Nathan Becker

External respiratory motion analysis and statistics for patients and volunteers

We analyzed a large patient and volunteer study of external respiratory motion in order to develop a population database of respiratory information. We analyzed 120 lung, liver, and abdominal patients and 25 volunteers without lung disease to determine the extent of motion using the Varian Real‐Time Position Management system. The volunteer respiratory motion was measured for both abdominal and thoracic placement of the RPM box. Evaluation of a subset of 55 patients demonstrates inter‐ and intrafraction variation over treatment. We also calculated baseline drift and duty cycle for patients and volunteers. The mean peak‐to‐peak amplitude (SD) for the patients was 1.0 (0.5) cm, and for the volunteers it was abdomen 0.8 (0.3) cm and thoracic 0.2 (0.2) cm. The mean period (SD) was 3.6 (1.0) s, 4.2 (1.1) s, and 4.1 (0.8) s, and the mean end exhale position (SD) was 60% (6), 58% (7), and 56% (7) for patient, volunteer abdomen, and volunteer thoracic, respectively. Baseline drift was greater than 0.5 cm for 40% of patients. We found statistically significant differences between the patient and volunteer groups. Peak‐to‐peak amplitude was significantly larger for patients than the volunteer abdominal measurement and the volunteer abdominal measurement is significantly larger than the volunteer thoracic measurement. The patient group also exhibited significantly larger baseline drift than the volunteer group. We also found that peak‐to‐peak amplitude was the most variable parameter for both intra‐ and interfraction motion. This database compilation can be used as a resource for expected motion when using external surrogates in radiotherapy applications. PACS number: 87.19.Wx, 87.55.Km

Predicting Radiation Esophagitis Using 18F-FDG PET During Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer.

Introduction: Treatment of locally advanced non–small cell lung cancer with chemoradiotherapy (CRT) is limited by development of toxicity in normal tissue, including radiation esophagitis (RE). Increasingly, 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) is being used for adaptive planning. Our aim was to assess changes in esophageal FDG uptake during CRT and relate the changes to the onset and severity of RE. Methods: This prospective study in patients with stage II–III non–small cell lung cancer involved serial four‐dimensional computed tomography and PET scans during CRT (60–74Gy). RE was recorded weekly using the Common Terminology Criteria for Adverse Events (v4.0), and imaging was performed at weeks 0, 2, 4, and 7. Changes in the esophaguss peak standard uptake value (SUVpeak) were analyzed for each time point and correlated with grade of RE using the Wilcoxon rank‐sum test. The volume of esophagus receiving 50 Gy (V50) and volume of esophagus receiving 60 Gy (V60) were correlated with the development of RE, and the C‐statistic (area under the curve [AUC]) was calculated to measure predictivity of grade 3 RE. Results: RE developed in 20 of 27 patients (74%), with grade 3 reached in 6 (22%). A significant percentage increase in SUVpeak in the patients with RE was noted at week 4 (p = 0.01) and week 7 (p = 0.03). For grade 3 RE, a significant percentage increase in SUVpeak was noted at week 2 (p = 0.01) and week 7 (p = 0.03) compared with that for less than grade 3 RE. Median V50 (46.3%) and V60 (33.4%) were significantly higher in patients with RE (p = 0.04). The AUC measurements suggested that the percentage change in SUVpeak at week 2 (AUC = 0.69) and V50 (AUC = 0.67) and V60 (AUC = 0.66) were similarly predictive of grade 3 RE. Conclusions: Serial FDG‐PET images during CRT show significant increases in SUVpeak for patients in whom RE develops. The changes at week 2 may predict those at risk for the development of grade 3 RE and may be informative for adaptive planning and early intervention.

External respiratory motion: Shape analysis and custom realistic respiratory trace generation

PURPOSE The authors developed a realistic respiratory trace generating (RTG) tool for use with phantom and simulation studies. METHODS The authors analyzed the extent of abdominal wall motion from a real-time position management system database comprised of 125 lung, liver, and abdominal patients to determine the shape and extent of motion. Using Akaikes information criterion (AIC), the authors compared different model types to find the optimal realistic model of respiratory motion. RESULTS The authors compared a family of sigmoid curves and determined a four parameter sigmoid fit was optimal for over 98% patient inhale and exhale traces. This fit was also better than sin (2)(x) for 98% of patient exhale and 70% of patient inhale traces and better than sin (x) for 100% of both patient inhale and exhale traces. This analysis also shows that sin (2)(x) is better than sin (x) for over 95% of patient inhale and exhale traces. With results from shape and extent of motion analysis, we developed a realistic respiratory trace generating (RTG) software tool. The software can be run in two modes: population and user defined. In population mode, the RTG draws entirely from the population data including inter- and intra fraction amplitude and period variability and baseline drift. In user-defined mode, the user customizes the respiratory parameters by inputting the peak-to-peak amplitude, period, end exhale position, as well as controls variability in these parameters and baseline drift. CONCLUSIONS This work provides a method of generating custom respiratory data that can be used for initial implementation and testing of new technologies.

