Purpose
Lung stereotactic ablative body radiotherapy (SABR) is a radiation therapy success story with level 1 evidence demonstrating its efficacy. To provide real‐time respiratory motion management ...for lung SABR, several commercial and preclinical markerless lung target tracking (MLTT) approaches have been developed. However, these approaches have yet to be benchmarked using a common measurement methodology. This knowledge gap motivated the MArkerless lung target Tracking CHallenge (MATCH). The aim was to localize lung targets accurately and precisely in a retrospective in silico study and a prospective experimental study.
Methods
MATCH was an American Association of Physicists in Medicine sponsored Grand Challenge. Common materials for the in silico and experimental studies were the experiment setup including an anthropomorphic thorax phantom with two targets within the lungs, and a lung SABR planning protocol. The phantom was moved rigidly with patient‐measured lung target motion traces, which also acted as ground truth motion. In the retrospective in silico study a volumetric modulated arc therapy treatment was simulated and a dataset consisting of treatment planning data and intra‐treatment kilovoltage (kV) and megavoltage (MV) images for four blinded lung motion traces was provided to the participants. The participants used their MLTT approach to localize the moving target based on the dataset. In the experimental study, the participants received the phantom experiment setup and five patient‐measured lung motion traces. The participants used their MLTT approach to localize the moving target during an experimental SABR phantom treatment. The challenge was open to any participant, and participants could complete either one or both parts of the challenge. For both the in silico and experimental studies the MLTT results were analyzed and ranked using the prospectively defined metric of the percentage of the tracked target position being within 2 mm of the ground truth.
Results
A total of 30 institutions registered and 15 result submissions were received, four for the in silico study and 11 for the experimental study. The participating MLTT approaches were: Accuray CyberKnife (2), Accuray Radixact (2), BrainLab Vero, C‐RAD, and preclinical MLTT (5) on a conventional linear accelerator (Varian TrueBeam). For the in silico study the percentage of the 3D tracking error within 2 mm ranged from 50% to 92%. For the experimental study, the percentage of the 3D tracking error within 2 mm ranged from 39% to 96%.
Conclusions
A common methodology for measuring the accuracy of MLTT approaches has been developed and used to benchmark preclinical and commercial approaches retrospectively and prospectively. Several MLTT approaches were able to track the target with sub‐millimeter accuracy and precision. The study outcome paves the way for broader clinical implementation of MLTT. MATCH is live, with datasets and analysis software being available online at https://www.aapm.org/GrandChallenge/MATCH/ to support future research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT).
We included all patients with Stage I-IVA cervical carcinoma ...treated with IMRT at three different institutions from 2000-2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions.
The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I-IIA disease and 48 had Stage IIB-IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval CI, 68-88%) and 69% (95% CI, 59-81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6-22%) and 17% (95% CI, 8-25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0-7%) and 7% (95% CI, 2-13%), respectively.
Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Purpose
Although stereotactic body radiation therapy (SBRT) is an attractive noninvasive approach for liver irradiation, it presents specific challenges associated with respiration‐induced liver ...motion, daily tumor localization due to liver deformation, and poor visualization of target with respect to adjacent normal liver in computed tomography (CT). We aim to identify potential hazards and develop a set of mitigation strategies to improve the safety of our liver SBRT program, using failure mode and effect analysis (FMEA).
Materials and methods
A multidisciplinary group consisting of two physicians, three physicists, two dosimetrists, and two therapists was formed. A process map covering ten major stages of the liver SBRT program from the initial diagnosis to posttreatment follow‐up was generated. A total of 102 failure modes (FM), together with their causes and effects, were identified. The occurrence (O), severity (S), and lack of detectability (D) were independently scored using a scale from 1 (lowest risk) to 10 (largest risk). The ranking was done using the risk probability number (RPN) defined as the product of average O, S, and D numbers for each mode. Two fault tree analyses were performed. The failure modes with the highest RPN values as well as highest severity score were considered for investigation and a set of mitigation strategies was developed to address these.
