Stereotactic Body Radiotherapy (SBRT) to Localised Prostate Cancer in the Era of MRI-Guided Adaptive Radiotherapy: Doses Delivered in the HERMES Trial Comparing Two- and Five-Fraction Treatments.

HERMES is a phase II trial of MRI-guided daily-adaptive radiotherapy (MRIgART) randomising men with localised prostate cancer to either 2-fractions of SBRT with a boost to the tumour or 5-fraction SBRT. In the context of this highly innovative regime the dose delivered must be carefully considered. The first ten patients recruited to HERMES were analysed in order to establish the dose received by the targets and organs at risk (OARS) in the context of intrafraction motion. A regression analysis was performed to measure how the volume of air within the rectum might further impact rectal dose secondary to the electron return effect (ERE). One hundred percent of CTV target objectives were achieved on the MRI taken prior to beam-on-time. The post-delivery MRI showed that high-dose CTV coverage was achieved in 90% of sub-fractions (each fraction is delivered in two sub-fractions) in the 2-fraction cohort and in 88% of fractions the 5-fraction cohort. Rectal D1 cm3 was the most exceeded constraint; three patients exceeded the D1 cm3 < 20.8 Gy in the 2-fraction cohort and one patient exceeded the D1 cm3 < 36 Gy in the 5-fraction cohort. The volume of rectal gas within 1 cm of the prostate was directly proportional to the increase in rectal D1 cm3, with a strong (R = 0.69) and very strong (R = 0.90) correlation in the 2-fraction and 5-fraction cohort respectively. Dose delivery specified in HERMES is feasible, although for some patients delivered doses to both target and OARs may vary from those planned.

MRI-guided radiotherapy in twenty fractions for localised prostate cancer; results from the MOMENTUM study.

Background and purpose: MRI-guided radiotherapy (MRIgRT) offers multiple potential advantages over CT-guidance. This study examines the potential clinical benefits of MRIgRT for men with localised prostate cancer, in the setting of moderately hypofractionated radiotherapy. We evaluate two-year toxicity outcomes, early biochemical response and patient-reported outcomes (PRO), using data obtained from a multicentre international registry study, for the first group of patients with prostate cancer who underwent treatment on a 1.5 T MR-Linac. Materials and methods: Patients who were enrolled within the MOMENTUM study and received radical treatment with 60 Gy in 20 fractions were identified. PSA levels and CTCAE version 5.0 toxicity data were measured at follow-up visits. Those patients who consented to PRO data collection also completed EQ-5D-5L, EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Results: Between November 2018 and June 2022, 146 patients who had MRIgRT for localised prostate cancer on the 1.5 T MR-Linac were eligible for this study. Grade 2 and worse gastro-intestinal (GI) toxicity was reported in 3 % of patients at three months whilst grade 2 and worse genitourinary (GU) toxicity was 7 % at three months. There was a significant decrease in the median PSA at 12 months. The results from both the EQ-5D-5L data and EORTC global health status scale indicate a decline in the quality of life (QoL) during the first six months. The mean change in score for the EORTC scale showed a decrease of 11.4 points, which is considered clinically important. QoL improved back to baseline by 24 months. Worsening of hormonal symptoms in the first six months was reported with a return to baseline by 24 months and sexual activity in all men worsened in the first three months and returned to baseline at 12 months. Conclusion: This study establishes the feasibility of online-MRIgRT for localised prostate on a 1.5 T MR-Linac with low rates of toxicity, similar to that published in the literature. However, the clinical benefits of MRIgRT over conventional radiotherapy in the setting of moderate hypofractionation is not evident. Further research will focus on the delivery of ultrahypofractionated regimens, where the potential advantages of MRIgRT for prostate cancer may become more discernible.

Myocardial perfusion imaging-derived left ventricular strain: Regional abnormalities associated with transthyretin cardiac amyloidosis.

Background: Transthyretin (ATTR) cardiac amyloidosis is associated with an apical-sparing strain pattern on TTE. We hypothesize that strain indices derived from myocardial perfusion imaging (MPI) can identify this abnormality. Methods: A group with ATTR amyloidosis was compared to age-matched controls with LVH but without amyloidosis who underwent PET or SPECT MPI. Strain values were used to calculate the apical strain index (ASI), apex-to-base ratio (ABR), and ejection fraction to global strain ratio in multiple planes. Results: A direct comparison using Welch's t-tests reveals 6 statistically significant metrics. After regression analysis, the circumferential ASI and ABR at rest remain significantly greater in the ATTR group compared to controls. Conclusion: MPI-derived strain from the circumferential plane at rest may distinguish cardiac amyloidosis from other forms of LVH. If these findings are confirmed with validation studies, routine MPI-derived strain analysis could identify patients with subclinical amyloidosis who may benefit from further testing.

