Purpose: Build predictive radiomic models for early relapse and BRCA mutation based on a multicentric database of high-grade serous ovarian cancer (HGSOC) and validate them in a test set coming from different institutions. Methods: Preoperative CTs of patients with HGSOC treated at four referral centers were retrospectively acquired and manually segmented. Hand-crafted features and deep radiomics features were extracted respectively by dedicated software (MODDICOM) and a dedicated convolutional neural network (CNN). Features were selected with and without prior harmonization (ComBat harmonization), and models were built using different machine learning algorithms, including clinical variables. Results: We included 218 patients. Radiomic models showed low performance in predicting both BRCA mutation (AUC in test set between 0.46 and 0.59) and 1-year relapse (AUC in test set between 0.46 and 0.56); deep learning models demonstrated similar results (AUC in the test of 0.48 for BRCA and 0.50 for relapse). The inclusion of clinical variables improved the performance of the radiomic models to predict BRCA mutation (AUC in the test set of 0.74). Conclusions: In our multicentric dataset, representative of a real-life clinical scenario, we could not find a good radiomic predicting model for PFS and BRCA mutational status, with both traditional radiomics and deep learning, but the combination of clinical and radiomic models improved model performance for the prediction of BRCA mutation. These findings highlight the need for standardization through the whole radiomic pipelines and robust multicentric external validations of results.

In multicentric studies, data sharing between institutions might negatively impact patient privacy or data security. An alternative is federated analysis by secure multiparty computation. This pilot study demonstrates an architecture and implementation addressing both technical challenges and legal difficulties in the particularly demanding setting of clinical research on cancer patients within the strict European regulation on patient privacy and data protection: 24 patients from LMU University Hospital in Munich, Germany, and 24 patients from Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy, were treated for adrenal gland metastasis with typically 40 Gy in 3 or 5 fractions of online-adaptive radiotherapy guided by real-time MR. High local control (21% complete remission, 27% partial remission, 40% stable disease) and low toxicity (73% reporting no toxicity) were observed. Median overall survival was 19 months. Federated analysis was found to improve clinical science through privacy-friendly evaluation of patient data in the European health data space.

Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (nCRT). Methods: Pre- and post-nCRT MRIs of LARC patients treated at a single institution from May 2008 to November 2016 were retrospectively collected. Radiomic features were extracted from the GTV and mesorectum. The Wilcoxon–Mann–Whitney test and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the features in predicting pCR and 2yDFS. Results: Out of 203 LARC patients, a total of 565 variables were evaluated. The best performing pCR prediction model was based on two GTV features with an AUC of 0.80 in the training set and 0.69 in the validation set. The best performing 2yDFS prediction model was based on one GTV and two mesorectal features with an AUC of 0.79 in the training set and 0.70 in the validation set. Conclusions: The results of this study suggest a possible role for delta radiomics based on mesorectal features in the prediction of 2yDFS in patients with LARC.

An MR-Linac can provide motion information of tumour and organs-at-risk before, during, and after beam delivery. However, MR imaging cannot provide real-time high-quality volumetric images which capture breath-to-breath variability of respiratory motion. Surrogate-driven motion models relate the motion of the internal anatomy to surrogate signals, thus can estimate the 3D internal motion from these signals. Internal surrogate signals based on patient anatomy can be extracted from 2D cine-MR images, which can be acquired on an MR-Linac during treatment, to build and drive motion models. In this paper we investigate different MRI-derived surrogate signals, including signals generated by applying principal component analysis to the image intensities, or control point displacements derived from deformable registration of the 2D cine-MR images. We assessed the suitability of the signals to build models that can estimate the motion of the internal anatomy, including sliding motion and breath-to-breath variability. We quantitatively evaluated the models by estimating the 2D motion in sagittal and coronal slices of 8 lung cancer patients, and comparing them to motion measurements obtained from image registration. For sagittal slices, using the first and second principal components on the control point displacements as surrogate signals resulted in the highest model accuracy, with a mean error over patients around 0.80 mm which was lower than the in-plane resolution. For coronal slices, all investigated signals except the skin signal produced mean errors over patients around 1 mm. These results demonstrate that surrogate signals derived from 2D cine-MR images, including those generated by applying principal component analysis to the image intensities or control point displacements, can accurately model the motion of the internal anatomy within a single sagittal or coronal slice. This implies the signals should also be suitable for modelling the 3D respiratory motion of the internal anatomy.

Predicting pathological complete response (pCR) from pre or post-treatment features could be significant in improving the process of making clinical decisions and providing a more personalized treatment approach for better treatment outcomes. However, the lack of external validation of predictive models, missing in several published articles, is a major issue that can potentially limit the reliability and applicability of predictive models in clinical settings. Therefore, this systematic review described different externally validated methods of predicting response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) patients and how they could improve clinical decision-making. An extensive search for eligible articles was performed on PubMed, Cochrane, and Scopus between 2018 and 2023, using the keywords: (Response OR outcome) prediction AND (neoadjuvant OR chemoradiotherapy) treatment in 'locally advanced Rectal Cancer'. (i) Studies including patients diagnosed with LARC (T3/4 and N- or any T and N+) by pre-medical imaging and pathological examination or as stated by the author (ii) Standardized nCRT completed. (iii) Treatment with long or short course radiotherapy. (iv) Studies reporting on the prediction of response to nCRT with pathological complete response (pCR) as the primary outcome. (v) Studies reporting external validation results for response prediction. (vi) Regarding language restrictions, only articles in English were accepted. (i) We excluded case report studies, conference abstracts, reviews, studies reporting patients with distant metastases at diagnosis. (ii) Studies reporting response prediction with only internally validated approaches. Three researchers (DC-D, FB, HT) independently reviewed and screened titles and abstracts of all articles retrieved after de-duplication. Possible disagreements were resolved through discussion among the three researchers. If necessary, three other researchers (LB, GC, MG) were consulted to make the final decision. The extraction of data was performed using the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) template and quality assessment was done using the Prediction model Risk Of Bias Assessment Tool (PROBAST). A total of 4547 records were identified from the three databases. After excluding 392 duplicate results, 4155 records underwent title and abstract screening. Three thousand and eight hundred articles were excluded after title and abstract screening and 355 articles were retrieved. Out of the 355 retrieved articles, 51 studies were assessed for eligibility. Nineteen reports were then excluded due to lack of reports on external validation, while 4 were excluded due to lack of evaluation of pCR as the primary outcome. Only Twenty-eight articles were eligible and included in this systematic review. In terms of quality assessment, 89 % of the models had low concerns in the participants domain, while 11 % had an unclear rating. 96 % of the models were of low concern in both the predictors and outcome domains. The overall rating showed high applicability potential of the models with 82 % showing low concern, while 18 % were deemed unclear. Most of the external validated techniques showed promising performances and the potential to be applied in clinical settings, which is a crucial step towards evidence-based medicine. However, more studies focused on the external validations of these models in larger cohorts is necessary to ensure that they can reliably predict outcomes in diverse populations.

Objective. Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods. Approach. We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients. Main results. The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm ³ isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data. Significance. The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating.