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Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ([Formula: see text] and 3d full resolution of nnU-Net ([Formula: see text] to determine the best architecture ([Formula: see text]. BA was used with vessels ([Formula: see text] and spleen ([Formula: see text] to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ([Formula: see text]), 40 ([Formula: see text]), 33 ([Formula: see text]), 25 (C CH ) and 20 (C PVE ) CECT of LC patients. [Formula: see text] outperformed [Formula: see text] across all segments with median differences in Dice similarity coefficients (DSC) ranging 0.03-0.05 (p < 0.05). [Formula: see text], and [Formula: see text] were not statistically different (p > 0.05), however, both were slightly better than [Formula: see text] by DSC up to 0.02. The final model, [Formula: see text], showed a mean DSC of 0.89, 0.82, 0.88, 0.87, 0.96, and 0.95 for segments 1, 2, 3, 4, 5-8, and spleen, respectively on entire test sets. Qualitatively, more than 85% of cases showed a Likert score [Formula: see text] 3 on test sets. Our final model provides clinically acceptable contours of liver segments and spleen which are usable in treatment planning., (© 2024. The Author(s).)

Purpose: Discrepancies between planned and delivered dose to GI structures during radiation therapy (RT) of liver cancer may hamper the prediction of treatment outcomes. The purpose of this study is to develop a streamlined workflow for dose accumulation in a treatment planning system (TPS) during liver image-guided RT and to assess its accuracy when using different deformable image registration (DIR) algorithms., Materials and Methods: Fifty-six patients with primary and metastatic liver cancer treated with external beam radiotherapy guided by daily CT-on-rails (CTOR) were retrospectively analyzed. The liver, stomach and duodenum contours were auto-segmented on all planning CTs and daily CTORs using deep-learning methods. Dose accumulation was performed for each patient using scripting functionalities of the TPS and considering three available DIR algorithms based on: (i) image intensities only; (ii) intensities + contours; (iii) a biomechanical model (contours only). Planned and accumulated doses were converted to equivalent dose in 2Gy (EQD2) and normal tissue complication probabilities (NTCP) were calculated for the stomach and duodenum. Dosimetric indexes for the normal liver, GTV, stomach and duodenum and the NTCP values were exported from the TPS for analysis of the discrepancies between planned and the different accumulated doses., Results: Deep learning segmentation of the stomach and duodenum enabled considerable acceleration of the dose accumulation process for the 56 patients. Differences between accumulated and planned doses were analyzed considering the 3 DIR methods. For the normal liver, stomach and duodenum, the distribution of the 56 differences in maximum doses (D2%) presented a significantly higher variance when a contour-driven DIR method was used instead of the intensity only-based method. Comparing the two contour-driven DIR methods, differences in accumulated minimum doses (D98%) in the GTV were >2Gy for 15 (27%) of the patients. Considering accumulated dose instead of planned dose in standard NTCP models of the duodenum demonstrated a high sensitivity of the duodenum toxicity risk to these dose discrepancies, whereas smaller variations were observed for the stomach., Conclusion: This study demonstrated a successful implementation of an automatic workflow for dose accumulation during liver cancer RT in a commercial TPS. The use of contour-driven DIR methods led to larger discrepancies between planned and accumulated doses in comparison to using an intensity only based DIR method, suggesting a better capability of these approaches in estimating complex deformations of the GI organs., Competing Interests: Dr. PB reports support for sponsored research from RaySearch Laboratories and Varian. Dr. KB reports Licensing agreement with RaySearch Laboratories for Deformable Image Registration technologies, participation on RaySearch Clinical Advisory Board. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McCulloch, Cazoulat, Svensson, Gryshkevych, Rigaud, Anderson, Kirimli, De, Mathew, Zaid, Elganainy, Peterson, Balter, Koay and Brock.)

