Uptake rates and attitudes to influenza and COVID-19 vaccination in pregnancy - a prospective cohort study.

Influenza and COVID-19 are highly prevalent RNA viruses. Pregnancy increases the frequency of severe maternal morbidity and mortality associated with these viruses. Vaccination plays an important role in protecting pregnant women and their infants from adverse outcomes. In this prospective study, we aimed to determine the vaccination uptake rate for influenza and COVID-19 in a pregnant population and to explore reasons why women remained unvaccinated. A prospective cohort study was conducted over a two-week period in December 2022 in the National Maternity Hospital, Dublin. There were 588 women surveyed over the 2-week period. Overall, 377 (57%) were vaccinated that year for seasonal influenza, a significant rise from 39% in a similar study in 2016. The majority (n = 488, 83%) of women reported receiving at least one COVID-19 vaccine. However only 132 (22%) received a COVID-19 vaccine in pregnancy, despite 76% (n = 466) stating they would be happy to receive it. Factors such as age, obesity, co-morbidities, ethnic group, and type of antenatal care received were shown to influence vaccination rates. We recommend that the importance of vaccination be stressed regularly to eligible patients at their antenatal clinic visits and where possible combining influenza/COVID-19 vaccination on the same day to improve uptake.

The need for consensus on delineation and dose constraints of dentofacial structures in paediatric radiotherapy: Outcomes of a SIOP Europe survey.

Background and purpose: Children receiving radiotherapy for head-and-neck tumours often experience severe dentofacial side effects. Despite this, recommendations for contouring and dose constraints to dentofacial structures are lacking in clinical practice. We report on a survey aiming to understand current practice in contouring and dose assessment to dentofacial structures. Methods: A digital survey was distributed to European Society for Paediatric Oncology members of the Radiation Oncology Working Group, and member-affiliated centres in Europe, Australia, and New Zealand. The questions focused on clinical practice and aimed to establish areas for future development. Results: Results from 52 paediatric radiotherapy centres across 27 countries are reported. Only 29/52 centres routinely delineated some dentofacial structures, with the most common being the mandible (25 centres), temporo-mandibular joint (22), dentition (13), orbit (10) and maxillary bone (eight). For most bones contoured, an 'As Low As Reasonably Achievable' dose objective was implemented. Only four centres reported age-adapted dose constraints.The largest barrier to clinical implementation of dose constraints was firstly, the lack of contouring guidance (49/52, 94%) and secondly, that delineation is time-consuming (33/52, 63%). Most respondents who routinely contour dentofacial structures (25/27, 90%) agreed a contouring atlas would aid delineation. Conclusion: Routine delineation of dentofacial structures is infrequent in paediatric radiotherapy. Based on survey findings, we aim to 1) define a consensus-contouring atlas for dentofacial structures, 2) develop auto-contouring solutions for dentofacial structures to aid clinical implementation, and 3) carry out treatment planning studies to investigate the importance of delineation of these structures for planning optimisation.

Management of the vertebrae as an organ at risk in paediatric radiotherapy clinical trials: Initial QUARTET experience.

Irradiation of the vertebrae in prepubertal patients, if non-homogenous, can result in future growth deformities including kyphoscoliosis. Vertebral delineation and dosimetry were assessed for 101 paediatric cases reviewed within QUARTET-affiliated trials. Despite the availability of published consensus guidelines, a high variability in vertebral delineation was observed, with impact on dosimetry.

Deep-learning magnetic resonance imaging-based automatic segmentation for organs-at-risk in the brain: Accuracy and impact on dose distribution.

Background and purpose: Normal tissue sparing in radiotherapy relies on proper delineation. While manual contouring is time consuming and subject to inter-observer variability, auto-contouring could optimize workflows and harmonize practice. We assessed the accuracy of a commercial, deep-learning, MRI-based tool for brain organs-at-risk delineation. Materials and methods: Thirty adult brain tumor patients were retrospectively manually recontoured. Two additional structure sets were obtained: AI (artificial intelligence) and AIedit (manually corrected auto-contours). For 15 selected cases, identical plans were optimized for each structure set. We used Dice Similarity Coefficient (DSC) and mean surface-distance (MSD) for geometric comparison and gamma analysis and dose-volume-histogram comparison for dose metrics evaluation. Wilcoxon signed-ranks test was used for paired data, Spearman coefficient(ρ) for correlations and Bland-Altman plots to assess level of agreement. Results: Auto-contouring was significantly faster than manual (1.1/20 min, p < 0.01). Median DSC and MSD were 0.7/0.9 mm for AI and 0.8/0.5 mm for AIedit. DSC was significantly correlated with structure size (ρ = 0.76, p < 0.01), with higher DSC for large structures. Median gamma pass rate was 74% (71-81%) for Plan_AI and 82% (75-86%) for Plan_AIedit, with no correlation with DSC or MSD. Differences between Dmean_AI and Dmean_Ref were ≤ 0.2 Gy (p < 0.05). The dose difference was moderately correlated with DSC. Bland Altman plot showed minimal discrepancy (0.1/0) between AI and reference Dmean/Dmax. Conclusions: The AI-model showed good accuracy for large structures, but developments are required for smaller ones. Auto-segmentation was significantly faster, with minor differences in dose distribution caused by geometric variations.

Variation in prescribing for the prevention of postoperative nausea, vomiting, and pain following abdominal surgery: A retrospective study.

Background and Aims: Adequate postoperative analgesia and prevention of post-op nausea and vomiting (PONV) are core components of modern day anaesthesia and peri-operative care. As well as contributing to overall morbidity, postoperative pain and PONV are frequently cited as one of the most unpleasant and distressing aspects of surgery for patients. Variation in healthcare delivery is known to exist but has often been poorly described. A first step to understanding the consequences of variation is to describe the extent of variation. We aimed to assess variation in pharmacological strategies to prevent postoperative pain, nausea and vomiting in patients undergoing elective major abdominal surgery at a tertiary hospital in Perth, Western Australia, over a three-month period. Methods: Retrospective cross-sectional study. Results: We observed considerable variation in prescribing of postoperative analgesia and PONV prophylaxis and suggest that despite adequate evidence based guidelines, they are often overlooked in practice. Conclusion: Measurement of the consequences of variation requires randomised clinical trials that evaluate differences in outcome and cost, associated with the strategies that exist within the spectrum of variation.

Radiotherapy quality assurance in paediatric clinical trials: first report from six QUARTET-affiliated trials.

BACKGROUND AND PURPOSE: SIOP Europe's QUARTET project launched in 2016; aiming to improve access to high-quality radiotherapy for children and adolescents treated within clinical trials across Europe. The aim of this report is to present the profile of institutions participating in six QUARTET-affiliated trials and a description of the initial individual case review (ICR) outcomes. METHODS: This is a two-part analysis. Firstly, using facility questionnaires, beam output audit certificates, and advanced technique credentialing records to create a profile of approved institutions, and secondly, collating trial records for ICRs submitted prior to 31/10/2022. Trials included are: SIOPEN HR-NBL1, SIOPEN-LINES, SIOPEN- VERITAS, SIOP-BTG HRMB, EpSSG-FaR-RMS, and SIOPEN HR-NBL2. RESULTS: By 31/10/2022, a total of 103 institutions had commenced QUARTET site approval procedures to participate in QUARTET-affiliated trials; 66 sites across 20 countries were approved. These participating institutions were often paediatric referral sites with intensity modulated radiotherapy or proton beam therapy, designated paediatric radiation oncologists, and paediatric adapted facilities and imaging protocols available. In total, 263 patient plans were submitted for ICR, 254 ICRs from 15 countries were completed. ICRs had a rejection rate of 39.8%, taking an average of 1.4 submissions until approval was achieved. Target delineation was the most frequent reason for rejection. CONCLUSION: The QUARTET facility questionnaire is a valuable tool for mapping resources, personnel, and technology available to children and adolescents receiving radiotherapy. Prospective ICR is essential for paediatric oncology clinical trials and should be prioritised to reduce protocol violations.

