Assessment of autoantibodies associated with intravenous immunoglobulin replacement therapy in children with primary immunodeficiency.

While it is known that immunoglobulin replacement therapy (IgRT) used in the treatment of primary immunodeficiency disorders (PIDs) can lead to the passive transfer of autoantibodies, there is no data indicating that these antibodies can cause clinical symptoms in patients. This study aimed to investigate the presence of autoantibodies and their clinical correlation in patients diagnosed with PIDs receiving IgRT. Paediatric patients who were diagnosed with PIDs, and administered IgRT at our immunology clinic between 1 January 2012 and 31 December 2021, were included in the study. The medical records of these patients were retrospectively analysed, and autoantibodies were screened. Autoantibody screening was conducted at least once in 48 cases. Among these cases, 29 cases (60.4%) demonstrated positivity for at least one of the autoantibodies screened in the study. Among these cases, 23 tested positive for anti-TPO, 9 for anti-TG and 2 for both anti-TPO and anti-TG. Only two of these patients were confirmed to have Hashimoto's thyroiditis. In 30 cases, autoantibodies related to Celiac disease (CD) were screened, with at least one being positive in five different cases; CD was not confirmed. The results of our study suggest that passive transfer of autoantibodies to patients with IgRT does not cause any significant clinical findings. In addition, in cases of PID, autoantibodies detected in the blood passed to patients with IgRT can lead to misdiagnosis. Screening for autoantibodies in patients with PID undergoing IgRT may not yield accurate results in terms of detecting autoimmune diseases.

The Evolving Role of Novel Imaging Techniques for Radiotherapy Planning.

The ability to visualise cancer with imaging has been crucial to the evolution of modern radiotherapy (RT) planning and delivery. And as evolving RT technologies deliver increasingly precise treatment, the importance of accurate identification and delineation of disease assumes ever greater significance. However, innovation in imaging technology has matched that seen with RT delivery platforms, and novel imaging techniques are a focus of much research activity. How these imaging modalities may alter and improve the diagnosis and staging of cancer is an important question, but already well served by the literature. What is less clear is how novel imaging techniques may influence and improve practical and technical aspects of RT planning and delivery. In this review, current gold standard approaches to integration of imaging, and potential future applications of bleeding-edge imaging technology into RT planning pathways are explored.

Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis.

INTRODUCTION: Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs. MATERIALS AND METHODS: From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. RESULTS: In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection. CONCLUSION: SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.

Intrafraction organ movement in adaptive MR-guided radiotherapy of abdominal lesions - dosimetric impact and how to detect its extent in advance.

INTRODUCTION: Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs. MATERIALS & METHODS: Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future. RESULTS: A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5-10.5 mm) were detected within a median time of 17.1 min (range 1.6-28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement. CONCLUSION: Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.

Our Experience of OSAKA Regimen (Bladder Preservation) in Patients with Advanced Bladder Cancer.

Introduction and Objectives: OSAKA regimen is a novel bladder preservation therapy involving balloon-occluded selective arterial infusion of radio-sensitizing chemotherapeutic agent with concurrent hemodialysis (HD), followed by radiation therapy. Objectives are to study the feasibility of this novel regimen in patients with advanced cancer bladder (Ca Bladder). Methods: Two patients having advanced Ca Bladder with cisplatin ineligibility and poor performance status were managed with OSAKA regimen. Patients undergo super selective catheterisation of the anterior division of the internal iliac artery, followed by concurrent instillation of cisplatin (100 mg) via microcatheters and hemodialysis. Within 72 h, definitive radiation therapy is given. Image-guided radiation therapy (IGRT) with Helical Tomo using an Accuracy Radixact Tomography machine was used. 60 Gray/30 fractions is given to the bladder and nodes (50 Gray to bladder and nodes plus margin, with a boost of 10 Gray to bladder plus margin). Response is monitored by 3 monthly fluorodeoxyglucose positron emission tomography (FDG PET) imaging. Results: Our first patient tolerated the procedure well and showed a complete response at 3 months of FDG PET imaging, but unfortunately, 1 year of FDG PET showed bony metastases, and the patient was managed accordingly. Our second patient also tolerated the regimen well, showed a complete response at 3 and 12 months of FDG PET imaging, and is under follow-up. Conclusions: The OSAKA regimen, as a bladder preservation strategy, is feasible and safe in selective advanced Ca Bladder patients.

