Tumor downstaging after neoadjuvant chemoradiation (CRT) in rectal cancer patients is typically assessed via Magnetic Resonance Imaging (MRI) in order to determine follow-up surgical interventions, but is associated with marked inter-reader variability and limited performance. While radiomic features have shown promise for evaluating chemoradiation response and tumor stage in rectal cancers, there is a need to determine how reproducible these features are across different MRI scanners and acquisitions. In this study, we evaluated radiomic feature reproducibility in terms of feature instability within a uniquely curated true healthy" rectum cohort in order to construct a stability-informed radiomic classifier for differentiating poorly from markedly down-staged rectal tumors after chemoradiation in a multi-site setting. We utilized a cohort of 156 patients, with (a) 74 MRIs visualizing the healthy rectum, (b) 52 post-CRT MRI scans in the discovery cohort, and (c) 30 post-CRT MRI scans in a second-site validation cohort; the latter 2 being from rectal cancer patients. 764 radiomic features were extracted from within the entire rectal wall on each MRI scan. Feature instability was used to quantify how reproducible each radiomic feature was between the discovery cohort and the healthy rectum cohort, using locations along the rectum that were spatially distinct from the treated tumor region. From the resulting stability-informed" feature set, the most relevant features were identified to distinguish pathologic tumor stage groups in the discovery cohort via a QDA classifier with cross-validation to ensure robustness. The top 4 radiomic features were then evaluated in hold-out fashion on scans from the validation cohort. We found that utilizing a stability-informed radiomic model (which comprised features that were reproducible in 100% of all comparisons) was significantly more accurate in identifying pathological tumor stage regression in both discovery (AUC=0:66 ± 0:09) and validation (AUC=0.73) cohorts, compared to a basic radiomic model that used all extracted features (AUC=0:60 ± 0:07 in discovery, AUC=0.62 in validation). Evaluating feature instability with respect to healthy rectal tissue may thus enhance the performance of radiomic models in characterizing pathologic downstaging in rectal cancers, via MRI.
KEYWORDS: Magnetic resonance imaging, Tumors, Cancer, CRTs, Feature extraction, In vivo imaging, Medical research, Feature selection, Tissues, Lung cancer
A major clinical challenge in rectal cancer currently is non-invasive identification of tumor regression to standard- of-care neoadjuvant chemoradiation (CRT). Multi-parametric MRI is routinely acquired after CRT, but expert radiologists find it highly challenging to assess the degree of tumor regression on both T2-weighted (T2w) and Gadolinium contrast-enhanced (CE) MRI; resulting in poor agreement with gold-standard pathologic evaluation. In this study, we present initial results for integrating quantitative image appearance (radiomic) features from post-CRT T2w and CE MRI towards in vivo assessment of pathologic rectal tumor response to chemoradiation. 29 rectal cancer patients with post-CRT multi-parametric 3 T MRI (with T2w, initial and delayed CE phases) were included in this study. Through spatial co-registration, the treated region of the rectal wall was identified and annotated on T2w and all CE phases (as well as correcting for motion artifacts in CE MRI). 165 radiomic features (including Haralick, Gabor, Laws, Sobel/Kirsch) were separately extracted from each of T2w and 2 CE phases; within the entire rectal wall. The top 2 response-associated radiomic features for each of (a) T2w, (b) 2 CE phases, (c) combined T2w+CE phases were identified via feature selection and evaluated in a leave- one-patient-out cross validation setting. Integrating T2w and CE radiomic features was found to be markedly more accurate (AUC=0.93) for assessing post-CRT pathologic tumor stage, compared to T2w radiomic features (AUC=0.80) and CE radiomic features (AUC=0.63) individually. Top-ranked features captured heterogeneity of gradient responses on T2w MRI and macro-scale Gabor wavelet responses of contrast enhancement on CE MRI. Combining radiomic features from post-CRT T2w and CE MRI may hence enable more comprehensive evaluation of response to neoadjuvant therapy in rectal cancers, which can be used to better guide follow-up interventions.
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