A retrospective evaluation of inter-fraction motion in prostate cancer patients with involved nodes receiving prostate and pelvic ± para-aortic nodal irradiation.

INTRODUCTION: The inter-fraction motion of pelvic ± para-aortic (PA) nodal volumes in prostate cancer patients with involved nodes is yet to be quantified and the optimal IGRT strategy for these patients is currently unknown. METHODS: A single-centre retrospective evaluation was performed investigating inter-fraction motion in the prostate and involved nodal volumes of patients receiving pelvic ± PA nodal irradiation. Patients were selected for inclusion if they; were undergoing prostate + pelvic node +/- PA node radiation for prostate cancer with involved lymph nodes and had received daily online CBCT scans. The planning CT and subsequent CBCT images from each treatment fraction were selected for analysis. RESULTS: Out of 567 CBCTs, from 20 patients, there were no incidences where independent lymph node displacement was >0.5 cm from planning volumes. Lymph node motion relative to prostate was >0.5 cm on 15 occasions out of 567 scans (2.6%). Where the difference between prostate and lymph nodes was >0.5 cm, this was always a result of the rectum causing variation in the prostate position, not a change in nodal position. DISCUSSION: These results suggests that there is limited independent displacement between the involved pelvic ± PA nodal volumes and bony anatomy. Therefore, bony anatomy could be used as a lymph node match surrogate for prostate patients receiving nodal irradiation for active disease. The results also suggest additional emphasis should be placed on bowel preparation in these patients to reduce the risk of geographical miss. CONCLUSION: In conclusion, the results of this evaluation suggests that there is limited independent displacement between the involved pelvic ± PA nodal volumes and bony anatomy. This provides evidence to trials investigating the role of pelvic ± PA nodal irradiation to ensure appropriate margins and IGRT strategies are used when investigating this further.

Impact of on-trial IGRT quality assurance in an international adaptive radiotherapy trial for participants with bladder cancer.

BACKGROUND AND PURPOSE: Radiotherapy trial quality assurance (RT QA) is crucial for ensuring the safe and reliable delivery of radiotherapy trials, and minimizing inter-institutional variations. While previous studies focused on outlining and planning quality assurance (QA), this work explores the process of Image-Guided Radiotherapy (IGRT), and adaptive radiotherapy. This study presents findings from during-accrual QA in the RAIDER trial, evaluating concordance between online and offline plan selections for bladder cancer participants undergoing adaptive radiotherapy. RAIDER had two seamless stages; stage 1 assessed adherence to dose constraints of dose escalated radiotherapy (DART) and stage 2 assessed safety. The RT QA programme was updated from stage 1 to stage 2. MATERIALS AND METHODS: Data from all participants in the adaptive arms (standard dose adaptive radiotherapy (SART) and DART) of the trial was requested (33 centres across the UK, Australia and New Zealand). Data collection spanned September 2015 to December 2022 and included the plans selected online, on Cone-Beam Computed Tomography (CBCT) data. Concordance with the plans selected offline by the independent RT QA central reviewer was evaluated. RESULTS: Analysable data was received for 72 participants, giving a total of 884 CBCTs. The overall concordance rate was 83% (723/884). From stage 1 to stage 2 the concordance in the plans selected improved from 75% (369/495) to 91% (354/389). CONCLUSION: During-accrual IGRT QA positively influenced plan selection concordance, highlighting the need for ongoing support when introducing a new technique. Overall, it contributes to advancing the understanding and implementation of QA measures in adaptive radiotherapy trials.

Professional development through mentoring: Final evaluation of the pilot mentoring programme of the European society of radiotherapy and oncology.

The European SocieTy for Radiotherapy and Oncology (ESTRO) organized a one-year pilot mentoring programme. At evaluation after one year, both mentors and mentees scored the programme with a median score of 9 on a scale of 10. All of the mentors indicated that they wanted to participate again as mentors.

