRI technique to visualize a marker used for prostate cancer radiotherapy is reported. METHODS During the MRI acquisitions, a multi-shot turbo spin echo (TSE) technique (TR=3500 ms, TE=8.6 ms, ETL=17, recon voxel=0.42×0.42×3.5 mm3) was acquired in Philips 3T Ingenia together with a T2-weighted multi-shot TSE (TR=5381 ms, TE=110 ms, ETL=17, recon voxel=0.47×0.47×3 mm3) and a balanced turbo field echo (bTFE, flip angle 60, TR=2.76 ms, TE=1.3 ms, 0.85×0.85×3 mm3, NSA=4). In acquiring the MRI to visualize the fiducial marker, a particular emphasis was made to improve the spatial resolution and visibility in the generally dark, inhomogeneous prostate area by adjusting the slice profile ordering and TE values of TSE acquisition (in general, the lower value of TE in TSE acquisition generates a brighter signal but at the cost of high spatial resolution since the k-space, responsible for high spatial resolution, is filled with noisier data). RESULTS While clearly visible in CT, the marker was not visible in either T2-weighted TSE or bTFE, although the image qualities of both images were superior. In the new TSE acquisition (∼ a proton-density weighted image) adjusted by changing the profile ordering and the TE value, the marker was visible as a negative (but clear) contrast in the magnitude MRI, and as a positive contrast in the imaginary image of the phase-sensitive MRI. CONCLUSION A metallic fiducial marker used for image guidance before prostate cancer radiotherapy can be made visible in MRI, which may facilitate more use of MRI in planning and guiding such radiation therapy.

SU‐E‐J‐20: Adaptive Aperture Morphing for Online Correction for Prostate Cancer Radiotherapy

PURPOSE Online adaptive aperture morphing is desirable over translational couch shifts to accommodate not only the target position variation but also anatomic changes (rotation, deformation, and relation of target to organ-atrisks). We proposed quick and reliable method for adapting segment aperture leaves for IMRT treatment of prostate. METHODS The proposed method consists of following steps: (1) delineate the contours of prostate, SV, bladder and rectum on kV-CBCT; (2) determine prostate displacement from the rigid body registration of the contoured prostate manifested on the reference CT and the CBCT; (3) adapt the MLC segment apertures obtained from the pre-treatment IMRT planning to accommodate the shifts as well as anatomic changes. The MLC aperture adaptive algorithm involves two steps; first move the whole aperture according to prostate translational/rotational shifts, and secondly fine-tune the aperture shape to maintain the spatial relationship between the planning target contour and the MLC aperture to the daily target contour. Feasibility of this method was evaluated retrospectively on a seven-field IMRT treatment of prostate cancer patient by comparing dose volume histograms of the original plan and the aperture-adjusted plan, with/without additional segments weight optimization (SWO), on two daily treatment CBCTs selected with relative large motion and rotation. RESULTS For first daily treatment, the prostate rotation was significant (12degree around lateral-axis). With apertureadjusted plan, the D95 to the target was improved 25% and rectum dose (D30, D40) was reduced 20% relative to original plan on daily volumes. For second treatment-fraction, (lateral shift = 6.7mm), after adjustment target D95 improved by 3% and bladder dose (D30, maximum dose) was reduced by 1%. For both cases, extra SWO did not provide significant improvement. CONCLUSION The proposed method of adapting segment apertures is promising in treatment position correction, including target translational displacement, rotation and deformation. Additional SWO could improve ROIs dose distribution.

SU‐E‐J‐220: Evaluation of Atlas‐Based Auto‐Segmentation (ABAS) in Head‐And‐Neck Adaptive Radiotherapy

PURPOSE Evaluate the accuracy of atlas_based auto segmentation of organs at risk (OARs) on both helical CT (HCT) and cone beam CT (CBCT) images in head and neck (HN) cancer adaptive radiotherapy (ART). METHODS Six HN patients treated in the ART process were included in this study. For each patient, three images were selected: pretreatment planning CT (PreTx_HCT), in treatment CT for replanning (InTx_HCT) and a CBCT acquired in the same day of the InTx_HCT. Three clinical procedures of auto segmentation and deformable registration performed in the ART process were evaluated: a) auto segmentation on PreTx_HCT using multi_subject atlases, b) intra_patient propagation of OARs from PreTx_HCT to InTx_HCT using deformable HCT_to_HCT image registration, and c) intra_patient propagation of OARs from PreTx_HCT to CBCT using deformable CBCT_to_HCT image registration. Seven OARs (brainstem, cord, L/R parotid, L/R submandibular gland and mandible) were manually contoured on PreTx_HCT and InTx_HCT for comparison. In addition, manual contours on InTx_CT were copied on the same day CBCT, and a local region rigid body registration was performed accordingly for each individual OAR. For procedures a) and b), auto contours were compared to manual contours, and for c) auto contours were compared to those rigidly transferred contours on CBCT. Dice similarity coefficients (DSC) and mean surface distances of agreement (MSDA) were calculated for evaluation. RESULTS For procedure a), the mean DSC/MSDA of most OARs are >80%/±2mm. For intra_patient HCT_to_HCT propagation, the Resultimproved to >85%/±1.5mm. Compared to HCT_to_HCT, the mean DSC for HCT_to_CBCT propagation drops ∼2-3% and MSDA increases ∼0.2mm. This Resultindicates that the inferior imaging quality of CBCT seems only degrade auto propagation performance slightly. CONCLUSION Auto segmentation and deformable propagation can generate OAR structures on HCT and CBCT images with clinically acceptable accuracy. Therefore, they can be reliably implemented in the clinical HN ART process.

