Image-guided Radiotherapy Research Articles

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study

BackgroundOligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification.MethodsWe retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2).ResultsEighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24–50 Gy, mean BEDα/β10=93), while 41 Gy (range 16–50 Gy, mean BEDα/β10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1–10 Gy) and 3,7 Gy (range 1,6–8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%.ConclusionsMRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Automation to facilitate optimisation of breast radiotherapy treatments using EPID-based in vivo dosimetry

Objective. To use automation to facilitate the monitoring of each treatment fraction using an electronic portal imaging device (EPID) based in vivo dosimetry (IVD) system, allowing optimisation of breast radiotherapy delivery for individual patients and cohorts. Approach. A suite of in-house software was developed to reduce the number of manual interactions with the commercial IVD system, dosimetry check. An EPID specific pixel sensitivity map facilitated use of the EPID panel away from the central axis. Point dose difference and the change in standard deviation in dose were identified as useful dose metrics, with standard deviation used in preference to gamma in the presence of a systematic dose offset. Automated IVD was completed for 3261 fractions across 704 patients receiving breast radiotherapy. Main results. Multiple opportunities for treatment optimisation were identified for individual patients and across patient cohorts as a result of successful implementation of automated IVD. 5.1% of analysed fractions were out of tolerance with 27.1% of these considered true positives. True positive results were obtained on any fraction of treatment and if IVD had only been completed on the first fraction, 84.4% of true positive results would have been missed. This was made possible due to the automation that saved over 800 h of manual intervention and stored data in an accessible database. Significance. An improved EPID calibration to allow off-axis measurement maximises the number of patients eligible for IVD (36.8% of patients in this study). We also demonstrate the importance in selecting context-specific assessment metrics and how these can lead to a managable false positive rate. We have shown that the use of fully automated IVD facilitates use on every fraction of treatment. This leads to identification of areas for treatment improvement for both individuals and across a patient cohort, expanding the uses of IVD from simply gross error detection towards treatment optimisation.

Markerless liver online adaptive stereotactic radiotherapy: feasibility analysis

Objective. Radio-opaque markers are recommended for image-guided radiotherapy in liver stereotactic ablative radiotherapy (SABR), but their implantation is invasive. We evaluate in this in-silico study the feasibility of cone-beam computed tomography-guided stereotactic online-adaptive radiotherapy (CBCT-STAR) to propagate the target volumes without implanting radio-opaque markers and assess its consequence on the margin that should be used in that context. Approach. An emulator of a CBCT-STAR-dedicated treatment planning system was used to generate plans for 32 liver SABR patients. Three target volume propagation strategies were compared, analysing the volume difference between the GTVPropagated and the GTVConventional, the vector lengths between their centres of mass (l CoM), and the 95th percentile of the Hausdorff distance between these two volumes (HD95). These propagation strategies were: (1) structure-guided deformable registration with deformable GTV propagation; (2) rigid registration with rigid GTV propagation; and (3) image-guided deformable registration with rigid GTV propagation. Adaptive margin calculation integrated propagation errors, while interfraction position errors were removed. Scheduled plans (PlanNon-adaptive) and daily-adapted plans (PlanAdaptive) were compared for each treatment fraction. Main results. The image-guided deformable registration with rigid GTV propagation was the best propagation strategy regarding to l CoM (mean: 4.3 +/− 2.1 mm), HD95 (mean 4.8 +/− 3.2 mm) and volume preservation between GTVPropagated and GTVConventional. This resulted in a planning target volume (PTV) margin increase (+69.1% in volume on average). Online adaptation (PlanAdaptive) reduced the violation rate of the most important dose constraints (‘priority 1 constraints’, 4.2 versus 0.9%, respectively; p < 0.001) and even improved target volume coverage compared to non-adaptive plans (PlanNon-adaptive). Significance. Markerless CBCT-STAR for liver tumours is feasible using Image-guided deformable registration with rigid GTV propagation. Despite the cost in terms of PTV volumes, daily adaptation reduces constraints violation and restores target volumes coverage.

AAPM WGVRTO report 390: A survey of veterinary radiation oncology equipment and infrastructure in 2022.

Since 2010, there has been little published data on the state of equipment and infrastructure in veterinary radiation oncology clinical practice. These data are important not only to identify the status and use of technology within the veterinary radiation oncology community but also to help identify the extent of medical physics support. The purpose of our study is to report findings from a survey of veterinary radiation oncologists in the USA, Canada, and select centers outside of North America in 2022. A 40-question survey covering topics such as type of radiotherapy equipment, techniques offered, treatment planning systems and dose calculation algorithms, special techniques, board-certified radiation oncologists and residents, and extent of medical physics support was distributed through an online survey tool. Results from 40 veterinary radiation oncology institutions, with equipment explicitly used for veterinary care, suggest that the current state of practice is not dissimilar to what currently exists in human radiation oncology facilities; techniques and technologies commonly employed include flattening filter-free mode megavoltage beams, volumetric arc therapy, daily cone-beam computed tomography, image-guided radiation therapy, and sophisticated dose calculation algorithms. These findings suggest the need for modern radiation oncology acceptance testing, commissioning, and quality assurance programs within the veterinary community. The increase in veterinary radiation oncology residency positions and increasing sophistication of equipment suggests that increased levels of standardized medical physics support would benefit the veterinary radiation oncology community.

Characterization of a novel VenusX orthogonal dual-layer multileaf collimator.

To investigate and characterize the performance of a novel orthogonal dual-layer alpha multileaf collimator (αMLC) mounted on the LinaTech VenusX linac. We evaluated leaf positioning accuracy and reproducibility using an electronic portal imaging device through the picket fence test. The average, interleaf, intraleaf, and leaf tip transmissions of the single and dual layers were measured using an ionization chamber. Square and rhombus fields were used to evaluate the leaf penumbra of αMLC. To investigate the advantages of the orthogonal dual-layer multileaf collimator (MLC) in field shaping, right triangular and circular pattern fields were formed using both the dual layers and single layers of the αMLC. The average maximum positioning deviations of the upper and lower αMLC over 1 year were 0.76±0.09mm and 0.62±0.07mm, respectively. The average transmissions were 1.87%, 1.83%, and 0.03% for the upper-, lower- and dual-layer αMLC, respectively. The maximum interleaf transmissions of the lower- and dual-layer were 2.43% and 0.17%, respectively. The leaf tip transmissions were 9.34% and 0.25%, respectively. The penumbra of the square field was 6.2mm in the X direction and 8.0mm in the Y direction. The average penumbras of the rhombus fields with side lengths of 5 and 10cm were 3.6 and 4.9mm, respectively. For the right triangular and circular fields, the fields shaped by the dual-layer leaves were much closer to the set field than those shaped by single-layer leaves. The dose undulation amplitude of the 50% isodose lines and leaf stepping angle change of the dual-layer leaves were smaller than those of the single-layer leaves. The αMLC benefits from its orthogonal dual-layer design. Leaf transmission, dose undulations at the field edge, and MLC field dependence of the leaf stepping angle of the dual-layer αMLC were remarkably reduced.

Image quality characterization of an ultra-high-speed kilovoltage cone-beam computed tomography imaging system on an O-ring linear accelerator.

