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Adolescent and young adult (AYA) cancer patients receive palliative medicine consultation at a late stage and face diagnostic delays. Failure to address social determinants of health (SDOH) and AYA-specific needs can adversely impact patient experience. This retrospective observational cohort study used data from chart review to assess the frequency of SDOH impacting AYA patients and setting of initial diagnosis at a US urban safety-net hospital. The association of SDOH variables with delays in treatment, loss of follow-up, and no-shows was tested using Chi-square and t -tests. One hundred seventy five patient charts were reviewed. Sixty-two percent were diagnosed in acute care settings. Substance use disorders, financial, employment, and insurance issues were associated with delayed treatment, with weak to moderate effect sizes. Mental health diagnoses, substance use disorder, homelessness, and financial burdens were associated with patient no-shows, with moderate to large effect sizes. Twenty-five percent of patients received palliative medicine consultation; 70% of these occurred at end of life. This study demonstrates the impact of SDOH on AYA cancer care and the need for policy allowing for intervention on SDOH.

Abstract Objective We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. Methods We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. Results The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. Conclusions SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

Abstract Background The THUNDER-2 phase II single institutional trial investigates the benefits of MRI-guided radiotherapy (MRIgRT) in treating locally advanced rectal cancer (LARC). This study focuses on evaluating the impact of escalating radiation therapy dose in non-responder patients using the Early Tumour Regression Index (ERI) for predicting complete response (CR). The trial’s primary endpoint is to increase the CR rate in non-responders by 10% and assess the feasibility of the delta radiomics-based MRIgRT predictive model. This interim analysis assesses the feasibility and safety of the proposed MRIgRT dose escalation strategy in terms of acute toxicity (gastrointestinal, genitourinary and haematological) and treatment adherence. Methods Stage cT2-3, N0-2, or cT4 patients with anal sphincter involvement, N0-2a, M0, but without high-risk features were enrolled. MRIgRT treatment consisted of a standard dose of 55 Gy to the Gross Tumor Volume (GTV) and mesorectum, and 45 Gy to the mesorectum and drainage nodes in 25 fractions with concomitant chemotherapy. 0.35 T MRI was used for simulation imaging and daily alignment. ERI was calculated at the 10th fraction. Non-responders with an ERI above 13.1 received intensified dose escalation from the 11th fraction, resulting in a total dose of 60.1 Gy. Acute toxicity was assessed using the CTCAE v.5 scale. Results From March 2021 to November 2022, 33 out of the total number of 63 patients to be enrolled (52.4%) were included, with one withdrawal unrelated to treatment. Sixteen patients (50%) underwent dose escalation. Treatment was well tolerated, with only one patient (3.1%) in the standard treatment group experiencing acute Grade 3 diarrhea, proctitis, and cystitis. No significant differences in toxicity were observed between the two groups (p = 0.5463). Conclusions MRIgRT treatment with dose escalation up to 60.1 Gy is well tolerated in LARC patients predicted as non-responders by ERI, confirming the feasibility and safety of this approach. The THUNDER-2 trial’s primary and secondary endpoints will be fully analyzed when all planned patients will be enrolled.

PurposeMagnetic resonance imaging (MRI)-guided radiotherapy enables adaptive treatment plans based on daily anatomical changes and accurate organ visualization. However, the bias field artifact can compromise image quality, affecting diagnostic accuracy and quantitative analyses. This study aims to assess the impact of bias field correction on 0.35 T pelvis MRIs by evaluating clinical anatomy visualization and generative adversarial network (GAN) auto-segmentation performance.Materials and methods3D simulation MRIs from 60 prostate cancer patients treated on MR-Linac (0.35 T) were collected and preprocessed with the N4ITK algorithm for bias field correction. A 3D GAN architecture was trained, validated, and tested on 40, 10, and 10 patients, respectively, to auto-segment the organs at risk (OARs) rectum and bladder. The GAN was trained and evaluated either with the original or the bias-corrected MRIs. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95th) were computed for the segmented volumes of each patient. The Wilcoxon signed-rank test assessed the statistical difference of the metrics within OARs, both with and without bias field correction. Five radiation oncologists blindly scored 22 randomly chosen patients in terms of overall image quality and visibility of boundaries (prostate, rectum, bladder, seminal vesicles) of the original and bias-corrected MRIs. Bennett’s S score and Fleiss’ kappa were used to assess the pairwise interrater agreement and the interrater agreement among all the observers, respectively.ResultsIn the test set, the GAN trained and evaluated on original and bias-corrected MRIs showed DSC/HD95th of 0.92/5.63 mm and 0.92/5.91 mm for the bladder and 0.84/10.61 mm and 0.83/9.71 mm for the rectum. No statistical differences in the distribution of the evaluation metrics were found neither for the bladder (DSC: p = 0.07; HD95th: p = 0.35) nor for the rectum (DSC: p = 0.32; HD95th: p = 0.63). From the clinical visual grading assessment, the bias-corrected MRI resulted mostly in either no change or an improvement of the image quality and visualization of the organs’ boundaries compared with the original MRI.ConclusionThe bias field correction did not improve the anatomy visualization from a clinical point of view and the OARs’ auto-segmentation outputs generated by the GAN.

Interventional radiotherapy (IRT, brachytherapy) is a highly effective treatment method for non-melanoma skin cancer (NMSC). Traditionally, the maximum depth of NMSC lesions considered eligible for contact IRT was 5 mm; however, following several national surveys and recent recommendations, such cut-off, lesions thicker than 5 mm may be treated by contact IRT. The use of image guidance in defining the actual depth in treating NMSC to correctly identify clinical target volume (CTV) and prevent unnecessary toxicity is of paramount importance. The aim of the paper was to describe a multilayer arrangement of catheters to treat NMSC lesions thicker than 5 mm, thus proposing an example of dynamic intensity modulated IRT, using different catheter-to-skin distance of sources to reach the best CTV coverage and maximally reduce the excess of dose to the skin.

IntroductionPatients treatment compliance increases during free-breathing (FB) treatment, taking generally less time and fatigue with respect to deep inspiration breath-hold (DIBH). This study quantifies the gross target volume (GTV) motion on cine-MRI of apical lung lesions undergoing a SBRT in a MR-Linac and supports the patient specific treatment gating pre-selection.Material and methodsA total of 12 patients were retrospectively enrolled in this study. During simulation and treatment fractions, sagittal 0.35 T cine-MRI allows real-time GTV motion tracking. Cine-MRI has been exported, and an in-house developed MATLAB script performed image segmentation for measuring GTV centroid position on cine-MRI frames. Motion measurements were performed during the deep inspiration phase of DIBH patient and during all the session for FB patient. Treatment plans of FB patients were reoptimized using the same cost function, choosing the 3 mm GTV-PTV margin used for DIBH patients instead of the original 5 mm margin, comparing GTV and OARs DVH for the different TP.ResultsGTV centroid motion is

Introduction: Recent views posit that precise control of the interceptive timing can be achieved by combining on-line processing of visual information with predictions based on prior experience. Indeed, for interception of free-falling objects under gravity’s effects, experimental evidence shows that time-to-contact predictions can be derived from an internal gravity representation in the vestibular cortex. However, whether the internal gravity model is fully engaged at the target motion outset or reinforced by visual motion processing at later stages of motion is not yet clear. Moreover, there is no conclusive evidence about the relative contribution of internalized gravity and optical information in determining the time-to-contact estimates.Methods: We sought to gain insight on this issue by asking 32 participants to intercept free falling objects approaching directly from above in virtual reality. Object motion had durations comprised between 800 and 1100 ms and it could be either congruent with gravity (1 g accelerated motion) or not (constant velocity or -1 g decelerated motion). We analyzed accuracy and precision of the interceptive responses, and fitted them to Bayesian regression models, which included predictors related to the recruitment of a priori gravity information at different times during the target motion, as well as based on available optical information.Results: Consistent with the use of internalized gravity information, interception accuracy and precision were significantly higher with 1 g motion. Moreover, Bayesian regression indicated that interceptive responses were predicted very closely by assuming engagement of the gravity prior 450 ms after the motion onset, and that adding a predictor related to on-line processing of optical information improved only slightly the model predictive power.Discussion: Thus, engagement of a priori gravity information depended critically on the processing of the first 450 ms of visual motion information, exerting a predominant influence on the interceptive timing, compared to continuously available optical information. Finally, these results may support a parallel processing scheme for the control of interceptive timing.

IntroductionContouring of gas pockets is a time consuming step in the workflow of adaptive radiotherapy. We would like to better understand which gas pockets electronic densitiy should be used and the dosimetric impact on adaptive MRgRT treatment.Materials and methods21 CT scans of patients undergoing SBRT were retrospectively evaluated. Anatomical structures were contoured: Gross Tumour Volume (GTV), stomach (ST), small bowel (SB), large bowel (LB), gas pockets (GAS) and gas in each organ respectively STG, SBG, LBG. Average HU in GAS was converted in RED, the obtained value has been named as Gastrointestinal Gas RED (GIGED). Differences of average HU in GAS, STG, SBG and LBG were computed. Three treatment plans were calculated editing the GAS volume RED that was overwritten with: air RED (0.0012), water RED (1.000), GIGED, generating respectively APLAN, WPLAN and the GPLAN. 2-D dose distributions were analyzed by gamma analysis. Parameter called active gas volume (AGV) was calculated as the intersection of GAS with the isodose of 5% of prescription dose.ResultsAverage HU value contained in GAS results to be equal to -620. No significative difference was noted between the average HU of gas in different organ at risk. Value of Gamma Passing Rate (GPR) anticorrelates with the AGV for each plan comparison and the threshold value for GPR to fall below 90% is 41, 60 and 139 cc for WPLANvsAPLAN, GPLANvsAPLAN and WPLANvsGPLAN respectively.DiscussionsGIGED is the right RED for Gastrointestinal Gas. Novel AGV is a useful parameter to evaluate the effect of gas pocket on dose distribution.

Abstract Background Mesorectal motion (MM) is a source of uncertainty during neoadjuvant chemoradiotherapy (nCRT) delivery for locally advanced rectal cancer (LARC). Previously published experiences using cone-beam computed tomography imaging have already described significant movement. Aim of this analysis is to assess inter-fraction MM using the higher tissue contrast provided by hybrid magnetic resonance imaging (MRI) in LARC patients (pts) treated with MRI guided radiation therapy (MRgRT). Methods The total mesorectum, its superior (Msup), middle (Mmid) and lower (Mlow) regions were contoured on the positioning MRIs acquired on simulation day and on each treatment day. Six PTVs were obtained adding 0.5, 0.7, 1, 1.3, 1.5 and 2 cm margin to the whole mesorectum, starting from the simulation MRI. Margins including 95% of the mesorectal structures during whole treatment in 95% of patients (pts) were considered adequate. Results A total number of 312 fractions of 12 consecutive pts was retrospectively analyzed. The different mesorectum regions show specific motion variability. In particular, Msup shows larger variability in left, right and anterior directions, while the Mlow in caudal and posterior ones. The anterior margin is significantly larger in the Msup than in the other regions. Conclusion Different mesorectal regions move differently throughout the radiotherapy treatment, with the largest MM in the Msup anterior direction. Asymmetrical margins are recommended.

(1) Background: In 90Y-TARE treatments, lung-absorbed doses should be calculated according to the manufacturer’s instructions, using the MIRD-scheme. This scheme is derived from the assumption that 90Y-microspheres deliver the dose in a water-equivalent medium. Since the density of the lungs is quite different from that of the liver, the absorbed dose to the lungs could vary considerably, especially at the liver/lungs interface. The aim of this work is to compare the dosimetric results obtained by two dedicated software packages implementing a water-equivalent dose calculation and a Monte Carlo (MC) simulation, respectively. (2) Methods: An anthropomorphic IEC phantom and a retrospective selection of 24 patients with a diagnosis of HCC were taken into account. In the phantom study, starting from a 90Y-PET/CT acquisition, the liver cavity was manually fixed with a uniform activity concentration on PET series, while the lung compartment was manually expanded on a CT series to simulate a realistic situation in which the liver and lungs are adjacent. These steps were performed by using MIM 90Y SurePlan. Then, a first simulation was carried out with only the liver cavity filled, while a second one was carried out, in which the lung compartment was also manually fixed with a uniform activity concentration corresponding to 10% lung shunt fraction. MIM 90Y SurePlan was used to obtain Voxel S-Value (VSV) approach dose values; instead, Torch was used to obtain MC approach dose values for both the phantom and the patients. (3) Results: In the phantom study, the percentage mean dose differences (∆D%) between VSV and MC in the first and second simulation, respectively were found to be 1.2 and 0.5% (absolute dose variation, ∆D, of 0.7 and 0.3 Gy) for the liver, −56 and 70% (∆D of −0.3 and −16.2 Gy) for the lungs, and −48 and −60% (∆D of −4.3 and −16.5 Gy) for the Liver/Lungs Edge region. The patient study reports similar results with ∆D% between VSV and MC of 7.0%, 4.1% and 6.7% for the whole liver, healthy liver, and tumor, respectively, while the result was −61.2% for the left lung and −61.1% for both the right lung and lungs. (4) Conclusion: Both VSV and MC allowed accurate radiation dose estimation with small differences (50%) were observed for air-equivalent regions in the phantom simulation and the patient study.