BIR POSITION STATEMENT: Governance requirements for Non-Medical referrers to radiology.

The ability to request clinical imaging is included in many advanced roles of health-care professionals in the UK and is seen as a useful component in ensuring patients receive the right care, by the right person, at the right time. In order that diagnostic imaging referrals are appropriate, timely and safely made, the British Institute of Radiology has produced a position statement on the governance requirements covering clinical imaging requests from non-medical referrers (NMRs). This document is intended to help define the role of a NMR and to ensure they are practising responsibly and safely, within professional and legal frameworks, as part of the wider interprofessional team.

Study protocol for a real-world evaluation of an integrated child and family health hub for migrant and refugee women.

INTRODUCTION: Continuity of child and family healthcare is vital for optimal child health and development for developmentally vulnerable children. Migrant and refugee communities are often at-risk of poor health outcomes, facing barriers to health service attendance including cultural, language, limited health literacy, discrimination and unmet psychosocial needs. 'Integrated health-social care hubs' are physical hubs where health and social services are co-located, with shared referral pathways and care navigation. AIM: Our study will evaluate the impact, implementation and cost-benefit of the First 2000 Days Care Connect (FDCC) integrated hub model for pregnant migrant and refugee women and their infants. MATERIALS AND METHODS: This study has three components. Component 1 is a non-randomised controlled trial to compare the FDCC model of care with usual care. This trial will allocate eligible women to intervention and control groups based on their proximity to the Hub sites. Outcome measures include: the proportion of children attending child and family health (CFH) nurse services and completing their CFH checks to 12 months of age; improved surveillance of growth and development in children up to 12 months, post partum; improved breastfeeding rates; reduced emergency department presentations; and improved maternal well-being. These will be measured using linked medical record data and surveys. Component 2 will involve a mixed-method implementation evaluation to clarify how and why FDCC was implemented within the sites to inform future roll-out. Component 3 is a within-trial economic evaluation from a healthcare perspective to assess the cost-effectiveness of the Hubs relative to usual care and the implementation costs if Hubs were scaled and replicated. ETHICS AND DISSEMINATION: Ethical approval was granted by the South Eastern Sydney Local Health District Human Research Ethics Committee in July 2021 (Project ID: 020/ETH03295). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ACTRN12621001088831.

Implementation of a comprehensive set of optimised CBCT protocols and validation through imaging quality and dose audit.

OBJECTIVES: Cone-beam computed tomography (CBCT) for radiotherapy treatment verification has increased in frequency; therefore, it is crucial to optimise image quality and radiation dose to patients. The aim of this study was to implement optimised CBCT protocols for the Varian TrueBeams for most tumour sites in adult patients. METHODS: A combination of patient size-specific CBCT protocols from the literature and developed in-house was used. Scans taken before and after optimisation were compared by senior radiographers and physicists to evaluate how changes affected image quality and clinical usability for online image registration. The change in dose for each new CBCT protocol was compared to the Varian default. A clinical audit was performed following implementation to evaluate the changes in imaging dose for all patients receiving a CBCT during that period. RESULTS: Ten CBCT protocols were introduced including head and neck and patient-size-specific thorax and pelvis/abdomen protocols. Scans from 102 patients with images before and after optimisation were assessed, none of the scans showed image quality changes compromising clinical usability and for some image quality was improved. Between November 2020 and June 2021, 1185 patients had CBCTs using the new protocols. The imaging dose was reduced for 52% of patients, remained the same for 37% and increased for 12%. CONCLUSIONS: This study showed that substantial dose reductions and image quality improvements can be achieved with simple changes in the default settings of the Varian TrueBeam CBCT without affecting the radiographers' confidence in online image registration. ADVANCES IN KNOWLEDGE: This study represents a comprehensive assessment and optimisation of CBCT protocols for most sites, validated on a large cohort of patients.

Supporting self-determination of autistic students in transitions.

BACKGROUND: Despite awareness of the need to support autistic students in transitions, great variability is found in transition supports provided across different school environments and staff within schools. Moreover, strategies implemented may not provide autistic students with the supports they need to reduce their anxiety and build their sense of self-determination during transitions. AIM: The current paper aimed to determine what types of transition supports are employed in Australian schools to support autistic students and to consider these supports through the lens of self-determination theory. METHODS: Surveys were conducted with 422 parents, educators and education specialists who provided information on transition supports employed in schools in open-ended questions. Transition supports were explored in more depth through interviews with a subset of 30 participants. RESULTS: Findings indicate that schools provided a range of strategies, programmes and planning processes to support students in transitions. However, students were often passive recipients of supports who were rarely involved in the planning and implementation of strategies. CONCLUSION: The results of this study suggest that current transition supports implemented in schools may support autistic students in some transitions, but are not likely to develop their self-determination to successfully navigate transitions over the long-term. WHAT THIS PAPER ADDS?: Drawing on self-determination theory, this study provides a unique and much needed examination of the types of strategies employed in schools and offers a critical reflection as to whether these strategies are likely to support autistic students to develop a sense of autonomy, competence and relatedness to successfully manage future transitions.

Introduction of deep inspirational breath-hold and Butterfly-VMAT techniques into clinical practice for the treatment of mediastinal lymphoma - Lessons learned from an experienced centre.

Deep inspiration breath-hold, butterfly volumetric modulated arc therapy and daily imaging techniques for mediastinal lymphoma patients have been introduced in a single department. Whilst introducing these techniques, there were many practical lessons to be learned across the patient pathway, from pre-treatment through to treatment delivery.Therapeutic radiographers were key members of the multi-disciplinary team implementing these techniques. This work reflects on the experience of introducing these advanced techniques for mediastinal lymphoma patients and the lessons learnt.

Deep inspiration breath-hold for mediastinal lymphoma patients: Evaluation of a 5-year service.

Deep inspiration breath-hold (DIBH) is an advanced radiotherapy technique that has been shown to have dosimetric benefits in the treatment of patients with mediastinal lymphoma. Whilst there is much published data on the use of DIBH in breast radiotherapy, reports on the use of the technique in mediastinal lymphoma patients remain limited. As the first NHS centre in the UK to implement DIBH in this pt group, we have evaluated our experience and success in using this technique over a 5 year period.

A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer (APHRODITE): protocol for a multicentre, open-label randomised controlled trial.

INTRODUCTION: The standard of care for patients with localised rectal cancer is radical surgery, often combined with preoperative neoadjuvant (chemo)radiotherapy. While oncologically effective, this treatment strategy is associated with operative mortality risks, significant morbidity and stoma formation. An alternative approach is chemoradiotherapy to try to achieve a sustained clinical complete response (cCR). This non-surgical management can be attractive, particularly for patients at high risk of surgical complications. Modern radiotherapy techniques allow increased treatment conformality, enabling increased radiation dose to the tumour while reducing dose to normal tissue. The objective of this trial is to assess if radiotherapy dose escalation increases the cCR rate, with acceptable toxicity, for treatment of patients with early rectal cancer unsuitable for radical surgery. METHODS AND ANALYSIS: APHRODITE (A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer) is a multicentre, open-label randomised controlled phase II trial aiming to recruit 104 participants from 10 to 12 UK sites. Participants will be allocated with a 2:1 ratio of intervention:control. The intervention is escalated dose radiotherapy (62 Gy to primary tumour, 50.4 Gy to surrounding mesorectum in 28 fractions) using simultaneous integrated boost. The control arm will receive 50.4 Gy to the primary tumour and surrounding mesorectum. Both arms will use intensity-modulated radiotherapy and daily image guidance, combined with concurrent chemotherapy (capecitabine, 5-fluorouracil/leucovorin or omitted). The primary endpoint is the proportion of participants with cCR at 6 months after start of treatment. Secondary outcomes include early and late toxicities, time to stoma formation, overall survival and patient-reported outcomes (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires QLQ-C30 and QLQ-CR29, low anterior resection syndrome (LARS) questionnaire). ETHICS AND DISSEMINATION: The trial obtained ethical approval from North West Greater Manchester East Research Ethics Committee (reference number 19/NW/0565) and is funded by Yorkshire Cancer Research. The final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines. TRIAL REGISTRATION NUMBER: ISRCTN16158514.

Recognising the challenges of implementing multi-centre adaptive plan of the day radiotherapy.

Two multicentre adaptive radiotherapy trials utilising Plan of the Day (PoD) with a library of plans were introduced in 35 centres. The common issues that arose from all centres when introducing PoD were collated retrospectively, through reviewing the data pertaining to the pre-trial and on-trial quality assurance programme. It was found that 1,295 issues arose when introducing PoD in outlining, planning, treatment delivery i.e., PoD selection, and in the overall process of delivering PoD. There was no difference in the number of issues that arose from pre-trial to on-trial. Thus, it is recommended that the implementation of PoD is supported by guidance, reviews, and continuous monitoring.

Classroom Teachers' Implementation of the Social Stations Intervention to Improve the Verbal Initiations and Responses of Students with Autism.

Students with autism often show challenges in social communication, particularly in initiating and responding behaviors. While the classroom offers a natural context for peer interactions, few interventions are designed specifically for classroom settings. This study investigated the effects of a classroom-teacher implemented social communication intervention, known as Social Stations, on the initiating and responding behaviors of students with autism. The study was set in an inclusive primary school, with the teacher embedding the intervention into the student's daily literacy lessons. All students with autism showed significant improvements in the targeted behaviors, with improvements maintained over time. This study suggests that social communication interventions can be implemented by teachers as part of a daily classroom program.

Protocol for hypofractionated adaptive radiotherapy to the bladder within a multicentre phase II randomised trial: radiotherapy planning and delivery guidance.

INTRODUCTION: Patients with muscle invasive bladder cancer (MIBC) who are unfit and unsuitable for standard radical treatment with cystectomy or daily radiotherapy present a large unmet clinical need. Untreated, they suffer high cancer specific mortality and risk significant disease-related local symptoms. Hypofractionated radiotherapy (delivering higher doses in fewer fractions/visits) is a potential treatment solution but could be compromised by the mobile nature of the bladder, resulting in target misses in a significant proportion of fractions. Adaptive 'plan of the day' image-guided radiotherapy delivery may improve the precision and accuracy of treatment. We aim to demonstrate within a randomised multicentre phase II trial feasibility of plan of the day hypofractionated bladder radiotherapy delivery with acceptable rates of toxicity. METHODS AND ANALYSIS: Patients with T2-T4aN0M0 MIBC receiving 36 Gy in 6-weekly fractions are randomised (1:1) between treatment delivered using a single-standard plan or adaptive radiotherapy using a library of three plans (small, medium and large). A cone beam CT taken prior to each treatment is used to visualise the anatomy and select the most appropriate plan depending on the bladder shape and size. A comprehensive radiotherapy quality assurance programme has been instituted to ensure standardisation of radiotherapy planning and delivery. The primary endpoint is to exclude >30% acute grade >3 non-genitourinary toxicity at 3 months for adaptive radiotherapy in patients who received >1 fraction (p0=0.7, p1=0.9, α=0.05, ß=0.2). Secondary endpoints include local disease control, symptom control, late toxicity, overall survival, patient-reported outcomes and proportion of fractions benefiting from adaptive planning. Target recruitment is 62 patients. ETHICS AND DISSEMINATION: The trial is approved by the London-Surrey Borders Research Ethics Committee (13/LO/1350). The results will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities. TRIAL REGISTRATION NUMBER: NCT01810757.

