Challenges and opportunities for implementing hypofractionated radiotherapy in Africa: lessons from the HypoAfrica clinical trial.

The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy. Trial registration: Not available yet.

Clinical Outcomes and Predictors of Lung Toxicity After Multiple Courses of Lung Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: The clinical outcomes of multicourse lung stereotactic body radiotherapy (SBRT) have yet to be validated in a prospective study, and there are a lack of data on allowable composite dosimetry. PATIENTS AND METHODS: Forty-four patients underwent multicourse lung SBRT for recurrent or metachronous NSCLC. The median biologically effective dose (BED10) for the first course and subsequent courses were 132 and 100 Gy, respectively. Patient and treatment characteristics were evaluated to determine the correlation with the development of radiation pneumonitis (RP). RESULTS: The local control rate was 91%. A total of 13.6% developed a grade 2+ RP, and 4.5% developed a grade 3+ RP, including one grade 5. On univariable analysis, multiple composite dosimetric factors (V5 [proportion of lung structure receiving at least 5 Gy], V10, V20, V40, and mean lung dose) were correlated with the development of RP. When comprised of the first and second course of SBRT, a composite lung V5 of < 30% and > 50% was associated with a 0 and 75% incidence of grade 2+ RP, respectively. We identified no significant correlation on multivariable analysis but observed a strong trend between composite lung V5 and the development of grade 2+ RP (hazard ratio, 1.157; P = .058). Evaluation of multiple clinical factors also identified a significant correlation between the timing of repeat lung SBRT and the development of grade 2+ RP after the second course (P = .0028). CONCLUSION: Subsequent courses of lung SBRT, prescribed to a median BED10 of 100 Gy, can provide a high rate of local control with a 4.5% incidence of grade 3+ toxicity. Composite lung V5 and the timing of the second course of lung SBRT may be correlated to the development of RP.

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer.

PURPOSE: Given the uncertainty with regard to the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether patients with prostate cancer who are treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL). METHODS AND MATERIALS: The electronic charts of 886 consecutive patients treated with radiation therapy for prostate cancer between 2006 and 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts within 1 year before and 3 to 24 months after the start of radiation therapy. Lymphopenia was the primary outcome, and overall survival and biochemical progression-free survival were secondary outcomes. RESULTS: Thirty-six patients with and 95 patients without PNI qualified for inclusion. In the PNI cohort, 61.1% of patients developed RRL (median follow-up total lymphocyte count < 1000 cells/µL) versus 26.3% of non-PNI patients (P < .001). On univariate analysis, initial prostate-specific antigen level, baseline lymphopenia, treatment modality, PNI status, increased planned target volume, and androgen deprivation therapy administration were all significant predictors of RRL (P < .05). On multivariate analysis, PNI status was a significant predictor of RRL (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.22-9.61; P < .001), as were initial prostate-specific antigen values (HR, 1.05; 95% CI, 1.00-1.11; P = .006) and baseline lymphopenia (HR, 8.32; 95% CI, 2.19-31.6; P = .007). RRL was not predictive for biochemical progression-free survival, distant metastasis, or overall survival on multivariate analysis, but the number of events was likely insufficient for these analyses. CONCLUSIONS: The higher risk of RRL among patients with PNI comports with other papers that show that increased treatment volumes are associated with higher rates of RRL. Mounting evidence for the adverse effects of RRL on clinical outcomes supports the significance of our findings and suggests that further studies are needed on RRL as a potential harm of PNI that may affect the interpretation of results from clinical trials of PNI.

Part II: Verification of the TrueBeam head shielding model in Varian VirtuaLinac via out-of-field doses.

