Objectives: To develop and validate a predictive model for early refractoriness of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: In this multicenter retrospective study, a total of 204 consecutive patients who initially underwent TACE were included. Early TACE refractoriness was defined as patients presented with TACE refractoriness after initial two consecutive TACE procedures. Of all patients, 147 patients (approximately 70%) were assigned to a training set, and the remaining 57 patients (approximately 30%) were assigned to a validation set. Predictive model was established using forward stepwise logistic regression and nomogram. Based on factors selected by logistic regression, a one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) between patients who were present or absent of early TACE refractoriness. PFS curve was estimated by Kaplan-Meier method and compared by log-rank test. Results: Logistic regression revealed that bilobar tumor distribution (p = 0.002), more than three tumors (p = 0.005) and beyond up-to-seven criteria (p = 0.001) were significantly related to early TACE refractoriness. The discriminative abilities, as determined by the area under the receiver operating characteristic (ROC) curve, were 0.788 in the training cohort and 0.706 in the validation cohort. After PSM, the result showed that patients who were absent of early TACE refractoriness had a significantly higher PFS rate than those of patients who were present (p < 0.001). Conclusion: This study presents a predictive model with moderate accuracy to identify patients with high risk of early TACE refractoriness, and patients with early TACE refractoriness may have a poor prognosis.

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