Recommendation for reducing the crystalline lens exposure dose by reducing imaging field width in cone-beam computed tomography for image-guided radiation therapy: an anthropomorphic phantom study.

In cone-beam computed tomography (CBCT) for image-guided radiation therapy (IGRT) of the head, we evaluated the exposure dose reduction effect to the crystalline lens and position-matching accuracy by narrowing one side (X2) of the X-ray aperture (blade) in the X-direction. We defined the ocular surface dose of the head phantom as the crystalline lens exposure dose and measured using a radiophotoluminescence dosimeter (RPLD, GD-352 M) in the preset field (13.6 cm) and in each of the fields when blade X2 aperture was reduced in 0.5 cm increments from 10.0 to 5.0 cm. Auto-bone matching was performed on CBCT images acquired five times with blade X2 aperture set to 13.6 cm and 5.0 cm at each position when the head phantom was moved from - 5.0 to + 5.0 mm in 1.0 mm increment. The maximum reduction rate in the crystalline lens exposure dose was - 38.7% for the right lens and - 13.2% for the left lens when blade X2 aperture was 5.0 cm. The maximum difference in the amount of position correction between blade X2 aperture of 13.6 cm and 5.0 cm was 1 mm, and the accuracy of auto-bone matching was similar. In CBCT of the head, reduced blade X2 aperture is a useful technique for reducing the crystalline lens exposure dose while ensuring the accuracy of position matching.

Clinical physicists' perceptions of weekly chart checks and the potential role for automated image review assessed by structured interviews.

BACKGROUND: This study utilizes interviews of clinical medical physicists to investigate self-reported shortcomings of the current weekly chart check workflow and opportunities for improvement. METHODS: Nineteen medical physicists were recruited for a 30-minute semi-structured interview, with a particular focus placed on image review and the use of automated tools for image review in weekly checks. Survey-type questions were used to gather quantitative information about chart check practices and importance placed on reducing chart check workloads versus increasing chart check effectiveness. Open-ended questions were used to probe respondents about their current weekly chart check workflow, opinions of the value of weekly chart checks and perceived shortcomings, and barriers and facilitators to the implementation of automated chart check tools. Thematic analysis was used to develop common themes across the interviews. RESULTS: Physicists ranked highly the value of reducing the time spent on weekly chart checks (average 6.3 on a scale from 1 to 10), but placed more value on increasing the effectiveness of checks with an average of 9.2 on a 1-10 scale. Four major themes were identified: (1) weekly chart checks need to adapt to an electronic record-and-verify chart environment, (2) physicists could add value to patient care by analyzing images without duplicating the work done by physicians, (3) greater support for trending analysis is needed in weekly checks, and (4) automation has the potential to increase the value of physics checks. CONCLUSION: This study identified several key shortcomings of the current weekly chart check process from the perspective of the clinical medical physicist. Our results show strong support for automating components of the weekly check workflow in order to allow for more effective checks that emphasize follow-up, trending, failure modes and effects analysis, and allow time to be spent on other higher value tasks that improve patient safety.

Image guided radiotherapy in curative treatment for prostate cancer. 5-year results from a randomized controlled trial (RIC-trial).

BACKGROUND: Between 2012 and 2015 we conducted a randomized controlled trial in prostate cancer patients comparing weekly 2-D portal imaging versus daily 3-D verification. AIM: To evaluate the clinical outcomes of image guided radiotherapy by presenting rectal and urinary side effects, health related quality of life and progression free survival after 5-years follow up of a randomized controlled trial. METHODS: We randomized 260 men with intermediate or high-risk prostate cancer to weekly 2-D portal imaging with 15 mm margin from CTV to PTV (Arm A) or daily 3-D cone-beam computer tomography with 7 mm margins (Arm B). Prescribed doses were 78 Gy/39 fractions. All patients received hormonal therapy. Primary end point was patient reported bowel symptoms and secondary outcomes were patient reported urinary symptoms, health- related quality of life and progression free survival. RESULTS: Of the 216 patients available for analyses at 5 years more than 90 % completed patient reported outcome measures. There were no significant differences between study arms for any single items nor scales evaluating bowel symptoms. There were also no differences in self-reported urinary symptoms nor in health-related quality of life. Symptom scores were low in both study arms. Progression free survival was similar in Arm B as compared to arm A (Hazard ratio 1.01; 95 % CI 0.57 to 1.97). CONCLUSIONS: Our results support that both 2-D weekly and 3-D daily image guided radiotherapy are safe and efficient treatments for PC and emphasize the need to evaluate technological progress in clinical trials with long follow-up.