Abstract Objective Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and 6 months) but no HF. Methods This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752). Results 16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054). Conclusions SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752

Agoraphobia is a visuo-vestibular-spatial disorder that may involve dysfunction of the vestibular network, which includes the insular and limbic cortex. We sought to study the neural correlates of this disorder in an individual who developed agoraphobia after surgical removal of a high-grade glioma located in the right parietal lobe, by assessing pre- and post-surgery connectivities in the vestibular network. The patient underwent surgical resection of the glioma located within the right supramarginal gyrus. The resection interested also portions of the superior and inferior parietal lobe. Structural and functional connectivities were assessed through magnetic resonance imaging before and 5 and 7 months after surgery. Connectivity analyses focused on a network comprising 142 spherical regions of interest (4 mm radius) associated with the vestibular cortex: 77 in the left and 65 in the right hemisphere (excluding lesioned regions). Tractography for diffusion-weighted structural data and correlation between time series for functional resting-state data were calculated for each pair of regions in order to build weighted connectivity matrices. Graph theory was applied to assess post-surgery changes in network measures, such as strength, clustering coefficient, and local efficiency. Structural connectomes after surgery showed a decrease of strength in the preserved ventral portion of the supramarginal gyrus (PFcm) and in a high order visual motion area in the right middle temporal gyrus (37dl), and decrease of the clustering coefficient and of the local efficiency in several areas of the limbic, insular cortex, parietal and frontal cortex, indicating general disconnection of the vestibular network. Functional connectivity analysis showed both a decrease in connectivity metrics, mainly in high-order visual areas and in the parietal cortex, and an increase in connectivity metrics, mainly in the precuneus, parietal and frontal opercula, limbic, and insular cortex. This post-surgery reorganization of the vestibular network is compatible with altered processing of visuo-vestibular-spatial information, yielding agoraphobia symptoms. Specifically, post-surgical functional increases of clustering coefficient and local efficiency in the anterior insula and in the cingulate cortex might indicate a more predominant role of these areas within the vestibular network, which could be predictive of the fear and avoiding behavior characterizing agoraphobia.

Abstract Cities have always been the place where 'diversity' has settled, within a substantial ethnic, cultural, religious and linguistic identity. The author's emphasis on the need for a cultural policy on migration and welcoming not in 'moral' terms but in relation to a mutual interest between different peoples and cultures. A policy which highlights 'diversity' and allows for peaceful coexistence and sharing, provides the basis for what can be called a policy of coexistence, or a strategy for coexistence. Such a policy can only be the result of a collective debate and effort which can propose new ideas of citizenship.

IntroductionMonomorphic ventricular tachycardia (VT) is a life-threatening condition often observed in patients with structural heart disease. Ventricular tachycardia ablation through radiation therapy (VT-ART) for sustained monomorphic ventricular tachycardia seems promising, effective, and safe. VT-ART delivers focused, high-dose radiation, usually in a single fraction of 25 Gy, allowing ablation of VT by inducing myocardial scars. The procedure is fully non-invasive; therefore, it can be easily performed in patients with contraindications to invasive ablation procedures. Definitive data are lacking, and no direct comparison with standard procedures is available.DiscussionThe aim of this multicenter observational study is to evaluate the efficacy and safety of VT-ART, comparing the clinical outcome of patients undergone to VT-ART to patients not having received such a procedure. The two groups will not be collected by direct, prospective accrual to avoid randomization among the innovative and traditional arm: A retrospective selection through matched pair analysis will collect patients presenting features similar to the ones undergone VT-ART within the consortium (in each center independently). Our trial will enroll patients with optimized medical therapy in whom endocardial and/or epicardial radiofrequency ablation (RFA), the gold standard for VT ablation, is either unfeasible or fails to control VT recurrence. Our primary outcome is investigating the difference in overall cardiovascular survival among the group undergoing VT-ART and the one not exposed to the innovative procedure. The secondary outcome is evaluating the difference in ventricular event-free survival after the last procedure (i.e., last RFA vs. VT-ART) between the two groups. An additional secondary aim is to evaluate the reduction in the number of VT episodes comparing the 3 months before the procedure to the ones recorded at 6 months (from the 4th to 6th month) following VT-ART and RFA, respectively. Other secondary objectives include identifying the benefits of VT-ART on cardiac function, as evaluated through an electrocardiogram, echocardiographic, biochemical variables, and on patient quality of life. We calculated the sample size (in a 2:1 ratio) upon enrolling 149 patients: 100 in the non-exposed control group and 49 in the VT-ART group. Progressively, on a multicentric basis supervised by the promoting center in the VT-ART consortium, for each VT-ART patient enrollment, a matched pair patient profile according to the predefined features will be shared with the consortium to enroll a patient that has not undergone VT-ART.ConclusionOur trial will provide insight into the efficacy and safety of VT-ART through a matched pair analysis, via an observational, multicentric study of two groups of patients with or without VT-ART in the multicentric consortium (with subgroup stratification into dynamic cohorts).