Objectives: To develop radiomics-based nomograms for preoperative microvascular invasion (MVI) and recurrence-free survival (RFS) prediction in patients with solitary hepatocellular carcinoma (HCC) ≤ 5 cm. Methods: Between March 2012 and September 2019, 356 patients with pathologically confirmed solitary HCC ≤ 5 cm who underwent preoperative gadoxetate disodium–enhanced MRI were retrospectively enrolled. MVI was graded as M0, M1, or M2 according to the number and distribution of invaded vessels. Radiomics features were extracted from DWI, arterial, portal venous, and hepatobiliary phase images in regions of the entire tumor, peritumoral area ≤ 10 mm, and randomly selected liver tissue. Multivariate analysis identified the independent predictors for MVI and RFS, with nomogram visualized the ultimately predictive models. Results: Elevated alpha-fetoprotein, total bilirubin and radiomics values, peritumoral enhancement, and incomplete or absent capsule enhancement were independent risk factors for MVI. The AUCs of MVI nomogram reached 0.920 (95% CI: 0.861–0.979) using random forest and 0.879 (95% CI: 0.820–0.938) using logistic regression analysis in validation cohort (n = 106). With the 5-year RFS rate of 68.4%, the median RFS of MVI-positive (M2 and M1) and MVI-negative (M0) patients were 30.5 (11.9 and 40.9) and > 96.9 months (p < 0.001), respectively. Age, histologic MVI, alkaline phosphatase, and alanine aminotransferase independently predicted recurrence, yielding AUC of 0.654 (95% CI: 0.538–0.769, n = 99) in RFS validation cohort. Instead of histologic MVI, the preoperatively predicted MVI by MVI nomogram using random forest achieved comparable accuracy in MVI stratification and RFS prediction. Conclusions: Preoperative radiomics-based nomogram using random forest is a potential biomarker of MVI and RFS prediction for solitary HCC ≤ 5 cm. Key Points: • The radiomics score was the predominant independent predictor of MVI which was the primary independent risk factor for postoperative recurrence. • The radiomics-based nomogram using either random forest or logistic regression analysis has obtained the best preoperative prediction of MVI in HCC patients so far. • As an excellent substitute for the invasive histologic MVI, the preoperatively predicted MVI by MVI nomogram using random forest (MVI-RF) achieved comparable accuracy in MVI stratification and outcome, reinforcing the radiologic understanding of HCC angioinvasion and progression.

Background: Whether peritumoral dilation radiomics can excellently predict early recrudescence (≤ 2 years) in hepatocellular carcinoma (HCC) remains unclear. Methods: Between March 2012 and June 2018, 323 pathologically confirmed HCC patients without macrovascular invasion, who underwent liver resection and preoperative gadoxetate disodium (Gd-EOB-DTPA) MRI, were consecutively recruited into this study. Multivariate logistic regression identified independent clinicoradiologic predictors of 2-year recrudescence. Peritumoral dilation (tumor and peritumoral zones within 1cm) radiomics extracted features from 7-sequence images for modeling and achieved average but robust predictive performance through 5-fold cross validation. Independent clinicoradiologic predictors were then incorporated with the radiomics model for constructing a comprehensive nomogram. The predictive discrimination was quantified with the area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI). Results: With the median recurrence-free survival (RFS) reaching 60.43 months, 28.2% (91/323) and 16.4% (53/323) patients suffered from early and delay relapse, respectively. Microvascular invasion, tumor size > 5 cm, alanine aminotransferase > 50 U/L, γ-glutamyltransferase > 60 U/L, prealbumin ≤ 250 mg/L, and peritumoral enhancement independently impaired 2-year RFS in the clinicoradiologic model with AUC of 0.694 (95% CI 0.628– 0.760). Nevertheless, these indexes were paucity of robustness (P > 0.05) when integrating with 38 most recurrence-related radiomics signatures for developing the comprehensive nomogram. The peritumoral dilation radiomics—the ultimate prediction model yielded satisfactory mean AUCs (training cohort: 0.939, 95% CI 0.908– 0.973; validation cohort: 0.842, 95% CI 0.736– 0.951) after 5-fold cross validation and fitted well with the actual relapse status in the calibration curve. Besides, our radiomics model obtained the best clinical net benefits, with significant improvements of NRI (35.9%-66.1%, P < 0.001) versus five clinical algorithms: the clinicoradiologic model, the tumor-node-metastasis classification, the Barcelona Clinic Liver Cancer stage, the preoperative and postoperative risks of Early Recurrence After Surgery for Liver tumor. Conclusion: Gd-EOB-DTPA MRI-based peritumoral dilation radiomics is a potential preoperative biomarker for early recurrence of HCC patients without macrovascular invasion.

Background: Whether microvascular invasion is a prognosis factor for small hepatocellular carcinoma (sHCC) is controversial, and a preoperatively predictive model based on gadoxetate disodium (Gd-EOB-DTPA) MRI is clinically needed for MVI in sHCC. Methods: Between March 2012 and September 2020, 455 consecutive patients with pathologically confirmed HCC ≤3 cm who underwent hepatectomy and preoperative Gd-EOB-DTPA MRI were retrospectively enrolled. Univariate and multivariate logistic regression combined with cox regression were conducted to find the confounding factors in the cohorts. Propensity score matching (PSM) was employed to balance the biases between MVI and non-MVI groups. Nomogram with C-index visualized the predictive model of MVI. Results: Multivariate logistic regression identified that 5 characteristics (AFP, tumor size, tumor margin, peritumoral enhancement, radiologic capsule) were markedly associated with MVI of sHCC and incorporated into the nomogram with excellent predictive performance in the training (AUC/C-index: 0.884/0.874, n=288), validation (AUC/C-index: 0.845/0.828, n=123) and test cohorts (AUC/C-index: 0.903/0.954, n=44). Before PSM, histologic MVI independently affected tumor recurrence (hazard ratio: 1.555, 95% CI: 1.055–2.293, P=0.026). However, due to the confounder of tumor size, there was a significant bias between MVI-positive and MVI-negative groups (propensity score: 0.249±0.105 vs. 0.179±0.106, P<0.001). Meanwhile, the frequency of MVI significantly increased as tumor size growing (P<0.001). After PSM, 70 of 79 MVI cases matched with 171 non-MVI (total 332), and no biases were observed between the two groups (propensity score: 0.238±0.104 vs. 0.217±0.109, P=0.186). Although the median recurrence time in non-MVI sHCC was still longer than that in MVI group (74.3 vs. 43.0 months, P=0.063), MVI was not an independent risk factor for RFS in sHCC. Additionally, MVI was not independently vulnerable to mortality in our population. Conclusions: A preoperative model, mainly based on the peritumoral hallmarks of Gd-EOB-DTPA MRI, showed an excellent performance to predict the occurrence of MVI. Nevertheless, MVI was a potential but not an independent risk factor for recurrence and mortality in sHCC ≤3 cm.