Developing and evaluating stereotactic lung RT trials: what we should know about the influence of inhomogeneity corrections on dose

Abstract Purpose To investigate the influence of inhomogeneity corrections on stereotactic treatment plans for non-small cell lung cancer and determine the dose delivered to the PTV and OARs. Materials and methods For 26 patients with stage-I NSCLC treatment plans were optimized with unit density (UD), an equivalent pathlength algorithm (EPL), and a collapsed-cone (CC) algorithm, prescribing 60 Gy to the PTV. After optimization the first two plans were recalculated with the more accurate CC algorithm. Dose parameters were compared for the three different optimized plans. Dose to the target and OARs was evaluated for the recalculated plans and compared with the planned values. Results For the CC algorithm dose constraints for the ratio of the 50% isodose volume and the PTV, and the V20 Gy are harder to fulfill. After recalculation of the UD and EPL plans large variations in the dose to the PTV were observed. For the unit density plans, the dose to the PTV varied from 42.1 to 63.4 Gy for individual patients. The EPL plans all overestimated the PTV dose (average 48.0 Gy). For the lungs, the recalculated V20 Gy was highly correlated to the planned value, and was 12% higher for the UD plans (R2 = 0.99), and 15% lower for the EPL plans (R2 = 0.96). Conclusion Inhomogeneity corrections have a large influence on the dose delivered to the PTV and OARs for SBRT of lung tumors. A simple rescaling of the dose to the PTV is not possible, implicating that accurate dose calculations are necessary for these treatment plans in order to prevent large discrepancies between planned and actually delivered doses to individual patients.</p

Quality assurance of radiotherapy in the ongoing EORTC 22042–26042 trial for atypical and malignant meningioma: Results from the dummy runs and prospective individual case Reviews

BACKGROUND: The ongoing EORTC 22042–26042 trial evaluates the efficacy of high-dose radiotherapy (RT) in atypical/malignant meningioma. The results of the Dummy Run (DR) and prospective Individual Case Review (ICR) were analyzed in this Quality Assurance (QA) study. MATERIAL/METHODS: Institutions were requested to submit a protocol compliant treatment plan for the DR and ICR, respectively. DR-plans (n=12) and ICR-plans (n=50) were uploaded to the Image-Guided Therapy QA Center of Advanced Technology Consortium server (http://atc.wustl.edu/) and were assessed prospectively. RESULTS: Major deviations were observed in 25% (n=3) of DR-plans while no minor deviations were observed. Major and minor deviations were observed in 22% (n=11) and 10% (n=5) of the ICR-plans, respectively. Eighteen% of ICRs could not be analyzed prospectively, as a result of corrupted or late data submission. CTV to PTV margins were respected in all cases. Deviations were negatively associated with the number of submitted cases per institution (p=0.0013), with a cutoff of 5 patients per institutions. No association (p=0.12) was observed between DR and ICR results, suggesting that DR’s results did not predict for an improved QA process in accrued brain tumor patients. CONCLUSIONS: A substantial number of protocol deviations were observed in this prospective QA study. The number of cases accrued per institution was a significant determinant for protocol deviation. These data suggest that successful DR is not a guarantee for protocol compliance for accrued patients. Prospective ICRs should be performed to prevent protocol deviations

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

The European Organisation for Research and Treatment of Cancer, State of Science in radiation oncology and priorities for clinical trials meeting report

Background: New technologies and techniques in radiation oncology and imaging offer opportunities to enhance the benefit of loco-regional treatments, expand treatment to new patient populations such as those with oligometastatic disease and decrease normal tissue toxicity. Furthermore, novel agents have become available which may be combined with radiation therapy, and identification of radiation-related biomarkers can be studied to refine treatment prescriptions. Finally, the use of artificial intelligence (AI) capabilities may also improve treatment quality assurance or the ease with which radiation dosing is prescribed. All of these potential advances present both opportunities and challenges for academic clinical researchers. Methods: Recently, the European Organisation for Research and Treatment of Cancer addressed these topics in a meeting of multiple stakeholders from Europe and North America. The following five themes radiobiology-based biomarkers, new technologies - particularly proton beam therapy, combination systemic and radiation therapy, management of oligometastatic disease and AI opportunities in radiation oncology were discussed in a State of Science format to define key controversies, unanswered questions and propose clinical trial priorities for development. Conclusions: Priorities for clinical trials implementing new science and technologies have been defined. Solutions to integrate the multidimensional complexity of data have been explored. New types of platforms and partnerships can support innovative approaches for clinical research in radiation oncology. (C) 2020 The Authors. Published by Elsevier Ltd

Characterisation and classification of oligometastatic disease : a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation

Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study

Re-irradiation in clinical practice:Results of an international patterns of care survey within the framework of the ESTRO-EORTC E²-RADIatE platform

Background: Re-irradiation is an increasingly utilized treatment for recurrent, metastatic or new malignancies after previous radiotherapy. It is unclear how re-irradiation is applied in clinical practice. We aimed to investigate the patterns of care of re-irradiation internationally. Material/Methods: A cross-sectional survey conducted between March and September 2022. The survey was structured into six sections, each corresponding to a specific anatomical region. Participants were instructed to complete the sections of their clinical expertise. A total of 15 multiple-choice questions were included in each section, addressing various aspects of the re-irradiation process. The online survey targeted radiation and clinical oncologists and was endorsed by the European Society for Radiotherapy and Oncology (ESTRO) and the European Organisation for Research and Treatment of Cancer (EORTC).Results: 371 physicians from 55 countries across six continents participated. Participants had a median professional experience of 16 years, and the majority (60%) were affiliated with an academic hospital. The brain region was the most common site for re-irradiation (77%), followed by the pelvis (65%) and head and neck (63%). Prolonging local control was the most common goal (90–96% across anatomical regions). The most common minimum interval between previous radiotherapy and re-irradiation was 6–12 months (45–55%). Persistent grade 3 or greater radiation-induced toxicity (77–80%) was the leading contraindication. Variability in organs at risk dose constraints for re-irradiation was observed. Advanced imaging modalities and conformal radiotherapy techniques were predominantly used. A scarcity of institutional guidelines for re-irradiation was reported (16–19%). Participants from European centers more frequently applied thoracic and abdominal re-irradiation. Indications did not differ between academic and non-academic hospitals. Conclusion: This study highlights the heterogeneity in re-irradiation practices across anatomical regions and emphasizes the need for high-quality evidence from prospective studies to guide treatment decisions and derive safe cumulative dose constraints.</p

Professional practice changes in radiotherapy physics during the COVID-19 pandemic.

Background and purpose The COVID-19 pandemic has imposed changes in radiotherapy (RT) departments worldwide. Medical physicists (MPs) are key healthcare professionals in maintaining safe and effective RT. This study reports on MPs experience during the first pandemic peak and explores the consequences on their work. Methods A 39-question survey on changes in departmental and clinical practice and on the impact for the future was sent to the global MP community. A total of 433 responses were analysed by professional role and by country clustered on the daily infection numbers. Results The impact of COVID-19 was bigger in countries with high daily infection rate. The majority of MPs worked in alternation at home/on-site. Among practice changes, implementation and/or increased use of hypofractionation was the most common (47% of the respondents). Sixteen percent of respondents modified patient-specific quality assurance (QA), 21% reduced machine QA, and 25% moved machine QA to weekends/evenings. The perception of trust in leadership and team unity was reversed between management MPs (towards increased trust and unity) and clinical MPs (towards a decrease). Changes such as home-working and increased use of hypofractionation were welcomed. However, some MPs were concerned about pressure to keep negative changes (e.g. weekend work). Conclusion COVID-19 affected MPs through changes in practice and QA procedures but also in terms of trust in leadership and team unity. Some changes were welcomed but others caused worries for the future. This report forms the basis, from a medical physics perspective, to evaluate long-lasting changes within a multi-disciplinary setting

Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer:Two externally validated nomograms

Introduction Commonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations. Methods 495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n = 214, patients treated in one hospital) and an external validation cohort n = 281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (<3 months) and long-term survival (>12 months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort. Results Prognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p < 0.05) than the unfavorable groups of the RPA, DS-GPA, GGS, SIR, and Rades 2015 (AUC = 0.70 versus range AUCs = 0.51–0.60 respectively). With an AUC of 0.67, the other nomogram predicted 1 year survival statistically significantly better (p < 0.05) than the favorable groups of four models (range AUCs = 0.57–0.61), except for the SIR (AUC = 0.64, p = 0.34). The models are available on www.predictcancer.org. Conclusion The nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice