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Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma. MCNPX calculations of out-of-field doses were done for ∼20 different organs considering realistic treatment plans and using computational phantoms representative of an adult male individual. Simulations showed higher secondary neutron doses for intracranial treatments, ∼14 mGy to the salivary glands, when compared with ocular treatments, ∼0.6 mGy to the non-treated eye. This secondary dose increase is mainly due to the higher proton beam energy (178 vs. 75 MeV) as well as to the impact of the different beam parameters (modulation, collimation, field size etc.). Moreover, when compared with published data, the assessed secondary neutron doses showed similar trends, but sometimes with sensitive differences. This confirms secondary neutrons to be directly dependent on beam energy, modulation technique, treatment configuration and methodology. [ABSTRACT FROM AUTHOR]

Following modifications on the beam line at the Orsay Protontherapy Center, dose measurements were performed in order to make a dose map in the treatment rooms and in the delimited radiation-controlled area around beam line. Measurements were performed using tissue-equivalent proportional counters and rem-counters. Analysis of TEPC single event measurements showed that high LET components (>10 keV.µm-1) represent 90 to 99% of total dose equivalent in the treatment rooms and 50 to 90% in the controlled area and quality factors range, respectively between 2 and 15. A fast neutron component was identified in the treatment rooms, where dose equivalent rate varied between few µSv.h-1 to some dozen of mSv.h-1. In high-energy radiation field rem-counters underestimated TEPC values for neutron component. The variation between instruments response according to the location is linked to energetic spectrum variations and instrument characteristics. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate practice patterns for patients with clinically node negative T2 or T3 muscle invasive bladder cancer. The NCDB Bladder cancer database was analyzed using statistical software in February-March 2024. Data from 773,366 cases from years 2004-2020 were available for analysis. The cohort was analyzed for pattern of initial therapy between either cystectomy or chemoradiation. Further analysis was performed by analyzing radiation therapy treatment information and stratifying patients based on dose/fractionation courses. Patients undergoing a course of EBRT with 55Gy in 20 fractions were considered as hypo-fractionated with remaining dose and fractionation combinations considered as not hypo-fractionated. Descriptive statistics were generated analyzing trends in local therapy, hypofractionation, concurrent chemotherapy (single agent vs. multi-agent or unspecified) and EBRT techniques (IMRT vs. not IMRT) over time. Of the 773,366 cases available in the dataset, 95,225 cases of clinical T2N0M0 or T3N0M0 transitional cell carcinoma of bladder primary were identified. 90.6% of cases were clinically T2 while 9.4% were clinically T3. Mean age at time of diagnosis was 73, [median age 74, 16-90]. 73.6% of patients were denoted Male and 26.4% Female. 90.4% were White race and 6.4% were Black race. In total, 47,441 (49.9%) of the patients did not receive definitive therapy while 40,422 (42.5%) underwent cystectomy and 7,226 (7.6%) underwent chemoRT. From 2013 to 2020 hypofractionation use increased from 1% to 15.2%. 141 of 270 (52.2%) patients treated with hypofractionation were treated at an Academic/Research program. Utilization of single agent concurrent chemotherapy increased from 46% to 61.1% in 2020. IMRT use increased from 7.5% in 2004 to 66.5% in 2020. Definitive treatment for MIBC remains underutilized with 50% of patients receiving curative intent treatment in 2020. Adoption and utilization of hypofractionation for T2 or T3N0 MIBC is increasing over time with wider adoption. [ABSTRACT FROM AUTHOR]

A hybrid experimental modeling approach for floating offshore wind turbines (FOWTs) in a wave tank is presented. The method called real-time hybrid method (RTHM) or software-in-the-loop (SIL) includes physically reproduced hydrodynamic loads in the wave tank, with a Froude-scaled model while aerodynamic loads are reproduced on the model by an actuator. The force is applied on the tower top and calculated by a numerical simulation running in real-time as a function of the measured velocity and position of the physical model. Couplings between the platform motion, the aerodynamic loads and the wind turbine controller are hence accounted for. A new SIL actuator enabling the reproduction of a multi-component force at the tower top of an experimental scaled wind turbine model is developed, and the quantification of the accuracy of the replicated forces is studied. The test case includes a floating spar platform carrying a 10 MW horizontal axis wind turbine. The results show that this SIL actuator can accurately replicate the low and wave-frequency aerodynamic loads, which are essential for wave tank testing. Lastly, a case study of the wind turbine model in colinear and misaligned wind and wave conditions is presented, showing 3D forces and induced motions. [Display omitted] • Software-in-the-loop (SIL) approach for wave tank testing of FOWTs. • Design of a new multi-component force actuator to reproduce rotor loads. • Quantification of the accuracy of the force reproduction with closed-loop control. • Application to the analysis of a FOWT in aligned and misaligned wind and waves. [ABSTRACT FROM AUTHOR]

Floating marine structures implement real-time wave excitation force prediction to address optimal control issues. The accuracy of force prediction relies on adequate wave forecasting. This paper presents a comprehensive analysis of deterministic wave forecasting by considering various wave steepnesses and directional spreads. In addition, we introduce new methods for predicting wave excitation forces acting on the floating body of interest. The methods are based on a set of frequency coefficients of wave excitation forces, which are generated in conjunction with wave amplitude parameters optimized in the data assimilation and frequency response functions obtained from boundary element method tools. These approaches offer the advantage of streamlining the calculation process, eliminating the need for simulating wave surfaces through wave propagation. Moreover, for the first time, we study a prediction zone for wave excitation forces by comparing predicted forces with theoretical forces. Lastly, the force prediction is validated against experiments conducted on a captive platform model in both unidirectional and multidirectional sea states. [ABSTRACT FROM AUTHOR]

Trimodality therapy (TMT) with maximal TURBT followed by chemoradiation (CRT) is a category 1 bladder preservation treatment option for patients with non-metastatic muscle invasive bladder cancer (MIBC). Radiation therapy increases PD-L1 expression in bladder cancer. This trial evaluates the activity of atezolizumab (atezo) in MIBC in combination with TMT. This trial was designed with pre-specified safety analyses of the first 80 patients (40 in each arm). The previous analyses did not show any significant increase in toxicity and DSMC recommended to proceed with further enrollment. This is the updated safety report of 213 patients. This is a randomized phase III trial testing atezo every 3 weeks for 6 months given concurrently and adjuvantly with TMT vs. TMT alone in 432 eligible patients with MIBC (T2-T4aN0M0). Patients are stratified based on performance status; T2 vs T3 or T4; choice of chemotherapy; and radiation field (bladder only vs small pelvis). Patients undergo biopsy 3 months after finishing CRT to assess treatment response and are followed for 5 years for bladder intact event free survival. 100 patients were randomized to the TMT alone (control) arm and 113 patients to the TMT+ atezo arm. Patient characteristics for the atezo vs control arm are: Median age (75 vs 72), T2 (82% vs 81%), chemotherapy regimen: cisplatin (48% vs 50%), 5-fluorouracil/mitomycin (15% vs 13%), gemcitabine (37% vs 37%), radiation field including small pelvis (57% vs 58%), bladder only (43% vs 42%), performance status 0-1 (96% vs 95%). Two patients in each arm reported grade 3 diarrhea. Two patients had grade 3 cystitis in the atezo arm as compared to 1 patient in the control arm. Only 1 patient had treatment related grade 3 radiation cystitis confirmed by cystoscopy and biopsy and continued atezo without worsening of symptoms. Overall, 65 patients reported treatment related grade 3 or higher toxicity events in the atezo arm vs 44 in control arm (57% vs 44%). Most common toxicity was hematological (43% vs 36%) which was considered non-immune related. Other Grade 3 or higher known immune related AEs (irAE's) of atezo like pancreatitis (1), rash (1), acute kidney Injury (2), gastritis (1), transaminitis (1), & dyspnea (1) were observed in the atezo arm. Table1. Toxicities observed were numerically higher in the atezo arm. One reason could be that more eligible patient data were available from the atezo arm (113 vs100). Most of them were hematological toxicities which did not require holding atezo and were considered non-immune related by the treating provider. Known irAE's were observed in the atezo arm. The trial is expected to finish accrual in next two years and this update demonstrates no safety concerns. [ABSTRACT FROM AUTHOR]

