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.

A Quality Control Study on Involved Node Radiation Therapy in the European Organisation for Research and Treatment of Cancer/Lymphoma Study Association/Fondazione Italiana Linfomi H10 Trial on Stages I and II Hodgkin Lymphoma: Lessons Learned.

PURPOSE: Involved node radiation therapy (INRT) was introduced in the European Organisation for Research and Treatment of Cancer/Lymphoma Study Association/Fondazione Italiana Linfomi H10 trial, a large multicenter trial in early-stage Hodgkin Lymphoma. The present study aimed to evaluate the quality of INRT in this trial. METHODS AND MATERIALS: A retrospective, descriptive study was initiated to evaluate INRT in a representative sample encompassing approximately 10% of all irradiated patients in the H10 trial. Sampling was stratified by academic group, year of treatment, size of the treatment center, and treatment arm, and it was done proportional to the size of the strata. The sample was completed for all patients with known recurrences to enable future research on relapse patterns. Radiation therapy principle, target volume delineation and coverage, and applied technique and dose were evaluated using the EORTC Radiation Therapy Quality Assurance platform. Each case was reviewed by 2 reviewers and, in case of disagreement also by an adjudicator for a consensus evaluation. RESULTS: Data were retrieved for 66 of 1294 irradiated patients (5.1%). Data collection and analysis were hampered more than anticipated by changes in archiving of diagnostic imaging and treatment planning systems during the running period of the trial. A review could be performed on 61 patients. The INRT principle was applied in 86.6%. Overall, 88.5% of cases were treated according to protocol. Unacceptable variations were predominately due to geographic misses of the target volume delineations. The rate of unacceptable variations decreased during trial recruitment. CONCLUSIONS: The principle of INRT was applied in most of the reviewed patients. Almost 90% of the evaluated patients were treated according to the protocol. The present results should, however, be interpreted with caution because the number of patients evaluated was limited. Individual case reviews should be done in a prospective fashion in future trials. Radiation therapy Quality Assurance tailored to the clinical trial objectives is strongly recommended.

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.

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.

Development of staffing, workload and infrastructure in member departments of the European Organisation for Research and Treatment of Cancer (EORTC) radiation oncology group.

PURPOSE: The EORTC Radiation Oncology Group uses a Facility Questionnaire (FQ) to collect information from its member radiation oncology departments. We analysed the FQ database for patient-related workload, staffing levels and infrastructure to determine developments in radiation oncology departments in the clinical trials community. MATERIALS & METHODS: We exported the FQ database in August 2019. Departments were included if their FQ was created or updated within the two preceding years. Observations were compared with previous evaluations of the FQ database. RESULTS: In total, 161 departments from 24 mostly European countries were analysed. The average number of patients per department increased by 3.0% to 2,453 (2013: 2,381). The annual number of patients decreased by 7.4% to 225 per radiation oncologist (2013: 243) and by 7.9% to 326 per medical physicist (2013: 354). In contrast, the number of patients increased by 23.3% to 106 per radiation therapist (RTT) (2013: 86) and per treatment unit by 3.9 % to 485 (2013: 467). In a pairwise comparison of departments that were available in 2013 and 2019, the number of patients per radiation oncologist (p = 0.02) and per physicist (p = 0.0003) decreased significantly. The number of departments that own a dedicated PET-CT scanner more than doubled (2013: 4%; 2019: 9%) and the availability of stereotactic body radiation therapy (SBRT) increased by 31.8% to 85.7% of the departments (2013: 65%). CONCLUSION: The case-related workload per radiation oncologist and per physicist continues to decrease but increases per RTT and treatment unit. This is likely driven by an increased use of complex techniques, multimodality imaging and the implementation of automation in radiation oncology departments.

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.