T1-VIBE and STIR MRI of lumbar pars interarticularis injuries in elite athletes: fracture characterisation and potential prognostic indicators.

OBJECTIVES: To assess how pars interarticularis fracture characteristics on T1-VIBE and STIR MRI relate to healing and identify anatomical parameters that may impact healing. MATERIALS AND METHODS: A retrospective review of an MRI series of lumbar pars interarticularis injuries in elite athletes over a 3-year period. Fracture configurations, signal intensities and anatomical parameters were recorded by two radiologists. Statistical analysis employed multilevel mixed-effects linear regressions, adjusted for repeated measures and baseline covariates. RESULTS: Forty-seven lumbar pars interarticularis injuries among 31 athletes were assessed. On final scans for each athlete, 15% (7/47) injuries had worsened, 23% (11/47) remained stable, 43% (20/47) partially healed and 19% (9/47) healed completely. Healing times varied, quickest was 49 days for a chronic fracture in a footballer. Bone marrow oedema signal was highest in worsened fractures, followed by improved, and lowest in stable fractures. As healing progressed, T1-VIBE signal at the fracture line decreased. Bone marrow oedema and fracture line signal peaked at 90-120 days before decreasing until 210-240 days. Fractures with smaller dimensions, more vertical orientation and a longer superior articular facet beneath were significantly associated with better healing (p < 0.05). CONCLUSION: Most diagnosed athletic pars interarticularis injuries improve. Normalising T1-VIBE signal at the fracture line is a novel measurable indicator of bony healing. Contrastingly, bone marrow oedema signal is higher in active fractures irrespective of healing or deterioration. Injuries initially perceived as worsening may be exhibiting the normal osteoclastic phase of healing. Better outcomes favour smaller, vertical fractures with a longer superior articular facet beneath.

Interim Toxicity Analysis From the Randomized HERMES Trial of 2- and 5-Fraction Magnetic Resonance Imaging-Guided Adaptive Prostate Radiation Therapy.

PURPOSE: Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival with no significant effect on genitourinary (GU) and gastrointestinal (GI) toxicity. METHODS AND MATERIALS: HERMES is a single-center noncomparative randomized phase 2 trial in men with intermediate or lower high risk prostate cancer. Patients were allocated (1:1) to 36.25 Gy in 5 fractions over 2 weeks or 24 Gy in 2 fractions over 8 days with an integrated boost to the magnetic resonance imaging (MRI) visible tumor of 27 Gy in 2 fractions. A minimization algorithm with a random element with risk group as a balancing factor was used for participant randomization. Treatment was delivered on the Unity MR-Linac (Elekta AB) with daily online adaption. The primary endpoint was acute GU Common Terminology Criteria for Adverse Events version 5.0 toxicity with the aim of excluding a doubling of the rate of acute grade 2+ GU toxicity seen in PACE. Analysis was by treatment received and included all participants who received at least 1 fraction of study treatment. This interim analysis was prespecified (stage 1 of a 2-stage Simon design) for when 10 participants in each treatment group had completed the acute toxicity monitoring period (12 weeks after radiation therapy). RESULTS: Acute grade 2 GU toxicity was reported in 1 (10%) patient in the 5-fraction group and 2 (20%) patients in the 2-fraction group. No grade 3+ GU toxicities were reported. CONCLUSIONS: At this interim analysis, the rate of GU toxicity in the 2-fraction and 5-fraction treatment groups was found to be below the prespecified threshold (5/10 grade 2+) and continuation of the study to complete recruitment of 23 participants per group was recommended.

Evaluation of non-vendor magnetic resonance imaging sequences for use in bladder cancer magnetic resonance image guided radiotherapy.

Hybrid systems that combine Magnetic Resonance Imaging (MRI) and linear accelerators are available clinically to guide and adapt radiotherapy. Vendor-approved MRI sequences are provided, however alternative sequences may offer advantages. The aim of this study was to develop a systematic approach for non-vendor sequence evaluation, to determine safety, accuracy and overall clinical application of two potential sequences for bladder cancer MRI guided radiotherapy. Non-vendor sequences underwent and passed clinical image qualitative review, phantom quality assurance, and radiotherapy planning assessments. Volunteer workflow tests showed the potential for one sequence to reduce workflow time by 27% compared to the standard vendor sequence.

Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling.

Differentiation of induced pluripotent stem cells to a range of target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs and then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, the organoids expressed ACE2 capable of binding SARS-CoV-2 spike proteins, demonstrating the physiological relevance of the organoids produced. This study presented a rapid production of pulmonary organoids using a multi-germ-layer approach that could be used for studying respiratory-related human conditions.

Pro-Inflammatory Proteins Associated with Frailty and Its Progression-A Longitudinal Study in Community-Dwelling Women.

The complex pathophysiology underlying biological aging creates challenges for identifying biomarkers associated with frailty. This longitudinal, nontargeted proteomics study aimed to identify proteins associated with frailty, particularly the change from nonfrail to frail. The population-based Osteoporosis Prospective Risk Assessment cohort includes women all of whom are 75 years old at inclusion (n = 1044) and reassessed at 80 years (n = 715) and 85 years (n = 382). A deficits in health frailty index (FI) and 92 plasma proteins (Olink CVD-II panel) were available at all ages. The identical age facilitated differentiating chronological and biological aging. Bidirectional analyses, performed cross-sectionally and longitudinally, used regression models controlled for false discovery rate (FDR), across 5- and 10-year time windows and longitudinal mixed models. Frailty outcomes were frailty index, frailty status (frail defined as FI ≥ 0.25), change in frailty index, and change in frailty status, together with protein expression or change in protein expression. Elevated levels of 32 proteins were positively associated with the FI, cross-sectionally at all ages (range: ß-coefficients 0.22-2.06; FDR 0.021-0.024), of which 18 were also associated with frailty status (range: odds ratios 1.40-5.77; FDR 0.022-0.016). Based on the accrued data, eight core proteins (CD4, FGF23, Gal-9, PAR-1, REN, TNFRSF10A TNFRSF11A, and TNFRSF10B) are proposed. A one-unit change in the FI was additively associated with increased protein expression over 5 and 10 years (range: ß-coefficients 0.52-1.59; p < 0.001). Increments in baseline FI consistently associated with a change in protein expression over time (5 years, ß-range 0.05-1.35; 10 years, ß-range 0.51-1.48; all p < 0.001). A one-unit increase in protein expression was also associated with an increased probability of being frail (FI ≥ 0.25) (ß-range: 0.14-0.61). Mirroring the multisystem deterioration that typifies frailty, the proteins and their associated biological pathways reflect pathologies, including the renal system, skeletal homeostasis, and TRAIL-activated apoptotic signaling. The core proteins are compelling candidates for understanding the development and progression of frailty with advancing age, including the intrinsic musculoskeletal component. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction.

Myocardial ischemia reperfusion injury (IRI) in acute coronary syndromes is a condition in which ischemic/hypoxic injury to cells subtended by the occluded vessel continues despite successful resolution of the thrombotic obstruction. For decades, most efforts to attenuate IRI have focused on interdicting singular molecular targets or pathways, but none have successfully transitioned to clinical use. In this work, we investigate a nanoparticle-based therapeutic strategy for profound but local thrombin inhibition that may simultaneously mitigate both thrombosis and inflammatory signaling pathways to limit myocardial IRI. Perfluorocarbon nanoparticles (PFC NP) were covalently coupled with an irreversible thrombin inhibitor, PPACK (Phe[D]-Pro-Arg-Chloromethylketone), and delivered intravenously to animals in a single dose prior to ischemia reperfusion injury. Fluorescent microscopy of tissue sections and 19F magnetic resonance images of whole hearts ex vivo demonstrated abundant delivery of PFC NP to the area at risk. Echocardiography at 24 h after reperfusion demonstrated preserved ventricular structure and improved function. Treatment reduced thrombin deposition, suppressed endothelial activation, inhibited inflammasome signaling pathways, and limited microvascular injury and vascular pruning in infarct border zones. Accordingly, thrombin inhibition with an extraordinarily potent but locally acting agent suggested a critical role for thrombin and a promising therapeutic strategy in cardiac IRI.

Evaluation of therapeutic radiographer contouring for magnetic resonance image guided online adaptive prostate radiotherapy.