Adaptive Radiotherapy: Next-Generation Radiotherapy.

Radiotherapy, a crucial technique in cancer therapy, has traditionally relied on the premise of largely unchanging patient anatomy during the treatment course and encompassing uncertainties by target margins. This review introduces adaptive radiotherapy (ART), a notable innovation that addresses anatomy changes and optimizes the therapeutic ratio. ART utilizes advanced imaging techniques such as CT, MRI, and PET to modify the treatment plan based on observed anatomical changes and even biological changes during the course of treatment. The narrative review provides a comprehensive guide on ART for healthcare professionals and trainees in radiation oncology and anyone else interested in the topic. The incorporation of artificial intelligence in ART has played a crucial role in improving effectiveness, particularly in contour segmentation, treatment planning, and quality assurance. This has expedited the process to render online ART feasible, lowered the burden for radiation oncology practitioners, and enhanced the precision of dynamically personalized treatment. Current technical and clinical progress on ART is discussed in this review, highlighting the ongoing development of imaging technologies and AI and emphasizing their contribution to enhancing the applicability and effectiveness of ART.

Late orbital radiotherapy combined with intravenous methylprednisolone in the management of long-lasting active graves' orbitopathy: a case report and literature review.

PURPOSE: To present a case and review the literature on Orbital Radiotherapy (OR) combined with intravenous methylprednisolone, focusing on its late application in patients with long-lasting active Graves' Orbitopathy (GO). Additionally, we suggest emerging perspective for future research in this context. METHOD: Relevant literature (randomized controlled studies, retrospective studies and reviews) was explored on PubMed from January 1973 to January 2024, searching "orbital radiotherapy" & "Graves disease". RESULTS: OR is a well-established second-line treatment for moderate-to-severe active GO, providing response rates comparable to glucocorticoids. Its anti-inflammatory effect makes OR particularly suitable for early active GO, and when combined with glucocorticoids, outcomes are synergistically improved. The emergence of the new Volumetric Modulated Arc Image-Guided Radiation Therapy (VMAT-IGRT) technique enables precise radiation delivery to the target, significantly reducing associated toxicity. This technological advancement enhances the feasibility of radiotherapy in benign diseases like GO. A retrospective study indicated that late OR in patients with long-lasting active GO may improve diplopia and visual acuity, decreasing disease activity. Our case report supports this conclusion. CONCLUSIONS: This report and literature review underscores the importance of considering late OR combined with intravenous methylprednisolone as a viable treatment option for GO patients with prolonged disease activity, emphasizing the crucial role of personalized therapy in managing GO. However, further investigations are warranted to validate this approach in cases of long-lasting active GO.

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 190 cm and 40 to 125 kg. 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 1-7 mGy/100 mAs to the thyroid, compared to 0.4-1 mGy/100 mAs when it was excluded. Similarly, on average, testes doses could be 6 mGy/100 mAs for the male pelvis protocol compared to 3 mGy/100 mAs 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.

The effects of mega-voltage CT scan parameters on offline adaptive radiation therapy.

TomoTherapy involves image-guided radiation therapy (IGRT) using Mega-voltage CT (MVCT) for each treatment session. The acquired MVCT images can be utilized for the retrospective assessment of dose distribution. The TomoTherapy provides 18 distinct imaging conditions that can be selected based on a combination of algorithms, acquisition pitch, and slice interval. We investigated the accuracy of dose calculation and deformable image registration (DIR) depending on MVCT scan parameters and their effects on adaptive radiation therapy (ART). We acquired image values for density calibration tables (IVDTs) under 18 different MVCT conditions and compared them. The planning CT (pCT) was performed using a thoracic phantom, and an esophageal intensity-modulated radiation therapy (IMRT) plan was created. MVCT images of the thoracic phantom were acquired under each of the 18 conditions, and dose recalculation was performed. DIR was performed on the MVCT images acquired under each condition. The accuracy of DIR, depending on the MVCT scan parameters, was compared using the mean distance to agreement (MDA) and Dice similarity coefficient (DSC). The dose distribution calculated on the MVCT images was deformed using deformed vector fields (DVF). No significant differences were observed in the results of the 18 IVDTs. The esophageal IMRT plan also showed a small dose difference. Regarding verifying the DIR accuracy, the MDA increased, and the DSC decreased as the acquisition pitch and slice interval increased. The difference between the dose distributions after dose mapping was comparable to that before DIR. The MVCT scan parameters had little effect on ART.