PURPOSE: A good Monte Carlo model with an accurate head shielding model is important in estimating the long-term risks of unwanted radiation exposure during radiation therapy. The aim of this paper was to validate the Monte Carlo simulation of a TrueBeam linear accelerator (linac) head shielding model. We approach this by evaluating the accuracy of out-of-field dose predictions at extended distances which are comprised of scatter from within the patient and treatment head leakage and thus reflect the accuracy of the head shielding model. We quantify the out-of-field dose of a TrueBeam linac for low-energy photons, 6X and 6X-FFF beams, and compare measurements to Monte Carlo simulations using Varian VirtuaLinac that include a realistic head shielding model, for a variety of jaw sizes and angles up to a distance of 100 cm from the isocenter, in both positive and negative directions. Given the high value and utility of the VirtuaLinac model, it is critical that this model is validated thoroughly and the results be available to the medical physics community. MATERIALS AND METHOD: Simulations were done using VirtuaLinac, the GEANT4-based Monte Carlo model of the TrueBeam treatment head from Varian Medical Systems, and an in-house GEANT4-based code. VirtuaLinac included a detailed model of the treatment head shielding and was run on the Amazon Web Services cloud to generate spherical phase space files surrounding the treatment head. These phase space files were imported into the in-house code, which modeled the measurement setup with a solid water buildup, the carbon fiber couch, and the gantry stand. For each jaw size (2 × 2 cm2 , 4 × 4 cm2 , 10 × 10 cm2 , and 20 × 20 cm2 ) and angular setting (0°, 90°, 45°, 135°), the dose was calculated at intervals of 5 cm along each measurement direction. RESULTS: For the 10 × 10 cm2 jaw size, both 6X and 6X-FFF showed very good agreement between simulation and measurement in both in-plane directions, with no apparent systematic bias. The percentage deviations for these settings were as follows: (mean, STDEV, maximum) (8.34, 6.44, 24.84) for 6X and (13.21, 8.93, 35.56) for 6X-FFF. For all jaw sizes, simulation agreed well in the in-plane direction going away from the gantry, but, some deviations were observed moving toward the gantry at larger distances. At larger distances, for the jaw sizes smaller than 10 × 10 cm2 , the simulation underestimates the dose compared with measurement, while for jaw sizes larger than 10 × 10 cm2 , it overestimates dose. For all comparisons between ±50 cm from isocenter, average absolute agreement between simulation and measurement was better than 28%. CONCLUSION: We have validated the Varian VirtuaLinac's head shielding model via out-of-field doses and quantified the differences between TrueBeam head shielding model created out-of-field doses and measurements for an extended distance of 100 cm.

Part I: Out-of-field dose mapping for 6X and 6X-flattening-filter-free beams on the TrueBeam for extended distances.

PURPOSE: With increasing cancer treatment success rates, many patients go on to live long, productive lives following recovery. Therefore, minimizing potential side effects due to dose outside the treated field is becoming a significant consideration in radiation therapy. With many potential treatment configurations available, it is important to quantify how out-of-field dose varies with common variables such as distance from isocenter, couch angle, jaw size, and flattening-filter setting. The accurate quantification of out-of-field dose at extended distances could also benefit researchers and detector developers. While data exist for out-of-field dose from older linear accelerator (Linac) models, the phenomenon has not been described for the latest generation of machines, such as the Varian TrueBeam. The purpose of this study was to comprehensively quantify out-of-field dose for the Varian TrueBeam Linac low energy photons in a wide range of positions and treatment geometries. METHOD AND MATERIALS: Out-of-field doses were measured using two phantom setups: (a) A large volume ion chamber with a buildup sleeve to quantify head leakage and collimator scatter background dose; and (b) A farmer ion chamber in solid water to incorporate phantom scatter in addition to collimator scatter, and head leakage background dose. In both cases, the ion chamber was positioned with its length along the slowly varying transverse direction (perpendicular to the radial from isocenter). Doses were measured for four symmetric jaw settings (2 × 2 cm2 , 4 × 4 cm2 , 10 × 10 cm2 , and 20 × 20 cm2 ) for a range of distances from the isocenter (0-100 cm). The angular dependence of the out-of-field dose was measured using four different angles: 0°, 45°, 90°, and 135° with respect to the in-plane direction. All measurements were performed for both 6X and 6X-flattening-filter-free (FFF) beams. RESULTS: The lowest out-of-field doses were observed at 60 cm away from isocenter in both in-plane and cross-plane directions for fields smaller than 10 × 10 cm2 . Out-of-field dose decreased with decreasing jaw size (a factor of 4.7 for 6X-FFF and a factor of 3.1 for 6X going from 20 × 20 cm2 to 2 × 2 cm2 at 60 cm from isocenter in the in-plane direction). The 6X-FFF beam produced out-of-field doses as low as 64% of the 6X beam. CONCLUSION: This study presents a comprehensive description of 6X and 6X-FFF out-of-field doses on a Varian TrueBeam Linac including measurements at a range of positions, angles, and jaw settings and with and without phantom scatter.

