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

Abstract

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.

Keywords: Chemoradiotherapy; Magnetic resonance imaging; Rectal neoplasms.

Fig. 1

In- and exclusion flowchart. Note, mucinous tumors were excluded because these are known to exhibit distinctly different signal characteristics on both T2W-MRI and DWI

Fig. 2

Examples illustrating differences in image quality and acquisition for T2W-MRI (a–d) and DWI (e–h) between centers, related to for example field-of-view, tissue contrast (e.g., TR/TE settings), image resolution, and noise. For the DWI scans, the highest acquired b-values shown in these examples were b1000 (e), b600 (f), b800 (g), and b1000 (h)

Fig. 3

Schematic overview of the study workflow and statistical analysis. From a total cohort of 509 patients from 9 centers, 412 patients (from 6 centers) were used to develop a prediction model to predict two respective outcomes (complete response, good response) using repeated hold-out validation. For both outcomes, the best-performing model was tested on an external and independent validation cohort consisting of 97 patients (from 3 different centers)