A. Dekker

A global calibration model for a-Si EPIDs used for transit dosimetry

Electronic portal imaging devices (EPIDs) are not only applied for patient setup verification and detection of organ motion but are also increasingly used for dosimetric verification. The aim of our work is to obtain accurate dose distributions from a commercially available amorphous silicon (a-Si) EPID for transit dosimetry applications. For that purpose, a global calibration model was developed, which includes a correction procedure for ghosting effects, field size dependence and energy dependence of the a-Si EPID response. In addition, the long-term stability and additional buildup material for this type of EPID were determined. Differences in EPID response due to photon energy spectrum changes have been measured for different absorber thicknesses and field sizes, yielding off-axis spectrum correction factors based on transmission measurements. Dose measurements performed with an ionization chamber in a water tank were used as reference data, and the accuracy of the dosimetric calibration model was determined for a large range of treatment conditions. Gamma values using 3% as dose-difference criterion and 3mm as distance-to-agreement criterion were used for evaluation. The field size dependence of the response could be corrected by a single kernel, fulfilling the gamma evaluation criteria in case of virtual wedges and intensity modulated radiation therapy fields. Differences in energy spectrum response amounted up to 30%-40%, but could be reduced to less than 3% using our correction model. For different treatment fields and (in)homogeneous phantoms, transit dose distributions satisfied in almost all situations the gamma criteria. We have shown that a-Si EPIDs can be accurately calibrated for transit dosimetry purposes.

Phased attenuation correction in respiration correlated computed tomography/positron emitted tomography

The motion of lung tumors with respiration causes difficulties in the imaging with computed tomography (CT) and positronemitted tomography (PET). Since an accurate knowledge of the position of the tumor and the surrounding tissues is needed for radiation treatment planning, it is important to improve CT/PET image acquisition. The purpose of this study was to evaluate the potential to improve image acquisition using phased attenuation correction in respiration correlated CT/PET, where data of both modalities were binned retrospectively. Respiration correlated scans were made on a Siemens Biograph Sensation 16 CT/PET scanner which was modified to make a low pitch CT scan and list mode PET scan possible. A lollipop phantom was used in the experiments. The sphere with a diameter of 3.1 cm was filled with approximately 20 MBq 18F-FDG. Three longitudinal movement amplitudes were tested: 2.5, 3.9, and 4.8 cm. After collection of the raw CT data, list mode PET data, and the respiratory signal CT/PET images were binned to ten phases with the help of in-house-built software. Each PET phase was corrected for attenuation with CT data of the corresponding phase. For comparison, the attenuation correction was also performed with nonrespiration correlated (non-RC) CT data. The volume and the amplitude of the movement were calculated for every phaseof both the CT and PET data (with phased attenuation correction). Maximum and average activity concentrations were compared between the phased and nonphased attenuation corrected PET. With a standard non-RC CT/PET scan, the volume was underestimated by as much as 46% in CT and the PET volume was overestimated to 370%. The volumes found with RC-CT/PET scanning had average deviations of 1.9% (+/- 4.8%) and 1.5% (+/- 3.4%) from the actual volume, for the CT and PET volumes, respectively. Evaluation of the maximum activity concentration showed a clear displacement in the images with non-RC attenuation correction, and activity values were on average14% (+/- 12%) lower than with phased attenuation correction. The standard deviation of the maximum activity values found in the different phases was a factor of 10 smaller when phased attenuation correction was applied. In this phantom study, we have shown that a combination of respiration correlated CT/PET scanning with application of phased attenuation correction can improve the imaging of moving objects and can lead to improved volume estimation and a more precise localization and quantification of the activity.

Prediction of DVH parameter changes due to setup errors for breast cancer treatment based on 2D portal dosimetry.

