Comparison of the use of a clinically implemented deep learning segmentation model with the simulated study setting for breast cancer patients receiving radiotherapy.

BACKGROUND: Deep learning (DL) models for auto-segmentation in radiotherapy have been extensively studied in retrospective and pilot settings. However, these studies might not reflect the clinical setting. This study compares the use of a clinically implemented in-house trained DL segmentation model for breast cancer to a previously performed pilot study to assess possible differences in performance or acceptability. MATERIAL AND METHODS: Sixty patients with whole breast radiotherapy, with or without an indication for locoregional radiotherapy were included. Structures were qualitatively scored by radiotherapy technologists and radiation oncologists. Quantitative evaluation was performed using dice-similarity coefficient (DSC), 95th percentile of Hausdorff Distance (95%HD) and surface DSC (sDSC), and time needed for generating, checking, and correcting structures was measured. RESULTS: Ninety-three percent of all contours in clinic were scored as clinically acceptable or usable as a starting point, comparable to 92% achieved in the pilot study. Compared to the pilot study, no significant changes in time reduction were achieved for organs at risks (OARs). For target volumes, significantly more time was needed compared to the pilot study for patients including lymph node levels 1-4, although time reduction was still 33% compared to manual segmentation. Almost all contours have better DSC and 95%HD than inter-observer variations. Only CTVn4 scored worse for both metrics, and the thyroid had a higher 95%HD value. INTERPRETATION: The use of the DL model in clinical practice is comparable to the pilot study, showing high acceptability rates and time reduction.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Inter-observer variability in library plan selection on iterative CBCT and synthetic CT images of cervical cancer patients.

INTRODUCTION: In the Library-of-Plans (LoP) approach, correct plan selection is essential for delivering radiotherapy treatment accurately. However, poor image quality of the cone-beam computed tomography (CBCT) may introduce inter-observer variability and thereby hamper accurate plan selection. In this study, we investigated whether new techniques to improve the CBCT image quality and improve consistency in plan selection, affects the accuracy of LoP selection in cervical cancer patients. MATERIALS AND METHODS: CBCT images of 12 patients were used to investigate the inter-observer variability of plan selection based on different CBCT image types. Six observers were asked to individually select a plan based on clinical X-ray Volumetric Imaging (XVI) CBCT, iterative reconstructed CBCT (iCBCT) and synthetic CTs (sCT). Selections were performed before and after a consensus meeting with the entire group, in which guidelines were created. A scoring by all observers on the image quality and plan selection procedure was also included. For plan selection, Fleiss' kappa (κ) statistical test was used to determine the inter-observer variability within one image type. RESULTS: The agreement between observers was significantly higher on sCT compared to CBCT. The consensus meeting improved the duration and inter-observer variability. In this manuscript, the guidelines attributed the overall results in the plan selection. Before the meeting, the gold standard was selected in 76% of the cases on XVI CBCT, 74% on iCBCT, and 76% on sCT. After the meeting, the gold standard was selected in 83% of the cases on XVI CBCT, 81% on iCBCT, and 90% on sCT. CONCLUSION: The use of sCTs can increase the agreement of plan selection among observers and the gold standard was indicated to be selected more often. It is important that clear guidelines for plan selection are implemented in order to benefit from the increased image quality, accurate selection, and decrease inter-observer variability.

European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus on re-irradiation: definition, reporting, and clinical decision making.

Re-irradiation can be considered for local recurrence or new tumours adjacent to a previously irradiated site to achieve durable local control for patients with cancer who have otherwise few therapeutic options. With the use of new radiotherapy techniques, which allow for conformal treatment plans, image guidance, and short fractionation schemes, the use of re-irradiation for different sites is increasing in clinical settings. Yet, prospective evidence on re-irradiation is scarce and our understanding of the underlying radiobiology is poor. Our consensus on re-irradiation aims to assist in re-irradiation decision making, and to standardise the classification of different forms of re-irradiation and reporting. The consensus has been endorsed by the European Society for Radiotherapy and Oncology and the European Organisation for Research and Treatment of Cancer. The use of this classification in daily clinical practice and research will facilitate accurate understanding of the clinical implications of re-irradiation and allow for cross-study comparisons. Data gathered in a uniform manner could be used in the future to make recommendations for re-irradiation on the basis of clinical evidence. The consensus document is based on an adapted Delphi process and a systematic review of the literature was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

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.

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.

LINAC based stereotactic radiosurgery for multiple brain metastases: guidance for clinical implementation.

