Challenges and opportunities for early phase clinical trials of novel drug-radiotherapy combinations: recommendations from NRG Oncology, the American Society for Radiation Oncology (ASTRO), the American College of Radiology (ACR), the Sarah Cannon Research Institute, and the American College of Radiation Oncology (ACRO).

NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug-drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug-radiotherapy combinations.

Pilot study of radiation oncology peer review in low middle income country (LMIC) through cloud-based platform.

PURPOSE: Peer review is an essential step in clinical quality assurance for radiation therapy. There are very little data on peer reviews from low-middle-income countries (LMIC). With increasing access to advanced technologies in LMIC also, peer review is becoming more important to ensure quality and standard of care. We evaluated cloud-based e-Peer review in our network of cancer centers in India with an aim to study its feasibility and impact on care. MATERIALS AND METHODS: Four out of 13 cancer centers across India were selected for this pilot study. All team members were trained on the e-Peer review platform before the initiation of the study. A lead dosimetrist from a centralized planning site was selected to share new cases every week. Cases treated with only definitive intent were selected. The link to the cases was sent through an email to reviewing physicians. The following aspects were reviewed for each case. 1) Work up and staging. 2) Treatment intent and prescription. 3) Target contours. 4) Normal organ at risk contours. 5) Dose-volume-histogram (DVH) with clinical goals attached. Cases were marked as "Not Appropriate," "Appropriate," "Appropriate with minor finding," and "Represent with major revisions" as per volume and plan review. RESULTS: Over a period of 3 months, 100 cases underwent peer review before the start of treatment. Median turnover time was 48 (interquartile range: 24-96) hours. The median time for review was 8 min with time to review cases requiring major and minor changes being 12 and 6 min, respectively (P < 0.001). Of all the cases reviewed, no changes, minor changes, and major changes were suggested for 36%, 48%, and 16% of cases, respectively. The most frequent reason for major changes was contouring corrections (15%). Also, 31.3% of major changes underwent recontouring and replanning before initiation of treatment. CONCLUSION: Peer review was feasible in our setting through this cloud-based peer review system, with median turnover time and time taken for review being 48 h and 8 min, respectively. Like published data from the Western world, peer review led to changes that could impact patient care delivery and outcome. We plan to implement this across the remaining centers in our network.

The Future of Safety and Quality in Radiation Oncology.

The increasing complexity of radiation therapy treatment presents new potentials for error and suboptimal care. High-performing programs thus not only require adherence to, but also ongoing improvement of, key safety and quality practices. In this article, we review these practices including standardization, risk analysis, peer review, and maintenance of strong safety culture, while also describing recent innovations and promising future directions. We specifically highlight the growing role of artificial intelligence in radiation oncology, both as a tool to deliver safe, high-quality care and as a potential new source of safety challenges.

Implementing a Nurse-Driven Pregnancy Screening Protocol in the Radiation Oncology Setting.

Verification of pregnancy status prior to initiating radiation treatment for cancer is important to preserve patient and fetal safety. However, many institutions lack clear guidelines for pregnancy screening prior to treatmen.

Peer Review in Radiation Oncology: Where Does the Middle East, North Africa, and Türkiye Region Stand?

PURPOSE: This study aims to assess the status of radiation oncology peer review procedures across the Middle East, North Africa, and Türkiye (MENAT) region. METHODS: A cross-sectional electronic survey was conducted among radiotherapy centers in the MENAT region in March 2024. It assessed peer review practices, departmental demographics, perceived importance of peer review, and potential barriers. RESULTS: Data from 177 radiation oncology centers revealed varying peer review implementation across the MENAT region. Egypt had the highest participation (16.4%) among all responders. Most centers (31%) treated 500-1,000 cases annually. The majority (77.4%) implemented peer review, with varying levels between countries and across different centers. Advanced radiotherapy techniques significantly correlated with implementation of peer review (P < .05). Peer review meetings were mostly scheduled on a weekly basis (46%) and organized by radiation oncologists (84.7%). Target volume contouring (89%) and radiotherapy prescription (82%) were frequently peer-reviewed. Respondents with peer review at their institutions significantly valued peer review for education, adherence to guidelines, improving planning protocols, and reducing variation in practice institutions without peer review (P < .05). The most frequently reported barriers to peer review were having a high number of patients (56%) and shortage of time (54%). CONCLUSION: Peer review is essential for improving the quality of practice in radiation oncology. Despite some discrepancies, numerous obstacles, and challenges in implementation, it is instrumental in the improvement of patient care in most centers throughout the region. Raising awareness among radiation oncologists about the importance of peer review is paramount to lead to better outcomes.

