Diagnostic performance of gadoxetic acid-enhanced abbreviated magnetic resonance imaging protocol in small hepatocellular carcinoma (≤2 cm) in high-risk patients.

BACKGROUND: Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time. PURPOSE: To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients. MATERIAL AND METHODS: Two hundred and four consecutive patients with 166 pathologically confirmed small HCC who underwent preoperative gadoxetic acid-enhanced MRI were retrospectively included. A-MRI set comprised T1-weighted hepatobiliary phase imaging, T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient mapping. Two independent radiologists blinded to clinical data assessed the A-MRI set and F-MRI set. Per-patient HCC and per-lesion HCC diagnostic performance were compared. RESULTS: Per-patient HCC detection sensitivity of A-MRI set was 93.8% and 91.2% for observer 1 and observer 2, and, for the F-MRI set, the per-patient HCC detection sensitivity was 96.6% and 95.2%, respectively. There was no significant difference in per-patient sensitivity, specificity and per-lesion HCC detection sensitivity between the two imaging sets for both readers. (P = 0.06-0.25) The A-MRI set showed higher sensitivity on HCC without arterial phase hyperenhancement, and the F-MRI set demonstrated with higher sensitivity on HCC with arterial phase hyperenhancement (P < 0.05). CONCLUSION: A-MRI using diagnostic criteria including hypointensity on hepatobiliary phase plus mild to moderate hyperintensity on T2-weighted imaging or restricted diffusion demonstrated comparable sensitivity and specificity for small HCC compared to the F-MRI protocol in high-risk patients.

Tumor Radiomic Features on Pretreatment MRI to Predict Response to Lenvatinib plus an Anti-PD-1 Antibody in Advanced Hepatocellular Carcinoma: A Multicenter Study.

Introduction: Lenvatinib plus an anti-PD-1 antibody has shown promising antitumor effects in patients with advanced hepatocellular carcinoma (HCC), but with clinical benefit limited to a subset of patients. We developed and validated a radiomic-based model to predict objective response to this combination therapy in advanced HCC patients. Methods: Patients (N = 170) who received first-line combination therapy with lenvatinib plus an anti-PD-1 antibody were retrospectively enrolled from 9 Chinese centers; 124 and 46 into the training and validation cohorts, respectively. Radiomic features were extracted from pretreatment contrast-enhanced MRI. After feature selection, clinicopathologic, radiomic, and clinicopathologic-radiomic models were built using a neural network. The performance of models, incremental predictive value of radiomic features compared with clinicopathologic features and relationship between radiomic features and survivals were assessed. Results: The clinicopathologic model modestly predicted objective response with an AUC of 0.748 (95% CI: 0.656-0.840) and 0.702 (95% CI: 0.547-0.884) in the training and validation cohorts, respectively. The radiomic model predicted response with an AUC of 0.886 (95% CI: 0.815-0.957) and 0.820 (95% CI: 0.648-0.984), respectively, with good calibration and clinical utility. The incremental predictive value of radiomic features to clinicopathologic features was confirmed with a net reclassification index of 47.9% (p < 0.001) and 41.5% (p = 0.025) in the training and validation cohorts, respectively. Furthermore, radiomic features were associated with overall survival and progression-free survival both in the training and validation cohorts, but modified albumin-bilirubin grade and neutrophil-to-lymphocyte ratio were not. Conclusion: Radiomic features extracted from pretreatment MRI can predict individualized objective response to combination therapy with lenvatinib plus an anti-PD-1 antibody in patients with unresectable or advanced HCC, provide incremental predictive value over clinicopathologic features, and are associated with overall survival and progression-free survival after initiation of this combination regimen.

Circulating immune index predicting the prognosis of patients with hepatocellular carcinoma treated with lenvatinib and immunotherapy.