The quality of on-board imaging systems, including cone-beam computed tomography (CBCT), plays a vital role in image-guided radiation therapy (IGRT) and adaptive radiotherapy. Recently, there has been an upgrade of the CBCT systems fused in the O-ring linear accelerators called HyperSight, featuring a high imaging performance. As the characterization of a new imaging system is essential, we evaluated the image quality of the HyperSight system by comparing it with Halcyon 3.0 CBCT and providing benchmark data for routine imaging quality assurance. The HyperSight features ultra-fast scan time, a larger kilovoltage (kV) detector, a more substantial kV tube, and an advanced reconstruction algorithm. Imaging protocols in the two modes of operation, treatment mode with IGRT and the CBCT for planning(CBCTp) mode were evaluated and compared with Halcyon 3.0 CBCT. Image quality metrics, including spatial resolution, contrast resolution, uniformity, noise, computed tomography (CT) number linearity, and calibration error, were assessed using a Catphan and an electron density phantom and analyzed with TotalQA software. HyperSight demonstrated substantial improvements in contrast-to-noise ratio and noise in both IGRT and CBCTp modes compared to Halcyon 3.0 CBCT. CT number calibration error of HyperSight CBCTp mode (1.06%) closely matches that of a full CT scanner (0.72%), making it suitable for adaptive planning. In addition, the advanced hardware of HyperSight, such as ultra-fast scan time (5.9s) or 2.5 times larger heat unit capacity, enhanced the clinical efficiency in our experience. HyperSight represented a significant advancement in CBCT imaging. With its image quality, CT number accuracy, and ultra-fast scans, HyperSight has a potential to transform patient care and treatment outcomes. The enhanced scan speed and image quality of HyperSight are expected to significantly improve the quality and efficiency of treatment, particularly benefiting patients.

XTransCT: ultra-fast volumetric CT reconstruction using two orthogonal x-ray projections for image-guided radiation therapy via a transformer network

Objective. The aim of this study was to reconstruct volumetric computed tomography (CT) images in real-time from ultra-sparse two-dimensional x-ray projections, facilitating easier navigation and positioning during image-guided radiation therapy. Approach. Our approach leverages a voxel-sapce-searching Transformer model to overcome the limitations of conventional CT reconstruction techniques, which require extensive x-ray projections and lead to high radiation doses and equipment constraints. Main results. The proposed XTransCT algorithm demonstrated superior performance in terms of image quality, structural accuracy, and generalizability across different datasets, including a hospital set of 50 patients, the large-scale public LIDC-IDRI dataset, and the LNDb dataset for cross-validation. Notably, the algorithm achieved an approximately 300% improvement in reconstruction speed, with a rate of 44 ms per 3D image reconstruction compared to former 3D convolution-based methods. Significance. The XTransCT architecture has the potential to impact clinical practice by providing high-quality CT images faster and with substantially reduced radiation exposure for patients. The model's generalizability suggests it has the potential applicable in various healthcare settings.

Investigating the Dosimetric Leaf Gap Correction Factor of Mobius3D Dose Calculation for Volumetric-modulated Arc Radiotherapy Plans.

The dosimetric leaf gap (DLG) is a parameter for correcting radiation transmission through the round leaf end of multileaf collimators. The purpose of this study was to determine and investigate the optimal DLG correction factor for 6 MV volumetric-modulated arc radiotherapy (VMAT) plan dose calculations in Mobius3D. Seventeen VMAT plans were selected for the DLG correction factor optimization process. The optimal DLG correction factor was defined as the minimum difference between the measured dose and the Mobius3D-calculated dose on the Mobius Verification Phantom™ with different DLG correction factors. Subsequently, the optimal DLG correction factor was applied for Mobius3D dose calculation, and accuracy was assessed by comparing the measured and calculated doses. For verification and validation, the 17 previous plans and 10 newly selected plans underwent Mobius3D calculations with the optimal DLG correction factor, and gamma analysis was performed to compare them to the treatment planning system (TPS). Gamma analysis was also performed between the electronic portal imaging device (EPID) and the TPS for cross-comparison between systems. The DLG correction factor was optimized to -1.252, which reduced the average percentage differences between measured and Mobius3D-calculated doses from 2.23% ±1.21% to 0.03% ±1.82%. The cross-comparison between Mobius3D/TPS and EPID/TPS revealed a similar trend in gamma passing rate (>95%) in both the verification and validation plans. The DLG correction factor strongly influences the accuracy of Mobius3D-calculated doses. Applying the optimal DLG correction factor can increase dose agreement and gamma passing rate between calculation and delivered doses of VMAT plans, which emphasizes the importance of optimizing this factor during the commissioning process.

Evaluation of the Treatment Planning and Delivery for Hip Implant Cases on Tomotherapy.

The metal present in the implant creates artifacts during the treatment simulation, which impacts the treatment planning and delivery of the prescribed dose to the target and sparing normal tissues. This retrospective study evaluated the uncertainties in the planning and delivery of doses for prosthesis cases with dedicated phantom. In this retrospective study, 11 patients with a hip prosthesis having cervix carcinoma were selected. Two treatment plans were generated on treatment planning system (TPS) for each case. Plan_No_Res was without any beam restriction, and Plan_exit_only was the plan with restricted beam entry through the metallic implant. An indigenous phantom was utilized to verify the accuracy of the treatment. In the phantom, some groves were present, which could be filled by implants that mimic the patient's geometries, like left, right and bilateral femur implants. The delivered doses were recorded using optically stimulated luminescence dosimeters (OSLDs), which were placed at different positions in the phantom. The plans were further calculated using megavoltage computed tomography (MVCT) scans acquired during treatment. The patient data showed no significant dose changes between the two planning methods. The treatment time increases from 412.18 ± 86.65 to 427.36 ± 104.80 with P = 0.03 for Plan_No_Res and Plan_exit_only, respectively. The difference between planned and delivered doses of various points across phantom geometries was within ± 9.5% in each case as left, right, and bilateral implant. The variations between OSLDs and MVCT calculated doses were also within ± 10.8%. The study showed the competency of tomotherapy planning for hip prosthesis cases. The phantom measurements demonstrate the errors in dosimetry near the implant material, suggesting the need for precise methods to deal with artifact-related issues.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiation Therapy for Locally Advanced Lung Cancer

Real-time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiation therapy (o-ART) on the ETHOS system with image guided radiation therapy delivery on a Halcyon unit for conventional fractionated radiation therapy of locally advanced lung cancer (LALC). We analyzed 26 patients with LALC treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real-world clinic. Target coverage and organ at risk (OAR) doses were compared between adaptive plans (ADP) and nonadaptive scheduled plans (SCH). Planning robustness was evaluated by the frequency of preplanning goals achieved in ADP plans, stratified by tumor volume change. The AOD workflow was achievable within 30 minutes for most radiation fractions. Over the course of therapy, we observed an average 26.6% ± 23.3% reduction in internal target volume (ITV). Despite these changes, with o-ART, ITV and planning target volume (PTV) coverage (V100%) was 99.2% and 93.9% for all members of the cohort, respectively. This represented a 2.9% and 6.8% improvement over nonadaptive plans (P < .05), respectively. For tumors that grew >10%, V100% was 93.1% for o-ART and 76.4% for nonadaptive plans, representing a median 17.2% improvement in the PTV coverage (P < .05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in nonadaptive plans, this figure was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in the heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. The AOD workflow is efficient and robust in responding to anatomic changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiation therapy.

Validation and Efficiency Evaluation of Automated Quality Assurance Software SunCHECK™ Machine for Mechanical and Dosimetric Quality Assurance.

Recent decades have witnessed transformative advances in radiation physics and computer technology, revolutionizing the precision of radiation therapy. The adoption of intricate treatment techniques such as three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, volumetric-modulated arc therapy, and image-guided radiotherapy necessitates robust quality assurance (QA) programs. This study introduces the SunCHECK™ Machine (SCM), a web-based QA platform, presenting early results from its integration into a comprehensive QA program. linear accelerators (LINAC) demand QA programs to uphold machine characteristics within accepted tolerances. The increasing treatment complexity underscores the need for streamlined procedures. The selection of QA tools is vital, requiring efficiency, accuracy, and alignment with clinic needs, as per recommendations such as the AAPM task group 142 report. The materials and methods section details SCM implementation in various QA aspects, encompassing daily QA (DQA), imaging QA with Catphan, conventional output assessment with a water phantom, and LINAC isocenter verification through the Winston-Lutz test. Challenges in QA processes, such as manual data transcription and limited device integration, are highlighted. Early results demonstrate SCM's significant reduction in QA time, ensuring accuracy and efficiency. Its automation eliminates interobserver variation and human errors, contributing to time savings and near-immediate result publication. SCM's role in consolidating and storing DQA data within a single platform is emphasized, offering potential in resource optimization, especially in resource-limited settings. In conclusion, SCM shows promise for efficient and accurate mechanical and dosimetric QA in radiation therapy. The study underscores SCM's potential to address contemporary QA challenges, contributing to improved resource utilization without compromising quality and safety standards.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 1. Brain and head and neck.

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/β ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

Research on Position Verification of Multi-Leaf Collimator (MLC) and Dose Verification Based on Electronic Portal Imaging Device

A quality control (QC) system based on the electronic portal imaging device (EPID) system was used to realize the Multi-Leaf Collimator (MLC) position verification and dose verification functions on Primus and VenusX accelerators. The MLC positions were calculated by the maximum gradient method of gray values to evaluate the deviation. The dose of images acquired by EPID were reconstructed using the algorithm combining dose calibration and dose calculation. The dose data obtained by EPID and two-dimensional matrix (MapCheck/PTW) were compared with the dose calculated by Pinnacle/TiGRT TPS for passing rate analysis. The position error of VenusX MLC was less than 1 mm. The position error of Primus MLC was significantly reduced after being recalibrated under the instructions of EPID. For the dose reconstructed by EPID, the average passing rates of Primus were 98.86% and 91.39% under the criteria of 3%/3 mm, 10% threshold and 2%/2 mm, 10% threshold, respectively. The average passing rates of VenusX were 98.49% and 91.11%, respectively. The EPID-based accelerator quality control system can improve the efficiency of accelerator quality control and reduce the workload of physicists.

Integrating cine EPID, dynamic delivery, and the off-axis Winston-Lutz test to enhance quality control in multiple brain metastasis stereotactic radiotherapy

PurposeStereotactic radiotherapy (SRT) has transformed cancer treatment, especially for brain metastases. Ensuring accurate SRT delivery is crucial, with the Winston-Lutz test being an important quality control tool. Off-axis Winston-Lutz (OAWL) tests are designed for accuracy assessment, but most are limited to fixed angles and hampered by local-field shifts caused by suboptimal Multi-Leaf Collimator (MLC) positioning. This study introduces a new OAWL approach for quality control in multi-brain-metastasis SRT. Utilizing cine Electronic Portal Imaging Device (EPID) images, it can be used with dynamic conformal arc (DCA) therapy. However, dynamic OAWL (DOAWL) is prone to more local-field shifts due to dynamic MLC movements. A two-step DOAWL is proposed: step 1 calculates local-field shifts using dynamic MLC movements in the beam-eye view data from the Treatment Planning System (TPS), while step 2 processes cine EPID images with an OAWL algorithm to isolate true deviations. MethodsValidation involved an anthropomorphic head phantom with metallic ball-bearings, Varian TrueBeam STx accelerator delivering six coplanar/non-coplanar DCA beams, cine EPID, and ImageJ's OAWL analysis algorithm. ResultsInherent local-field shifts ranged from 0.11 to 0.49 mm; corrected mean/max EPID-measured displacement was 0.34/1.03 mm. Few points exceeded 0.75/1.0-mm thresholds. ConclusionsThis two-step DOAWL test merges cine-EPID acquisitions, DCA, OAWL, and advanced analysis and offers effective quality control for multi-brain-metastasis SRT. Its routine implementation may also improve physicist knowledge of the treatment precision of their machines.

A model that predicts a real-time tumour surface using intra-treatment skin surface and end-of-expiration and end-of-inhalation planning CT images.

To develop a mapping model between skin surface motion and internal tumour motion and deformation using end-of-exhalation (EOE) and end-of-inhalation (EOI) 3D CT images for tracking lung tumours during respiration. Before treatment, skin and tumour surfaces were segmented and reconstructed from the EOE and the EOI 3D CT images. A non-rigid registration algorithm was used to register the EOE skin and tumour surfaces to the EOI, resulting in a displacement vector field that was then used to construct a mapping model. During treatment, the EOE skin surface was registered to the real-time, yielding a real-time skin surface displacement vector field. Using the mapping model generated, the input of a real-time skin surface can be used to calculate the real-time tumour surface. The proposed method was validated with and without simulated noise on 4D CT images from 15 patients at Léon Bérard Cancer Center and the 4D-lung dataset. The average centre position error, dice similarity coefficient (DSC), 95%-Hausdorff distance and mean distance to agreement of the tumour surfaces were 1.29 mm, 0.924, 2.76 mm, and 1.13 mm without simulated noise, respectively. With simulated noise, these values were 1.33 mm, 0.920, 2.79 mm, and 1.15 mm, respectively. A patient-specific model was proposed and validated that was constructed using only EOE and EOI 3D CT images and real-time skin surface images to predict internal tumour motion and deformation during respiratory motion. The proposed method achieves comparable accuracy to state-of-the-art methods with fewer pre-treatment planning CT images, which holds potential for application in precise image-guided radiation therapy.

Estimation of organ and effective doses of CBCT scans of radiotherapy using size-specific field of view (FOV): a Monte Carlo study.

The kV cone beam computed tomography (CBCT) is one of the most common imaging modalities used for image-guided radiation therapy (IGRT) procedures. Additional doses are delivered to patients, thus assessment and optimization of the imaging doses should be taken into consideration. This study aimed to investigate the influence of using fixed and patient-specific FOVs on the patient dose. Monte Carlo simulations were performed to simulate kV beams of the imaging system integrated into Truebeam linear accelerator using BEAMnrc code. Organ and size-specific effective doses resulting from chest and pelvis scanning protocols were estimated with DOSXYZnrc code using a phantom library developed by the National Cancer Institute (NCI) of the US. The library contains 193 (100 male and 93 female) mesh-type computational human adult phantoms, and it covers a large ratio of patient sizes with heights and weights ranging from 150 to 190cm and 40 to 125kg. The imaging doses were assessed using variable FOV of three sizes, small (S), medium (M), and large (L) for each scan region. The results show that the FOV and the patient size played a major role in the scan dose. The average percentage differences (PDs) for doses of organs that were fully inside the different FOVs were relatively low, all within 11% for both protocols. However, doses to organs that were scanned partially or near the FOVs were affected significantly. For the chest protocol, the inclusion of the thyroid in the scan field could give a dose of 1-7mGy/100mAs to the thyroid, compared to 0.4-1mGy/100mAs when it was excluded. Similarly, on average, testes doses could be 6mGy/100mAs for the male pelvis protocol compared to 3mGy/100mAs when it did not lie in the field irradiated. These dose differences resulted in an average increase of up to 27% in the size-specific effective dose of the protocols. Since changing the field size is possible for CBCT scans, the results suggest that patient-specific scanning protocols could be applied for each scan area in a manner similar to that used for CT scans. Adjustment of the FOV size should be subject to the clinical needs, and assist in improving the treatment accuracy. The patient's height and weight might be considered as the main factors upon which, the selection of the appropriate patient-specific protocol is based. This approach should optimize the imaging doses used for IGRT procedures by minimizing doses of a large ratio of patients.

Assessing the adequacy of a 5-mm planning target volume margin for 4D-CT scan-based image-guided radiotherapy for locally advanced carcinoma of the lung

In developed nations, 4D-computed tomography (4D-CT)-based image-guided radiotherapy (IGRT) has become the standard for treating lung carcinoma patients, with the primary goal of achieving disease cure. However, its usage in India remains limited. Here, we compared target volume delineation for radical radiation planning in patients with locally advanced lung carcinoma using helical free-breathing CT (FBCT) and 4D-CT. In addition, we assessed the adequacy of a 5-mm planning target volume (PTV) margin with 4D-CT planning. Fifty patients with locally advanced lung cancer were enrolled in the study. Each patient underwent contouring based on 4D-CT to generate an internal target volume, and a 5-mm PTV margin (PTV_4D) was added for radical radiation. Subsequently, each patient underwent two intensity-modulated radiation therapy (IMRT) plans with comparable planning and optimization parameters. One plan was based on the FBCT-based volume (PTV_3D), while the other was based on the 4D-CT-based volume (PTV_4D). PTV, organ at risk (OAR) dose, and PTV coverage by 95% of the prescribed dose (PTVD 95_3D vs. PTVD 95_4D) were compared between the two schemes. Results revealed that 4D-CT-based planning reduced PTV (mean PTV volume: 539 cc vs. 782 cc) and lowered OAR doses (mean lung dose: 13 Gy vs. 15 Gy; mean esophagus dose: 18.5 Gy vs. 21.15 Gy; mean spinal cord max dose: 35.59 Gy vs. 37.39 Gy). At 3 months after treatment imaging, 40% of the patients showed a complete response, 48% showed a partial response, 4% showed stable disease, and 8% showed progressive disease. In conclusion, 4D-CT-based radiation planning for locally advanced lung carcinoma with a reduced PTV margin of 5 mm can dramatically decrease the PTV and OAR doses without sacrificing PTV coverage compared to FBCT-based planning. However, daily online image guidance or at least a well-defined offline image guidance protocol is recommended when employing such a small PTV margin.

PET/SPECT/Spectral-CT/CBCT imaging in a small-animal radiation therapy platform: A Monte Carlo study-Part II: Biologically guided radiotherapy.

This study addresses the technical gap between clinical radiation therapy (RT) and preclinical small-animal RT, hindering the comprehensive validation of innovative clinical RT approaches in small-animal models of cancer and the translation of preclinical RT studies into clinical practices. The main aim was to explore the feasibility of biologically guided RT implemented within a small-animal radiation therapy (SART) platform, with integrated quad-modal on-board positron emission tomography (PET), single-photon emission computed tomography, photon-counting spectral CT, and cone-beam CT (CBCT) imaging, in a Monte Carlo model as a proof-of-concept. We developed a SART workflow employing quad-modal imaging guidance, integrating multimodal image-guided RT and emission-guided RT (EGRT). The EGRT algorithm was outlined using positron signals from a PET radiotracer, enabling near real-time adjustments to radiation treatment beams for precise targeting in the presence of a 2-mm setup error. Molecular image-guided RT, incorporating a dose escalation/de-escalation scheme, was demonstrated using a simulated phantom with a dose painting plan. The plan involved delivering a low dose to the CBCT-delineated planning target volume (PTV) and a high dose boosted to the highly active biological target volume (hBTV) identified by the 18F-PET image. Additionally, the Bayesian eigentissue decomposition method illustrated the quantitative decomposition of radiotherapy-related parameters, specifically iodine uptake fraction and virtual noncontrast (VNC) electron density, using a simulated phantom with Kidney1 and Liver2 inserts mixed with an iodine contrast agent at electron fractions of 0.01-0.02. EGRT simulations generated over 4,000 beamlet responses in dose slice deliveries and illustrated superior dose coverage and distribution with significantly lower doses delivered to normal tissues, even with a 2-mm setup error introduced, demonstrating the robustness of the novel EGRT scheme compared to conventional image-guided RT. In the dose-painting plan, doubling the dose to the hBTV while maintaining a low dose for the PTV resulted in an organ-at-risk (OAR) dose comparable to the low-dose treatment for the PTV alone. Furthermore, the decomposition of radiotherapy-related parameters in Kidney1 and Liver2 inserts, including iodine uptake fractions and VNC electron densities, exhibited average relative errors of less than 1.0% and 2.5%, respectively. The results demonstrated the successful implementation of biologically guided RT within the proposed quad-model image-guided SART platform, with potential applications in preclinical RT and adaptive RT studies.

Enhancing Image-Guided Radiation Therapy for Pancreatic Cancer: Utilizing Aligned Peak Response Beamforming in Flexible Array Transducers.

To develop ultrasound-guided radiotherapy, we proposed an assistant structure with embedded markers along with a novel alternative method, the Aligned Peak Response (APR) method, to alter the conventional delay-and-sum (DAS) beamformer for reconstructing ultrasound images obtained from a flexible array. We simulated imaging targets in Field-II using point target phantoms with point targets at different locations. In the experimental phantom ultrasound images, image RF data were acquired with a flexible transducer with in-house assistant structures embedded with needle targets for testing the accuracy of the APR method. The lateral full width at half maximum (FWHM) values of the objective point target (OPT) in ground truth ultrasound images, APR-delayed ultrasound images with a flat shape, and images acquired with curved transducer radii of 500 mm and 700 mm were 3.96 mm, 4.95 mm, 4.96 mm, and 4.95 mm. The corresponding axial FWHM values were 1.52 mm, 4.08 mm, 5.84 mm, and 5.92 mm, respectively. These results demonstrate that the proposed assistant structure and the APR method have the potential to construct accurate delay curves without external shape sensing, thereby enabling a flexible ultrasound array for tracking pancreatic tumor targets in real time for radiotherapy.

Abstract 2874: Cancer metabolism in radiation resistance: Complementary roles of O-GlcNAc transferase and PARP1

Abstract The efficacy of image-guided radiotherapy (RT) has been linked to directing increased chromosomal double strand breaks (DSBs) to tumor cells while sparing surrounding normal tissue. DSBs can block cell cycle progression and promote mitotic catastrophe, cell death and senescence. End processing of persistent DSBs releases single strand DNA (ssDNA), driving cGAS/STING signaling and anti-tumor immune response. DSB repair, whether by non-homologous end-joining (NHEJ) or homologous recombination (HR), is a resistance mechanism, supporting cell survival, repopulation and immune evasion. Decades of effort to block DSB repair to enhance benefits of RT has yet to produce approved agents. Toxicity due to lack of cancer specificity may prevent the current generation of targeted agents from reaching the clinic. An answer may come from examining cancer metabolic reprogramming as a determinant of intrinsic radiation resistance. Along with other glucose metabolites, the Warburg effect increases N-acetyl glucosamine (GlcNAc) biosynthesis, which not only supports N-glycosylation but also modification of nucleocytoplasmic proteins by O-GlcNAc transferase (OGT). OGT-dependent O-GlcNAcylation confers radiation resistance, in part by accelerating DSB repair. OGT regulates γH2AX, 53BP1 and BRCA1 foci kinetics and suppresses ssDNA formation at DSB ends, limiting HR but favoring NHEJ for S/G2 DSB repair. Blocking OGT induces radiation sensitization in vitro and in vivo. In cells, OGT inhibition results in hyperresection, persistent RPA and RAD51 foci and accumulation of cytosolic DNA. One mediator may be the histone methyltransferase EZH2, which is rapidly recruited to deposit H3K27me3 at DSBs, promoting NHEJ repair. Irradiation of EZH2 KO cells results in hyperresection that cannot be suppressed by O-GlcNAcylation. Cancer cells may also accumulate NAD+, a substrate for PARP1 incorporated into poly-ADP-ribose to initiate DSB repair. Much like OGT inhibition, blocking PARP1 induces hyperresection and shifts repair toward HR and away from NHEJ. Importantly, increasing O-GlcNAcylation can suppress ssDNA formation even in PARP1 KO cells. In turn, inhibiting PARP1 enhances hyperesection in EZH2 KO cells, leading to a marked increase in cytosolic ssDNA. Our data assign complementary roles for EZH2 and PARP1 in DSB repair pathway choice by independently limiting 5' end resection. This directs DSBs to rapid, imprecise repair by NHEJ over slow and precise repair by HR. An implication is that PARP inhibitor resistance due to the Warburg effect may be mediated by EZH2. Driving hyperresection by targeting O-GlcNAcylation or H3K27 trimethylation along with PARP inhibition may saturate the capacity of HR and produce irreversible damage in cancer cells. Targeting impacts of metabolic reprogramming on DSB repair may not only enhance the therapeutic index of radiation but also sharpen synthetic lethality with HR deficiency. Citation Format: Elena E. Efimova, Sera Averbek, Donald J. Wolfgeher, Ding Wu, Yue Liu, Stephen J. Kron. Cancer metabolism in radiation resistance: Complementary roles of O-GlcNAc transferase and PARP1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2874.