Introduction: Stereotactic radiosurgery (SRS) is a promising treatment option for patients with multiple brain metastases (BM). Recent technical advances have made LINAC based SRS a patient friendly technique, allowing for accurate patient positioning and a short treatment time. Since SRS is increasingly being used for patients with multiple BM, it remains essential that SRS be performed with the highest achievable quality in order to prevent unnecessary complications such as radionecrosis. The purpose of this article is to provide guidance for high-quality LINAC based SRS for patients with BM, with a focus on single isocenter non-coplanar volumetric modulated arc therapy (VMAT). Methods: The article is based on a consensus statement by the study coordinators and medical physicists of four trials which investigated whether patients with multiple BM are better palliated with SRS instead of whole brain radiotherapy (WBRT): A European trial (NCT02353000), two American trials and a Canadian CCTG lead intergroup trial (CE.7). This manuscript summarizes the quality assurance measures concerning imaging, planning and delivery. Results: To optimize the treatment, the interval between the planning-MRI (gadolinium contrast-enhanced, maximum slice thickness of 1.5 mm) and treatment should be kept as short as possible (< two weeks). The BM are contoured based on the planning-MRI, fused with the planning-CT. GTV-PTV margins are minimized or even avoided when possible. To maximize efficiency, the preferable technique is single isocenter (non-)coplanar VMAT, which delivers high doses to the target with maximal sparing of the organs at risk. The use of flattening filter free photon beams ensures a lower peripheral dose and shortens the treatment time. To bench mark SRS treatment plan quality, it is advisable to compare treatment plans between hospitals. Conclusion: This paper provides guidance for quality assurance and optimization of treatment delivery for LINAC-based radiosurgery for patients with multiple BM.

Whole brain radiotherapy versus stereotactic radiosurgery for 4-10 brain metastases: a phase III randomised multicentre trial.

BACKGROUND: Maintenance of quality of life is the primary goal during treatment of brain metastases (BM). This is a protocol of an ongoing phase III randomised multicentre study. This study aims to determine the exact additional palliative value of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with 4-10 BM. METHODS: The study will include patients with 4-10 BM from solid primary tumours diagnosed on a high-resolution contrast-enhanced MRI scan with a maximum lesional diameter of 2.5 cm in any direction and a maximum cumulative lesional volume of 30 cm3. Patients will be randomised between WBRT in five fractions of 4 Gy to a total dose of 20 Gy (standard arm) and single dose SRS to the BMs (study arm) in the range of 15-24 Gy. The largest BM or a localisation in the brainstem will determine the prescribed SRS dose. The primary endpoint is difference in quality of life (EQ5D EUROQOL score) at 3 months after radiotherapy with regard to baseline. Secondary endpoints are difference in quality of life (EQ5D EUROQOL questionnaire) at 6, 9 and 12 months after radiotherapy with regard to baseline. Other secondary endpoints are at 3, 6, 9 and 12 months after radiotherapy survival, Karnofsky ≥ 70, WHO performance status, steroid use (mg), toxicity according to CTCAE V4.0 including hair loss, fatigue, brain salvage during follow-up, type of salvage, time to salvage after randomisation and Barthel index. Facultative secondary endpoints are neurocognition with the Hopkins verbal learning test revised, quality of life EORTC QLQ-C30, quality of life EORTC BN20 brain module and fatigue scale EORTC QLQ-FA13. DISCUSSION: Worldwide, most patients with more than 4 BM will be treated with WBRT. Considering the potential advantages of SRS over WBRT, i.e. limiting radiation doses to uninvolved brain and a high rate of local tumour control by just a single treatment with fewer side effects, such as hair loss and fatigue, compared to WBRT, SRS might be a suitable alternative for patients with 4-10 BM. TRIAL REGISTRATION: Trial registration number: NCT02353000 , trial registration date 15th January 2015, open for accrual 1st July 2016, nine patients were enrolled in this trial on 14th April 2017.

Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.

BACKGROUND: The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. METHODS: Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). FINDINGS: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). INTERPRETATION: SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. FUNDING: Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.

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.

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.

Real-time motion management in MRI-guided radiotherapy: Current status and AI-enabled prospects.

MRI-guided radiotherapy (MRIgRT) is a highly complex treatment modality, allowing adaptation to anatomical changes occurring from one treatment day to the other (inter-fractional), but also to motion occurring during a treatment fraction (intra-fractional). In this vision paper, we describe the different steps of intra-fractional motion management during MRIgRT, from imaging to beam adaptation, and the solutions currently available both clinically and at a research level. Furthermore, considering the latest developments in the literature, a workflow is foreseen in which motion-induced over- and/or under-dosage is compensated in 3D, with minimal impact to the radiotherapy treatment time. Considering the time constraints of real-time adaptation, a particular focus is put on artificial intelligence (AI) solutions as a fast and accurate alternative to conventional algorithms.

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.

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113-08113 LungTech Phase II Trial Results.

INTRODUCTION: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. 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 for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. RESULTS: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six 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%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [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 three 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 adverse events and late adverse events ≥ 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. CONCLUSIONS: 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 a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.

Refining Treatment Planning in STereotactic Arrhythmia Radioablation: Benchmark Results and Consensus Statement From the STOPSTORM.eu Consortium.

