Combined Hounsfield units of hepatocellular carcinoma on computed tomography and PET as a noninvasive predictor of early recurrence after living donor liver transplantation: Time-to-recurrence survival analysis.

BACKGROUND: Liver transplantation is an effective treatment for preventing hepatocellular carcinoma (HCC) recurrence. This retrospective study aimed to quantitatively evaluate the attenuation in Hounsfield units (HU) on contrast-enhanced computed tomography (CECT) as a prognostic factor for hepatocellular carcinoma (HCC) following liver transplantation as a treatment. Our goal is to optimize its predictive ability for early tumor recurrence and compare it with the other imaging modality-positron emission tomography (PET). METHODS: In 618 cases of LDLT for HCC, only 131 patients with measurable viable HCC on preoperative CECT and preoperative positron emission tomography (PET) evaluations were included, with a minimum follow-up period of 6 years. Cox regression models were developed to identify predictors of postoperative recurrence. Performance metrics for both CT and PET were assessed. The correlation between these two imaging modalities was also evaluated. Survival analyses were conducted using time-dependent receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) to assess accuracy and determine optimized cut-off points. RESULTS: Univariate and multivariate analyses revealed that both arterial-phase preoperative tumor attenuation (HU) and PET were independent prognostic factors for recurrence-free survival. Both lower arterial tumor enhancement (Cut-off value = 59.2, AUC 0.88) on CT and PET positive (AUC 0.89) increased risk of early tumor recurrence 0.5-year time-dependent ROC. Composites with HU < 59.2 and a positive PET result exhibited significantly higher diagnostic accuracy in detecting early tumor recurrence (AUC = 0.96). CONCLUSION: Relatively low arterial tumor enhancement values on CECT effectively predict early HCC recurrence after LDLT. The integration of CT and PET imaging may serve as imaging markers of early tumor recurrence in HCC patients after LDLT.

Yttrium-90 Radioembolization as the Major Treatment of Hepatocellular Carcinoma.

Background: The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma. Methods: From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported. Results: Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level >100. Conclusion: Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.

Efficacy and Safety of Combined Ethanol-Lipiodol Mixture and Drug-Eluting Bead TACE for Large HCC.

Purpose: To evaluate treatment response, survival and safety of a novel TACE using combination of ethanol-Lipiodol mixture and drug-eluting beads in patients with large unresectable HCC, single tumor >8 cm or multiple tumors with the largest tumor diameter >5 cm and total tumor diameter >10 cm. Patients and Methods: Between June 2016 and February 2020, a total of 27 patients were enrolled in this retrospective cohort study. Treatment response was assessed at first month after the treatment; progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded. Results: The maximum diameter of the tumors ranged from 5 cm to 17 cm (mean 10.48 cm). The objective response and disease control rates were 56% and 78%, respectively, at 1-month follow-up. The median survival time was 15.9 months (95% CI, 9.03-34.76 months). The OS rates were 76.9% at six months, 65.2% at one year and 44.8% at two years. AFP >400 ng/mL (p = 0.0306), maximum tumor size >10cm (p = 0.0240) were potential risk factors for OS. Regarding safety, major complications occurred in one patient (1/27, 3.7%), presenting with transient hepatic encephalopathy. Conclusion: Combined DEB-TACE appeared to have favorable objective tumor response. It can be an effective treatment option for large unresectable HCC.

Transarterial Chemoembolization Using 100-µm Drug-Eluting Microspheres in Patients with Hepatocellular Carcinoma: A Prospective Study and Midterm Follow-up.

PURPOSE: The purpose of this study was to assess the safety and efficacy of drug-eluting embolic (DEE) transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients who are ineligible for curative treatment, using doxorubicin-loaded Tandem (Varian Medical) microspheres. MATERIALS AND METHODS: Between October 2015 and December 2017, 98 patients with unresectable HCC (69 males, 29 females; mean age, 60.5 ± 10.0 years of age; and American Joint Committee on Cancer [AJCC] stage ≦T3a) treated with DEE transarterial chemoembolization using 100-µm doxorubicin-loaded microspheres were enrolled prospectively. All studies were reviewed and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging 1 month after treatment was used for tumor response assessment according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Outcomes included overall survival (OS), progression-free survival (PFS), and downstaging profile. RESULTS: Median follow-up was 21.2 months. At follow-up examinations at 0.5-, 1-, 1.5- and 2.5-year follow-up, OS rates were 93.8%, 89.5%, 79.4%, and 77.0%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were noted in 50 (51.0%), 23 (23.5%), 18 (18.4%), and 7 (7.1%) patients, respectively, with 93.9% disease control rate and 74.5% objective response rate. Mean OS was 28.7 months, and mean PFS was 19.6 months. Number of nodules >3, bilobar disease, larger tumor, and higher AJCC stage correlated with worse CR. No serious adverse events occurred after DEE transarterial chemoembolization. Successful downstage rate was 73.3% (22 of 30) and number of nodules predicting successful downstaging was 7 nodules (cutoff). CONCLUSIONS: Tandem DEE transarterial chemoembolization provides safe and effective treatment for HCC and a bridge or downstage therapy for liver transplantation.

Quantification of Functional MR Predicts Early Response in Post-doxorubicin Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma.

BACKGROUND: The purpose of this study was to assess the value of functional MRI (fMRI) of post-doxorubicin drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) as an early imaging biomarker of response to therapy. METHODS: This prospective analysis included 21 consecutive patients undergoing fMRI before and after DEB-TACE at a single medical center from January 2013 to December 2014. Functional MRI, including relative changes in apparent diffusion coefficient (ADC) and choline levels measured at hydrogen-1 magnetic resonance spectroscopy (MRS) of treated lesions, was recorded at baseline before DEB-TACE, and at 1, 2, and 4 weeks after DEB-TACE therapy. Assessment of tumor response was based on dynamic contrast-enhanced computer tomography imaging response according to modified response evaluation criteria in solid tumors. RESULTS: At post-therapy, 76% (n = 16) of patients demonstrated objective tumor response, 10% (n = 2) had stable disease, and 3 (14%) had progressive disease. Stable disease and progressive disease were designated as non-response. At week 2, the mean change in ADC value of responsive tumors was 0.35 ± 0.24 mm2/s, which was greater than that of non-response tumors (mean 0.01 ± 0.13 × 10-3 mm2/s) (P = 0.006). Significant differences were found in mean choline/water ratio between responsive (7.8 ± 4.9 × 10-3) and non-responsive (17.2 ± 4.9 × 10-3) tumors (P = 0.005). Composite scores of choline/water ratio and relative change of ADC showed significantly better diagnostic accuracy in non-responsive tumors than responsive tumors (area under the curve = 1.0; P < 0.001). CONCLUSIONS: Combined DWI and MRS may be used as an early imaging biomarker of therapy response in HCC patients after chemoembolization therapy.

Diffusion-weighted imaging for identifying patients at high risk of tumor recurrence following liver transplantation.

BACKGROUND: Tumor recurrence is the major risk factor affecting post-transplant survival. In this retrospective study, we evaluate the prognostic values of magnetic resonance (MR) diffusion-weighted imaging (DWI) in liver transplantation for hepatocellular carcinoma (HCC). METHODS: From April 2014 to September 2016, 106 HCC patients receiving living donor liver transplantation (LDLT) were enrolled. Nine patients were excluded due to postoperative death within 3 months and incomplete imaging data. The association between tumor recurrence, explant pathologic findings, and DWI parameters was analyzed (tumor-to-liver diffusion weighted imaging ratio, DWIT/L; apparent diffusion coefficients, ADC). The survival probability was calculated using the Kaplan-Meier method. RESULTS: Sixteen of 97 patients (16%) developed tumor recurrence during the follow-up period (median of 40.9 months; range 5.2-56.5). In those with no viable tumor (n = 65) on pretransplant imaging, recurrence occurred only in 5 (7.6%) patients. Low minimum ADC values (p = 0.001), unfavorable tumor histopathology (p <  0.001) and the presence of microvascular invasion (p <  0.001) were risk factors for tumor recurrence, while ADCmean (p = 0.111) and DWIT/L (p = 0.093) showed no significant difference between the groups. An ADCmin ≤ 0.88 × 10- 3 mm2/s was an independent factor associated with worse three-year recurrence-free survival (94.4% vs. 23.8%) and overall survival rates (100% vs. 38.6%). CONCLUSIONS: Quantitative measurement of ADCmin is a promising prognostic indicator for predicting tumor recurrence after liver transplantation.

Predicting post-hepatectomy liver failure by combined volumetric, functional MR image and laboratory analysis.

BACKGROUND & AIMS: To assess the efficacy of functional MR image with volumetric, liver function test and indocyanine green clearance (ICG) in identifying the patients who are at risk of post-hepatectomy liver failure (PHLF). METHODS: We retrospectively included 115 patients undergoing gadoxetic acid-enhanced MR imaging before hepatectomy at one medical centre from January 2013 to December 2015. Contrast enhancement ratio (CER) between transitional and hepatobiliary phases (3 and 30 minutes post-contrast) was calculated. Total liver volume (TLV) and spleen volume (Sp) were measured. Post-operatively, the histological Ishak fibrosis score was collected. Potential risk factors for liver failure were analysed, and the performance was examined by receiver operating characteristic curve. RESULTS: Post-hepatectomy liver failure (PHLF) occurred in 16 patients (13.9%). TLV/SLV, ADC value, CERHBP/TP and total liver contrast enhancement ratio (tCER) were associated with PHLF (P < .05). Between PHLF and non-PHLF groups, remnant liver volume (RLV), RLV/SLV, Sp/RLV, remnant liver contrast enhancement ratio (rCER) and Ishak fibrosis score showed statistical difference. rCER showed superiority in diagnostic performance (AUC = 0.78) with the optimal cut-off value of 1.23. CONCLUSIONS: Gadoxetic acid-enhanced MR imaging with volumetric is a reliable method for evaluating functional liver volume and determining the risk of PHLF.