Electromagnetic Transmitter-Based Prostate Gating for Dose-Escalated Linac-Based Stereotactic Body Radiation Therapy: An Evaluation of Intrafraction Motion.

BACKGROUND: Stereotactic Body Radiotherapy (SBRT) is as a standard treatment for prostate cancer (PCa). Tight margins and high dose gradients are needed, and the precise localization of the target is mandatory. Our retrospective study reports our experience regarding the evaluation of intrafraction prostate motion during LINAC-based SBRT evaluated with a novel electromagnetic (EM) tracking device. This device consists of an integrated Foley catheter with a transmitter connected to a receiver placed on the treatment table. METHODS: We analyzed 31 patients who received LINAC-based SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The patients were scheduled to be treated for primary (n = 27) or an intraprostatic recurrent PCa (n = 4). A simulation CT scan was conducted while the patients had a filled bladder (100-150 cc) and an empty rectum, and an EM tracking device was used. The same rectal and bladder conditions were employed during the treatment. The patients received 36.25 Gy delivered over five consecutive fractions on the whole prostate and 40 Gy on the nodule(s) visible via MRI, both delivered with a Simultaneous Integrated Boost approach. The CTV-to-PTV margin was 2 mm for both the identified treatment volumes. Patient positioning was verified with XVI ConeBeam-CT (CBCT) matching before each fraction. When the signals exceeded a 2 mm threshold in any of the three spatial directions, the treatment was manually interrupted. A new XVI CBCT was performed if this offset lasted >20 s. RESULTS: We analyzed data about 155 fractions. The median and mean treatment times, calculated per fraction, were 10 m31 s and 12 m44 s (range: 6 m36 s-65 m28 s), and 95% of the fractions were delivered with a maximum time of 27 m48 s. During treatment delivery, the mean and median number of XVI CBCT operations realized during the treatment were 2 and 1 (range: 0-11). During the treatment, the prostate was outside the CTV-to-PTV margin (2 mm), thus necessitating the stoppage of the delivery +/- a reacquisition of the XVI CBCT for 11.2%, 8.9%, and 3.9% of the delivery time in the vertical, longitudinal, and lateral direction, respectively. CONCLUSIONS: We easily integrated an EM-transmitter-based gating for prostate LINAC-based SBRT into our normal daily workflow. Using this system, a 2 mm CTV-to-PTV margin could be safely applied. A small number of fractions showed a motion exceeding the predefined 2 mm threshold, which would have otherwise gone undetected without intrafraction motion management.

Pseudo-medical image-guided technology based on 'CBCT-only' mode in esophageal cancer radiotherapy.

Purpose To minimize the various errors introduced by image-guided radiotherapy (IGRT) in the application of esophageal cancer treatment, this study proposes a novel technique based on the 'CBCT-only' mode of pseudo-medical image guidance. Methods The framework of this technology consists of two pseudo-medical image synthesis models in the CBCT→CT and the CT→PET direction. The former utilizes a dual-domain parallel deep learning model called AWM-PNet, which incorporates attention waning mechanisms. This model effectively suppresses artifacts in CBCT images in both the sinogram and spatial domains while efficiently capturing important image features and contextual information. The latter leverages tumor location and shape information provided by clinical experts. It introduces a PRAM-GAN model based on a prior region aware mechanism to establish a non-linear mapping relationship between CT and PET image domains.  As a result, it enables the generation of pseudo-PET images that meet the clinical requirements for radiotherapy. Results The NRMSE and multi-scale SSIM (MS-SSIM) were utilized to evaluate the test set, and the results were presented as median values with lower quartile and upper quartile ranges. For the AWM-PNet model, the NRMSE and MS-SSIM values were 0.0218 (0.0143, 0.0255) and 0.9325 (0.9141, 0.9410), respectively. The PRAM-GAN model produced NRMSE and MS-SSIM values of 0.0404 (0.0356, 0.0476) and 0.9154 (0.8971, 0.9294), respectively. Statistical analysis revealed significant differences (p < 0.05) between these models and others. The numerical results of dose metrics, including D98 %, Dmean, and D2 %, validated the accuracy of HU values in the pseudo-CT images synthesized by the AWM-PNet. Furthermore, the Dice coefficient results confirmed statistically significant differences (p < 0.05) in GTV delineation between the pseudo-PET images synthesized using the PRAM-GAN model and other compared methods. Conclusion The AWM-PNet and PRAM-GAN models have the capability to generate accurate pseudo-CT and pseudo-PET images, respectively. The pseudo-image-guided technique based on the 'CBCT-only' mode shows promising prospects for application in esophageal cancer radiotherapy.