PURPOSE: STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia. However, clinical data are scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization. METHODS AND MATERIALS: Planning target volumes (PTVs) overlapping extracardiac organs-at-risk and/or cardiac substructures were generated for 3 STAR cases. Participating centers were asked to create single-fraction treatment plans with 25 Gy dose prescriptions based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for International Commission on Radiation Units and Measurements report 91 relevant parameters and crowd dose-volume histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process. RESULTS: Twenty centers submitted 67 treatment plans for this study. In most plans (75%) intensity modulated arc therapy with 6 MV flattening filter free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96%-100% (19%). Many participants preferred to spare close extracardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged from 25.5 to 34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged from 2 to 80 minutes. For the consensus statements, a strong agreement was reached for beam technique planning, dose calculation, prescription methods, and trade-offs between target and extracardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target. CONCLUSIONS: This STOPSTORM multicenter treatment planning benchmark study not only showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established; however, clinical data are urgently needed for actionable guidelines for treatment planning.

Evaluation of a clinically introduced deep learning model for radiotherapy treatment planning of breast cancer.

Deep learning (DL) models are increasingly studied to automate the process of radiotherapy treatment planning. This study evaluates the clinical use of such a model for whole breast radiotherapy. Treatment plans were automatically generated, after which planners were allowed to manually adapt them. Plans were evaluated based on clinical goals and DVH parameters. Thirty-seven of 50plans did fulfill all clinical goals without adjustments. Thirteen of these 37 plans were still adjusted but did not improve mean heart or lung dose. These results leave room for improvement of both the DL model as well as education on clinically relevant adjustments.

Comparison of the output of a deep learning segmentation model for locoregional breast cancer radiotherapy trained on 2 different datasets.

Introduction: The development of deep learning (DL) models for auto-segmentation is increasing and more models become commercially available. Mostly, commercial models are trained on external data. To study the effect of using a model trained on external data, compared to the same model trained on in-house collected data, the performance of these two DL models was evaluated. Methods: The evaluation was performed using in-house collected data of 30 breast cancer patients. Quantitative analysis was performed using Dice similarity coefficient (DSC), surface DSC (sDSC) and 95th percentile of Hausdorff Distance (95% HD). These values were compared with previously reported inter-observer variations (IOV). Results: For a number of structures, statistically significant differences were found between the two models. For organs at risk, mean values for DSC ranged from 0.63 to 0.98 and 0.71 to 0.96 for the in-house and external model, respectively. For target volumes, mean DSC values of 0.57 to 0.94 and 0.33 to 0.92 were found. The difference of 95% HD values ranged 0.08 to 3.23 mm between the two models, except for CTVn4 with 9.95 mm. For the external model, both DSC and 95% HD are outside the range of IOV for CTVn4, whereas this is the case for the DSC found for the thyroid of the in-house model. Conclusions: Statistically significant differences were found between both models, which were mostly within published inter-observer variations, showing clinical usefulness of both models. Our findings could encourage discussion and revision of existing guidelines, to further decrease inter-observer, but also inter-institute variability.

Corrigendum to "Harmonization of breast cancer radiotherapy treatment planning in the Netherlands" [Tech. Innov. Patient Support Radiat. Oncol. 19 (2021) 26-32].

[This corrects the article DOI: 10.1016/j.tipsro.2021.06.004.].

Anatomical evaluation of deep-learning synthetic computed tomography images generated from male pelvis cone-beam computed tomography.

Background and purpose: To improve cone-beam computed tomography (CBCT), deep-learning (DL)-models are being explored to generate synthetic CTs (sCT). The sCT evaluation is mainly focused on image quality and CT number accuracy. However, correct representation of daily anatomy of the CBCT is also important for sCTs in adaptive radiotherapy. The aim of this study was to emphasize the importance of anatomical correctness by quantitatively assessing sCT scans generated from CBCT scans using different paired and unpaired dl-models. Materials and methods: Planning CTs (pCT) and CBCTs of 56 prostate cancer patients were included to generate sCTs. Three different dl-models, Dual-UNet, Single-UNet and Cycle-consistent Generative Adversarial Network (CycleGAN), were evaluated on image quality and anatomical correctness. The image quality was assessed using image metrics, such as Mean Absolute Error (MAE). The anatomical correctness between sCT and CBCT was quantified using organs-at-risk volumes and average surface distances (ASD). Results: MAE was 24 Hounsfield Unit (HU) [range:19-30 HU] for Dual-UNet, 40 HU [range:34-56 HU] for Single-UNet and 41HU [range:37-46 HU] for CycleGAN. Bladder ASD was 4.5 mm [range:1.6-12.3 mm] for Dual-UNet, 0.7 mm [range:0.4-1.2 mm] for Single-UNet and 0.9 mm [range:0.4-1.1 mm] CycleGAN. Conclusions: Although Dual-UNet performed best in standard image quality measures, such as MAE, the contour based anatomical feature comparison with the CBCT showed that Dual-UNet performed worst on anatomical comparison. This emphasizes the importance of adding anatomy based evaluation of sCTs generated by dl-models. For applications in the pelvic area, direct anatomical comparison with the CBCT may provide a useful method to assess the clinical applicability of dl-based sCT generation methods.

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.