Magnetron Sputtered CsPbCl3 Perovskite Detectors as Real-Time Dosimeters for Clinical Radiotherapy

The aim of this study is to investigate the feasibility of manufacturing thin real-time relative dosimeters for clinical radiotherapy (RT) with potential applications for transmission monitoring in vivo dosimetry and pre-treatment dose verifications. Thin (≈1 μm) layers of a high sensitivity, wide bandgap semiconductor, the inorganic perovskite CsPbCl₃, have been grown for the first time by magnetron sputtering on plastic substrates equipped with electrode arrays. Prototype devices have been tested in real-time configuration to evaluate the dose delivered by a 6 MV photon beam from a linear accelerator. Linearity of the charge with the dose has been verified over three order of magnitudes, linearity of the current signal with the dose rate has been also successfully tested in the range 0.5-4.3 Gy/min. The combination of high sensitivity per unit volume and wide bandgap provides high signal-to-noise ratios, up to 70, even at moderate applied voltages. The Schottky diode configuration allows the detector to operate without bias voltage (null bias).The blocking-barrier structure allows to confine the active volume within sub-millimetric sizes, a quite attractive feature in view to increase granularity and achieve the high spatial resolutions required in modern RT techniques. All the above-mentioned features indeed pave the way to a novel generation of flexible, transmission, real time dosimeters for clinical radiotherapy.     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

Étude de faisabilité : l’utilisation de l’imagerie médicale en éducation thérapeutique en radiothérapie

PurposeAssess the feasibility of a randomized controlled trial (RCT) exploring the use of medical imaging as a therapeutic education (TPE) intervention in external radiation therapy.Materials and methodsExperimental feasibility trial of “RCT” type carried out in a single-center, between November 2019 and March 2020, following adult patients treated by thoracic radiotherapy. In addition to the information usually given, the experimental group benefited from an intervention consisting in the visualization of their own medical images using the open-source software “Stone of Orthanc”.ResultsForty-nine patients were recruited with a refusal rate of 8.16% (4/49). 20 patients were withdrawn from the study for health reasons (COVID), 10 for medical reasons. All the remaining 15 participants completed the process. Although not significant, the experimental group showed a median gain in the perception of knowledge compared to the control group (+ 1.9 (1.6 – 2.2)) vs (+ 1.4 (1.4 – 1.8)), as well as a decrease in scores related to anxiety (? 3.0 (?4.5 - (?2.0)) vs ? 1.0 (?5.0 - 0.0)) and emotional distress ((? 5.0 (? 7.5 - (? 3.5)) vs (? 2.0 (? 5.0 - (? 1.0)) A significant reduction (p = 0.043) is observed for the depression score ((? 2.0 (?3.0 - (?1.5)) vs (0.0 (0.0 – 0.0)).ConclusionThis study demonstrates the feasibility of the project, with promising preliminary results. Some adaptations in order to conduct a larger-scale RCT are highlighted.     

颈椎终板弧形高度与椎间隙后缘骨赘的相关性研究

目的：通过对颈椎病患者上下终板弧形高度、椎间隙高度与椎间隙后骨赘的影像学测量，研究其相关性及其临床应用价值。方法：收集2017年9月至2018年9月颈椎病手术108例患者的临床资料，男48例，年龄30~72岁，平均52岁，女60例，年龄37~79岁，平均54岁。其中C_2，3 6例，C_3，4 15例，C_4，5 32例，C_5，6 42例，C_6，7 13例。术前及术后摄颈椎X线片，利用PACS（Picture Archiving and Communication Systems）调阅影像，测量椎间隙的下上终板弧形高度（L₁，L₂），椎间隙高度（L₃）及后方骨赘的宽度（L₄）。利用Spearman分析它们之间的相关性。结果：L₁与L₄对比（r=-0.34，P<0.05），L₃与L₄对比（r=-0.36，P<0.05），存在负相关。L₁与L₃对比（r=0.38，P<0.05），L₂与L₃对比（r=0.48，P<0.05），存在正相关。L₁与L₂对比（P>0.05），L₂与L₄对比（P>0.05），差异无统计学意义。结论：下终板弧形高度与椎间隙后缘骨赘宽度呈负相关，通过其测量可明确颈椎退变程度，对颈椎病的早期防治有指导意义。     

Outcomes of Prostatectomy versus Radiation Therapy in the Management of Clinically Localized Prostate Cancer Patients Within the PLCO Trial

Background

The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.

Simulated versus traditional therapeutic radiography placements: A randomised controlled trial

IntroductionClinical placements provide rich learning environments for health professional pre-registration education but add significant workload pressure to clinical departments. Advances in simulation approaches mean that many aspects of students’ clinical learning can be undertaken in the academic environment. There is, however, little data identifying specific pedagogical gains afforded by simulation compared to clinical placement. This study measured the impact of a comprehensive integrated simulation placement on student clinical skill acquisition.MethodsA virtual department was developed using a range of simulation equipment and software, with actors and service users providing a range of patients for students to engage with. A cohort of 29 first-year undergraduate therapeutic radiography students were randomly assigned to either simulated or conventional clinical placement. Clinical skills assessment scores provided by a blinded assessor were then compared.ResultsMean overall assessment scores for each cohort were within 3% of each other. The simulation cohort had over 10% higher “communication” scores than the traditional group (p = 0.028). The ability to gain both technical and interpersonal skills simultaneously improved learning compared to clinical placement. Students valued the structured approach of the simulated placement and the opportunity to practice techniques in a safe unpressured environment.ConclusionAn integrated simulated placement can help students to achieve clinical learning outcomes and lead to improved interpersonal skills.Implications for practiceUse of blended simulation resources can enable students to acquire technical, procedural and interpersonal skills which in turn may enable reduction of overall clinical placement time and departmental training burden.     

Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.     

Radiotherapy-specific interprofessional learning through simulation

IntroductionInterprofessional learning (IPL) is a vital aspect of training in radiation oncology professions, yet is rarely delivered to those professionals who work most closely together in clinical practice. Scenario-based learning using simulation facilities provides a unique opportunity to facilitate this learning and this project aimed to determine the impact and value of this initiative.MethodsSmall groups comprising post-graduate diploma pre-registration therapeutic radiographers, medical physics trainees and radiation oncology registrars were challenged with 4 plausible and challenging radiotherapy scenarios within an academic simulation centre. Pre- and post-event completion of the “Readiness for Interprofessional Learning Scale” measured impact and a Likert-style survey gathered feedback from participants.ResultsThe session increased participants' teamwork and collaboration skills as well as strengthening professional identities. Participants reported high levels of enjoyment related to collaborative working, communication and observing other professionals deploying their technical skills and specialist knowledge.ConclusionAlthough beneficial, simulated scenarios offering equal opportunities for engagement across the professions are challenging to plan and timetabling issues between the 3 groups present significant difficulties. The safe environment and unique opportunity for these groups to learn together was particularly well received and future oncology-specific simulated scenario sessions are planned with larger cohorts.Implications for practiceSimulated scenario training can be used to improve team working across the radiotherapy interprofessional team and may have wider use in other specialist interdisciplinary team development.     

The influence of environmental and health indicators on premature mortality: An empirical analysis of the City of Toronto's 140 neighborhoods

The objective of this paper was to assess the link between premature mortality and a combination of neighbourhood contextual (environmental and health) and compositional (socioeconomic and demographic) characteristics. We statistically and spatially examined six environmental variables (ultrafine particles, carcinogenic and non-carcinogenic pollutants, pollution released to air, tree cover, and walkability index), six health service indicators (number health providers, breast, colorectal and cervical cancer screening uptake rates, student nutrition program uptake rates, and healthy food index), and eight socioeconomic indicators (total income, Gini coefficient, two age categories – below and above 40 years, proportion of females to males, visible minorities, Indigenous peoples, education, less than grade 9) among 140 neighbourhoods of the City of Toronto in Ontario (Canada). We applied principal component analysis to identify patterns and to reduce the number of explanatory variables into combined component axes that represent unique variation in these confounded and overlapping factors. We then applied regression analysis to model the relationship between the indices of enviro-health and socioeconomics and their potential relationship with premature mortality. Residual spatial analysis was used to investigate any remaining spatial structure (such as neighbourhoods with higher residual premature mortality rates). Neighbourhood Equity Index was correlated with our enviro-health and socioeconomic indices. Premature mortality within neighbourhoods was predicted by poor cancer screenings, pollution, lack of tree canopy, increased uptake of student nutrition programs and high walkability index. A negative association between premature mortality and pollution was associated low walkability index and presence of visible minorities within neighbourhoods. There was some unexplained residual spatial variation in our model of premature mortality - especially along the shores of Lake Ontario and in neighbourhoods with major highways or road corridors: premature mortality in Toronto neighbourhoods was higher than expected along highway-corridor neighbourhoods and shorelines. Our analysis revealed a significant relationship between neighbourhood contextual features – both environmental and health – and premature mortality, suggesting that these contextual components of neighbourhoods can predict rates of urban premature mortality in Toronto.