Electronic portal imaging devices (EPIDs) are increasingly used for portal dosimetry applications. In our department, EPIDs are clinically used for two-dimensional (2D) transit dosimetry. Predicted and measured portal dose images are compared to detect dose delivery errors caused for instance by setup errors or organ motion. The aim of this work is to develop a model to predict dose-volume histogram (DVH) changes due to setup errors during breast cancer treatment using 2D transit dosimetry. First, correlations between DVH parameter changes and 2D gamma parameters are investigated for different simulated setup errors, which are described by a binomial logistic regression model. The model calculates the probability that a DVH parameter changes more than a specific tolerance level and uses several gamma evaluation parameters for the planning target volume (PTV) projection in the EPID plane as input. Second, the predictive model is applied to clinically measured portal images. Predicted DVH parameter changes are compared to calculated DVH parameter changes using the measured setup error resulting from a dosimetric registration procedure. Statistical accuracy is investigated by using receiver operating characteristic (ROC) curves and values for the area under the curve (AUC), sensitivity, specificity, positive and negative predictive values. Changes in the mean PTV dose larger than 5%, and changes in V90 and V95 larger than 10% are accurately predicted based on a set of 2D gamma parameters. Most pronounced changes in the three DVH parameters are found for setup errors in the lateral-medial direction. AUC, sensitivity, specificity, and negative predictive values were between 85% and 100% while the positive predictive values were lower but still higher than 54%. Clinical predictive value is decreased due to the occurrence of patient rotations or breast deformations during treatment, but the overall reliability of the predictive model remains high. Based on our predictive model, 2D transit dosimetry measurements can now directly be translated in clinically more relevant DVH parameter changes for the PTV during conventional breast treatment. In this way, the possibility to design decision protocols based on extracted DVH changes is created instead of undertaking elaborate actions such as repeated treatment planning or 3D dose reconstruction for a large group of patients.

SU-D-110-02: Evaluation of the Differences between Locoregional Lung Ventilation Estimation Methods Using a Single Deformable Image Registration Algorithm

Purpose: Three methods of calculating ventilation from 4D CTimage sets have been explored by several research groups. This study is to investigate the differences of these three local ventilation calculations. Methods: Optical flow (OF) deformable image registration of the normal end expiration and inspiration phases of 4D‐CT images was used to correlate the voxels between the two phases. The OF was validated using a 4D pixel‐ based and point‐validated breathing thorax model, consisting of a 4D‐CT image data set along with associated landmarks. Ventilation derived from 4D‐CTs from 20 esophageal patients were retrospectively analyzed. Differences between the ventilation images generated by three methods, the Jacobian, the DeltaV, and the HU, were examined on a voxel‐to‐voxel basis. The Jacobian method uses the first derivative of the deformation field to approximate the change in volume of voxels. The DeltaV method directly calculates the volume change. The HU method uses the change in Houndsfield Units (HUs) of corresponding voxels to calculate ventilation. Results: The target registration error (TRE) for the deformable image registration was an average of 1.6±0.68 mm and maximum of 3.1 mm. Average difference between the DeltaV and the Jacobian ventilation as a percentage of the maximum ventilation value was 0.51±0.3% (range 0.33% to 1.32%). Average difference between the DeltaV and HU ventilation was 2.4±4.5 % (range 0.4% to 19.2 %). A small number of voxels show significant differences. We speculate that the larger differences were due to some image registration variances. Regions of highest and lowest ventilation matched well for all methods. Conclusions: Highs and lows in ventilation were more pronounced in the DeltaV method compared to the Jacobian. In general the differences between the two ventilation methods were small. However, the differences between the DeltaV and the HU methods were considerably larger.

PV-0318: External Validation of Radiation-Induced Dyspnea Models on Esophageal Cancer Radiotherapy Patients

Purpose: Radiation-induced lung disease (RILD), defined as dyspnea in this study, is a risk for patients receiving high-dose thoracic irradiation. [A1-4.2] This study is a TRIPOD (Transparent Reporting of A Multivariable Prediction Model for Individual Prognosis or Diagnosis) Type 4 validation of previously-published dyspnea models via secondary analysis of esophageal cancer SCOPE1 trial data. [A1-4.1] We quantify the predictive performance of these two models for predicting the maximal dyspnea grade ≥ 2 within 6 months after the end of high-dose chemo-radiotherapy for primary esophageal cancer.

OC-0068: Can atlas-based auto-contouring ever be perfect?

ESTRO 35 2016 _____________________________________________________________________________________________________ quantitative measures such as the target registration error can be used during commissioning, such measures are not fully spatial and too user intensive in clinical practice. Therefore, we propose a fully automatic and quantitative approach to DIR quality assessment including multiple measures of numerical robustness and biological plausibility.

OC-0257: A Bayesian network model for acute dysphagia prediction in the clinic for NSCLC patients

ESTRO 35 2016 _____________________________________________________________________________________________________ October 2015 and retrospectively analysed, providing 141 dose measurements for all the MOSkins. Measured and calculated contributions by each single catheter were quantified separately. Discrepancies were plotted depending on weighted average polar angles and distances between MOSkins and source, and a linearly fitting CF was calculated.

OC-0205: Prognostic value of pre-RT PET metrics of lymph nodes vs. primary tumor in NSCLC: which holds more information?

Purpose/Objective: Loco-regional recurrences remain frequent in locally advanced non-small cell lung cancer (NSCLC) patients and are predominantly located in the area of the primary tumor. Improved tumor control might be accomplished by dose-escalation and dose-redistribution. The PET-boost trial (NCT01024829) is an ongoing randomized phase II trial investigating individualized accelerated doseescalation to the entire primary tumor (arm A) or redistributed to regions of high FGD-uptake within the primary tumor (arm B). We present a planned interim analysis of the toxicity of 63 randomized patients. Materials and Methods: Patients with NSCLC stage IB-III, a primary tumor (PT) ≥4 cm and a SUVmax ≥5 are treated with chemo-radiation or radiotherapy alone. Treatment plans are designed using a pre-treatment FDG-PET-CT-scan with similar dose limits to OAR as in conventionally treated patients. If normal tissue constraints allow dose-escalation using an integrated boost ≥72 Gy in 24 fractions to the PT and with equal mean lung dose for both study arms, a patient is randomized to arm A or arm B. Involved lymph nodes are treated to a fractionation dose of 66 Gy in 24 fractions. Toxicity is scored according to the CTCAEv3.0 criteria. Endpoints are local progression-free survival at 1 year, toxicity, overall survival and quality of life. Results: From April 2010 to March 2014, 32 patients were randomized to arm A and 31 patients to arm B. Forty-eight patients received concurrent chemo-radiotherapy. Median follow-up was 25.5 months. The mean PT volume in arm A was 123.4cc and in arm B 181.5cc. Mean prescribed dose to the planning target volume of the primary tumor was 3.3 Gy (range 3.0-4.0 Gy) in arm A and 3.9 Gy (range 3.2-5.4 Gy) in arm B. Grade ≥3 dysphagia and dyspnea during treatment occurred in 7 and 2 patients (11 and 3%). Grade ≥3 esophagitis and pneumonitis after treatment was seen in 11 and 6 patients (17.5% and 9.5%). Hematologic toxicity grade ≥3 was observed in 5%. Four out of 63 patients (6.3%) died due to pulmonary hemorrhage. Conclusions: This interim toxicity analysis of the randomized phase II PET-boost trial shows that dose-escalation is feasible in 63 randomized patients. The toxicity observed during and after treatment shows no excess or unexpected toxicity.