Purpose: Re-planning for four-dimensional computed tomography (4DCT)-based lung adaptive radiotherapy commonly requires deformable dose mapping between the planning average-intensity image (AVG) and the newly acquired AVG. However, such AVG-AVG deformable image registration (DIR) lacks accuracy assessment. The current work quantified and compared geometric accuracies of AVG-AVG DIR and corresponding phase-phase DIRs, and subsequently investigated the clinical impact of such AVG-AVG DIR on deformable dose mapping., Methods and Materials: Hybrid intensity-based AVG-AVG and phase-phase DIRs were performed between the planning and mid-treatment 4DCTs of 28 non-small cell lung cancer patients. An automated landmark identification algorithm detected vessel bifurcation pairs in both lungs. Target registration error (TRE) of these landmark pairs was calculated for both DIR types. The correlation between TRE and respiratory-induced landmark motion in the planning 4DCT was analyzed. Global and local dose metrics were used to assess the clinical implications of AVG-AVG deformable dose mapping with both DIR types., Results: TRE of AVG-AVG and phase-phase DIRs averaged 3.2 ± 1.0 and 2.6 ± 0.8 mm respectively (p < 0.001). Using AVG-AVG DIR, TREs for landmarks with <10 mm motion averaged 2.9 ± 2.0 mm, compared to 3.1 ± 1.9 mm for the remaining landmarks (p < 0.01). Comparatively, no significant difference was demonstrated for phase-phase DIRs. Dosimetrically, no significant difference in global dose metrics was observed between doses mapped with AVG-AVG DIR and the phase-phase DIR, but a positive linear relationship existed (p = 0.04) between the TRE of AVG-AVG DIR and local dose difference., Conclusions: When the region of interest experiences <10 mm respiratory-induced motion, AVG-AVG DIR may provide sufficient geometric accuracy; conversely, extra attention is warranted, and phase-phase DIR is recommended. Dosimetrically, the differences in geometric accuracy between AVG-AVG and phase-phase DIRs did not impact global lung-based metrics. However, as more localized dose metrics are needed for toxicity assessment, phase-phase DIR may be required as its lower mean TRE improved voxel-based dosimetry., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Deformable image registration (DIR) of longitudinal liver cancer computed tomographic (CT) images can be challenging owing to anatomic changes caused by radiation therapy (RT) or disease progression. We propose a workflow for the DIR of longitudinal contrast-enhanced CT scans of liver cancer based on a biomechanical model of the liver driven by boundary conditions on the liver surface and centerline of an autosegmentation of the vasculature., Methods and Materials: Pre- and post-RT CT scans acquired with a median gap of 112 (32-217) days for 28 patients who underwent RT for intrahepatic cholangiocarcinoma were retrospectively analyzed. For each patient, 5 corresponding anatomic landmarks in pre- and post-RT scans were identified in the liver by a clinical expert for evaluation of the accuracy of different DIR strategies. The first strategy corresponded to the use of a biomechanical model-based DIR method with boundary conditions specified on the liver surface (BM&#95;DIR). The second strategy corresponded to the use of an expansion of BM&#95;DIR consisting of the auto-segmentation of the liver vasculature to determine additional boundary conditions in the biomechanical model (BM&#95;DIR&#95;VBC). The 2 strategies were also compared with an intensity-based DIR strategy using a Demons algorithms., Results: The group mean target registration errors were 12.4 ± 7.5, 7.7 ± 3.7 and 4.4 ± 2.5 mm, for the Demons, BM&#95;DIR and BM&#95;DIR&#95;VBC, respectively., Conclusions: In regard to the large and complex deformation observed in this study and the achieved accuracy of 4.4 mm, the proposed BM&#95;DIR&#95;VBC method might reveal itself as a valuable tool in future studies on the relationship between delivered dose and treatment outcome., (© 2019 The Authors.)

Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC)., Methods: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT., Discussion: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC., Trial Registration: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.

Background: Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a "standard" IMRT (IMRTstd); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia., Material and Methods: Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched., Results: Compared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p<0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p<0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p<0.001)., Conclusion: During the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

In the context of head and neck cancer (HNC) adaptive radiation therapy (ART), the two purposes of the study were to compare the performance of multiple deformable image registration (DIR) methods and to quantify their impact for dose accumulation, in healthy structures. Fifteen HNC patients had a planning computed tomography (CT0) and weekly CTs during the 7 weeks of intensity-modulated radiation therapy (IMRT). Ten DIR approaches using different registration methods (demons or B-spline free form deformation (FFD)), preprocessing, and similarity metrics were tested. Two observers identified 14 landmarks (LM) on each CT-scan to compute LM registration error. The cumulated doses estimated by each method were compared. The two most effective DIR methods were the demons and the FFD, with both the mutual information (MI) metric and the filtered CTs. The corresponding LM registration accuracy (precision) was 2.44 mm (1.30 mm) and 2.54 mm (1.33 mm), respectively. The corresponding LM estimated cumulated dose accuracy (dose precision) was 0.85 Gy (0.93 Gy) and 0.88 Gy (0.95 Gy), respectively. The mean uncertainty (difference between maximal and minimal dose considering all the 10 methods) to estimate the cumulated mean dose to the parotid gland (PG) was 4.03 Gy (SD = 2.27 Gy, range: 1.06-8.91 Gy).

This paper addresses the issue of cumulative dose estimation from cone beam computed tomography (CBCT) images in prostate cancer radiotherapy. It focuses on the dose received by the surfaces of the main organs at risk, namely the bladder and rectum. We have proposed both a surface-constrained dose accumulation approach and its extensive evaluation. Our approach relied on the nonrigid registration (NRR) of daily acquired CBCT images on the planning CT image. This proposed NRR method was based on a Demons-like algorithm, implemented in combination with mutual information metric. It allowed for different levels of geometrical constraints to be considered, ensuring a better point to point correspondence, especially when large deformations occurred, or in high dose gradient areas. The three following implementations: 1) full iconic NRR; 2) iconic NRR constrained with landmarks (LCNRR); 3) NRR constrained with full delineation of organs (DBNRR). To obtain reference data, we designed a numerical phantom based on finite-element modeling and image simulation. The methods were assessed on both the numerical phantom and real patient data in order to quantify uncertainties in terms of dose accumulation. The LCNRR method appeared to constitute a good compromise for dose monitoring in clinical practice.