BACKGROUND AND PURPOSE: The implementation of MRI-guided online adaptive radiotherapy has facilitated the extension of therapeutic radiographers' roles to include contouring, thus releasing the clinician from attending daily treatment. Following undergoing a specifically designed training programme, an online interobserver variability study was performed. MATERIALS AND METHODS: 117 images from six patients treated on a MR Linac were contoured online by either radiographer or clinician and the same images contoured offline by the alternate profession. Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD) and volume metrics were used to analyse contours. Additionally, the online radiographer contours and optimised plans (n = 59) were analysed using the offline clinician defined contours. After clinical implementation of radiographer contouring, target volume comparison and dose analysis was performed on 20 contours from five patients. RESULTS: Comparison of the radiographers' and clinicians' contours resulted in a median (range) DSC of 0.92 (0.86 - 0.99), median (range) MDA of 0.98 mm (0.2-1.7) and median (range) HD of 6.3 mm (2.5-11.5) for all 117 fractions. There was no significant difference in volume size between the two groups. Of the 59 plans created with radiographer online contours and overlaid with clinicians' offline contours, 39 met mandatory dose constraints and 12 were acceptable because 95 % of the high dose PTV was covered by 95 % dose, or the high dose PTV was within 3 % of online plan. A clinician blindly reviewed the eight remaining fractions and, using trial quality assurance metrics, deemed all to be acceptable. Following clinical implementation of radiographer contouring, the median (range) DSC of CTV was 0.93 (0.88-1.0), median (range) MDA was 0.8 mm (0.04-1.18) and HD was 5.15 mm (2.09-8.54) respectively. Of the 20 plans created using radiographer online contours overlaid with clinicians' offline contours, 18 met the dosimetric success criteria, the remaining 2 were deemed acceptable by a clinician. CONCLUSION: Radiographer and clinician prostate and seminal vesicle contours on MRI for an online adaptive workflow are comparable and produce clinically acceptable plans. Radiographer contouring for prostate treatment on a MR-linac can be effectively introduced with appropriate training and evaluation. A DSC threshold for target structures could be implemented to streamline future training.

Stereotactic Radiosurgery for Spinal Haemangioblastoma: A Retrospective Single-Centre Experience from the United Kingdom.

INTRODUCTION: Haemangioblastoma is a benign, vascular tumour of the central nervous system. Stereotactic radiosurgery (SRS) is increasingly being used as a treatment for spinal lesions to avoid complex surgery, especially in patients with multi-focal tumours associated with von Hippel-Lindau syndrome (VHL). Here, we present the outcomes of patients treated in our centre using a CyberKnife VSI (Accuray, Inc.). METHODS: Retrospective analysis of all patients treated at our institution was conducted. Assessment of radiological response was based upon RANO criteria. Solid and overall tumour progression-free survival (PFS) was calculated using the Kaplan-Meier method. The development of a symptomatic new or enlarging cyst was included in the definition of progression when determining overall PFS. RESULTS: Fourteen tumours in 10 patients were included. Seven patients were male, and nine had VHL. Nine (64%) tumours had an associated cyst. The median (IQR) age at treatment was 45.5 (43.5-53) years. The median gross tumour volume was 0.355cc. Patients received a mean marginal prescribed dose of 9.6 Gy in a single fraction (median maximum dose: 14.3 Gy), which was constrained by spinal cord tolerance. Mean follow-up was 15.4 months. Radiologically, 11 (78.6%) tumours were stable or regressed and three (21.4%) progressed. Eight patients' symptoms improved or were stable, and two worsened, both of which were secondary to cyst enlargement. The 1-year solid-tumour and overall PFS was 92.3% and 75.7%, respectively. All patients were alive at the most recent follow-up. One patient developed grade 1 back pain following treatment. DISCUSSION/CONCLUSION: SRS appears to be a safe and effective treatment for spinal haemangioblastoma. Prospective trials with longer follow-up are required to establish the optimum management.

Interobserver variation of clinical oncologists compared to therapeutic radiographers (RTT) prostate contours on T2 weighted MRI.

The implementation of MRI-guided online adaptive radiotherapy has enabled extension of therapeutic radiographers' roles to include contouring. An offline interobserver variability study compared five radiographers' and five clinicians' contours on 10 MRIs acquired on a MR-Linac from 10 patients. All contours were compared to a "gold standard" created from an average of clinicians' contours. The median (range) DSC of radiographers' and clinicians' contours compared to the "gold standard" was 0.91 (0.86-0.96), and 0.93 (0.88-0.97) respectively illustrating non-inferiority of the radiographers' contours to the clinicians. There was no significant difference in HD, MDA or volume size between the groups.