WE‐G‐BRF‐08: Robust Characterization and Patient Experience of a Time‐Resolved Ultrasound System for Prostate Tracking

PURPOSE Characterization of a time resolved ultrasound device (4D-US), used for localization and motion monitoring of prostate radiotherapy. METHODS The 4D-US system accuracy to reproduce prostate motion was investigated and artifacts were determined under detailed experimental and ultimately clinical conditions. Two fields of view (FOV) of 30 and 60 degrees and two corresponding acquisition speeds were evaluated under experimental conditions with gradual increased complexity. The reconstruction ability and trajectory tracking depends on the relative speed between the ultrasound probe and the moving object. Two different types of phantoms were developed; one capable of following a predetermined trajectory with variable speeds, and a second one designed to test the US ability to a track dynamically-deformed prostate. Four hypo-prostate patients (10fx) were monitored during the treatment to detect intrafraction motion. RESULTS Prostate speeds up to 6mm/s and 3mm/s can be successfully tracked by the system when using the small and large FOV, respectively. The system response time, calculated based on the speedinduced volumetric distortion, is dependent on the FOV, with 1.1s for the small FOV and 1.4s for the large FOV. The response time was also found dependent on the size of target, increasing from 1.4s to 1.7s for target diameters of 4cm to 2.8cm. The deformable dynamic phantom has shown that the system is able to successfully follow a highly-deformed, slowmoving prostate with an error < 0.5mm. The overall range of patient intrafraction motion was (-2.4 to 2.2)mm, (-2.6 to 2.4)mm, (-3.0 to 4.3)mm in the RL, SI and AP directions, respectively. CONCLUSION The 4DUS system using a large FOV is appropriate to monitor the prostate motion as well as the adjacent organs at risk. However, infrequent abrupt motion can be problematic and the small FOV system is preferred for such patients, particularly for future applications as online prostate monitoring employed for MLC tracking.

SU‐E‐U‐12: Evaluation of a Time‐Resolved Ultrasound System for Prostate Tracking Using a Novel, Multimodality KV‐Ultrasound Dynamic Phantom

Purpose: Development of novel multi‐modality dynamic phantom and technique designed to evaluate the accuracy of a time‐resolved ultrasound device (4D‐US), used for localization and motion monitoring of the prostate during hypo‐fractionated radiotherapy. Methods: A modified dynamic thorax phantom was designed using a spherical, ultrasound compatible, prostate phantom. The phantom end of the 90° arm was submerged in a water filled plastic container. A coupling cavity between the ultrasound probe and the container wall was developed. The motion of the dynamic phantom was pre‐programmed to test the 4D‐US capability to accurately reproduce the input trajectories. The Clarity 4D‐US presents two types of scanning modes: a volumetric mode for reference volume acquisition; and an auto‐scan mode for real‐time monitoring of the target. Using the monitoring mode, the amplitude detected was compared with the input amplitude in order to determine speed‐dependent, amplitude under‐sampling effects. Using the volumetric mode, the system time lag and manifestation of volumetric distortion due to increase in the phantom speed was determined. The difference between the largest dimension of the detected volume and the reference volume diameter divided by the phantom speed, determined the time lag of the 4D‐US system. Results: In monitoring mode, the system was capable to accurately reproduce a Sup‐Inf sinusoidal phantom trajectory with 2cm amplitude and a period of ∼15s ( speed∼2.7mm/s), showing an increased amplitude under‐sampling effect as the motion period was gradually decreased to 4s. In volumetric acquisition mode, the system average time lag, calculated based on the speed induced volumetric distortion, was found to be 0.31s. Conclusion: We have developed a novel kV‐US dynamic phantom to establish the 4D‐US scanning system parameters in order to accurately detect prostate motion. The novel phantom can be used in a multi‐modality concomitant imaging scheme allowing a direct, on‐line comparison of different real‐time tracking modalities.