High-grade cT1 (HGT1) urothelial carcinoma of the bladder (UC) is an aggressive disease with a 4-year cancer-specific mortality of 36% in a large cystectomy series. NCCN guidelines recommend radical cystectomy as the preferred treatment for patients with (1) BCG-naive HGT1 with high-risk features or (2) for HGT1 disease that is BCG unresponsive or intolerant. Definitive concurrent chemoradiotherapy (CRT) has emerged as a promising bladder-sparing alternative treatment for HGT1 with the recent presentation of the single-arm RTOG 0926 trial. However, while there is level 1 evidence that CRT is superior to radiotherapy (RT) alone for muscle-invasive bladder cancer (MIBC), there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT for patients with HGT1 bladder cancer. Patients with cT1N0M0, high-grade urothelial carcinoma diagnosed between 2004-2017 and treated with transurethral resection of the bladder tumor followed by RT alone or concurrent CRT were identified in the National Cancer Database (NCDB). All patient received a cumulative RT dose ≥ 50 Gy. Patients with a Charlson-Deyo comorbidity index (CDCI) score > 1 or missing key information were excluded. Propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) between groups. Covariables included age, race, ethnicity, gender, year of diagnosis, CDCI score, insurance status, educational and socioeconomic metrics, and treatment at an academic center. A total of 192 patients with HGT1 UC were treated with: (i) RT alone (n = 78) or (ii) CRT (n = 114). Median age was 81 (range: 50-90), and 70% were male. The median tumor size was 4.0 cm (range: 0.4-10.5 cm). The median follow-up time was 46 months (range: 10-168 months). The mean radiation dose was 62.4 Gy (SD: ±5 Gy) and 63.2 Gy (SD: ±12 Gy) in the RT and CRT cohorts, respectively. Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone [Hazard Ratio (HR): 0.56, 95% Confidence Interval (95% CI): 0.36-0.89, p = 0.012]. Female gender was associated with worse OS (HR: 1.75, 95% CI 1.16-2.66, p =.008). 4-year OS for the RT alone versus CRT arm was 22% and 38%, respectively. For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone. These results complement the findings of RTOG 0926 showing the promise of CRT for the treatment of HGT1 disease and support the decision by NRG Oncology investigators to omit RT alone as a treatment arm in the successor trial to RTOG 0926 for HGT1 disease. [ABSTRACT FROM AUTHOR]

Résumé: L’hadronthérapie, radiothérapie par les particules lourdes chargées, bénéficie depuis une dizaine d’années d’un engouement sans précédent, tant sur le plan technologique que clinique. Le premier est lié au développement commercial d’installations de protons compactes, relativement bon marché, et équipées de source rotatives isocentriques. L’arrivée du pencil beam scanning devrait simplifier et accélérer les procédures de traitement. Le second est lié aux succès rapportés dans, premièrement, le traitement de tumeurs localement agressives, non ou peu résécables, et placées au voisinage immédiat de structures saines radiosensibles : mélanomes oculaires, sarcomes de bas grade de la base du crâne et du rachis, carcinomes de la sphère ORL évolués (cylindromes) ; secondement, la protection des tissus sains : à long terme, particulièrement dans les tumeurs pédiatriques, en raison de la grande radiosensibilité des tissus en croissance (incluant le risque carcinogène) ; immédiate, sur la moelle osseuse, les muqueuses… notamment dans les associations concomitantes chimioradiothérapiques (étudiées dans les cancer du poumon et de l’œsophage). Les patients irradiés par ions carbone ne représentent qu’une minorité des 115 000 traités dans le monde mais, dans les mains des équipes japonaises, entraînent des résultats surprenants dans les formes les plus résistantes, telles que le mélanome muqueux, les sarcomes de haut grade, le cancer du pancréas. Les modifications du fractionnement utilisées, posent d’intéressantes questions biologiques et économiques. Une vive polémique s’est récemment développée autour d’une expansion des indications vers des maladies communes (cancer de la prostate). [ABSTRACT FROM AUTHOR]

