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INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P

Purpose: To use imaging data from stereotactic MR-guided online adaptive radiotherapy (SMART) of ultracentral lung tumors (ULT) for development of a safe non-adaptive approach towards stereotactic body radiotherapy (SBRT) of ULT. Patients and Methods: Analysis is based on 19 patients with ULT who received SMART (10 × 5.0–5.5 Gy) on a 0.35 T MR-Linac (MRIdian®) in the prospective MAGELLAN trial. 4D-planning CT data of six patients served to quantify proximal bronchial tree (PBT) breathing motion. Daily fraction MRIs are used to calculate interfractional translations (mediolateral (ML), anterior-posterior (AP), superior-inferior (SI)) and their dosimetric consequences for the PBT. A planning risk volume (PRV) is calculated for an assumed non-adaptive SBRT in deep-inspiration breath hold (DIBH) with surface-guidance (AlignRT®). Finally, non-adaptive volumetric modulated arc (VMAT) SBRT is simulated with and without a PRV for N = 10 patients (10 × 5.5 Gy). Results: The PBT shows relevant breathing motion, especially in superior-inferior direction (median ML: 2.5 mm, AP: 1.9 mm and SI: 9.2 mm). Furthermore, moderate interfractional translations are observed (mean absolute translation ML: 1.3 mm, AP: 1.3 mm, SI: 1.1 mm), with an estimated 2 mm PRV margin for interfractional changes alone. Simulated non-adaptive SBRT leads to PBT overdoses in 60 % of patients (median overdosed fractions VMAT: 2.5, predicted MR-linac plans 4). Both MR-guided online plan adaptation (SMART) and PRV-based non-adaptive VMAT prevent PBT overdoses, but SMART yields significantly higher planning target volume (PTV) coverage (SMART: median 96 % [IQR 95–96], VMAT: median 89 % [IQR 77–94], p = 0.014). Conclusions: Both intrafractional breathing motion and interfractional translations may impact doses to the PBT during SBRT of ULT. SMART protects the PBT from overdoses while maintaining high PTV coverage. Non-adaptive SBRT appears safe with advanced breathing motion management and PRV, but yields inferior PTV coverage.

With the emergence of high-precision radiotherapy technologies such as stereotactic ablative radiotherapy (SABR), MR guided brachytherapy, image guided intensity modulated photon and proton radiotherapy and most recently daily adaptive radiotherapy, reirradiation is increasingly recognized as a viable treatment option for many patients. This includes those with recurrent, metastatic or new malignancies post initial radiotherapy. The primary challenge in reirradiation lies in balancing tumor control against the risk of severe toxicity from cumulative radiation doses to previously irradiated normal tissue.Although technology for precise delivery has advanced at a fast pace, clinical practice of reirradiation still mostly relies on individual expertise, as prospective evidence is scarce, the level of reporting in clinical studies is not standardized and of low quality − especially with respect to cumulative doses received by organs at risk.A recent ESTRO/EORTC initiative proposed a standardized definition of reirradiation and formulated general requirements for minimal reporting in clinical studies [1].As a consequence we found it timely to convene for an international and interdisciplinary meeting with experts in the field to summarize the current evidence, identify knowledge gaps and explore which best practices can be derived for safe reirradiation. The meeting was held on 15.06.2023 in Zurich and was endorsed by the scientific societies SASRO, DEGRO and ESTRO. Here, we report on available evidence and research priorities in the field of reirradiation, as discussed during the meeting.

Aims: Multidisciplinary tumor boards (MDTs) are an integral part of ensuring high-quality, evidence-based and personalized cancer care. In this study, we aimed to evaluate the adherence to and implementation of MDT recommendations in patients with oligometastatic disease (OMD). Methods: We screened all oncologic positron emission tomography (PET) scans conducted at a single comprehensive cancer center in 2020. Patients were included if they had evidence of imaging-based OMD from a solid organ malignancy on the index scans, had their OMD case discussed at an MDT, and were treated and followed up at the same center. A switch away from the MDT-recommended treatment modalities was classified as a major deviation; non-MDT-mandated adjustments to a recommended treatment modality were coded as minor deviation. Clinical data was obtained via chart review; statistical calculations were computed using the R software. Results: After review of PET and/or concurrent brain scans, 787 cases of OMD were identified. Thereof, 347 (44.1 %) cases were discussed at MDT, of which 331 (42.1 %) were therapeutically managed and subsequently followed. The three most commonly recommended therapies were systemic therapy (35.6 %), multimodality treatment including definitive local therapy (17.8 %), and radiotherapy (13.9 %). A major deviation was recorded in 16.3 % of cases (most commonly: none of the MDT-recommended treatment modalities were performed: 19 (35.2 %); not all MDT-planned treatment modalities were performed: 12 (22.2 %); and additional treatment modality was performed: 11 (20.3 %). A minor deviation was found in 1.5 % of cases. On multivariable regression, number of distant metastases (n > 1) was associated with a major deviation (OR: 1.85; 95 % CI, 1.0–3.52). Major deviations were associated with a significantly worse OS (p = 0.0034). Conclusions: Adherence to and implementation of MDT recommendations in OMD patients was generally high (83.7%). Major deviations might be further reduced by more careful and elaborate discussions of OMD patient characteristics s and patient preferences.

BackgroundAccurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable.MethodsA single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed.ResultsIV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed.ConclusionNS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others.

IntroductionThere is a cumulative risk of 20-40% of developing brain metastases (BM) in solid cancers. Stereotactic radiotherapy (SRT) enables the application of high focal doses of radiation to a volume and is often used for BM treatment. However, SRT can cause adverse radiation effects (ARE), such as radiation necrosis, which sometimes cause irreversible damage to the brain. It is therefore of clinical interest to identify patients at a high risk of developing ARE. We hypothesized that models trained with radiomics features, deep learning (DL) features, and patient characteristics or their combination can predict ARE risk in patients with BM before SRT.MethodsGadolinium-enhanced T1-weighted MRIs and characteristics from patients treated with SRT for BM were collected for a training and testing cohort (N = 1,404) and a validation cohort (N = 237) from a separate institute. From each lesion in the training set, radiomics features were extracted and used to train an extreme gradient boosting (XGBoost) model. A DL model was trained on the same cohort to make a separate prediction and to extract the last layer of features. Different models using XGBoost were built using only radiomics features, DL features, and patient characteristics or a combination of them. Evaluation was performed using the area under the curve (AUC) of the receiver operating characteristic curve on the external dataset. Predictions for individual lesions and per patient developing ARE were investigated.ResultsThe best-performing XGBoost model on a lesion level was trained on a combination of radiomics features and DL features (AUC of 0.71 and recall of 0.80). On a patient level, a combination of radiomics features, DL features, and patient characteristics obtained the best performance (AUC of 0.72 and recall of 0.84). The DL model achieved an AUC of 0.64 and recall of 0.85 per lesion and an AUC of 0.70 and recall of 0.60 per patient.ConclusionMachine learning models built on radiomics features and DL features extracted from BM combined with patient characteristics show potential to predict ARE at the patient and lesion levels. These models could be used in clinical decision making, informing patients on their risk of ARE and allowing physicians to opt for different therapies.

Abstract Background Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75–85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. Objective A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. Methods Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. Discussion DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure. Trial registration NCT05594368.

Background and introduction: Growing evidence supports a combined modality treatment strategy for patients with oligometastatic disease. However, lack of phase III trial data and uncertainties around patient selection highlight the importance of multidisciplinary tumor boards (MDT) in therapeutic decision-making. This study aimed to analyze the recognition of and treatment recommendations for oligometastatic patients by MDTs at a large comprehensive cancer center in order to better understand current treatment patterns of oligometastasis. Materials and methods: For this retrospective single-center cross-sectional study, oligometastatic patients were identified by screening oncological PET and concurrent brain MRI scans conducted at our center in 2020. MDT discussions and recommendations within four weeks of the imaging diagnosis of oligometastasis were analyzed. Logistic regression analysis was used to identify predictors for the addition of local therapy to standard-of-care. Results: A total of 787 oligometastatic cases were identified. Lung cancer and mesothelioma, skin cancer, and prostate cancer were the most common histologies with 231 (29 %), 160 (20 %), and 84 (11 %) cases, respectively. Almost half of the cases (46 %) had one distant metastasis on imaging only. More than half (56 %) of all oligometastatic cases were discussed at an MDT. In 47 % of cases, for which a therapeutic recommendation was reached in an MDT, local therapy was part of the therapeutic strategy. On logistic regression analysis, oligometastatic skin cancer was significantly associated with a recommendation for local therapy (p

Radiotherapy in expiration breath-hold (EBH) has the potential to reduce treatment volumes of abdominal targets compared to an internal target volume concept in free-breathing. The reproducibility of EBH and required safety margins were investigated to quantify this volumetric benefit. Pre- and post-treatment diaphragm position difference and the positioning variability were determined on computed tomography. Systematic and random errors for EBH position reproducibility and positioning variability were calculated, resulting in margins of 7 to 12 mm depending on the prescription isodose and fractionation. A reduced volume was shown for EBH for lesions with superior-inferior breathing motion above 4 to 8 mm.