SU‐E‐J‐66: Effects of Noise in 4D‐CT On Deformable Image Registration and Derived Ventilation Data

PURPOSE Deformable image registration (DIR) and 4D-CT have been proposed to generate ventilation images. Quantum noise is common in CT images. This study focuses on the effects of noise in 4D-CT on DIR and the derived ventilation data. METHODS Diffeomorphic morphons (DM), diffeomorphic demons (DD), optical flow and B-Spline were used to register the end-inspiration phase to the end-expiration phase of 6 4D-CT sets with landmarks delineated on different phases, called point-validated pixel-based breathing thorax models (POPI). Landmarks at expiration were mapped to inspiration using DIR deformation matrices (DIRDM) for each POPI model. Target registration errors (TRE) were calculated as the distances between the delineated and the mapped landmarks. Gaussian noise with different standard deviations (SD) of the amplitude was added to the POPI models to simulate different levels of quantum noise. Ventilation estimations were performed by calculating the volume change geometrically, based on the DIRDM. Ventilation images with different CT noise levels were compared using Dice similarity coefficient (DSC). RESULTS The root mean square (RMS) values of the landmark TRE over the 6 POPI models for the 4 DIR algorithms were stable when the noise level was below SD=150 Hounsfield Units (HU), and increased with the noise level. The most accurate DIR was DD with mean RMS of 1.5±0.5 and 1.8+-0.5 mm at the added noise SD=0 and 200 HU respectively. The DSC values between the ventilation images with and without added noise decreased with the noise level. The most consistent DIR was DM with mean DSC=0.89+- 0.01 and 0.66+-0.02 for the top 50% ventilation volumes with the added noise of 0 and 30, 0 and 200 HU respectively. CONCLUSION While the landmark TRE was stable with noise level for low noise, the differences between ventilation images increased, indicating that 4D-CT based ventilation imaging is sensitive to image noise. This work was partially supported by a grant from the Varian Medical Systems, Inc.

OC-0501 IRRADIATION OF THE LEFT VENTRICLE OF THE HEART IS CORRELATED WITH POST-TREATMENT DYSPNEA IN NSCLC PATIENTS

Purpose/Objective: High-dose thoracic radiation therapy can cause significant adverse effects. Therefore, radical radiotherapy has historically been reserved for patients with stage I-III disease nonsmall cell lung cancer (NSCLC), and the most common indication for radiation therapy to the primary site for patients with metastatic (stage IV) NSCLC has been palliation for pain or other symptoms directly resulting from tumor. However, stage IV NSCLC contains a broad spectrum of patients, and prior studies have suggested that select patients with stage IV disease with a limited number of distant metastases (‘oligometastasis’) may benefit from radical therapy. We investigated prognostic factors associated with survival in patients with NSCLC and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Materials and Methods: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis without prior thoracic surgery or radiation therapy, no prior or concurrent other malignancy and who underwent aggressive radio(chemo)therapy (≥45 Gy) to the primary site were assessed. Forty-four of these patients also received definitive local treatment for the oligometastases. Pulmonary and esophageal acute toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3.0. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: The median follow-up time for patients alive at the time of analysis was 35 months (range, 2–109). Rates of grade 2 radiation pneumonitis and esophagitis were 16.7% and 39.7%. Rates of severe (grade ≥3) pulmonary and esophageal toxicity were 6.4% and 19.4%. The locoregional relapse rate was 22% (17 patients, with 10 experiencing recurrence inside the radiation field), and 50 of the original 78 patients had new sites of distant metastases. For all patients, the 1-, 2-, and 3-year overall survival (OS) rates were 62%, 32%, and 25%, respectively. Univariate Cox proportional hazard analysis revealed better OS for those patients who received at least 63 Gy of radiation to the primary site (P=0.002), received definitive local treatment for oligometastasis (P=0.041), had a Karnofsky performance status (KPS) score >80 (P=0.007), had a gross tumor volume ≤124 cm3 (P=0.002), had adenocarcinoma histology (P=0.002), or had no history of respiratory disease (P=0.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=0.004, P=0.006, and P<0.001, respectively). Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from aggressive local therapy.