Individual fascicles of the ankle lateral ligaments and the lateral fibulotalocalcaneal ligament complex can be identified on 3D volumetric MRI.

PURPOSE: Lateral ligament ankle sprains are common and the anatomy on imaging studies is vital for accurate diagnosis. The lateral fibulotalocalcaneal ligament (LFTCL) complex consists of the inferior fascicle of the anterior talofibular ligament (ATFL) which is connected by arciform fibres with the calcaneofibular ligament (CFL). The superior fascicle of ATFL is an independent structure that should be assessed individually. MRI evaluation of these distinct fascicles and the arciform fibres has not been described. The aim of this study is to identify the anatomical relationship of these components of the LFTCL complex in healthy individuals on MRI. METHODS: Thirty ankles from healthy volunteers were imaged using 3D volumetric MRI. The ATFL fascicles and size were evaluated. Presence of arciform fibres connecting the inferior ATFL fascicle and CFL to form the LFTCL complex and anatomical relationship around the lateral ligament complex were assessed. RESULTS: Both the superior and inferior ATFL fascicles were observed in 26 (86.7%) ankles. The superior ATFL fascicle was significantly larger in all specimens (39% longer and 80.7% wider). For the specimens with a single fascicle, this was similar in size to the superior fascicle observed in the other 26 specimens. These measurements were not affected by age or gender. Arciform fibres of the LFTCL complex were identified in 22 (84.6%) specimens with two ATFL fascicles and three (75%) ankles with a single ATFL fascicle. Connecting fibres from the ATFL to PTFL were observed in 19 (63.3%) ankles while connections between the CFL and PTFL were identified in 21 (70%) ankles. Five ankles had a perforating artery visualized in the intervening space between the superior and inferior ATFL fascicles (a branch of the lateral tarsal artery of the dorsalis pedis artery). CONCLUSION: Two distinct ATFL fascicles may be identified in the majority of ankles on MRI. Isolated injury to the superior fascicle identified on MRI may be useful when diagnosing patients presenting with symptoms of subtle instability without overt ankle laxity on clinical examination. The current study is the first to identify the arciform fibres of the LFTCL complex supporting isolated ATFL repair in the presence of intact LFTCL complex. LEVEL OF EVIDENCE: Level III.

Left Ventricular Strain from Myocardial Perfusion PET Imaging: Method Development and Comparison to 2-Dimensional Echocardiography.

This study aimed to develop a measure of longitudinal, radial, and circumferential myocardial strain at rest and regadenoson during pharmacologic stress using 82Rb PET electrocardiography-gated myocardial perfusion imaging (MPI). Methods: We retrospectively identified 80 patients who underwent rest and regadenoson-stress CT attenuation-corrected 82Rb PET and had a standard resting transthoracic echocardiogram (TTE) with global longitudinal strain (GLS) analysis within 3 mo. A method was developed to compute longitudinal, radial, and circumferential strain from PET MPI at stress and rest. PET MPI-derived strain and left ventricular function were compared with resting TTE measures as the clinical reference standard. Interobserver agreement of PET MPI strain and left ventricular ejection fraction processing was reported. Results: Longitudinal strain assessed with resting TTE GLS showed good correlation with PET MPI at stress (r = 0.68, P < 0.001) and rest (r = 0.58, P < 0.001). Resting TTE GLS also correlated with PET MPI radial strain at stress (r = -0.70, P < 0.001) and rest (r = -0.59, P < 0.001) and circumferential strain at stress (r = 0.67, P < 0.001) and rest (r = 0.69, P < 0.001). The left ventricular ejection fraction showed good correlation between resting TTE and PET MPI at stress (r = 0.83, P < 0.001) and rest (r = 0.80, P < 0.001). Bland-Altman analysis indicated positive bias of TTE GLS compared with PET MPI longitudinal strain at stress (mean difference = 5.1%, 95% CI = [-2.5, 12.7]) and rest (mean difference = 4.2%, 95% CI = [-4.3, 12.8]). Reproducibility of PET MPI longitudinal strain showed good agreement at stress (concordance correlation coefficient = 0.73, P < 0.001) and rest (concordance correlation coefficient = 0.74, P < 0.001), with Bland-Altman analysis showing a small bias in the longitudinal direction at stress (mean difference = -0.2%) and rest (mean difference = -1.0%). Conclusion: Strain measured with PET MPI using an automated technique correlated well with resting GLS strain obtained by TTE, and the measure is reproducible. Strain from PET MPI should be investigated further to establish reference ranges and assess its value in routine clinical practice.

Lumbar spine MRI findings in asymptomatic elite male academy footballers: a case series.

BACKGROUND: Understanding common MRI findings may allow clinicians to appreciate the sport-specific effects on the lumbar spine, and to discern clinically significant pathology. Prevalence data regarding radiological abnormalities seen during the surveillance of asymptomatic elite footballers is, therefore, important to help understand injury mechanisms and to prevent associated injuries. The purpose of this study was to evaluate the magnetic resonance imaging (MRI) findings in the lumbar spines of asymptomatic elite male adolescent footballers. METHODS: A prospective case-series study was carried out. MRI was performed using a 3T Siemens Prisma scanner including a 3D VIBE sequence in 18 asymptomatic male elite adolescent footballers recruited from a professional academy in England (mean age 17.8, range 16.9-18.6 years). The images were independently reported by two consultant musculoskeletal radiologists to achieve consensus opinion. Standardised classification criteria were used to assess and report abnormalities descriptively. RESULTS: Fifteen players (15/18, 83%) showed ≥1 abnormalities, included facet degeneration, synovial cysts, disc degeneration, disc herniation, and pars injury. One player (1/18, 6%) had mild (Grade 1) facet joint arthropathy at L4/L5 and 3/18 (16.7%) showing evidence of bilateral facet joint effusions. Three synovial cysts were identified in 2/18 players (11%), 4/18 players (22%) presented asymptomatic pars injuries, with 4 showing a grade 2 subtotal stress fracture and 1 player a grade 4 chronic stress fracture seen on 3D VIBE sequencing. Disc degeneration at one or more levels was demonstrated in 7/18 players (38%). Disc herniation was present in 5/18 players (27%). CONCLUSION: A range of unsuspected findings on MRI of the lumbar spine are common in elite adolescent footballers.

Dosimetric comparison of automatically propagated prostate contours with manually drawn contours in MRI-guided radiotherapy: A step towards a contouring free workflow?

Background: The prostate demonstrates inter- and intra- fractional changes and thus adaptive radiotherapy would be required to ensure optimal coverage. Daily adaptive radiotherapy for MRI-guided radiotherapy can be both time and resource intensive when structure delineation is completed manually. Contours can be auto-generated on the MR-Linac via a deformable image registration (DIR) based mapping process from the reference image. This study evaluates the performance of automatically generated target structure contours against manually delineated contours by radiation oncologists for prostate radiotherapy on the Elekta Unity MR-Linac. Methods: Plans were generated from prostate contours propagated by DIR and rigid image registration (RIR) for forty fractions from ten patients. A two-dose level SIB (simultaneous integrated boost) IMRT plan is used to treat localised prostate cancer; 6000 cGy to the prostate and 4860 cGy to the seminal vesicles. The dose coverage of the PTV 6000 and PTV 4860 created from the manually drawn target structures was evaluated with each plan. If the dose objectives were met, the plan was considered successful in covering the gold standard (clinician-delineated) volume. Results: The mandatory PTV 6000 dose objective (D98% > 5580 cGy) was met in 81 % of DIR plans and 45 % of RIR plans. The SV were mapped by DIR only and for all the plans, the PTV 4860 dose objective met the optimal target (D98% > 4617 cGy). The plans created by RIR led to under-coverage of the clinician-delineated prostate, predominantly at the apex or the bladder-prostate interface. Conclusion: Plans created from DIR propagation of prostate contours outperform those created from RIR propagation. In approximately 1 in 5 DIR plans, dosimetric coverage of the gold standard PTV was not clinically acceptable. Thus, at our institution, we use a combination of DIR propagation of contours alongside manual editing of contours where deemed necessary for online treatments.

Radiation-induced coronary artery disease: a difficult clinical conundrum.