Development and psychometric validation of a patient safety assessment tool in German Radiation Oncology: the PaSaGeRO Study protocol.

INTRODUCTION: Ensuring patient safety in radiation oncology is crucial for delivering high-quality healthcare. Patient safety indicators (PSIs) provide a mechanism for identifying, quantifying and evaluating risks and the effectiveness of safety measures. However, there is currently no specialised set of PSIs tailored for radiation oncology in Germany. This study seeks to: (1) create PSIs specifically designed for radiation oncology settings, (2) develop and psychometrically validate an instrument for assessing safety in German radiation oncology facilities and (3) evaluate the feasibility of implementing this instrument in routine clinical practice. The finalised questionnaire will serve as a self-assessment instrument for radiation oncology departments, aiding them in evaluating their efficacy in ensuring patient safety, prioritising safety interventions and tracking performance over time. METHODS AND ANALYSIS: We are undertaking a 3-year, mixed methods study to address our objectives. For the identification of PSIs, we will conduct a comprehensive review on the PubMed database, along with reviewing national and international guidelines and recommendations. To refine the initial set of indicators, we will consult with experts, including physicians, medical physicists, nurses, administrators and radiation therapists through focus groups. We will employ a Delphi study for the final consensus and selection of indicators. Additionally, the perspectives of patients will be incorporated by formation of a project patient's committee which meets throughout the project phases. We will reformulate the identified PSIs into questionnaire items. The questionnaire's clarity and comprehensibility will be validated through cognitive interviews, followed by psychometric testing in a pilot group of over 150 participants from German radiation oncology departments. The final version of the questionnaire will then be implemented in routine healthcare settings and we will interview individual users about their experiences with the questionnaire in semistructured interviews. We will convene a subsequent expert workshop to discuss the study results and explore avenues for the questionnaire's broader implementation. The finalised questionnaire will be made accessible via a web app. We hereby present the study potocol as a pre-results report. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Hamburg Ethics Committee (Approval Number: 2023-101018-BO-ff). This trial is registered by the ARO (Arbeitsgemeinschaft Radioonkologie /working group for radiation oncology of the German Cancer Society), protocol number 2023-03 and in the German register for clinical trials with the number DRKS00034690. Study results will be published in conference papers and talks as well as journal papers with focus on open access journals. The results will be also disseminated during the implementation workshop in phase III, which will involve a diverse group of stakeholders. TRIAL REGISTRATION NUMBER: DRKS00034690.

Measuring the quality of care in metastatic colorectal cancer: a scoping review of quality indicators.

BACKGROUND: Quality indicators are essential for measuring and benchmarking the quality of cancer care. Although there are well-established metrics for early-stage colorectal cancer (CRC), few exist for advanced CRC. This scoping review aimed to collate and review all quality indicators for metastatic CRC. METHODS: A dedicated search was performed of Web of Science, PubMed, CINAHL, and relevant gray literature to identify quality indicators for metastatic CRC, evaluating the diagnostic workup, systemic anticancer treatments, surgical approaches, radiation approaches, supportive care, and palliative or terminal care provided to patients. RESULTS: We identified 11 articles, of which 5 were systematized reviews and 6 concerned the development, validation, or operationalization of quality indicators. Thirty-five distinct quality indicators for metastatic CRC were extracted across 6 domains of care: 1) diagnosis, staging, and treatment planning; 2) systemic anticancer treatment; 3) radiation oncology; 4) surgical approaches; 5) supportive care; and 6) palliative and end-of-life care, with a general quality indicator of overall survival. Of the 35 quality indicators extracted, 8 (23%) were unique to metastatic CRC and 27 (77%) were generic quality indicators across different tumor types but applicable to metastatic CRC. CONCLUSION: There are few quality indicators specifically relevant to metastatic CRC. Those that do exist are generally generic process measures used across tumor types and do not measure the nuance or complexity of current multidisciplinary treatment of patients with metastatic CRC.