Prioritizing clinical trial quality assurance for photons and protons: A failure modes and effects analysis (FMEA) comparison.

BACKGROUND AND PURPOSE: The Global Clinical Trials RTQA Harmonization Group (GHG) set out to evaluate and prioritize clinical trial quality assurance. METHODS: The GHG compiled a list of radiotherapy quality assurance (QA) tests performed for proton and photon therapy clinical trials. These tests were compared between modalities to assess whether there was a need for different types of assessments per modality. A failure modes and effects analysis (FMEA) was performed to assess the risk of each QA failure. RESULTS: The risk analysis showed that proton and photon therapy shared four out of five of their highest-risk failures (end-to-end anthropomorphic phantom test, phantom tests using respiratory motion, pre-treatment patient plan review of contouring/outlining, and on-treatment/post-treatment patient plan review of dosimetric coverage). While similar trends were observed, proton therapy had higher risk failures, driven by higher severity scores. A sub-analysis of occurrence × severity scores identified high-risk scores to prioritize for improvements in RTQA detectability. A novel severity scaler was introduced to account for the number of patients affected by each failure. This scaler did not substantially alter the ranking of tests, but it elevated the QA program evaluation to the top 20th percentile. This is the first FMEA performed for clinical trial quality assurance. CONCLUSION: The identification of high-risk errors associated with clinical trials is valuable to prioritize and reduce errors in radiotherapy and improve the quality of trial data and outcomes, and can be applied to optimize clinical radiotherapy QA.

Tomotherapy for cranio-spinal irradiation.

Tomotherapy is a method of delivering rotational IMRT offering various advantages, notably for complex and large targets such as the cranio-spinal axis. This systematic literature review reports on main clinical outcomes and toxicities in patients with various cancer types that received whole craniospinal axis irradiation (CSI) using Tomotherapy and offers a comprehensive comparison between Tomotherapy and other radiotherapy delivery techniques. Databases including PubMed, PubMed Central, Embase, and Cochrane were searched using the keywords "tomotherapy" AND "craniospinal". Fifty-six papers were included in the review. Patient population was adult in 9 papers, paediatric in 26 papers and mixed in 14 papers. Patients treated with helical Tomotherapy had similar disease-specific clinical outcomes and toxicities as patients treated using other techniques. Compared to any other technique, Tomotherapy provides better target coverage, homogeneity, and conformity in 23, 34 and 22 reports. Tomotherapy showed better organ-at-risk sparing for the thyroid, parotids, cochlea, eyes, heart and esophagus. Beam-On-Time (BOT) was reported to be longer for Tomotherapy in most studies (Median BOT: HT = 11 min, VMAT = 5.49 min, 3DCRT = 1.46 min). In conclusion, Tomotherapy offers good cranio-spinal axis coverage with improved homogeneity and conformity compared to other techniques, but with a considerably longer treatment time. Clinical outcome and toxicities suggest using Tomotherapy for CSI is efficient and safe.

QUARTET: A SIOP Europe project for quality and excellence in radiotherapy and imaging for children and adolescents with cancer.

The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe. QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms' tumour. With nine prospective clinical trials and two retrospective studies within the active portfolio in March 2022, QUARTET will collect one of the largest repositories of paediatric radiotherapy and imaging data, support the clinical assessment of radiotherapy, and evaluate the role and benefit of radiotherapy quality assurance for this cohort of patients within the context of clinical trials.

The spleen as an organ at risk in paediatric radiotherapy: A SIOP-Europe Radiation Oncology Working Group report.

BACKGROUND: Radiation may cause long-term splenic dysfunction, risking potentially fatal late sepsis. We aimed to review this complication's magnitude in paediatric radiotherapy and gauge the level of awareness of the spleen as an organ at risk. METHODS: Clinical trial protocols and radiotherapy guidelines, patient/parent information sheets, and professional guidance documents were reviewed to assess the perceived risk of radiotherapy-related splenic dysfunction. Paediatric oncologists and paediatric radiation oncologists across Europe were surveyed to estimate the level of understanding of this risk and to ascertain current practice. Spleen doses received in practice were examined. A systematic review of relevant publications was undertaken. RESULTS: The risk is not mentioned in most clinical trials, patient information leaflets, or professional guidance documents. When mentioned, a threshold dose of 40 Gy is cited. The survey showed only limited awareness. More than half of patients assessed received spleen doses in excess of 10 Gy. The systematic review identified one paper reporting a relative mortality risk of 5.5 with spleen doses in the 10-20 Gy range. CONCLUSIONS: The risk of mortality from overwhelming infection is poorly recognised. We therefore recommend routine delineation of the spleen. Protocols and guidelines should give a spleen dose objective as low as reasonably achievable, ideally mean <10 Gy without compromise to target volumes. Revised evidence-based guidelines and continuing professional development activities should inform oncologists. Patient/parent information should mention the risk and the dose received be communicated to colleagues. Antibiotic prophylaxis and/or (re)vaccination should be considered if the mean spleen dose is ≥10 Gy.

Organ at risk delineation for radiation therapy clinical trials: Global Harmonization Group consensus guidelines.

BACKGROUND AND PURPOSE: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonization Group (GHG) is a collaborative group of Radiation Therapy Quality Assurance (RTQA) Groups harmonizing and improving RTQA for multi-institutional clinical trials. The objective of the GHG OAR Working Group was to unify OAR contouring guidance across RTQA groups by compiling a single reference list of OARs in line with AAPM TG 263 and ASTRO, together with peer-reviewed, anatomically defined contouring guidance for integration into clinical trial protocols independent of the radiation therapy delivery technique. MATERIALS AND METHODS: The GHG OAR Working Group comprised of 22 multi-professional members from 6 international RTQA Groups and affiliated organizations conducted the work in 3 stages: (1) Clinical trial documentation review and identification of structures of interest (2) Review of existing contouring guidance and survey of proposed OAR contouring guidance (3) Review of survey feedback with recommendations for contouring guidance with standardized OAR nomenclature. RESULTS: 157 clinical trials were examined; 222 OAR structures were identified. Duplicates, non-anatomical, non-specific, structures with more specific alternative nomenclature, and structures identified by one RTQA group were excluded leaving 58 structures of interest. 6 OAR descriptions were accepted with no amendments, 41 required minor amendments, 6 major amendments, 20 developed as a result of feedback, and 5 structures excluded in response to feedback. The final GHG consensus guidance includes 73 OARs with peer-reviewed descriptions (Appendix A). CONCLUSION: We provide OAR descriptions with standardized nomenclature for use in clinical trials. A more uniform dataset supports the delivery of clinically relevant and valid conclusions from clinical trials.

The Development of Activity Profiles in Adolescent Females and their Association with Adiposity.

OBJECTIVES: This study aims to (1) use the objective activPAL activity monitor to assess physical activity behaviors, including sitting/lying, standing, and both light (LIPA) and moderate-to-vigorous physical activity (MVPA); (2) to develop distinct activity profiles based on time spent in each behavior in a sample of adolescent females; and (3) examine whether levels of adiposity differ across these activity profiles. METHODS: Female adolescents (n = 195; 14-18 y) had body mass index (median = 21.7 [IQR = 5.2] kg/m2) and 4-site skinfold thickness (median 62.0 mm; IQR = 37.1) measured. Physical activity behaviors were measured using the activPAL. Hierarchical cluster analysis grouped participants into activity profiles based on similar physical activity characteristics. Linear mixed models explored differences in body composition across activity profiles. RESULTS: Three activity profiles were identified, a low (n = 35), moderate (n = 110), and a high activity profile (n = 50). Significant differences across activity profiles were observed for skinfold thickness (p = .046), with higher values observed in the low activity profile compared with the high activity profile. CONCLUSIONS: Profiling free-living activity using behaviors from across the activity intensity continuum may account for more of the variability in energy expenditure then examining specific activity intensities, such as MVPA alone. The use of activity profiles may enable the identification of individuals with unhealthy activity behaviors, leading to the development and implementation of more targeted interventions.