Stereotactic body radiotherapy for centrally located inoperable early-stage NSCLC: EORTC 22113-08113 LungTech phase II trial results.

BACKGROUND: The international EORTC phase II single-arm LungTech trial 22113-08113 assessed safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance (RTQA) for any eligible patient, SBRT (8x7.5 Gy, ICRU 83) was delivered. The primary endpoint was freedom from local progression probability at three years after start of SBRT. RESULTS: The trial was closed earlier due to poor accrual related to repeated safety-related pauses in recruitment. Between 08/2015 and 12/2017, 39 patients from 6 European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range, 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Median follow-up was 3.6 years. The 3-year freedom from local progression and overall survival rates were 81.5% (90% CI: 62.7-91.4%) and 61.1% (90%CI: 44.1-74.4%), respectively. Cumulative incidence rates of local, regional and distant progression at 3 years were 6.7% (90% CI: 1.6-17.1%), 3.3% (90% CI: 0.4 - 12.4%) and 29.8% (90% CI: 16.8 - 44.1%), respectively. SBRT-related acute and late AEs ≥ G3 were reported in 6.5% (n=2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4 % (n=6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. CONCLUSION: The LungTech trial suggests that SBRT with 8×7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints and post-SBRT interventions is crucial.

Assessment of bias in scoring of AI-based radiotherapy segmentation and planning studies using modified TRIPOD and PROBAST guidelines as an example.

BACKGROUND AND PURPOSE: Studies investigating the application of Artificial Intelligence (AI) in the field of radiotherapy exhibit substantial variations in terms of quality. The goal of this study was to assess the amount of transparency and bias in scoring articles with a specific focus on AI based segmentation and treatment planning, using modified PROBAST and TRIPOD checklists, in order to provide recommendations for future guideline developers and reviewers. MATERIALS AND METHODS: The TRIPOD and PROBAST checklist items were discussed and modified using a Delphi process. After consensus was reached, 2 groups of 3 co-authors scored 2 articles to evaluate usability and further optimize the adapted checklists. Finally, 10 articles were scored by all co-authors. Fleiss' kappa was calculated to assess the reliability of agreement between observers. RESULTS: Three of the 37 TRIPOD items and 5 of the 32 PROBAST items were deemed irrelevant. General terminology in the items (e.g., multivariable prediction model, predictors) was modified to align with AI-specific terms. After the first scoring round, further improvements of the items were formulated, e.g., by preventing the use of sub-questions or subjective words and adding clarifications on how to score an item. Using the final consensus list to score the 10 articles, only 2 out of the 61 items resulted in a statistically significant kappa of 0.4 or more demonstrating substantial agreement. For 41 items no statistically significant kappa was obtained indicating that the level of agreement among multiple observers is due to chance alone. CONCLUSION: Our study showed low reliability scores with the adapted TRIPOD and PROBAST checklists. Although such checklists have shown great value during development and reporting, this raises concerns about the applicability of such checklists to objectively score scientific articles for AI applications. When developing or revising guidelines, it is essential to consider their applicability to score articles without introducing bias.

Cancer-specific dose and fractionation schedules in stereotactic body radiotherapy for oligometastatic disease: An interim analysis of the EORTC-ESTRO E2-RADIatE OligoCare study.

BACKGROUND AND INTRODUCTION: Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. MATERIALS AND METHODS: Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/ß of 10 Gy for all primaries, and cancer-specific α/ß of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). RESULTS: Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. CONCLUSION: This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).

Knowledge-based versus deep learning based treatment planning for breast radiotherapy.