Results
The median RPN (RPNmed) values for all modes ranged from of 9 to 105 and the highest median S score (Smed) was 8. Fourteen FMs were identified to be significant by both RPNmed and Smed (top ten RPNmed ranked and highest Smed FMs) and 12 of them were considered for risk mitigation efforts. The remaining two were omitted due to either sufficient checks already in place, or lack of practical mitigation strategies. Implemented measures consisted of five physics tasks, two physician tasks, and three workflow changes.
Conclusions
The application of FMEA to our liver SBRT program led to the identification of potential FMs and allowed improvement measures to enhance the safety of our clinical practice.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To compare bone marrow-sparing intensity-modulated pelvic radiotherapy (BMS-IMRT) with conventional (four-field box and anteroposterior-posteroanterior AP-PA) techniques in the treatment of cervical ...cancer.
The data from 7 cervical cancer patients treated with concurrent chemotherapy and IMRT without BMS were analyzed and compared with data using four-field box and AP-PA techniques. All plans were normalized to cover the planning target volume with the 99% isodose line. The clinical target volume consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprised the lumbosacral spine and ilium and the ischium, pubis, and proximal femora (lower pelvis bone marrow). Dose-volume histograms for the planning target volume and normal tissues were compared for BMS-IMRT vs. four-field box and AP-PA plans.
BMS-IMRT was superior to the four-field box technique in reducing the dose to the PBM, small bowel, rectum, and bladder. Compared with AP-PA plans, BMS-IMRT reduced the PBM volume receiving a dose >16.4 Gy. BMS-IMRT reduced the volume of ilium, lower pelvis bone marrow, and bowel receiving a dose >27.7, >18.7, and >21.1 Gy, respectively, but increased dose below these thresholds compared with the AP-PA plans. BMS-IMRT reduced the volume of lumbosacral spine bone marrow, rectum, small bowel, and bladder at all dose levels in all 7 patients.
BMS-IMRT reduced irradiation of PBM compared with the four-field box technique. Compared with the AP-PA technique, BMS-IMRT reduced lumbosacral spine bone marrow irradiation and reduced the volume of PBM irradiated to high doses. Therefore BMS-IMRT might reduce acute hematologic toxicity compared with conventional techniques.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Purpose
To evaluate markerless tumor tracking (MTT) using fast‐kV switching dual‐energy (DE) fluoroscopy on a bench top system.
Methods
Fast‐kV switching DE fluoroscopy was implemented on a bench top ...which includes a turntable stand, flat panel detector, and x‐ray tube. The customized generator firmware enables consecutive x‐ray pulses that alternate between programmed high and low energies (e.g., 60 and 120 kVp) with a maximum frame rate of 15 Hz. In‐house software was implemented to perform weighted DE subtraction of consecutive images to create an image sequence that removes bone and enhances soft tissues. The weighting factor was optimized based on gantry angle. To characterize this system, a phantom was used that simulates the chest anatomy and tumor motion in the lung. Five clinically relevant tumor sizes (5–25 mm diameter) were considered. The targets were programmed to move in the inferior‐superior direction of the phantom, perpendicular to the x‐ray beam, using a cos4 waveform to mimic respiratory motion. Target inserts were then tracked with MTT software using a template matching method. The optimal computed tomography (CT) slice thickness for template generation was also evaluated. Tracking success rate and accuracy were calculated in regions of the phantom where the target overlapped ribs vs spine, to compare the performance of single energy (SE) and DE imaging methods.
Results
For the 5 mm target, a CT slice thickness of 0.75 mm resulted in the lowest tracking error. For the larger targets (≥10 mm) a CT slice thickness ≤2 mm resulted in comparable tracking errors for SE and DE images. Overall DE imaging improved MTT accuracy, relative to SE imaging, for all tumor targets in a rotational acquisition. Compared to SE, DE imaging increased tracking success rate of small target inserts (5 and 10 mm). For fast motion tracking, success rates improved from 23% to 64% and 74% to 90% for 5 and 10 mm targets inserts overlapping ribs, respectively. For slow moving targets success rates improved from 19% to 59% and 59% to 91% in 5 and 10 mm targets overlapping the ribs, respectively. Similar results were observed when the targets overlapped the spine. For larger targets (≥15 mm) tracking success rates were comparable using SE and DE imaging.
