Development and multicenter validation of a multiparametric imaging model to predict treatment response in rectal cancer.

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.

Sources of variation in multicenter rectal MRI data and their effect on radiomics feature reproducibility.

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.