The value of adaptive preoperative radiotherapy in management of soft tissue sarcoma

PURPOSE To determine the value of preoperative adaptive radiotherapy (ART) for soft tissue sarcoma patients (STS) by modeling the dosimetric consequences of tumour volume changes (TVC) using different external beam radiotherapy techniques. METHODS AND MATERIALS A subset of 22 STS patients from a recent trial (NCT00188175) underwent a repeat CT scan (CT2) prompted by TVC>1cm during IMRT; 14 tumours grew, 8 shrank. Conformal and conventional plans were modelled in addition to IMRT replicating original criteria from the initial planning dataset (CT1):95% PTV encompassed by 97% prescribed dose. CT1 RT parameters for all plans were applied to CT2 for dosimetric assessment of TVC. Co-registration of CT1 and CT2 permitted comparison of original and new contours. RESULTS Mean TVC was 45% for growing and 33% for the shrinking cohort with TVC prompting CT2 at a mean of 13 fractions. For growers, the lack of target coverage on CT2 was statistically significant but was adequate for shrinkers. CONCLUSION GTV expansion of >1cm during RT may result in target underdosage independent of RT technique. ART applied offline for TV increases >1cm is a practical adaptive strategy to ensure tumour coverage during RT. TV shrinkage may allow for normal tissue sparing, which should be investigated prospectively.

Serial 4DCT/4DPET imaging to predict and monitor response for locally-advanced non-small cell lung cancer chemo-radiotherapy

BACKGROUND AND PURPOSE A FDG-PET/CT image feature with optimal prognostic potential for locally-advanced non-small cell lung cancer (LA-NSCLC) patients has yet to be identified, and neither has the optimal time for FDG-PET/CT response assessment; furthermore, nodal features have been largely ignored in the literature. We propose to identify image features or imaging time point with maximal prognostic power. MATERIALS AND METHODS Consecutive consenting patients with LA-NSCLC receiving curative intent CRT were enrolled. 4DPET/4DCT scans were acquired 0, 2, 4, and 7 weeks during IMRT treatment. Eleven image features and their rates of change were recorded for each time point and tested for each of the possible outcome 2 years post CRT using the Kaplan-Meier method. RESULTS 32 consecutive patients were recruited, 27 completing all scans. Restricting analysis to 4DPET/4DCT features and rates of change with p < 0.005, several volume-based features and their rates of change reached significance. Image features involving nodal disease were the only ones associated with overall survival. CONCLUSIONS Several 4DPET/CT features and rates of change can reach significant association (p < 0.005) with outcomes, including overall survival, at many time points. The optimal time for adaptive CRT is therefore not constrained uniquely on imaging.

A comparison of phase, amplitude, and velocity binning for cone-beam computed tomographic projection-based motion reconstruction

PURPOSE We previously developed a motion estimation technique based on direct cone-beam projection analysis. It is able to reconstruct the complete motion trajectory of a radio-opaque marker, including cycle-to-cycle variability, using respiratory binning of the projection images. This paper investigates the use of phase, amplitude, and amplitude-velocity binning in the context of projection-based cone-beam motion estimation (CBME). METHODS AND MATERIALS We simulated cone-beam computed tomographic scans of 160 tumor trajectories estimated by a CyberKnife Synchrony System (Accuray, Sunnyvale, CA), and reconstructed the complete trajectory with CBME using phase, amplitude, and amplitude-velocity binning of the projection data. Various numbers of respiratory bins, from 1 (no binning) to 100, were used for phase and amplitude binning, while 1 to 100 amplitude bins with 4 velocity bins were used for amplitude-velocity binning. From this large pool of data, we correlated the reconstruction accuracy with bin type, total number of bins, number of breathing cycles per bin, and the position of the bin within the breathing cycle. RESULTS CBME predicted the true motion of the marker with a 3-dimensional (3D) mean root mean square (RMS) error of 0.24 mm for amplitude-velocity binning, 0.31 mm for amplitude binning, and 0.52 mm for phase binning. Reconstruction 3D RMS error increased to over 1 mm when less than 3 breathing cycles contributed to a bin. We found that reconstruction accuracy was optimized when about 20 bins were used. Accuracy also decreased in bins located around the inhale portion of the breath cycle, compared with the mid- and end-exhale positions. CONCLUSIONS This study provides a quantitative assessment of phase, amplitude, and amplitude-velocity binning for CBME. A joint binning approach should be used to give both the accuracy of amplitude binning, as well as the robustness of phase binning, in areas of limited motion sampling.

Evidence-based region of interest matching guidelines for sarcoma volumetric image-guided radiation therapy

Highlights • Region-of-interest (ROI) guidelines for soft tissue sarcoma CBCT-guidance were developed.• ROI guidelines were developed for four anatomic sites using the PDSA cycle.• ROI guidelines are intended to increase image registration reproducibility.• Results include improved image guidance decision making and workflow efficiencies.

Performance characterization of an integrated cone-beam CT system for dedicated gamma radiosurgery

PURPOSE This work describes the performance characterization of a cone-beam CT-guided radiosurgery device, the Gamma Knife® Icon™. METHODS The performance tests have been categorized into: (a) image quality and mechanical integrity; (b) image coregistration fidelity; (c) adaptive treatment delivery quality; (d) high definition motion management performance characterization; (e) software communication performance testing of the integrated cone-beam CT (CBCT) system. RESULTS All image quality performance characterization satisfied or exceeded manufacturer specifications. The image quality and mechanical stability of the CBCT system over a 3-month period was within tolerance with negligible (<0.1°) detector tilt angle. The CBCT definition of the stereotactic space had a measured average discrepancy of 0.15-0.16 mm in x, y, and z directions. On average, the high definition motion management system performance was within 0.05 mm with a residual offset of 0.15 mm when large displacements in a given direction were taken. The adaptive treatment delivery component as measured with CBCT coregistration of daily setups against reference setup images was accurate to within 0.2°. Comprehensive end-to-end testing showed a total uncertainty of better than 0.2 mm in positioning and 0.4% in dosimetry for treatment of centrally located lesions. CONCLUSIONS A set of system performance characterization tests spanning all aspects of the Gamma Knife Icon are presented. Overall, the system performance was in line with manufacturer specifications.

Poster — Thur Eve — 20: Serial FDG 4DPET imaging during radiotherapy in advanced lung cancer patients

The availability of respiratory synchronized PET (4DPET) imaging has enabled more accurate analysis of metabolic response since motion blur is minimized. We present our preliminary analysis of serial FDG 4DPET images acquired at weeks 0, 2, 4, and 7 during radiotherapy of seven stage II-III NSCLC patients. The tumor and nodal PTV of the week 0 images restrained a 4DPET image thresholding algorithm to automatically contour SUV levels ranging from 20 to 80% of the maximum SUV, creating an intensity volume histogram (IVH) for each week. These contours allowed analysis of PET volumes and standard PET metrics such as SUVmax and SUVmean . We found a trend for decreasing SUVmax and SUVmean over a treatment course in both the tumor and nodal regions. On average, the SUVmax within the tumor decreased by 17±13% (1 SD) after 2 weeks, 30±13% after 4 weeks, and 39±19% after 7 weeks of radiotherapy. Decreasing volume trends were also observed in the 20 to 80% max SUV autocontours, ranging from 26±29% to 50±40% respectively, over 7 weeks of treatment. Only one patient demonstrated an increase in FDG uptake within the tumor volume between week 0 and week 2 of treatment, and was also the only patient to recur locally at 3 months following treatment. Changes in tumor metabolism over the course of advanced NSCLC radiotherapy are quantifiable with serial FDG 4DPET imaging. Preliminary analysis suggests that variations in these trends could be useful in identifying non-responding patients that may require an alternative radiotherapeutic approach.

Poster — Thur Eve — 11: A realistic respiratory trace generator and its application to respiratory management techniques

Respiratory motion complicates radiotherapy treatment of thoracic and abdominal tumours. Simplified respiratory motions such as sinusoidal and single patient traces are often used to determine the impact of motion on respiratory management techniques in radiotherapy. Such simplifications only accurately model a small portion of patients, as most patients exhibit variability and irregularity beyond these models. We have preformed a comprehensive analysis of respiratory motion and developed a software tool that allows for explicit inclusion of variability. We utilize our realistic respiratory generator to customize respiratory traces to test the robustness of the estimate of internal gross target volumes (IGTV) by 4DCT and CBCT. We confirmed that good agreement is found between 4DCT and CBCT for regular breathing motion. When amplitude variability was introduced the accuracy of the estimate slightly, but the absolute differences were still < 3 mm for both modalities. Poor agreement was shown with the addition of baseline drifts. Both modalities were found to underestimate the IGTV by as much as 30% for 4DCT and 25% for CBCT. Both large and small drifts deteriorated the estimate accuracy. The respiratory trace generator was advantageous for examining the difference between 4DCT and CBCT IGTV estimation under variable motions. It provided useful implementation abilities to test specific attributes of respiratory motion and detected issues that were not seen with the regular motion studies. This is just one example of how the respiratory trace generator can be utilized to test applications of respiratory management techniques.