Early prediction of response to chemotherapy with Cetuximab in colorectal liver metastasis with contrast-enhanced ultrasound perfusion analysis

BACKGROUND: To evaluate the feasibility of contrast-enhanced ultrasound (CEUS) for early prediction of treatment response to chemotherapy combined with Cetuximab (Cet) in colorectal liver metastasis (CRLM). METHODS: From June 2023 and October 2024, 139 consecutive patients with CRLM who underwent chemotherapy with Cet were sequentially allocated into a training cohort (n = 105) and a validation cohort (n = 34). CEUS examinations were conducted pre-treatment at baseline (week 0) and at weeks 2, 4, 6 and 8 post-treatment, with one target lesion consistently monitored throughout the therapeutic course. Perfusion parameters were derived using SonoLiver software. The reductions (Δ) and ratios of these parameters from baseline to each subsequent follow-up time point were compared between responders and non-responders. RESULTS: According to mRECIST criteria, 83 patients (training cohort: n = 62, validation cohort: n = 21) and 56 patients (training cohort: n = 43, validation cohort: n = 13) were classified as responders and non-responders, respectively. In the training cohort, responders demonstrated significantly smaller tumor diameters compared to non-responders beginning at week 4 (4.6 ± 2.3 cm vs. 5.4 ± 2.8 cm, p = 0.027). From week 2 onward, the reductions and ratios of maximum intensity (IMAX) and area under curve (AUC) in responders were significantly higher compared to non-responders. At all time points (weeks 2, 4, and 6), the diagnostic performance of IMAX and AUC ratios was superior to that of ΔIMAX and ΔAUC. Furthermore, the AUROCs of IMAX and AUC ratios at week 4 were significantly higher than those at week 2 (Z = 3.531, p < 0.05; Z = 3.550, p < 0.05, respectively) and comparable to those at week 6 (Z = 1.596, p = 0.11; Z = 1.566, p = 0.12, respectively). In the validation cohort at week 4 post-treatment, the AUROCs of IMAX and AUC ratios were 0.896 and 0.905 (both p < 0.05), with corresponding accuracies of 85.3% and 85.3%. CONCLUSION: The ratios of AUC and IMAX at week 4 post-treatment may serve as reliable early predictors of treatment response to chemotherapy combined with Cetuximab in patients with CRLM.