Respiratory motion modelling for MR-guided lung cancer radiotherapy: model development and geometric accuracy evaluation.

Objective.Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods.Approach.We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients.Main results.The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm3isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data.Significance.The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating.

Rectal deformation management with IGRT in prostate radiotherapy: Can it be managed with rigid alignment alone?

PURPOSE: It is challenging to achieve appropriate target coverage of the prostate with Image Guided Radiation Therapy (IGRT) while simultaneously constraining rectal doses within planned values when there is significant variability in rectal filling and shape. We investigated if rectum planning goals can be fulfilled using rigid CBCT-based on-board alignment to account for interfraction rectal deformations. METHODS: Delivered rectal doses corresponding to prostate alignment ("PR") and anterior rectum alignment ("AR") for 239 daily treatments from 13 patients are reported. Rectal doses were estimated by rigidly mapping the planned dose on the daily CT derived from the daily CBCT according to respective alignment shifts. Rectum V95% (rV95%) was used for analyses. RESULTS: Compared to "PR", "AR" alignment increased rV95% for an average of 34.4% across all patients. rV95% (cc) averaged over all fractions was significant from planning values for 10/13 patients for "PR" and for 9/13 for "AR". 3/13 patients had reproducible anatomy. Of patients with non-reproducible anatomy, three had dosimetrically more favorable, while seven had less favorable anatomies. Most shift differences (82.3%) between the "PR" and "AR" alignments larger than 2 mm resulted in rV95% changes larger than 2 cc. Most shift differences (82.2%) of 2 mm or less between the "PR" and "AR" alignments resulted in rV95% changes less than 2 cc. The average percentage of fractions among patients in which anterior or posterior shifts for "AR" and "PR" alignment was larger than the PTV margins was 9.1% (0.0%-37.5%) and 1.3% (0%-10%). CONCLUSION: Rectal deformation and subsequent inconsistent interfraction separation between prostate and rectal wall translate into anatomical changes that cannot always be mitigated with rigid alignment. If systematic differences exist due to a non-reproducible planning anatomy, attempts to restore the planned rectal doses through anterior rectum alignment produce rather small improvements and may result in unacceptable target underdosage.

The first clinical implementation of real-time 6 degree-of-freedom image-guided radiotherapy for liver SABR patients.

PURPOSE: Multiple survey results have identified a demand for improved motion management for liver cancer IGRT. Until now, real-time IGRT for liver has been the domain of dedicated and expensive cancer radiotherapy systems. The purpose of this study was to clinically implement and characterise the performance of a novel real-time 6 degree-of-freedom (DoF) IGRT system, Kilovoltage Intrafraction Monitoring (KIM) for liver SABR patients. METHODS/MATERIALS: The KIM technology segmented gold fiducial markers in intra-fraction x-ray images as a surrogate for the liver tumour and converted the 2D segmented marker positions into a real-time 6DoF tumour position. Fifteen liver SABR patients were recruited and treated with KIM combined with external surrogate guidance at three radiotherapy centres in the TROG 17.03 LARK multi-institutional prospective clinical trial. Patients were either treated in breath-hold or in free breathing using the gating method. The KIM localisation accuracy and dosimetric accuracy achieved with KIM + external surrogate were measured and the results were compared to those with the estimated external surrogate alone. RESULTS: The KIM localisation accuracy was 0.2±0.9 mm (left-right), 0.3±0.6 mm (superior-inferior) and 1.2±0.8 mm (anterior-posterior) for translations and -0.1◦±0.8◦ (left-right), 0.6◦±1.2◦ (superior-inferior) and 0.1◦±0.9◦ (anterior-posterior) for rotations. The cumulative dose to the GTV with KIM + external surrogate was always within 5% of the plan. In 2 out of 15 patients, >5% dose error would have occurred to the GTV and an organ-at-risk with external surrogate alone. CONCLUSIONS: This work demonstrates that real-time 6DoF IGRT for liver can be implemented on standard radiotherapy systems to improve treatment accuracy and safety. The observations made during the treatments highlight the potential false assurance of using traditional external surrogates to assess tumour motion in patients and the need for ongoing improvement of IGRT technologies.