Conclusion
This work presents the first results of MTT using fast‐kV switching DE fluoroscopy. Using DE imaging has improved the tracking accuracy of MTT, especially for small targets. The results of this study will guide the future implementation of fast‐kV switching DE imaging using the on‐board imager of a linear accelerator.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract The accuracy of artificial intelligence (AI) generated contours for intact‐breast and post‐mastectomy radiotherapy plans was evaluated. Geometric and dosimetric comparisons were performed ...between auto‐contours (ACs) and manual‐contours (MCs) produced by physicians for target structures. Breast and regional nodal structures were manually delineated on 66 breast cancer patients. ACs were retrospectively generated. The characteristics of the breast/post‐mastectomy chestwall (CW) and regional nodal structures (axillary AxN, supraclavicular SC, internal mammary IM) were geometrically evaluated by Dice similarity coefficient (DSC), mean surface distance, and Hausdorff Distance. The structures were also evaluated dosimetrically by superimposing the MC clinically delivered plans onto the ACs to assess the impact of utilizing ACs with target dose (Vx%) evaluation. Positive geometric correlations between volume and DSC for intact‐breast, AxN, and CW were observed. Little or anti correlations between volume and DSC for IM and SC were shown. For intact‐breast plans, insignificant dosimetric differences between ACs and MCs were observed for AxN V95% ( p = 0.17) and SC V95% ( p = 0.16), while IMN V90% ACs and MCs were significantly different. The average V95% for intact‐breast MCs (98.4%) and ACs (97.1%) were comparable but statistically different ( p = 0.02). For post‐mastectomy plans, AxN V95% ( p = 0.35) and SC V95% ( p = 0.08) were consistent between ACs and MCs, while IMN V90% was significantly different. Additionally, 94.1% of AC‐breasts met ΔV95% variation <5% when DSC > 0.7. However, only 62.5% AC‐CWs achieved the same metrics, despite AC‐CW V95% ( p = 0.43) being statistically insignificant. The AC intact‐breast structure was dosimetrically similar to MCs. The AC AxN and SC may require manual adjustments. Careful review should be performed for AC post‐mastectomy CW and IMN before treatment planning. The findings of this study may guide the clinical decision‐making process for the utilization of AI‐driven ACs for intact‐breast and post‐mastectomy plans. Before clinical implementation of this auto‐segmentation software, an in‐depth assessment of agreement with each local facilities MCs is needed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A shallow neural network was trained to accurately calculate the microdosimetric parameters, 〈
〉 and 〈
〉 (the first and second moments of the single-event specific energy spectra, respectively) for ...use in alpha-particle microdosimetry calculations. The regression network of four inputs and two outputs was created in MATLAB and trained on a data set consisting of both previously published microdosimetric data and recent Monte Carlo simulations. The input data consisted of the alpha-particle energies (3.97-8.78 MeV), cell nuclei radii (2-10
m), cell radii (2.5-20
m), and eight different source-target configurations. These configurations included both single cells in suspension and cells in geometric clusters. The mean square error (MSE) was used to measure the performance of the network. The sizes of the hidden layers were chosen to minimize MSE without overfitting. The final neural network consisted of two hidden layers with 13 and 20 nodes, respectively, each with tangential sigmoid transfer functions, and was trained on 1932 data points. The overall training/validation resulted in a MSE = 3.71 × 10
. A separate testing data set included input values that were not seen by the trained network. The final test on 892 separate data points resulted in a MSE = 2.80 × 10
. The 95th percentile testing data errors were within ±1.4% for 〈
〉 outputs and ±2.8% for 〈
〉 outputs, respectively. Cell survival was also predicted using actual versus neural network generated microdosimetric moments and showed overall agreement within ±3.5%. In summary, this trained neural network can accurately produce microdosimetric parameters used for the study of alpha-particle emitters. The network can be exported and shared for tests on independent data sets and new calculations.
Purpose
To present a novel method, based on convolutional neural networks (CNN), to automate weighted log subtraction (WLS) for dual‐energy (DE) fluoroscopy to be used in conjunction with markerless ...tumor tracking (MTT).