Tolerance limits and methodologies for IMRT measurement-based verification QA: Recommendations of AAPM Task Group No. 218.

PURPOSE: Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA. METHODS: The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented. RESULTS: Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined. CONCLUSION: Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions.

How dose sparing of cardiac structures correlates with in-field heart volume and sternal displacement.

Cardiac irradiation increases the risk of coronary artery disease in patients with left-sided breast cancer. Techniques exist to reduce cardiac irradiation, but the optimum technique depends on individual patient anatomy and physiology. We investigated the correlation of delta heart volume in field (dHVIF) and sternal excursion with dose sparing in heart and left anterior descending artery (LAD) to develop quantitative predictive models for expected dose to heart and LAD. A treatment planning study was performed on 97 left-breast cancer patients who underwent whole breast radiotherapy (prescription dose = 50 Gy) under deep inspiratory breath hold (DIBH). Two CT datasets, free breathing (FB) and DIBH, were utilized for treatment planning and for determination of the internal anatomy-based DIBH amplitude. The mean heart and LAD dose were compared between FB and DIBH plans and dose to the heart and LAD as a function of dHVIF and sternal excursion were determined. The [Average (STD); Range] mean heart doses from free breathing and DIBH are [120.5(65.2); 28.9 ~ 393.8] cGy and [67.5(25.1); 19.7 ~ 145.6] cGy, respectively. The mean LAD doses from free breathing and DIBH are [571.0(582.2); 42.2 ~ 2332.2] cGy and [185.9(127.0); 41.2 ~ 898.4] cGy, respectively. The mean dose reductions with DIBH are [53.1(50.6); -15.4 ~ 295.1] cGy for the heart and [385.1(513.4); -0.6 ~ 2105.8] cGy for LAD. Percent mean dose reductions to the heart and LAD with DIBH are 44% (p < 0.0001) and 67% (p < 0.0001), respectively, compared to FB. The dHVIF mean dose reduction correlation is 8.1 cGy/cc for the heart and 81.6 cGy/cc for LAD (with linear trend and y intercept: 26.0 cGy for the heart, 109.1 cGy for LAD). DIBH amplitude using sternal position was [1.3(.48); .38 ~ 2.5] cm. The DIBH amplitude mean dose reduction correlation is 14 cGy/cm for the heart and 212cGy/cm for LAD (with linear trend with y intercept: 35.6 cGy for the heart, 102.4 cGy for LAD). The strong correlation of dose sparing to the heart and LAD with dHVIF and sternal excursion suggests that mean dose sparing to heart and LAD can be predicted with either dHVIF or sternal excursion equally well. The metrics proposed could be utilized to allow providers to determine the relative dosimetric benefits of different heart-sparing techniques as early as time of consultation.

A clinically observed discrepancy between image-based and log-based MLC positions.

PURPOSE: To present a clinical case in which real-time intratreatment imaging identified an multileaf collimator (MLC) leaf to be consistently deviating from its programmed and logged position by >1 mm. METHODS: An EPID-based exit-fluence dosimetry system designed to prevent gross delivery errors was used to capture cine during treatment images. The author serendipitously visually identified a suspected MLC leaf displacement that was not otherwise detected. The leaf position as recorded on the EPID images was measured and log-files were analyzed for the treatment in question, the prior day's treatment, and for daily MLC test patterns acquired on those treatment days. Additional standard test patterns were used to quantify the leaf position. RESULTS: Whereas the log-file reported no difference between planned and recorded positions, image-based measurements showed the leaf to be 1.3 ± 0.1 mm medial from the planned position. This offset was confirmed with the test pattern irradiations. CONCLUSIONS: It has been clinically observed that log-file derived leaf positions can differ from their actual position by >1 mm, and therefore cannot be considered to be the actual leaf positions. This cautions the use of log-based methods for MLC or patient quality assurance without independent confirmation of log integrity. Frequent verification of MLC positions through independent means is a necessary precondition to trust log-file records. Intratreatment EPID imaging provides a method to capture departures from MLC planned positions.

