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Multiparametric Magnetic Resonance Imaging (MRI) can provide detailed information of the physical characteristics of rectum tumours. Several investigations suggest that volumetric analyses on anatomical and functional MRI contain clinically valuable information. However, manual delineation of tumours is a time consuming procedure, as it requires a high level of expertise. Here, we evaluate deep learning methods for automatic localization and segmentation of rectal cancers on multiparametric MR imaging. MRI scans (1.5T, T2-weighted, and DWI) of 140 patients with locally advanced rectal cancer were included in our analysis, equally divided between discovery and validation datasets. Two expert radiologists segmented each tumor. A convolutional neural network (CNN) was trained on the multiparametric MRIs of the discovery set to classify each voxel into tumour or non-tumour. On the independent validation dataset, the CNN showed high segmentation accuracy for reader1 (Dice Similarity Coefficient (DSC = 0.68) and reader2 (DSC = 0.70). The area under the curve (AUC) of the resulting probability maps was very high for both readers, AUC = 0.99 (SD = 0.05). Our results demonstrate that deep learning can perform accurate localization and segmentation of rectal cancer in MR imaging in the majority of patients. Deep learning technologies have the potential to improve the speed and accuracy of MRI-based rectum segmentations.

Radiomics provides quantitative tissue heterogeneity profiling and is an exciting approach to developing imaging biomarkers in the context of precision medicine. Normal-appearing parenchymal tissues surrounding primary tumors can harbor microscopic disease that leads to increased risk of distant metastasis (DM). This study assesses whether computed-tomography (CT) imaging features of such peritumoral tissues can predict DM in locally advanced non-small cell lung cancer (NSCLC). 200 NSCLC patients of histological adenocarcinoma were included in this study. The investigated lung tissues were tumor rim, defined to be 3mm of tumor and parenchymal tissue on either side of the tumor border and the exterior region extended from 3 to 9mm outside of the tumor. Fifteen stable radiomic features were extracted and evaluated from each of these regions on pre-treatment CT images. For comparison, features from expert-delineated tumor contours were similarly prepared. The patient cohort was separated into training and validation datasets for prognostic power evaluation. Both univariable and multivariable analyses were performed for each region using concordance index (CI). Univariable analysis reveals that six out of fifteen tumor rim features were significantly prognostic of DM (p-value < 0.05), as were ten features from the visible tumor, and only one of the exterior features was. Multivariablely, a rim radiomic signature achieved the highest prognostic performance in the independent validation sub-cohort (CI = 0.64, p-value = 2.4×10-5) significantly over a multivariable clinical model (CI = 0.53), a visible tumor radiomics model (CI = 0.59), or an exterior tissue model (CI = 0.55). Furthermore, patient stratification by the combined rim signature and clinical predictor led to a significant improvement on the clinical predictor alone and also outperformed stratification using the combined tumor signature and clinical predictor. We identified peritumoral rim radiomic features significantly associated with DM. This study demonstrated that peritumoral imaging characteristics may provide additional valuable information over the visible tumor features for patient risk stratification due to cancer metastasis.

PurposeTo compare the performance of advanced radiomics analysis to morphological assessment by expert radiologists to predict a good or complete response to chemoradiotherapy in rectal cancer using baseline staging MRI.Materials and methodsWe retrospectively assessed the primary staging MRIs [prior to chemoradiotherapy (CRT)] of 133 rectal cancer patients from 2 centers. First, two expert radiologists subjectively estimated the likelihood of achieving a “complete response” (ypT0) and “good response” (TRG 1–2), using a 5-point score (based on TN-stage, MRF/EMVI-status, size/signal/shape). Next, tumor volumes were segmented on high b value DWI (semi-automated, corrected by 2 non-expert and 2-expert readers, resulting in 5 segmentations), copied to the remaining sequences after which a total of 2505 radiomic features were extracted from T2W, low and high b value DWI and ADC. Stability of features for noise due to inter-reader and inter-scanner and protocol variations was assessed using intraclass correlation (ICC) and the Kruskal–Wallis test. Using data from center 1 (n = 86; training set), top 9 features were selected using minimum Redundancy Maximum Relevance and combined in a logistic regression model. Finally, diagnostic performance of the fitted models was assessed on data from center 2 (n = 47; validation set) and compared to the performance of the radiologists.ResultsThe Radiomic models resulted in AUCs of 0.69–0.79 (with similar results for the segmentations performed by expert/non-expert readers) to predict response, results similar to the morphologic prediction by the expert radiologists (AUC 0.67–0.83). Radiomics using semi-automatically generated segmentations (without manual input) did not result in significant predictive performance.ConclusionsRadiomics could predict response to therapy with comparable diagnostic performance as expert radiologists, regardless of whether image segmentation was performed by non-expert or expert readers, indicating that expert input is not required in order for the radiomics workflow to produce significant predictive performance.

Objectives To investigate sources of variation in a multicenter rectal cancer MRI dataset focusing on hardware and image acquisition, segmentation methodology, and radiomics feature extraction software. Methods T2W and DWI/ADC MRIs from 649 rectal cancer patients were retrospectively acquired in 9 centers. Fifty-two imaging features (14 first-order/6 shape/32 higher-order) were extracted from each scan using whole-volume (expert/non-expert) and single-slice segmentations using two different software packages (PyRadiomics/CapTk). Influence of hardware, acquisition, and patient-intrinsic factors (age/gender/cTN-stage) on ADC was assessed using linear regression. Feature reproducibility was assessed between segmentation methods and software packages using the intraclass correlation coefficient. Results Image features differed significantly ( p  < 0.001) between centers with more substantial variations in ADC compared to T2W-MRI. In total, 64.3% of the variation in mean ADC was explained by differences in hardware and acquisition, compared to 0.4% by patient-intrinsic factors. Feature reproducibility between expert and non-expert segmentations was good to excellent (median ICC 0.89–0.90). Reproducibility for single-slice versus whole-volume segmentations was substantially poorer (median ICC 0.40–0.58). Between software packages, reproducibility was good to excellent (median ICC 0.99) for most features (first-order/shape/GLCM/GLRLM) but poor for higher-order (GLSZM/NGTDM) features (median ICC 0.00–0.41). Conclusions Significant variations are present in multicenter MRI data, particularly related to differences in hardware and acquisition, which will likely negatively influence subsequent analysis if not corrected for. Segmentation variations had a minor impact when using whole volume segmentations. Between software packages, higher-order features were less reproducible and caution is warranted when implementing these in prediction models. Key Points • Features derived from T2W-MRI and in particular ADC differ significantly between centers when performing multicenter data analysis. • Variations in ADC are mainly (> 60%) caused by hardware and image acquisition differences and less so (< 1%) by patient- or tumor-intrinsic variations. • Features derived using different image segmentations (expert/non-expert) were reproducible, provided that whole-volume segmentations were used. When using different feature extraction software packages with similar settings, higher-order features were less reproducible.

Objectives To externally validate a pre-treatment MR-based radiomics model predictive of locoregional control in oropharyngeal squamous cell carcinoma (OPSCC) and to assess the impact of differences between datasets on the predictive performance. Methods Radiomic features, as defined in our previously published radiomics model, were extracted from the primary tumor volumes of 157 OPSCC patients in a different institute. The developed radiomics model was validated using this cohort. Additionally, parameters influencing performance, such as patient subgroups, MRI acquisition, and post-processing steps on prediction performance will be investigated. For this analysis, matched subgroups (based on human papillomavirus (HPV) status of the tumor, T-stage, and tumor subsite) and a subgroup with only patients with 4-mm slice thickness were studied. Also the influence of harmonization techniques (ComBat harmonization, quantile normalization) and the impact of feature stability across observers and centers were studied. Model performances were assessed by area under the curve (AUC), sensitivity, and specificity. Results Performance of the published model (AUC/sensitivity/specificity: 0.74/0.75/0.60) drops when applied on the validation cohort (AUC/sensitivity/specificity: 0.64/0.68/0.60). The performance of the full validation cohort improves slightly when the model is validated using a patient group with comparable HPV status of the tumor (AUC/sensitivity/specificity: 0.68/0.74/0.60), using patients acquired with a slice thickness of 4 mm (AUC/sensitivity/specificity: 0.67/0.73/0.57), or when quantile harmonization was performed (AUC/sensitivity/specificity: 0.66/0.69/0.60). Conclusion The previously published model shows its generalizability and can be applied on data acquired from different vendors and protocols. Harmonization techniques and subgroup definition influence performance of predictive radiomics models. Key Points • Radiomics, a noninvasive quantitative image analysis technique, can support the radiologist by enhancing diagnostic accuracy and/or treatment decision-making . • A previously published model shows its generalizability and could be applied on data acquired from different vendors and protocols .

Objectives To explore the potential impact of a dedicated virtual training course on MRI staging confidence and performance in rectal cancer. Methods Forty-two radiologists completed a stepwise virtual training course on rectal cancer MRI staging composed of a pre-course (baseline) test with 7 test cases (5 staging, 2 restaging), a 1-day online workshop, 1 month of individual case readings ( n  = 70 cases with online feedback), a live online feedback session supervised by two expert faculty members, and a post-course test. The ESGAR structured reporting templates for (re)staging were used throughout the course. Results of the pre-course and post-course test were compared in terms of group interobserver agreement (Krippendorf’s alpha), staging confidence (perceived staging difficulty), and diagnostic accuracy (using an expert reference standard). Results Though results were largely not statistically significant, the majority of staging variables showed a mild increase in diagnostic accuracy after the course, ranging between + 2% and + 17%. A similar trend was observed for IOA which improved for nearly all variables when comparing the pre- and post-course. There was a significant decrease in the perceived difficulty level ( p  = 0.03), indicating an improved diagnostic confidence after completion of the course. Conclusions Though exploratory in nature, our study results suggest that use of a dedicated virtual training course and web platform has potential to enhance staging performance, confidence, and interobserver agreement to assess rectal cancer on MRI virtual training and could thus be a good alternative (or addition) to in-person training. Clinical relevance statement Rectal cancer MRI reporting quality is highly dependent on radiologists’ expertise, stressing the need for dedicated training/teaching. This study shows promising results for a virtual web-based training program, which could be a good alternative (or addition) to in-person training. Key Points • Rectal cancer MRI reporting quality is highly dependent on radiologists’ expertise, stressing the need for dedicated training and teaching. • Using a dedicated virtual training course and web-based platform, encouraging first results were achieved to improve staging accuracy, diagnostic confidence, and interobserver agreement. • These exploratory results suggest that virtual training could thus be a good alternative (or addition) to in-person training.

Objective To investigate whether quantifying local tumour heterogeneity has added benefit compared to global tumour features to predict response to chemoradiotherapy using pre-treatment multiparametric PET and MRI data. Methods Sixty-one locally advanced rectal cancer patients treated with chemoradiotherapy and staged at baseline with MRI and FDG-PET/CT were retrospectively analyzed. Whole-tumour volumes were segmented on the MRI and PET/CT scans from which global tumour features (T2W volume /T2W entropy /ADC mean /SUV mean /TLG/CT mean-HU ) and local texture features (histogram features derived from local entropy/mean/standard deviation maps) were calculated. These respective feature sets were combined with clinical baseline parameters (e.g. age/gender/TN-stage) to build multivariable prediction models to predict a good (Mandard TRG1-2) versus poor (Mandard TRG3-5) response to chemoradiotherapy. Leave-one-out cross-validation (LOOCV) with bootstrapping was performed to estimate performance in an ‘independent’ dataset. Results When using only imaging features, local texture features showed an AUC = 0.81 versus AUC = 0.74 for global tumour features. After internal cross-validation (LOOCV), AUC to predict a good response was the highest for the combination of clinical baseline variables + global tumour features (AUC = 0.83), compared to AUC = 0.79 for baseline + local texture and AUC = 0.76 for all combined (baseline + global + local texture). Conclusion In imaging-based prediction models, local texture analysis has potential added value compared to global tumour features to predict response. However, when combined with clinical baseline parameters such as cTN-stage, the added value of local texture analysis appears to be limited. The overall performance to predict response when combining baseline variables with quantitative imaging parameters is promising and warrants further research. Key Points • Quantification of local tumour texture on pre-therapy FDG-PET/CT and MRI has potential added value compared to global tumour features to predict response to chemoradiotherapy in rectal cancer. • However, when combined with clinical baseline parameters such as cTN-stage, the added value of local texture over global tumour features is limited. • Predictive performance of our optimal model—combining clinical baseline variables with global quantitative tumour features—was encouraging (AUC 0.83), warranting further research in this direction on a larger scale.