Methods
A CNN was developed to automate WLS (aWLS) of DE fluoroscopy to enhance soft tissue visibility. Briefly, this algorithm consists of two phases: training a CNN architecture to predict pixel‐wise weighting factors followed by application of WLS subtraction to reduce anatomical noise. To train the CNN, a custom phantom was built consisting of aluminum (Al) and acrylic (PMMA) step wedges. Per‐pixel ground truth (GT) weighting factors were calculated by minimizing the contrast of Al in the step wedge phantom to train the CNN. The pretrained model was then utilized to predict pixel‐wise weighting factors for use in WLS. For comparison, the weighting factor was manually determined in each projection (mWLS). A thorax phantom with five simulated spherical targets (5–25 mm) embedded in a lung cavity, was utilized to assess aWLS performance. The phantom was imaged with fast‐kV dual‐energy (120 and 60 kVp) fluoroscopy using the on‐board imager of a commercial linear accelerator. DE images were processed offline to produce soft tissue images using both WLS methods. MTT was compared using soft tissue images produced with both mWLS and aWLS techniques.
Results
Qualitative evaluation demonstrated that both methods achieved soft tissue images with similar quality. The use of aWLS increased the number of tracked frames by 1–5% compared to mWLS, with the largest increase observed for the smallest simulated tumors. The tracking errors for both methods produced agreement to within 0.1 mm.
Conclusions
A novel method to perform automated WLS for DE fluoroscopy was developed. Having similar soft tissue quality as well as bone suppression capability as mWLS, this method allows for real‐time processing of DE images for MTT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to ...develop a normal tissue complication probability (NTCP) model for HT.
We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving≥10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints.
In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V10 (regression coefficient (β)=-0.060, p=0.009) and V20 (β=-0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V10 and V20 were as follows: -0.022 (p=0.025) and -0.021 (p=0.002), respectively. Patients with V10≥95% were more likely to experience Grade≥3 leukopenia (68.8% vs. 24.6%, p<0.001) than were patients with V20>76% (57.7% vs. 21.8%, p=0.001).
These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10<95% and V20<76% may reduce HT.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Purpose:
To evaluate the efficacy of dual‐energy (DE) vs single‐energy (SE) fluoroscopic imaging of lung tumors using a markerless template‐based tracking algorithm.
Methods:
Ten representative ...patient breathing patterns were programmed into a Quasar™ motion phantom. The phantom was modified by affixing pork ribs to the surface, and a cedar insert with a small spherical volume was used to simulate lung and tumor, respectively. Sequential 60 kVp (6 mA) and 120 kVp (1.5 mA) fluoroscopic sequences were acquired. Frame‐by‐frame weighted logarithmic subtraction was performed resulting in a DE fluoroscopic sequence. A template‐based algorithm was then used to track tumor motion throughout the DE and SE fluoroscopy sequences. Tracking coordinates were evaluated against ground‐truth tumor locations. Fluoroscopic images were also acquired for two lung cancer patients, neither of which had implanted fiducials.
Results:
For phantom imaging, a total of 1925 frames were analyzed. The algorithm successfully tracked the target on 99.9% (1923/1925) of DE frames vs 90.7% (1745/1925) SE images (p < 0.01). The displacement between tracking coordinates and ground truth for the phantom was 1.4 mm ± 1.1 mm for DE vs 2.0 mm ± 1.3 mm for SE (p < 0.01). Images from two patients, one with a larger tumor and one with a smaller tumor, were also analyzed. For the patient with the larger tumor, the average displacement from physician defined ground truth was 1.2 mm ± 0.6 mm for DE vs 1.4 mm ± 0.7 mm for SE (p = 0.016). For the patient that presented with a smaller tumor, the average displacement from physician defined ground truth was 2.2 mm ± 1.0 mm for DE vs 3.2 mm ± 1.4 mm for SE (p < 0.01). Importantly, for this single patient with the smaller tumor, 15.6% of the SE frames had >5 mm displacements from the ground truth vs 0% for DE fluoroscopy.
Conclusions:
This work indicates the potential for markerless tumor tracking utilizing DE fluoroscopy. With DE imaging, the algorithm showed improved detectability vs SE fluoroscopy and was able to accurately track the tumor in nearly all cases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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