A Voxel-by-Voxel Comparison of Deformable Vector Fields Obtained by Three Deformable Image Registration Algorithms Applied to 4DCT Lung Studies.

BACKGROUND: Commonly used methods of assessing the accuracy of deformable image registration (DIR) rely on image segmentation or landmark selection. These methods are very labor intensive and thus limited to relatively small number of image pairs. The direct voxel-by-voxel comparison can be automated to examine fluctuations in DIR quality on a long series of image pairs. METHODS: A voxel-by-voxel comparison of three DIR algorithms applied to lung patients is presented. Registrations are compared by comparing volume histograms formed both with individual DIR maps and with a voxel-by-voxel subtraction of the two maps. When two DIR maps agree one concludes that both maps are interchangeable in treatment planning applications, though one cannot conclude that either one agrees with the ground truth. If two DIR maps significantly disagree one concludes that at least one of the maps deviates from the ground truth. We use the method to compare 3 DIR algorithms applied to peak inhale-peak exhale registrations of 4DFBCT data obtained from 13 patients. RESULTS: All three algorithms appear to be nearly equivalent when compared using DICE similarity coefficients. A comparison based on Jacobian volume histograms shows that all three algorithms measure changes in total volume of the lungs with reasonable accuracy, but show large differences in the variance of Jacobian distribution on contoured structures. Analysis of voxel-by-voxel subtraction of DIR maps shows differences between algorithms that exceed a centimeter for some registrations. CONCLUSION: Deformation maps produced by DIR algorithms must be treated as mathematical approximations of physical tissue deformation that are not self-consistent and may thus be useful only in applications for which they have been specifically validated. The three algorithms tested in this work perform fairly robustly for the task of contour propagation, but produce potentially unreliable results for the task of DVH accumulation or measurement of local volume change. Performance of DIR algorithms varies significantly from one image pair to the next hence validation efforts, which are exhaustive but performed on a small number of image pairs may not reflect the performance of the same algorithm in practical clinical situations. Such efforts should be supplemented by validation based on a longer series of images of clinical quality.

A comparative analysis of 3D conformal deep inspiratory-breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer.

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory-breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumes of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.

RapidArc patient specific mechanical delivery accuracy under extreme mechanical limits using linac log files.

PURPOSE: To assess the accuracy of RapidArc (RA) delivery for treatment machine operation near allowable mechanical limits in dynamic multileaf collimator (DMLC) leaf velocities, gantry speeds, and dose rates. METHODS: Thirty RA patient plans were created for treatment of lung, gastrointestinal, and head and neck cancers on a Trilogy unit. For each patient, three RA plans were generated; one with medium MLC velocities, highest gantry speeds, and dose rates (case A); one with maximal allowable MLC leaf velocities (case B); and one with lowest gantry speeds (case C). Combinations of dose rates (140-600 MU/min), gantry speeds (2-5.4°/s), and DMLC leaf velocities (1.3-2.4 cm/s) were utilized to test the RapidArc delivery accuracy. Linac delivery log files were acquired after delivery of each plan. In-house developed software was used to read in the original RapidArc DICOM plan and update the plan to reflect the delivered plan by using the leaf position (L), gantry position (G), and MU dose values (D) extracted from the linac log files. This modified DICOM RT plan was imported back to ECLIPSE and the delivered 3D dose map recomputed. Finally, the planned and delivered 3D isodose maps were compared under three criteria to evaluate the dosimetric differences: maximum percentage dose difference, 3D gamma analysis criteria for 3%/3mm DTA, number of dose voxels having a dose difference that is greater than 1%, 2%, or 3% of the maximum dose, and their respective percentages. RESULTS: For the three cases indicated above, MLC leaf position discrepancies between planned and delivered values are 0.8 ± 0.2, 1.2 ± 0.2, and 0.8 ± 0.2 mm; the maximum gantry position discrepancies are 0.9° ± 0.2°, 0.9° ± 0.2°, and 0.6° ± 0.1°, and the maximum differences in delivered MU per control point are 0.2 ± 0.1, 0.2 ± 0.1, and 0.04 ± 0.01, respectively. Maximum percentage dose difference observed is 6.7%, for a case where 1 cm MLC leaves were used with high MLC leaf velocity. Maximum number (percentage) of dose voxels having a dose difference that is greater than 1%, 2%, and 3% of the maximum dose were 4761 (0.35%), 897 (0.07%), and 188 (0.01%). This also corresponds to the plan utilizing the most number of 1 cm MLC leaves. The 3D Gamma factor acceptance rates are better than 99%. CONCLUSIONS: This work shows that the accuracy of RapidArc delivery holds across the full range of gantry speeds, leaf velocities, and dose rates with small dosimetric uncertainties for 0.5 cm MLC leaves. However, caution should be exercised when using large MLC leaves in RapidArc. A novel technique to obtain the delivered 3D dose distributions using machine log files is also presented.

Quantifying the reproducibility of heart position during treatment and corresponding delivered heart dose in voluntary deep inhalation breath hold for left breast cancer patients treated with external beam radiotherapy.

PURPOSE: Voluntary deep inhalation breath hold (VDIBH) reduces heart dose during left breast irradiation. We present results of the first study performed to quantify reproducibility of breath hold using bony anatomy, heart position, and heart dose for VDIBH patients at treatment table. METHODS AND MATERIALS: Data from 10 left breast cancer patients undergoing VDIBH whole-breast irradiation were analyzed. Two computed tomography (CT) scans, free breathing (FB) and VDIBH, were acquired to compare dose to critical structures. Pretreatment weekly kV orthogonal images and tangential ports were acquired. The displacement difference from spinal cord to sternum across the isocenter between coregistered planning Digitally Reconstructed Radiographs (DRRs) and kV imaging of bony thorax is a measure of breath hold reproducibility. The difference between bony coregistration and heart coregistration was the measured heart shift if the patient is aligned to bony anatomy. RESULTS: Percentage of dose reductions from FB to VDIBH: mean heart dose (48%, SD 19%, p = 0.002), mean LAD dose (43%, SD 19%, p = 0.008), and maximum left anterior descending (LAD) dose (60%, SD 22%, p = 0.008). Average breath hold reproducibility using bony anatomy across the isocenter along the anteroposterior (AP) plane from planning to treatment is 1 (range, 0-3; SD, 1) mm. Average heart shifts with respect to bony anatomy between different breath holds are 2 ± 3 mm inferior, 1 ± 2 mm right, and 1 ± 3 mm posterior. Percentage dose changes from planning to delivery: mean heart dose (7%, SD 6%); mean LAD dose, ((9%, SD 7%)S, and maximum LAD dose, (11%, SD 11%) SD 11%, p = 0.008). CONCLUSION: We observed excellent three-dimensional bony registration between planning and pretreatment imaging. Reduced delivered dose to heart and LAD is maintained throughout VDIBH treatment.

Dosimetric comparison of 6 MV and 15 MV single arc rapidarc to helical TomoTherapy for the treatment of pancreatic cancer.

We conducted a planning study to compare Varian's RapidArc (RA) and helical TomoTherapy (HT) for the treatment of pancreatic cancer. Three intensity-modulated radiotherapy (IMRT) plans were generated for 8 patients with pancreatic cancer: one using HT with 6-MV beam (Plan_(HT6)), one using single-arc RA with 6-MV beam (Plan_(RA6)), and one using single-arc RA with 15-MV beam (Plan_(RA15)). Dosimetric indices including high/low conformality index (CI(100%)/CI(50%)), heterogeneity index (HI), monitor units (MUs), and doses to organs at risk (OARs) were compared. The mean CI(100%) was statistically equivalent with respect to the 2 treatment techniques, as well as beam energy (0.99, 1.01, and 1.02 for Plan_(HT6), Plan_(RA6), and Plan_(RA156,) respectively). The CI(50%) and HI were improved in both RA plans over the HT plan. The RA plans significantly reduced MU (MU(RA6) = 697, MU(RA15) = 548) compared with HT (MU(HT6) = 6177, p = 0.008 in both cases). The mean maximum cord dose was decreased from 29.6 Gy in Plan_(HT6) to 21.6 Gy (p = 0.05) in Plan_(RA6) and 21.7 Gy (p = 0.04) in Plan_(RA15). The mean bowel dose decreased from 17.2 Gy in Plan_(HT6) to 15.2 Gy (p = 0.03) in Plan_(RA6) and 15.0 Gy (p = 0.03) Plan_(RA15). The mean liver dose decreased from 8.4 Gy in Plan_(HT6) to 6.3 Gy (p = 0.04) in Plan_(RA6) and 6.2 Gy in Plan_(RA15). Variations of the mean dose to the duodenum, kidneys, and stomach were statistically insignificant. RA and HT can both deliver conformal dose distributions to target volumes while limiting the dose to surrounding OARs in the treatment of pancreatic cancer. Dosimetric advantages might be gained by using RA over HT by reducing the dose to OARs and total MUs used for treatment.

Quantifying the accuracy of automated structure segmentation in 4D CT images using a deformable image registration algorithm.

Four-dimensional (4D) radiotherapy is the explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy. One key component of 4D radiotherapy planning is the ability to automatically ("auto") create contours on all of the respiratory phase computed tomography (CT) datasets comprising a 4D CT scan, based on contours manually drawn on one CT image set from one phase. A tool that can be used to automatically propagate manually drawn contours to CT scans of other respiratory phases is deformable image registration. The purpose of the current study was to geometrically quantify the difference between automatically generated contours with manually drawn contours. Four-DCT data sets of 13 patients consisting of ten three-dimensional CT image sets acquired at different respiratory phases were used for this study. Tumor and normal tissue structures [gross tumor volume (GTV), esophagus, right lung, left lung, heart and cord] were manually drawn on each respiratory phase of each patient. Large deformable diffeomorphic image registration was performed to map each CT set from the peak-inhale respiration phase to the CT image sets corresponding with subsequent respiration phases. The calculated displacement vector fields were used to deform contours automatically drawn on the inhale phase to the other respiratory phase CT image sets. The code was interfaced to a treatment planning system to view the resulting images and to obtain the volumetric, displacement, and surface congruence information; 692 automatically generated structures were compared with 692 manually drawn structures. The auto- and manual methods showed similar trends, with a smaller difference observed between the GTVs than other structures. The auto-contoured structures agree with the manually drawn structures, especially in the case of the GTV, to within published interobserver variations. For the GTV, fractional volumes agree to within 0.2+/-0.1, center of mass displacements agree to within 0.5+/-1.5 mm, and agreement of surface congruence is 0.0+/-1.1 mm. The surface congruence between automatic and manual contours for the GTV, heart, left lung, right lung and esophagus was less than 5 mm in 99%, 94%, 94%, 91% and 89%, respectively. Careful assessment of the performance of automatic algorithms is needed in the presence of 4D CT artifacts.

Esophagus and spinal cord motion relative to GTV motion in four-dimensional CTs of lung cancer patients.

Respiration-related variations in the distance between the center of mass of gross tumor volume and both esophagus and spinal cord in the transversal plane were on average 3mm (range 1-10mm) and 2mm (range 1-5mm), respectively. Depending on the tumor location and treatment technique, variations might become important for treatment planning.

Comparison of intensity-modulated radiotherapy planning based on manual and automatically generated contours using deformable image registration in four-dimensional computed tomography of lung cancer patients.