Accelerated coronary artery disease seen following radiation exposure is termed 'radiation-induced coronary artery disease' (RICAD) and results from both the direct and indirect effects of radiation exposure. Long-term data are available from survivors of nuclear explosions and accidents, nuclear workers as well as from radiotherapy patients. The last group is, by far, the biggest cause of RICAD presentation.The incidence of RICAD continues to increase as cancer survival rates improve and it is now the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin's lymphoma and other mediastinal malignancies. RICAD will frequently present atypically or even asymptomatically with a latency period of at least 10 years after radiotherapy treatment. An awareness of RICAD, as a long-term complication of radiotherapy, is therefore essential for the cardiologist, oncologist and general medical physician alike.Prior cardiac risk factors, a higher radiation dose and a younger age at exposure seem to increase a patient's risk ratio of developing RICAD. Significant radiation exposure, therefore, requires a low threshold for screening for early diagnosis and timely intervention.

Risk Factors Associated With New-Onset Myocardial Perfusion Abnormalities in Kidney Transplant Candidates.

The optimal coronary artery disease surveillance strategy for end-stage renal disease patients being evaluated for kidney transplantation is unknown. It is unclear what risk factors are associated with the development of new-onset perfusion abnormalities on serial myocardial perfusion imaging. Potential kidney transplant recipients who underwent 2 myocardial perfusion imaging studies at Emory University Hospital between January 2010 and December 2019 were identified. We assessed the frequency of development of any new perfusion defect and development of moderate to severe ischemia (reversible perfusion defect >10%) on serial imaging. Finally, we identified the clinical and imaging factors associated with new perfusion defects and explored the association between new perfusion defects and all-cause mortality. History of myocardial infarction (MI) and peripheral artery disease was associated with an increased risk of developing a new perfusion defect. History of MI was also associated with the risk of developing moderate-severe ischemia. Female patients were less likely to develop new perfusion defects or moderate-severe ischemia. There was no association between either outcome and all-cause mortality. In conclusion, a history of MI, peripheral artery disease, and male gender are risk factors for developing new perfusion defects, although only the history of MI and male gender predict moderate to severe ischemia. Interval development of any abnormal perfusion is not associated with increased mortality.

Online adaptive radiotherapy for head and neck cancers on the MR linear Accelerator: Introducing a novel modified Adapt-to-Shape approach.

INTRODUCTION: The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS). METHODS: Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans. RESULTS: 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s - 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s - 44 mins 27 s), respectively. CONCLUSIONS: Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL.

High incidence of superficial and deep medial collateral ligament injuries in 'isolated' anterior cruciate ligament ruptures: a long overlooked injury.

PURPOSE: In anterior cruciate ligament (ACL) injuries, concomitant damage to peripheral soft tissues is associated with increased rotatory instability of the knee. The purpose of this study was to investigate the incidence and patterns of medial collateral ligament complex injuries in patients with clinically 'isolated' ACL ruptures. METHODS: Patients who underwent ACL reconstruction for complete 'presumed isolated' ACL rupture between 2015 and 2019 were retrospectively included in this study. Patient's characteristics and intraoperative findings were retrieved from clinical and surgical documentation. Preoperative MRIs were evaluated and the grade and location of injuries to the superficial MCL (sMCL), dMCL and the posterior oblique ligament (POL) recorded. All patients were clinically assessed under anaesthesia with standard ligament laxity tests. RESULTS: Hundred patients with a mean age of 22.3 ± 4.9 years were included. The incidence of concomitant MCL complex injuries was 67%. sMCL injuries occurred in 62%, dMCL in 31% and POL in 11% with various injury patterns. A dMCL injury was significantly associated with MRI grade II sMCL injuries, medial meniscus 'ramp' lesions seen at surgery and bone oedema at the medial femoral condyle (MFC) adjacent to the dMCL attachment site (p < 0.01). Logistic regression analysis identified younger age (OR 1.2, p < 0.05), simultaneous sMCL injury (OR 6.75, p < 0.01) and the presence of bone oedema at the MFC adjacent to the dMCL attachment site (OR 5.54, p < 0.01) as predictive factors for a dMCL injury. CONCLUSION: The incidence of combined ACL and medial ligament complex injuries is high. Lesions of the dMCL were associated with ramp lesions, MFC bone oedema close to the dMCL attachment, and sMCL injury. Missed AMRI is a risk factor for ACL graft failure from overload and, hence, oedema in the MCL (especially dMCL) demands careful assessment for AMRI, even in the knee lacking excess valgus laxity. This study provides information about specific MCL injury patterns including the dMCL in ACL ruptures and will allow surgeons to initiate individualised treatment. LEVEL OF EVIDENCE: III.