Background: Immune checkpoint inhibitor (ICI)-based combination therapy has opened a new avenue for the treatment of multiple malignancies including hepatocellular carcinoma (HCC). However, considering the unsatisfactory efficacy, biomarkers are urgently needed to identify the patients most likely to benefit from ICI-based combination therapy. Methods: A total of 194 patients undergoing ICI-based combination therapy for unresectable HCC were retrospectively enrolled and divided into a training cohort (n = 129) and a validation cohort (n = 65) randomly. A novel circulating immune index (CII) defined as the ratio of white blood cell count (×109/L) to lymphocyte proportion (%) was constructed and its prognostic value was determined and validated. Results: Patients with CII ≤ 43.1 reported prolonged overall survival (OS) compared to those with CII > 43.1 (median OS: 24.7 vs 15.1 months; 6-, 12-, 18-month OS: 94.2%, 76.7%, 66.1% vs 86.4%, 68.2%, 22.8%, P = 0.019), and CII was identified as an independent prognostic factor for OS (hazard ratio, 2.24; 95% confidence interval, 1.17-4.31; P = 0.015). These results were subsequently verified in the validation cohort. Additionally, patients with low CII levels had improved best radiological tumor response (complete response, partial response, stable disease, progressive disease: 3%, 36%, 50%, 11% vs 0%, 27%, 46%, 27%; P = 0.037) and disease control rate (89% vs 73%; P = 0.031) in the pooled cohort and better pathologic response (pathologic complete response, major pathologic response, partial pathologic response, no pathologic response: 20%, 44%, 28%, 8% vs 0%, 0%, 40%, 60%; P = 0.005) in the neoadjuvant cohort. Detection of lymphocyte subsets revealed that an elevated proportion of CD4+ T cells was related to better OS, while the proportion of CD8+ T cells was not. Conclusions: We constructed a novel circulating immune biomarker that was capable of predicting OS and therapeutic efficacy for HCC patients undergoing ICI and lenvatinib combination therapy.

Prognostic model for predicting outcome and guiding treatment decision for unresectable hepatocellular carcinoma treated with lenvatinib monotherapy or lenvatinib plus immunotherapy.

Background: Lenvatinib monotherapy and combination therapy with immune checkpoint inhibitors (ICI) were widely applied for unresectable hepatocellular carcinoma (uHCC). However, many patients failed to benefit from the treatments. A prognostic model was needed to predict the treatment outcomes and guide clinical decisions. Methods: 304 patients receiving lenvatinib monotherapy or lenvatinib plus ICI for uHCC were retrospectively included. The risk factors derived from the multivariate analysis were used to construct the predictive model. The C-index and area under the receiver-operating characteristic curve (AUC) were calculated to assess the predictive efficiency. Results: Multivariate analysis revealed that protein induced by vitamin K absence or antagonist-II (PIVKA-II) (HR, 2.05; P=0.001) and metastasis (HR, 2.07; P<0.001) were independent risk factors of overall survival (OS) in the training cohort. Herein, we constructed a prognostic model called PIMET score and stratified patients into the PIMET-low group (without metastasis and PIVKA-II<600 mAU/mL), PIMET-int group (with metastasis or PIVKA-II>600 mAU/mL) and PIMET-high group (with metastasis and PIVKA-II>600 mAU/mL). The C-index of PIMET score for the survival prediction was 0.63 and 0.67 in the training and validation cohort, respectively. In the training cohort, the AUC of 12-, 18-, and 24-month OS was 0.661, 0.682, and 0.744, respectively. The prognostic performances of the model were subsequently validated. The AUC of 12-, 18-, and 24-month OS was 0.724, 0.726, and 0.762 in the validation cohort. Subgroup analyses showed consistent predictive value for patients receiving lenvatinib monotherapy and patients receiving lenvatinib plus ICI. The PIMET score could also distinguish patients with different treatment responses. Notably, the combination of lenvatinib and ICI conferred survival benefits to patients with PIMET-int or PIMET-high, instead of patients with PIMET-low. Conclusion: The PIMET score comprising metastasis and PIVKA-II could serve as a helpful prognostic model for uHCC receiving lenvatinib monotherapy or lenvatinib plus ICI. The PIMET score could guide the treatment decision and facilitate precision medicine for uHCC patients.

Prognostic value of preoperative CT features for disease-free survival in patients with primary gastric gastrointestinal stromal tumors after resection.

PURPOSE: Tumor size is an important prognostic factor without consideration of the necrotic and cystic components within tumor for patients with gastrointestinal stromal tumors (GISTs). We aimed to extract the enhancing viable component from the tumor using computed tomography (CT) post-processing software and evaluate the value of preoperative CT features for predicting the disease-free survival (DFS) after curative resection for patients with primary gastric GISTs. METHODS: 132 Patients with primary gastric GISTs who underwent preoperative contrast-enhanced CT and curative resection were retrospectively analyzed. We used a certain CT attenuation of 30 HU to extract the enhancing tissue component from the tumor. Enhancing tissue volume and other CT features were assessed on venous-phase images. We evaluated the value of preoperative CT features for predicting the DFS after surgery. Univariate and multivariate Cox regression analyses were performed to find the independent risk factor for predicting the DFS. RESULTS: Of the 132 patients, 68 were males and 64 were females, with a mean age of 61 years. The median follow-up duration was 60 months, and 28 patients experienced disease recurrence and distant metastasis during the follow-up period. Serosal invasion (p < 0.001; HR = 5.277) and enhancing tissue volume (p = 0.005; HR = 1.447) were the independent risk factors for predicting the DFS after curative resection for patients with primary gastric GISTs. CONCLUSION: Preoperative contrast-enhanced CT could be useful for predicting the DFS after the surgery of gastric GISTs, and serosal invasion and enhancing tissue volume were the independent risk factors.

Diagnostic Performance of Contrast Enhanced CT Alone or in Combination with (Non-)Enhanced MRI for Colorectal Liver Metastasis.

RATIONALE AND OBJECTIVES: To compare the diagnostic performance of contrast enhanced CT (CE-CT), CE-CT combined with non-enhanced MRI (NE-MRI) or contrast enhanced MRI (CE-MRI) for colorectal liver metastasis (CRLM). MATERIALS AND METHODS: Sixty-six colorectal cancer patients with 198 focal liver lesions who underwent preoperative abdominal CE-CT and MRI examinations were included respectively. The images were assessed independently by two readers in three protocols (1: CE-CT, 2: CE-CT+NE-MRI, 3: CE-CT+CE-MRI). The diagnostic performance of each protocol was analyzed by receiver operating characteristic (ROC) curve and the areas under ROC (AUCs) were calculated and compared. RESULTS: The detection rates of protocol 2 were 90.9%-92.9% for liver lesions and 86.4%-89.6% for CRLM, and both significantly higher than protocol 1 of 82.8%-85.4% and 76.8%-80.8% (p<0.001-0.001), whereas similar to protocol 3 of 91.9%-94.4% and 87.2%-91.2% (p 0.250-1.000). The AUCs of protocol 2 were greater than protocol 1 for all lesions (0.914-0.934 vs. 0.779-0.799, p<0.001) and lesions < 10mm (0.726-0.776 vs. 0.528-0.561, p<0.001), and were not inferior to that of protocol 3 (0.929-0.949 in all lesions and 0.754-0.821 in lesion < 10mm, p 0.053-0.162). CONCLUSION: CE-CT combined with NE-MRI offered superior diagnostic performance for CRLM compared to CE-CT alone and showed comparable performance to CE-CT combined with CE-MRI.

Microvascular invasion of small hepatocellular carcinoma can be preoperatively predicted by the 3D quantification of MRI.

OBJECTIVES: To explore the importance of three-dimensional (3D) quantitative analysis during gadoxetic acid-enhanced magnetic resonance imaging (MRI) of microvascular invasion (MVI) and early recurrence (< 2 years) after surgery of single hepatocellular carcinoma (HCC) ≤ 3 cm. METHODS: Two hundred fourteen patients with pathologically confirmed HCC (training cohort: n = 169; validation cohort: n = 45) were included retrospectively. The 3D quantitative parameters (volume, sphericity, and compacity) and conventional MRI features were analyzed. The significant predictors for MVI were identified using univariate and multivariate logistic regression analyses. Nomograms were constructed from the prediction model, and the relationship between the significant predictors and early recurrence rates was evaluated using the Kaplan-Meier method. RESULTS: Tumor sphericity (odds ratio [OR] = 0.000; p < 0.001), non-smooth tumor margin (OR = 3.353; p = 0.015), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 14.067; p = 0.003) were independent significant factors for MVI. When these three factors were combined, the diagnostic specificity of the training and validation cohorts was 97.0 (128/132) and 87.9 (29/33), respectively. The nomogram based on the predictive model performed satisfactorily in the training (C-index: 0.885) and validation (C-index: 0.869) cohorts. Early recurrence rates of patients with two or three significant factors were significantly higher than those with none in the training (29.1% vs. 10.2%, p = 0.007) and validation (36.4% vs. 6.7%, p = 0.037) cohorts. CONCLUSIONS: Lower sphericity combined with non-smooth tumor margin and peritumoral hypointensity on HBP are potential predictive factors for MVI and associated with early recurrence after surgery of HCC ≤ 3 cm. KEY POINTS: • Lower sphericity, non-smooth tumor margin, and peritumoral hypointensity on HBP were important indicators of the occurrence of MVI in HCC. • The combinational model prepared from these findings satisfactorily predicted MVI, and the presence of these predictors was associated with an early recurrence rate after surgical resection in HCC patients. • This model could help clinicians in the preoperative management of small HCC ≤ 3 cm.

Hepatobiliary phase images of gadoxetic acid-enhanced MRI may improve accuracy of predicting the size of hepatocellular carcinoma at pathology.

BACKGROUND: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has been widely used in clinical practice. However, scientific evidence is lacking for recommending a particular sequence for measuring tumor size. PURPOSE: To retrospectively compare the size of hepatocellular carcinoma (HCC) measured on different gadoxetic acid-enhanced MRI sequences using pathology as a reference. MATERIAL AND METHODS: A total of 217 patients with single HCC who underwent gadoxetic acid-enhanced MRI before surgery were included. The size of the HCC was measured by two abdominal radiologists independently on the following sequences: T1-weighted; T2-weighted; b-500 diffusion-weighted imaging (DWI); and arterial, portal venous, transitional, and hepatobiliary phases. Tumor size measured on MRI was compared with pathological size by using Pearson correlation coefficient, independent-sample t test, and Bland-Altman plot. Agreement between two readers was evaluated with intraclass correlation coefficient (ICC). RESULTS: Correlation between the MR images and pathology was high for both readers (0.899-0.955). Absolute error between MRI and pathologic assessment was lowest on hepatobiliary phase images for both readers (reader 1, 2.8±4.2 mm; reader 2, 3.2±3.4 mm) and highest on arterial phase images for reader 1 (4.9±4.4 mm) and DWI phase images for reader 2 (5.1±4.9 mm). Absolute errors were significantly different for hepatobiliary phase compared with other sequences for both readers (reader 1, P≤0.012; reader 2, P≤0.037). Inter-reader agreements for all sequence measurements were strong (0.971-0.997). CONCLUSION: The performance of gadoxetic acid-enhanced MRI sequences varied with HCC size, and the hepatobiliary phase may be optimal among these sequences.

Utility of preoperative computed tomography features in predicting the Ki-67 labeling index of gastric gastrointestinal stromal tumors.

PURPOSE: To evaluate the value of preoperative computed tomography (CT) features including morphologic and quantitative features for predicting the Ki-67 labeling index (Ki-67LI) of gastric gastrointestinal stromal tumors (GISTs). METHODS: We retrospectively included 167 patients with gastric GISTs who underwent preoperative contrast-enhanced CT. We assessed the morphologic features of preoperative CT images and the quantitative features including the maximum diameter of tumor, total tumor volume, mean total tumor CT value, necrosis volume, necrosis volume ratio, enhanced tissue volume, and mean CT value of enhanced tissue. Potential predictive parameters to distinguish the high-level Ki-67LI group (>4%, n = 125) from the low-level Ki-67LI group (≤4%, n = 42) were compared and subsequently determined in multivariable logistic regression analysis. RESULTS: Growth pattern (p = 0.036), shape (p = 0.000), maximum diameter (p = 0.018), total tumor volume (p = 0.021), mean total tumor CT value (p = 0.009), necrosis volume (p = 0.006), necrosis volume ratio (p = 0.000), enhanced tissue volume (p = 0.027), and mean CT value of enhanced tissue (p = 0.004) were significantly different between the two groups. Multivariate logistic regression analysis indicated that lobulated/irregular shape (odds ratio [OR] = 3.817; p = 0.000) and high necrosis volume ratio (OR = 1.935; p = 0.024) were independent factors of high-level Ki-67LI. CONCLUSIONS: Higher necrosis volume ratio in combination with lobulated/irregular shape could potentially predict high expression of Ki-67LI for gastric GISTs.

CT-detected extramural venous invasion is corelated with presence of lymph node metastasis and progression-free survival in gastric cancer.

OBJECTIVE: This study aimed to investigate if CT-detected extramural venous invasion (ctEMVI) was associated with the presence of lymph node metastasis (LNM) and survival outcomes in patients with gastric cancer. METHODS: We retrospectively reviewed 105 patients with pathologically proved gastric cancer who underwent pre-operative CT examinations and received radical gastrectomy with extended lymphadenectomy. Differences in CT characteristics between the LNM-positive and -negative groups were assessed by two observers. Binary logistic regression analysis was performed to determine the risk factors of lymph node metastasis in gastric cancer. Progression-free survival analysis was performed by Kaplan-Meier method. RESULTS: Two observers reached good inter-reader agreements in ctEMVI and ctN status with κ values of 0.711 and 0.751, respectively. The frequency of ctEMVI-positive status was 58.1% (61/105) in patients with gastric cancer. The LNM-positive group showed higher possibility of ctEMVI-positive status (81.7% vs 26.7%, p＜0.001), larger tumor volume (mean volume, 40.77 vs 22.09 mL, p＜0.001), poor tumor margin (45.0% vs 26.7% , p = 0.054) and high enhancement on arterial phase (43.3% vs 26.7%, p = 0.023) and venous phase (60.0% vs 44.4%, p = 0.048), than LNM-negative group. In multivariate analysis, ctEMVI status and tumor volume were identified as independent risk factors for lymph node metastasis with odds ratio (OR) of 9.804 (95% CI, 3.076－31.246; p＜0.001) and 1.030 (95% CI, 1.001－1.060; p = 0.044). CT-detected EMVI presented better diagnostic efficiency for lymph node metastasis than CT-defined N status, with sensitivity (81.7% vs 70.0%), specificity (73.3% vs 71.1%), accuracy (78.1% vs 70.5), PPV (80.3% vs 76.4%), and NPV (75.0% vs 64.0%), respectively. Kaplan-Meier curves showed that patients with positive ctEMVI findings has lower PFS rate than patients with negative ctEMVI findings (Log-rank test, p = 0.007). CONCLUSION: CT-detected EMVI was significantly associated with lymph node metastasis and progression free survival in patients with gastric cancer. Compared to CT-defined N status, ctEMVI provided superior diagnostic performance to predict pathologic Nstatus. ADVANCES IN KNOWLEDGE: Our study proved that CT-detected EMVI is a promising imaging marker to predict lymph node metastasis and poor prognosis, which may contribute to the precise evaluation of gastric cancer before surgery.