A retrospective comparison of setup accuracy from CBCT and SGRT data in breast cancer patients.

INTRODUCTION: Both cone-beam computed tomography (CBCT) and surface-guided radiotherapy (SGRT) are used for breast patient positioning verification before treatment delivery. SGRT may reduce treatment time and imaging dose by potentially reduce the number of CBCT needed. The aim of this study was to compare the displacements resulting in positioning from the Image Guided Radiation Therapy (IGRT) 3D and SGRT methods and to design a clinical workflow for SGRT implementation in breast radiotherapy to establish an imaging strategy based on the data obtained. METHODS: For this study 128 breast cancer patients treated with 42.5 Gy in 16 fractions using 3D conformal radiotherapy with free breathing technique were enroled. A total of 366 CBCT images were evaluated for patient setup verification and compared with SGRT. Image registrations between planning CT images and CBCT images were performed in mutual agreement and in online mode by three health professionals. Student's paired t-test was used to compare the absolute difference in vector shift, measured in mm, for each orthogonal axis (x, y, z) between SGRT and CBCT methods. The multidisciplinary team evaluated a review of the original clinical workflow for SGRT implementation and data about patients treated with the updated workflow were reported. RESULTS: Comparison of the shifts obtained with IGRT and SGRT for each orthogonal axis (for the x-axes the average displacement was 0.9 ± 0.7 mm, y = 1.1 ± 0.8 mm and z = 1.0 ± 0.7 mm) revealed no significant statistical differences (p > 0.05). Using the updated workflow the difference between SGRT and IGRT displacements was <3 mm in 91.4 % of patients with a reduction in total treatment time of approximately 20 %, due to the reduce frequency of the CBCT images acquisition and matching. CONCLUSIONS: This study has shown that IGRT and SGRT agree in positioning patients with breast cancer within a millimetre tolerance. SGRT can be used for patient positioning, with the advantages of reducing radiation exposure and shorter overall treatment time.

[Analysis of Imaging Performance Standards of CBCT X-IGRT System Used in Radiotherapy].

This article briefly describes the imaging performance standards of the kilovolt X-ray image guidance system used in radiotherapy, analyzes the main aspects that should be considered in the image quality of X-IGRT system, and focuses on parameters that should be considered in the imaging performance evaluation criteria of the CBCT X-IGRT. The purpose is to sort out the imaging performance evaluation standards of kilovolt X-IGRT system, clarify the image quality requirements of X-IGRT equipment, and reach a consensus when evaluating the imaging performance of X-IGRT system.

SARS-CoV-2 pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) provides protection in inborn errors of immunity with antibody defects: a real-world experience.

Background: Preventive strategies against severe COVID-19 in Inborn Errors of Immunity (IEI) include bivalent vaccines, treatment with SARS-CoV-2 monoclonal antibodies (mAbs), early antiviral therapies, and pre-exposure prophylaxis (PrEP). Objective: To assess the effectiveness of the PrEP with tixagevimab/cilgavimab (AZD7442) in IEI with primary antibody defects during the COVID-19 Omicron wave. Methods: A six-month prospective study evaluated the SARS-CoV-2 infection rate and the COVID-19 severity in the AZD7442 group, in the no-AZD7442 group, and in a group of patients with a recent SARS-CoV-2 infection (< three months). Spike-specific IgG levels were measured at regular intervals. Results: Six out of thirty-three patients (18%) and 54/170 patients (32%) became infected in the AZD7442 group and in the no-AZD7442 group, respectively. Within 90 days post-administration, the AZD7442 group was 85% less likely to be infected and 82% less likely to have a symptomatic disease than the no-AZD7442 group. This effect was lost thereafter. In the entire cohort, no mortality/hospitalisation was observed. The control group of 35 recently infected patients was 88% and 92% less likely to be infected than the AZD7442 and no-AZD7442 groups. Serum anti-Spike IgG reached the highest peak seven days post-AZD7442 PrEP then decreased, remaining over 1000 BAU/mL 180 days thereafter. Conclusion: In patients with IEI and antibody defects, AZD7442 prophylaxis had a transient protective effect, possibly lost possibly because of the appearance of new variants. However, PrEP with newer mAbs might still represent a feasible preventive strategy in the future in this population.