An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans.

In the nematode C. elegans, insulin signaling regulates development and aging in response to the secretion of numerous insulin peptides. Here, we describe a novel, non-signaling isoform of the nematode insulin receptor (IR), DAF-2B, that modulates insulin signaling by sequestration of insulin peptides. DAF-2B arises via alternative splicing and retains the extracellular ligand binding domain but lacks the intracellular signaling domain. A daf-2b splicing reporter revealed active regulation of this transcript through development, particularly in the dauer larva, a diapause stage associated with longevity. CRISPR knock-in of mScarlet into the daf-2b genomic locus confirmed that DAF-2B is expressed in vivo and is likely secreted. Genetic studies indicate that DAF-2B influences dauer entry, dauer recovery and adult lifespan by altering insulin sensitivity according to the prevailing insulin milieu. Thus, in C. elegans alternative splicing at the daf-2 locus generates a truncated IR that fine-tunes insulin signaling in response to the environment.

What does success mean for autistic men? A narrative exploration of self-determination.

Background: Studies involving autistic adults have often focused on negative outcomes and quality of life ratings. Aims: This study provides a different viewpoint by examining the perspectives of autistic men who consider themselves to be successful. Methods: Data were gathered from 10 men who shared their experiences and perceptions regarding their journey to achieve success. Self-determination theory provided a useful lens for examining the men's narratives and understanding the factors that led to their success. Results: Analysis of interviews revealed four main themes: (1) being my own self, (2) a competent professional, (3) solving problems in a neurotypical world, and (4) relating and connecting. These themes reflect the men's perception of their own self-determination including their autonomy, competence, and relatedness with others. Conclusions: The men's sense of success was derived from their ability to achieve competence in their work, act without help or influence from others and demonstrate a high level of self-awareness and self-reflection. Despite this, many continued to experience difficulty in the social areas of their lives.Implications: These findings suggest that self-determination theory may present an alternative and more positive means of enacting support programs for autistic individuals, and males in particular.

Protocol for tumour-focused dose-escalated adaptive radiotherapy for the radical treatment of bladder cancer in a multicentre phase II randomised controlled trial (RAIDER): radiotherapy planning and delivery guidance.

INTRODUCTION: Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused 'plan of the day' radiotherapy delivery. We aim to test within a randomised multicentre phase II trial whether this technique will enable dose escalation with acceptable rates of toxicity. METHODS AND ANALYSIS: Patients with T2-T4aN0M0 unifocal MIBC will be randomised (1:1:2) between standard/control whole bladder single plan radiotherapy, standard dose adaptive tumour-focused radiotherapy or dose-escalated adaptive tumour-focused radiotherapy (DART). Adaptive tumour-focused radiotherapy will use a library of three plans (small, medium and large) for treatment. A cone beam CT taken prior to each treatment will be used to visualise the anatomy and inform selection of the most appropriate plan for treatment.Two radiotherapy fractionation schedules (32f and 20f) are permitted. A minimum of 120 participants will be randomised in each fractionation cohort (to ensure 57 evaluable DART patients per cohort).A comprehensive radiotherapy quality assurance programme including pretrial and on-trial components is instituted to ensure standardisation of radiotherapy planning and delivery.The trial has a two-stage non-comparative design. The primary end point of stage I is the proportion of patients meeting predefined normal tissue constraints in the DART group. The primary end point of stage II is late Common Terminology Criteria for Adverse Events grade 3 or worse toxicity aiming to exclude a rate of >20% (80% power and 5% alpha, one sided) in each DART fractionation cohort. Secondary end points include locoregional MIBC control, progression-free survival overall survival and patient-reported outcomes. ETHICS AND DISSEMINATION: This clinical trial is approved by the London-Surrey Borders Research Ethics Committee (15/LO/0539). The results when available will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities. TRIAL REGISTRATION NUMBER: NCT02447549; Pre-results.

Promoting a Collective Voice from Parents, Educators and Allied Health Professionals on the Educational Needs of Students on the Autism Spectrum.

Providing support for the educational needs of students on the autism spectrum continues to be challenging. Findings from this survey of parents, teachers and specialist staff highlight the need for collaboration between stakeholders who support the education of these students. The main themes to emerge were for school staff to be equipped with the knowledge and expertise to support each student in their learning, and for support with social/emotional needs. Findings highlighted the need for a transparent process for building school capacity to translate research and knowledge into practice by all stakeholders. This collective voice is important to ensure the needs of these students are identified and that appropriate support is implemented to maximise the educational success of these students.

A systematic review of school-based interventions targeting social communication behaviors for students with autism.

Initiating and responding to peers are social communication behaviors which are challenging for students with autism. We reviewed intervention studies set in mainstream elementary schools, which targeted these behaviors and reported on intervention outcomes as well as the resources required for their implementation. A total of 22 studies met the criteria for inclusion. Findings suggest that school-based interventions can increase the frequency and duration of initiating and responding behaviors in elementary school aged students with autism. These interventions were resource-intensive and usually delivered by researchers or teaching assistants away from the classroom. Future research should build on this emerging evidence base to consider interventions which could be implemented by classroom teachers as part of the classroom program.

Dysregulation of DAF-16/FOXO3A-mediated stress responses accelerates oxidative DNA damage induced aging.

DNA damage is presumed to be one type of stochastic macromolecular damage that contributes to aging, yet little is known about the precise mechanism by which DNA damage drives aging. Here, we attempt to address this gap in knowledge using DNA repair-deficient C. elegans and mice. ERCC1-XPF is a nuclear endonuclease required for genomic stability and loss of ERCC1 in humans and mice accelerates the incidence of age-related pathologies. Like mice, ercc-1 worms are UV sensitive, shorter lived, display premature functional decline and they accumulate spontaneous oxidative DNA lesions (cyclopurines) more rapidly than wild-type worms. We found that ercc-1 worms displayed early activation of DAF-16 relative to wild-type worms, which conferred resistance to multiple stressors and was important for maximal longevity of the mutant worms. However, DAF-16 activity was not maintained over the lifespan of ercc-1 animals and this decline in DAF-16 activation corresponded with a loss of stress resistance, a rise in oxidant levels and increased morbidity, all of which were cep-1/ p53 dependent. A similar early activation of FOXO3A (the mammalian homolog of DAF-16), with increased resistance to oxidative stress, followed by a decline in FOXO3A activity and an increase in oxidant abundance was observed in Ercc1-/- primary mouse embryonic fibroblasts. Likewise, in vivo, ERCC1-deficient mice had transient activation of FOXO3A in early adulthood as did middle-aged wild-type mice, followed by a late life decline. The healthspan and mean lifespan of ERCC1 deficient mice was rescued by inactivation of p53. These data indicate that activation of DAF-16/FOXO3A is a highly conserved response to genotoxic stress that is important for suppressing consequent oxidative stress. Correspondingly, dysregulation of DAF-16/FOXO3A appears to underpin shortened healthspan and lifespan, rather than the increased DNA damage burden itself.

The importance of critical life moments: An explorative study of successful women with autism spectrum disorder.

Ten women with autism spectrum disorder participated in oral interviews in order to share their experiences since their diagnosis and to discuss the factors that had enabled them to achieve success in different aspects of their life. Participants were encouraged to share their perspectives on their success and to discuss the challenges they encountered in their daily lives and how they overcame these. Interviews were analysed using a narrative-themed approach. Participants indicated that both internal and external factors enabled them to achieve success in different aspects of their lives. These included being an agent of change, a changed identity after diagnosis, experiencing the belief of others in their capability and seeing themselves as a mentor to others. Their experiences with overcoming obstacles in their lives enabled them to develop self-efficacy and to shape their own success.