Classification of Neoadjuvant Therapy Response in Patients With Colorectal Liver Metastases Using Contrast-Enhanced Ultrasound-With Histological Pathology as the Gold Standard

Objective: To evaluate the response to neoadjuvant therapy in patients with colorectal liver metastases (CRLMs) using ultrasound(US) and contrast-enhanced ultrasound(CEUS), with correction to the tumor regression grade (TRG) of pathological results. Methods: This study included patients with resectable CRLMs admitted from February to December 2022. After at least 4 cycles neoadjuvant therapy, all the patients received US and CEUS examinations within two weeks before hepatectomy. CEUS clips were postprocessed with color parameter imaging (CPI) and microflow imaging (MFI) analysis. Logistic regression analyses were used to develop an evaluation Nomogram. Ultrasound-based model was constructed to discriminate between the response (TRG1/2/3) and nonresponse (TRG4/5) groups at the lesion level. The model's predictive ability was evaluated using the C index and calibration curve, with decision curve analysis assessing the Nomogram's added value. Results: The study analyzed 105 CRLM lesions (the lesion with the highest diameter analyzed for each patient), with 43.8% showing a response to therapy. Univariate analysis identified calcification on US (p = 0.039), CEUS enhancement degree (p <0.001), CEUS enhancement pattern (p<0.001), CEUS washout type (p < 0.001), CEUS necrosis (p < 0.001), CPI feeding artery (p = 0.003) and MFI pattern (p < 0.001) were significantly associated with TRG. The multivariate analysis showed CEUS enhancement pattern (p = 0.026), CEUS washout type (p = 0.018) and CEUS necrosis (p = 0.005) were independently associated with the neoadjuvant therapy response. A Nomogram with the three independent predictors was developed, with an AUC of 0.898. Conclusion: The ultrasound-based model provided accurate evaluation of pathological tumor response to preoperative chemotherapy in patients with CRLM, and may help to decide the individualized treatment strategy.