PURPOSE: To evaluate the implications of differences between contours drawn manually and contours generated automatically by deformable image registration for four-dimensional (4D) treatment planning. METHODS AND MATERIALS: In 12 lung cancer patients intensity-modulated radiotherapy (IMRT) planning was performed for both manual contours and automatically generated ("auto") contours in mid and peak expiration of 4D computed tomography scans, with the manual contours in peak inspiration serving as the reference for the displacement vector fields. Manual and auto plans were analyzed with respect to their coverage of the manual contours, which were assumed to represent the anatomically correct volumes. RESULTS: Auto contours were on average larger than manual contours by up to 9%. Objective scores, D(2%) and D(98%) of the planning target volume, homogeneity and conformity indices, and coverage of normal tissue structures (lungs, heart, esophagus, spinal cord) at defined dose levels were not significantly different between plans (p = 0.22-0.94). Differences were statistically insignificant for the generalized equivalent uniform dose of the planning target volume (p = 0.19-0.94) and normal tissue complication probabilities for lung and esophagus (p = 0.13-0.47). Dosimetric differences >2% or >1 Gy were more frequent in patients with auto/manual volume differences > or =10% (p = 0.04). CONCLUSIONS: The applied deformable image registration algorithm produces clinically plausible auto contours in the majority of structures. At this stage clinical supervision of the auto contouring process is required, and manual interventions may become necessary. Before routine use, further investigations are required, particularly to reduce imaging artifacts.

Tumor and normal tissue motion in the thorax during respiration: Analysis of volumetric and positional variations using 4D CT.

PURPOSE: To investigate temporospatial variations of tumor and normal tissue during respiration in lung cancer patients. METHODS AND MATERIALS: In 14 patients, gross tumor volume (GTV) and normal tissue structures were manually contoured on four-dimensional computed tomography (4D-CT) scans. Structures were evaluated for volume changes, centroid (center of mass) motion, and phase dependence of variations relative to inspiration. Only volumetrically complete structures were used for analysis (lung in 2, heart in 8, all other structures in >10 patients). RESULTS: During respiration, the magnitude of contoured volumes varied up to 62.5% for GTVs, 25.5% for lungs, and 12.6% for hearts. The range of maximum three-dimensional centroid movement for individual patients was 1.3-24.0 mm for GTV, 2.4-7.9 mm for heart, 5.2-12.0 mm for lungs, 0.3-5.5 mm for skin markers, 2.9-10.0 mm for trachea, and 6.6-21.7 mm for diaphragm. During respiration, the centroid positions of normal structures varied relative to the centroid position of the respective GTV by 1.5-8.1 mm for heart, 2.9-9.3 mm for lungs, 1.2-9.2 mm for skin markers, 0.9-7.1 mm for trachea, and 2.7-16.4 mm for diaphragm. CONCLUSION: Using 4D-CT, volumetric changes, positional alterations as well as changes in the position of contoured structures relative to the GTV were observed with large variations between individual patients. Although the interpretation of 4D-CT data has considerable uncertainty because of 4D-CT artifacts, observer variations, and the limited acquisition time, the findings might have a significant impact on treatment planning.

Geometric accuracy of a real-time target tracking system with dynamic multileaf collimator tracking system.

PURPOSE: Dynamically compensating for target motion during radiotherapy will increase treatment accuracy. A laboratory system for real-time target tracking with a dynamic MLC has been developed. In this study, the geometric accuracy limits of this DMLC target tracking system were evaluated. METHODS AND MATERIALS: A motion simulator was programmed to follow patient-derived tumor motion paths, parallel to the leaf motion direction. A target attached to the simulator was optically tracked, and the leaf positions adjusted to continually align the DMLC beam aperture to the target. Analysis of the tracking accuracy was based on video images of the target and beam alignment. The system response time was determined and the tracking error measured. Response time-corrected tracking accuracy was also calculated to investigate the accuracy limits of an improved system. RESULTS: The response time of the system is 160 +/- 2 ms. The geometric precision for tracking patient motion is 0.6 to 1.1 mm (1 sigma) for the 3 patient datasets tested, with tracking errors relative to the original patient motion of 35, 40, and 100%. CONCLUSIONS: A DMLC target tracking system has been developed that can account for detected motion parallel to the leaf motion direction. The tracking error has a negligible systematic component. Reducing the response time will further increase the overall system accuracy.