Background and Purpose: To improve radiotherapy (RT) planning efficiency and plan quality, knowledge-based planning (KBP) and deep learning (DL) solutions have been developed. We aimed to make a direct comparison of these models for breast cancer planning using the same training, validation, and testing sets. Materials and Methods: Two KBP models were trained and validated with 90 RT plans for left-sided breast cancer with 15 fractions of 2.6 Gy. The versions either used the full dataset (non-clean model) or a cleaned dataset (clean model), thus eliminating geometric and dosimetric outliers. Results were compared with a DL U-net model (previously trained and validated with the same 90 RT plans) and manually produced RT plans, for the same independent dataset of 15 patients. Clinically relevant dose volume histogram parameters were evaluated according to established consensus criteria. Results: Both KBP models underestimated the mean heart and lung dose equally 0.4 Gy (0.3-1.1 Gy) and 1.4 Gy (1.1-2.8 Gy) compared to the clinical plans 0.8 Gy (0.5-1.8 Gy) and 1.7 Gy (1.3-3.2 Gy) while in the final calculations the mean lung dose was higher 1.9-2.0 Gy (1.5-3.5 Gy) for both KPB models. The U-Net model resulted in a mean planning target volume dose of 40.7 Gy (40.4-41.3 Gy), slightly higher than the clinical plans 40.5 Gy (40.1-41.0 Gy). Conclusions: Only small differences were observed between the estimated and final dose calculation and the clinical results for both KPB models and the DL model. With a good set of breast plans, the data cleaning module is not needed and both KPB and DL models lead to clinically acceptable results.

Health-related quality of life in men with oligometastatic prostate cancer following metastases-directed stereotactic body radiotherapy: Real-world data from the E2-RADIatE OligoCare cohort.

Objective: To evaluate the impact of metastases-directed stereotactic body radiotherapy (SBRT) on health-related quality of life (HRQoL) in men with oligometastatic prostate cancer (PCa) using real-world data from the OligoCare cohort. Materials and methods: OligoCare is a pragmatic, observational cohort designed to assess the impact of metastases-directed SBRT on patients with oligometastatic disease (OMD). We report an interim analyses of the secondary endpoint HRQoL, assessed using the EORTC QLQ-C30, within six months of metastases-directed SBRT for oligometastatic disease in men with PCa among the first 1600 registered patients. HRQoL data collection was optional within the OligoCare cohort. To compare HRQoL between baseline and first follow-up assessment, a Wilcoxon signed-rank test was used. A multiple linear regression model was used to explore the HRQoL associations with predefined factors. Results: Out of the 1600 registered patients, 658 were treated for oligometastatic PCa, of which 233 had baseline QoL data and 132 patients had both baseline and follow-up HRQoL data. At baseline, most patients had a WHO performance status of 0 or 1 (87 %), were de-novo oligometastatic (79 %), had one metastasis (90 %), and had a good overall global health status (mean 80.81, SD16.11, IQR 75-92). 51 % received hormonal therapy as concomitant systemic treatment. Patients with comorbidities as assessed by the Charlson Comorbidity index had a worse global health status at baseline (-4.88, 95 % CI:-9.35, -0.42). No clinically meaningful significant difference in global health status was observed at first assessment following SBRT (median 3.0 months) compared with baseline (mean difference 2.27, 95 % CI:-1.54, 6.08). Upon evaluating the proportions, meaningful clinically important differences (a 10-point or more difference) was observed in, 17 % and 11 % of the patients reporting deterioration and improvement of global health status, respectively. Conclusion: Metastases-directed stereotactic body radiotherapy had no negative impact on global HRQoL within the first six months after treatment.

Recommendation on the technical and dosimetric data to be included in stereotactic body radiation therapy clinical trial publications based on a systematic review.

The results of phase II and III trials on Stereotactic Body Radiation Therapy (SBRT) increased adoption of SBRT worldwide. The ability to replicate clinical trial outcomes in routine practice depends on the capability to reproduce technical and dosimetric procedures used in the clinical trial. In this systematic review, we evaluated if peer-reviewed publications of clinical trials in SBRT reported sufficient technical data to ensure safe and robust implementation in real world clinics. Twenty papers were selected for inclusion, and data was extracted by a working group of medical physicists created following the ESTRO 2021 physics workshop. A large variability in technical and dosimetric data were observed, with frequent lack of required information for reproducing trial procedures. None of the evaluated studies were judged completely reproducible from a technical perspective. A list of recommendations has been provided by the group, based on the analysis and consensus process, to ensure an adequate reproducibility of technical parameters in primary SBRT clinical trials. Future publications should consider these recommendations to assist transferability of the clinical trial in real world practice.

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.

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.

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.

Critical impact of radiotherapy protocol compliance and quality in the treatment of retroperitoneal sarcomas: Results from the EORTC 62092-22092 STRASS trial.

BACKGROUND: The European Organization for Research and Treatment of Cancer 22092-62092 STRASS trial failed to demonstrate the superiority of neoadjuvant radiotherapy (RT) over surgery alone in patients with retroperitoneal sarcoma. Therefore, an RT quality-assurance program was added to the study protocol to detect and correct RT deviations. The authors report results from the trial RT quality-assurance program and its potential effect on patient outcomes. METHODS: To evaluate the effect of RT compliance on survival outcomes, a composite end point was created. It combined the information related to planning target volume coverage, target delineation, total dose received, and overall treatment time into 2 groups: non-RT-compliant (NRC) for patients who had unacceptable deviation(s) in any of the previous categories and RT-compliant (RC) otherwise. Abdominal recurrence-free survival (ARFS) and overall survival were compared between the 2 groups using a Cox proportional hazard model adjusted for known prognostic factors. RESULTS: Thirty-six of 125 patients (28.8%) were classified as NRC, and the remaining 89 patients (71.2%) were classified as RC. The 3-year ARFS rate was 66.8% (95% confidence interval [CI], 55.8%-75.7%) and 49.8% (95% CI, 32.7%-64.8%) for the RC and NRC groups, respectively (adjusted hazard ratio, 2.32; 95% CI, 1.25-4.32; P = .008). Local recurrence after macroscopic complete resection occurred in 13 of 89 patients (14.6%) versus 2 of 36 patients (5.6%) in the RC and NRC groups, respectively. CONCLUSIONS: The current analysis suggests a significant benefit in terms of ARFS in favor of the RC group. This association did not translate into less local relapses after complete resection in the RC group. Multidisciplinary collaboration and review of cases are critical to avoid geographic misses, especially for rare tumors like retroperitoneal sarcoma.

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.

Generalizability assessment of head and neck cancer NTCP models based on the TRIPOD criteria.

This review aimed to provide an overview of the level of maturity of normal tissue complication probability (NTCP) models for head and neck cancer (HNC) patients. A systematic literature review was performed to retrieve NTCP models for HNC toxicities. Patient population characteristics, NTCP model and the predictors, treatment technique and endpoint definition were extracted per article. Models were then scored based on the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) consensus guidelines to evaluate their generalizability. 335 articles on photon and proton therapy of HNC were identified and 52 relevant articles were further analyzed. Eighteen articles on xerostomia and sticky saliva (TRIPOD types 1a-2b: 15; TRIPOD type 3: 1; TRIPOD types 4a: 1 & 4b:1), thirteen articles on dysphagia and tube feeding dependence (TRIPOD types 1a-2b: 7; TRIPOD type 3: 2; TRIPOD types 4a:2 & 4b:2), five articles on oral mucositis (TRIPOD types 1a-2b: 4; TRIPOD type 4b: 1), seven articles on hypothyroidism (TRIPOD types 1a-2b: 4; TRIPOD type 3: 1; TRIPOD types 4a: 1 & 4b:1), four articles on hearing loss and tinnitus (TRIPOD type 1a: 4) and ten articles on esophagitis (TRIPOD types 1a-2b: 9; TRIPOD type 4a: 1) were included. External validation studies of HNC NTCP models are scarce. Moreover, the majority of them were validating a model developed by the same researchers. Only 2 independent external validation studies were found. There is a strong need to publish external validation studies to get more mature NTCP models applicable in clinical practice.

Impact of deviations in target volume delineation - Time for a new RTQA approach?

The international radiotherapy community has recognised that non-adherence to RT protocols can influence trial endpoints. However this conclusion is based on studies predominantly assessing the impact of deviations in dosimetric or treatment delivery protocol parameters rather than target volume delineation (TVD). This review evaluates the assessment of TVD within Radiation Therapy Quality Assurance (RTQA) programmes in clinical trials and the clinical impact of TVD protocol deviations. The implications for RTQA programmes are discussed. MEDLINE, PreMEDLINE, Embase, Cochrane Library, Web of Science, OpenGrey, WHO International Clinical Trials Registry Platform portal and ClinicalTrials.gov were searched. Full-length articles and conference abstracts were included to avoid publication bias. 5864 abstracts were screened for relevance; 94 full-length articles were reviewed and 5 relevant trials identified. Various classification systems were used to assess protocol deviations; 'unacceptable' or 'major' deviations in TVD occurred in 2.9-13.4% of assessed RT plans (when reported). It was often not possible to establish deviation rates specifically related to TVD as these were frequently combined with other types of protocol deviations. Details on the nature of unacceptable deviations was also not routinely reported and difficulties in establishing a 'consensus' for appropriate TVD for on-trial patients highlighted. Results suggest that deviations in TVD were associated with poorer outcomes for overall survival, local control and treatment-related toxicity; however the data were heterogeneous. RTQA of TVD was retrospective and feedback on the quality of TVD to recruiting centres was not standard. In summary, few trials have published outcomes on the impact of assessing the quality of TVD in trials. We propose that a new approach is now required. Unacceptable TVD deviations must be clearly defined at the time of protocol development to minimise interobserver variation, thereby promoting consistency in RTQA feedback. Prospective TVD reviews should be implemented for trials involving novel or complex RT techniques to identify deviations that require modification prior to treatment delivery. Furthermore, the consistent reporting of RTQA programme outcomes, both within and across trial groups, is of paramount importance to accelerate the evidence-base for the best RTQA approach when assessing TVD and to enable the impact on clinical outcomes within RT trials to be assessed.

Radiotherapy practice for paediatric brain tumours across Europe and quality assurance initiatives: Current situation, international survey and future perspectives.

AIM: The aim of the study is to analyse radiotherapy quality assurance (RTQA) processes in the treatment of paediatric central nervous system (CNS) tumours across Europe. METHODS: The RTQA aspects of major past and current European trials for paediatric CNS tumours were reviewed based on study protocols and publications. A survey among radiation oncologists and paediatric oncologists about the practices of RTQA in paediatric CNS tumours across European countries was also performed. RESULTS: Several (inter)national initiatives to implement RTQA are being developed across Europe, with an apparent paradigm shift from retrospective to prospective RTQA. Experts from 21 of 29 contacted countries responded to the survey. National consensus guidelines for paediatric CNS tumours are available in 10 of 21 countries. Twenty-one of 33 experts believe that the level of involvement of paediatric radiation oncologists in the meetings and activities of the national paediatric oncology societies is adequate. Central storage of radiotherapy data is available in France, Germany and Denmark. RTQA programmes for paediatric brain tumours are available in 7 countries. Twelve of 21 experts believe that there is a well-established national referral network for the radiation treatment of paediatric patients in their respective countries. CONCLUSION: As a result of the review and survey, the following measures are proposed: (1) developing international RT guidelines for paediatric CNS tumours, (2) improving the collaboration between paediatric oncologists and paediatric radiation oncologists, (3) building a central storage system for RT data, (4) implementing international prospective RTQA platforms and (5) promoting European referral networks to reduce inequality.

Radiotherapy quality assurance of SBRT for patients with centrally located lung tumours within the multicentre phase II EORTC Lungtech trial: Benchmark case results.

PURPOSE: To report on the benchmark case (BC) study performed in the context of the European Organisation for Research and Treatment of Cancer prospective multicentre Lungtech trial of SBRT for patients with inoperable centrally located lung tumours. METHODS AND MATERIALS: Target volume and organs at risk (OARs) delineations first needed to be acceptable before the treatment plan was reviewed. Retrospectively, Dice similarity coefficients of the OARs and the target volumes were calculated and a set of gold standard contours adapted for each institution margins was applied on the accepted dose submissions to evaluate the influence of acceptable delineation variations on dosimetry. RESULTS: Twenty-five institutions participated. Five BCs were accepted at the first attempt. Twenty institutions had to revise their delineation at least once and seven had to revise their planning once. The V60 Gy dose coverage improved significantly (p = 0.05) between the first and final submissions from median (range) 94.8% (22.5-97.8) to 95.3% (70.5-99.3). The median Dice coefficient varied significantly between OARs: The lowest values were found for the brachial plexus 0.25 (0.01-0.54) and the highest for the spinal cord 0.89 (0.71-0.95). The mean PTV Dice coefficient was 0.82 (0.48-0.92). Applying the gold standard contours, only one institution remained compliant with the dose coverage criteria with V60 Gy median (range) of 83.4% (54.2-93.9). CONCLUSIONS: Clinical guidelines and radiotherapy protocols are not a substitute for timely radiotherapy quality assurance procedures, which improve dose coverage significantly. Delineation remains the main source of BC rejection and plan review without first reviewing delineation may not be efficient. Our results show that delineation variations seem to have a larger influence on PTV coverage than variations in planning and irradiation techniques and thus suggest that dose tolerance criteria should preferably take into account the accuracy of delineation.