Objective: the aim of this study is to observe whether there are ultrasound changes between men and women in the Achilles tendon at rest, at maximum passive force is applied and during walking., Material and Methods: it was a cross-sectional study involving 27 healthy young participants recruited as volunteers between April to July 2022. A variety of data was recorded: (age, Body Mass Index, sex, smoking, current injury status, allergies, medications, previous surgeries, type of sport, and number of weekly workouts) and ultrasound measurements at rest and at passive force (Cross Sectional Area Achilles Tendon length, tendon thickness, Cross Sectional Area and pennation angle of the soleus muscle to the Achilles Tendon)., Results: women demonstrated a statistically significant lower proximal and median thickness both at rest (4.5 vs 5.1 mm with p < 0.001 for proximal thickness; 4.4 vs 5.3 mm with p < 0.001 for median thickness) as well as during maximum eccentric contraction (4.3 vs 4.8 mm with p=<0.001 for proximal thickness; 4.1 vs 4.8 mm with p < 0.001 for median thickness)., Conclusion: there are significant sonoanatomical differences in vivo Achilles tendon between men and women., Competing Interests: Declaration of competing interest All the authors declare that they have no conflict of interest derived from the outcomes of this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) is an established therapy for the treatment of aortic valve disease in appropriately selected patients. Previous studies using the self-expanding Portico transcatheter heart valve (THV), (Abbott Structural Heart, St Paul, MN, USA) have demonstrated the technical feasibility of this system albeit in the hands of relatively inexperienced Portico users. The objective of this study was to assess the real-world safety and efficacy of the Portico THV (with and without the FlexNav delivery system, Abbott Structural Heart) at the 30-day timepoint in an Australian cohort., Methods and Results: This study was a retrospective real-world cohort analysis of 269 consecutive patients with severe aortic valve disease who underwent TAVI at multiple centres within Australia between February 2015 and April 2021. Of the 269 patients, 51.7% were female, mean Society of Thoracic Surgeons (STS) score was 5.2 (±6.8) and 98.5% had successful implantations. Thirty (30)-day post-implantation all-cause mortality was observed in one (0.4%) patient, major vascular complications in two (0.7%) patients, more-than-mild paravalvular leak in six (2.2%) patients and requirement for new permanent pacemaker implantation in 27 (10.2%) patients. Haemodynamic parameters at 30 days included mean effective orifice area (EOA) of 2.3 (±0.9) cm 2 and mean aortic valve gradient (AVG) of 9.6 (±6.2) mmHg., Conclusion: This analysis of the Portico THV in a real-world setting suggested that the system is associated with satisfactory safety and efficacy parameters. Previously published datasets may not have found similar findings owing to lower operator experience with the Portico THV system., (Copyright © 2022. Published by Elsevier B.V.)

Background: Insertable cardiac monitors (ICMs) are small subcutaneously implanted devices that detect changes in R-wave amplitudes (RWAs), effective in arrhythmia-monitoring. Although ICMs have proven to be immensely successful, electrical artefacts are frequent and can lead to misdiagnosis. Thus, there is a growing need to sustain and increase efficacy in detection rates by gaining insight into various patient-specific factors such as body postures and activities., Methods: RWAs were measured in 15 separate postures, including supine, lying on the right-side (RS) or left-side (LS) and sitting, and two separate ICM orientations, immediately after implantation of Confirm Rx™ ICM in 99 patients., Results: The patients (53 females and 46 males, mean ages 66.62 ± 14.7 and 66.40 ± 12.25 years, respectively) had attenuated RWAs in RS, LS and sitting by ~ 26.4%, ~ 27.8% and ~ 21.2% respectively, compared to supine. Gender-based analysis indicated RWAs in RS (0.32 mV (0.09-1.03 mV), p < 0.0001) and LS (0.37 mV (0.11-1.03 mV), p = 0.004) to be significantly attenuated compared to supine (0.52 mV (0.20-1.03 mV) for female participants. Similar attenuation was not evident for male participants. Further, parasternally oriented ICMs (n = 44), attenuated RWAs in RS (0.37 mV(0.09-1.03 mV), p = 0.05) and LS (0.34 mV (0.11-1.03 mV), p = 0.02) compared to supine (0.48 mV (0.09-1.03 mV). Similar differences were not observed in participants with ICMs in the 45°-relative-to-sternum (n = 46) orientation. When assessing the combined effect of gender and ICM orientation, female participants demonstrated plausible attenuation in RWAs for RS and LS postures compared to supine, an effect not observed in male participants., Conclusion: This is the first known study depicting the effects on RWA due to body postures and activities immediately post-implantation with an overt impact by gender and orientation of ICM. Future work assessing the cause of gender-based differences in RWAs may be critical., Trial Registration: Clinical Trials, NCT03803969. Registered 15 January 2019 - Retrospectively registered, https://clinicaltrials.gov/NCT03803969., (© 2022. The Author(s).)