Objectives To develop and validate a multiparametric model to predict neoadjuvant treatment response in rectal cancer at baseline using a heterogeneous multicenter MRI dataset. Methods Baseline staging MRIs (T2W (T2-weighted)-MRI, diffusion-weighted imaging (DWI) / apparent diffusion coefficient (ADC)) of 509 patients (9 centres) treated with neoadjuvant chemoradiotherapy (CRT) were collected. Response was defined as (1) complete versus incomplete response, or (2) good (Mandard tumor regression grade (TRG) 1–2) versus poor response (TRG3-5). Prediction models were developed using combinations of the following variable groups: (1) Non-imaging: age/sex/tumor-location/tumor-morphology/CRT-surgery interval (2) Basic staging: cT-stage/cN-stage/mesorectal fascia involvement, derived from (2a) original staging reports, or (2b) expert re-evaluation (3) Advanced staging: variables from 2b combined with cTN-substaging/invasion depth/extramural vascular invasion/tumor length (4) Quantitative imaging: tumour volume + first-order histogram features (from T2W-MRI and DWI/ADC) Models were developed with data from 6 centers ( n  = 412) using logistic regression with the Least Absolute Shrinkage and Selector Operator (LASSO) feature selection, internally validated using repeated ( n = 100) random hold-out validation, and externally validated using data from 3 centers ( n = 97). Results After external validation, the best model (including non-imaging and advanced staging variables) achieved an area under the curve of 0.60 (95%CI=0.48–0.72) to predict complete response and 0.65 (95%CI=0.53–0.76) to predict a good response. Quantitative variables did not improve model performance. Basic staging variables consistently achieved lower performance compared to advanced staging variables. Conclusions Overall model performance was moderate. Best results were obtained using advanced staging variables, highlighting the importance of good-quality staging according to current guidelines. Quantitative imaging features had no added value (in this heterogeneous dataset). Clinical relevance statement Predicting tumour response at baseline could aid in tailoring neoadjuvant therapies for rectal cancer. This study shows that image-based prediction models are promising, though are negatively affected by variations in staging quality and MRI acquisition, urging the need for harmonization. Key Points This multicenter study combining clinical information and features derived from MRI rendered disappointing performance to predict response to neoadjuvant treatment in rectal cancer. Best results were obtained with the combination of clinical baseline information and state-of-the-art image-based staging variables, highlighting the importance of good quality staging according to current guidelines and staging templates. No added value was found for quantitative imaging features in this multicenter retrospective study. This is likely related to acquisition variations, which is a major problem for feature reproducibility and thus model generalizability.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

ObjectivesTo explore the value of multiparametric MRI combined with FDG-PET/CT to identify well-responding rectal cancer patients before the start of neoadjuvant chemoradiation.MethodsSixty-one locally advanced rectal cancer patients who underwent a baseline FDG-PET/CT and MRI (T2W + DWI) and received long-course neoadjuvant chemoradiotherapy were retrospectively analysed. Tumours were delineated on MRI and PET/CT from which the following quantitative parameters were calculated: T2W volume and entropy, ADC mean and entropy, CT density (mean-HU), SUV maximum and mean, metabolic tumour volume (MTV42%) and total lesion glycolysis (TLG). These features, together with sex, age, mrTN-stage (“baseline parameters”) and the CRT-surgery interval were analysed using multivariable stepwise logistic regression. Outcome was a good (TRG 1–2) versus poor histopathological response. Performance (AUC) to predict response was compared for different combinations of baseline ± quantitative imaging parameters and performance in an ‘independent’ dataset was estimated using bootstrapped leave-one-out cross-validation (LOOCV).ResultsThe optimal multivariable prediction model consisted of a combination of baseline + quantitative imaging parameters and included mrT-stage (OR 0.004, p < 0.001), T2W-signal entropy (OR 7.81, p = 0.0079) and T2W volume (OR 1.028, p = 0.0389) as the selected predictors. AUC in the study dataset was 0.88 and 0.83 after LOOCV. No PET/CT features were selected as predictors.ConclusionsA multivariable model incorporating mrT-stage and quantitative parameters from baseline MRI can aid in identifying well-responding patients before the start of treatment. Addition of FDG-PET/CT is not beneficial.Key Points• A multivariable model incorporating the mrT-stage and quantitative features derived from baseline MRI can aid in identifying well-responding patients before the start of neoadjuvant chemoradiotherapy.• mrT-stage was the strongest predictor in the model and was complemented by the tumour volume and signal entropy calculated from T2W-MRI.• Adding quantitative features derived from pre-treatment PET/CT or DWI did not contribute to the model’s predictive performance.