Surgical Perspectives on the Updated ASTRO Guideline on Partial Breast Irradiation for Breast Cancer.

This is an executive summary of the most recent American Society for Radiation Oncology (ASTRO) guidelines on use of partial breast irradiation in early-stage breast cancer.In the conscientious pursuit of "right-sizing" the management of patients with early-stage breast cancer, there has been an emphasis on judicious de-escalation of therapy. A component of this paradigm shift is partial breast irradiation (PBI), an approach characterized by targeted radiation therapy (RT) to lumpectomy cavity margins rather than to the whole breast (i.e., whole breast irradiation [WBI]) after breast conservation surgery (BCS). The American Society for Radiation Oncology (ASTRO) recently completed a revision of its evidence-based guidelines for the application of PBI.1To accomplish this, recent PBI data were reviewed by panel members, including representatives of the American Society for Radiation Oncology (ASTRO), in collaboration with the American Society of Clinical Oncology (ASCO), and the Society of Surgical Oncology (SSO), which provided representatives and peer reviewers. The guideline was approved by the ASTRO Board of Directors and endorsed by the Canadian Association of Radiation Oncology, European Society for Radiotherapy and Oncology, Royal Australian and New Zealand College of Radiologists, and the Society of Surgical Oncology.The recommendations focused on indications for PBI as an alternative to WBI and technical considerations specific to PBI. This editorial provides a summary and comments on the updated ASTRO PBI guidelines, offering insights into the implications of these findings for clinical practice and multidisciplinary decision-making while underscoring technical considerations for optimal incorporation of PBI into patient care.

A method for empirically validating FMEA RPN scores in a radiation oncology clinic using physics QC data.

In failure modes and effects analysis (FMEA), the components of the risk priority number (RPN) for a failure mode (FM) are often chosen by consensus. We describe an empirical method for estimating the occurrence (O) and detectability (D) components of a RPN. The method requires for a given FM that its associated quality control measure be performed twice as is the case when a FM is checked for in an initial physics check and again during a weekly physics check. If instances of the FM caught by these checks are recorded, O and D can be computed. Incorporation of the remaining RPN component, Severity, is discussed. This method can be used as part of quality management design ahead of an anticipated FMEA or afterwards to validate consensus values.

A joint ESTRO and AAPM guideline for development, clinical validation and reporting of artificial intelligence models in radiation therapy.

BACKGROUND AND PURPOSE: Artificial Intelligence (AI) models in radiation therapy are being developed with increasing pace. Despite this, the radiation therapy community has not widely adopted these models in clinical practice. A cohesive guideline on how to develop, report and clinically validate AI algorithms might help bridge this gap. METHODS AND MATERIALS: A Delphi process with all co-authors was followed to determine which topics should be addressed in this comprehensive guideline. Separate sections of the guideline, including Statements, were written by subgroups of the authors and discussed with the whole group at several meetings. Statements were formulated and scored as highly recommended or recommended. RESULTS: The following topics were found most relevant: Decision making, image analysis, volume segmentation, treatment planning, patient specific quality assurance of treatment delivery, adaptive treatment, outcome prediction, training, validation and testing of AI model parameters, model availability for others to verify, model quality assurance/updates and upgrades, ethics. Key references were given together with an outlook on current hurdles and possibilities to overcome these. 19 Statements were formulated. CONCLUSION: A cohesive guideline has been written which addresses main topics regarding AI in radiation therapy. It will help to guide development, as well as transparent and consistent reporting and validation of new AI tools and facilitate adoption.

2024 Guidelines for reporting radiation therapy in veterinary medicine.

Evidence-based medicine drives patient care decision-making; thus, accurate and complete reporting in scientific publications is paramount. A checklist for complete reporting of veterinary radiation therapy was proposed in 2012 using the recommendations of the International Commission of Radiation Units and Measurements (ICRU). The purpose of this study is to review the 2012 checklist and propose updates based on changes in technology. Significant technology advancements have gained traction in veterinary medicine, including intensity-modulated radiation therapy (IMRT) and stereotactic radiation therapy (SRT), both of which have related modality-specific ICRU reporting recommendations. The 2012 checklist and proposed 2024 checklist are then used to assess the completeness of reporting in veterinary radiation oncology publications between 2015 and 2022, of which one hundred and eight publications met the inclusion criteria. Prior to the publication of the 2012 checklist (2005-2010), only nine checklist items showed a good level of completeness in reporting, and from 2015 to 2022, this increased to 16 items. Encouraging and/or requiring the use of reporting checklists at the time of manuscript submission may be responsible for this improvement in reporting. Using the 2024 checklist, which is more relevant to publications discussing IMRT and SRT treatments, only 14 of the analyzed checklist items (34%) show a good level of completeness in reporting, suggesting there is a need for updated guidelines to capture the nuances of advanced techniques. This study proposes a 2024 checklist that can be used as a guideline for future reporting of radiation therapy in veterinary medicine.

Re-irradiation practice and ESTRO/EORTC consensus recommendations: 2023 ASTRO education panel.

Indications for re-irradiation are increasing both for palliation and potentially curative attempts to achieve durable local control. This has been in part driven by the technological advances in the last decade including image-guided brachytherapy, volumetric-modulated arc therapy and stereotactic body radiotherapy. These enable high dose focal irradiation to be delivered to a limited target volume with minimal normal tissue re-irradiation. The European Society for Radiotherapy and Oncology (ESTRO) and the European Organisation for Research and Treatment of Cancer (EORTC) have collaboratively developed a comprehensive consensus on re-irradiation practices, aiming to standardise definitions, reporting, and clinical decision-making processes. The document introduces a universally applicable definition for re-irradiation, categorised into two primary types based on the presence of geometric overlap of irradiated volumes and concerns for cumulative dose toxicity. It also identifies "repeat organ irradiation" and "repeat irradiation" for cases without such overlap, emphasising the need to consider toxicity risks associated with cumulative doses. Additionally, the document presents detailed reporting guidelines for re-irradiation studies, specifying essential patient and tumour characteristics, treatment planning and delivery details, and follow-up protocols. These guidelines are designed to improve the quality and reproducibility of clinical research, thus fostering a more robust evidence base for future re-irradiation practices. The consensus underscores the necessity of interdisciplinary collaboration and shared decision-making, highlighting performance status, patient survival estimates, and response to initial radiotherapy as critical factors in determining eligibility for re-irradiation. It advocates for a patient-centric approach, with transparent communication about treatment intent and potential risks. Radiobiological considerations, including the application of the linear-quadratic model, are recommended for assessing cumulative doses and guiding re-irradiation strategies. By providing these comprehensive recommendations, the ESTRO-EORTC consensus aims to enhance the safety, efficacy, and quality of life for patients undergoing re-irradiation, while paving the way for future research and refinement of treatment protocols in the field of oncology.

Associations Between Radiation Oncologist Demographic Factors and Segmentation Similarity Benchmarks: Insights From a Crowd-Sourced Challenge Using Bayesian Estimation.

PURPOSE: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors. METHODS: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference standard benchmark. The Dice similarity coefficient (DSC) was primarily used as a metric for the comparisons. DSC was stratified into binary groups on the basis of structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Bayesian estimation were used to investigate the association between demographic variables and the binarized DSC for each disease site. Variables with a highest density interval excluding zero were considered to substantially affect the outcome measure. RESULTS: Five hundred seventy-four, 110, 452, 112, and 48 segmentations were used for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of segmentations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumors, respectively. Regression analysis revealed that the structure being tumor-related had a substantial negative impact on binarized DSC for the breast, sarcoma, H&N, and GI cases. There were no recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations. CONCLUSION: Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality relative to benchmarks.

The use of master protocols for efficient trial design to evaluate radiotherapy interventions: a systematic review.

The aim of this review was to highlight why the use of master protocols trial design is particularly useful for radiotherapy intervention trials where complex setup pathways (including quality assurance, user training, and integrating multiple modalities of treatment) may hinder clinical advances. We carried out a systematic review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, reviewing the findings using a landscape analysis. Results were summarized descriptively, reporting on trial characteristics highlighting the benefits, limitations, and challenges of developing and implementing radiotherapy master protocols, with three case studies selected to explore these issues in more detail. Twelve studies were suitable for inclusion (4 platform trials, 3 umbrella trials, and 5 basket trials), evaluating a mix of solid tumor sites in both curative and palliative settings. The interventions were categorized into 1) novel agent and radiotherapy combinations; 2) radiotherapy dose personalization; and 3) device evaluation, with a case study provided for each intervention. Benefits of master protocol trials for radiotherapy intervention include protocol efficiency for implementation of novel radiotherapy techniques; accelerating the evaluation of novel agent drug and radiotherapy combinations; and more efficient translational research opportunities, leading to cost savings and research efficiency to improve patient outcomes. Master protocols offer an innovative platform under which multiple clinical questions can be addressed within a single trial. Due to the complexity of radiotherapy trial setup, cost and research efficiency savings may be more apparent than in systemic treatment trials. Use of this research approach may be the change needed to push forward oncological innovation within radiation oncology.

Perceptions on and roadblocks to implementation of standardized nomenclature in radiation oncology: A survey from TG-263U1.

PURPOSE: AAPM Task Group No. 263U1 (Update to Report No. 263 - Standardizing Nomenclatures in Radiation Oncology) disseminated a survey to receive feedback on utilization, gaps, and means to facilitate further adoption. METHODS: The survey was created by TG-263U1 members to solicit feedback from physicists, dosimetrists, and physicians working in radiation oncology. Questions on the adoption of the TG-263 standard were coupled with demographic information, such as clinical role, place of primary employment (e.g., private hospital, academic center), and size of institution. The survey was emailed to all AAPM, AAMD, and ASTRO members. RESULTS: The survey received 463 responses with 310 completed survey responses used for analysis, of whom most had the clinical role of medical physicist (73%) and the majority were from the United States (83%). There were 83% of respondents who indicated that they believe that having a nomenclature standard is important or very important and 61% had adopted all or portions of TG-263 in their clinics. For those yet to adopt TG-263, the staffing and implementation efforts were the main cause for delaying adoption. Fewer respondents had trouble adopting TG-263 for organs at risk (29%) versus target (44%) nomenclature. Common themes in written feedback were lack of physician support and available resources, especially in vendor systems, to facilitate adoption. CONCLUSIONS: While there is strong support and belief in the benefit of standardized nomenclature, the widespread adoption of TG-263 has been hindered by the effort needed by staff for implementation.  Feedback from the survey is being utilized to drive the focus of the update efforts and create tools to facilitate easier adoption of TG-263.

NRG Oncology and Particle Therapy Co-Operative Group Patterns of Practice Survey and Consensus Recommendations on Pencil-Beam Scanning Proton Stereotactic Body Radiation Therapy and Hypofractionated Radiation Therapy for Thoracic Malignancies.

Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally fractionated PBSPT because of concerns of amplified uncertainties at the larger dose per fraction. The NRG Oncology and Particle Therapy Cooperative Group Thoracic Subcommittee surveyed proton centers in the United States to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Among other points, the recommendations highlight the need for volumetric image guidance and multiple computed tomography-based robust optimization and robustness tools to minimize further the effect of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques.

Radiotherapy statements of the 18th St. Gallen International Breast Cancer Consensus Conference-a German expert perspective.

PURPOSE: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. METHODS: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. RESULTS AND CONCLUSION: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy.