Anne M. Covey

Purpose: This study examines the association between tumor volume doubling time (TVDT) and clinical outcomes for patients with hepatocellular carcinoma (HCC) treated with transarterial embolization (TAE) and evaluates the impact of tumor genotype on TVDT. Methods: This was a retrospective cohort study at a single tertiary care cancer center, including treatment-naïve patients with biopsy-proven HCC treated with TAE from 1/2014 to 6/2022. The patients underwent initial baseline contrast-enhanced cross-sectional imaging more than 30 days prior to embolization. Index tumors were defined as the largest HCC present on baseline imaging treated with TAE, and TVDT was calculated using Schwartz’s equation with perpendicular trans-axial measurements. Genetic mutation analysis was performed on HCC tissue specimens using next-generation sequencing. Survival analysis was performed using the Kaplan–Meier method, and Cox regression was used to assess prognostic factors for survival. Results: Patients with a TVDT ≤ 2.5 months had a worse overall survival (OS) after TAE (p = 0.011). On multivariate regression analysis, predictors of worse OS following TAE included TVDT ≤ 2.5 months (p = 0.036), Eastern Cooperative Oncology Group (ECOG) performance score of 1 or 2 (p = 0.006), and alpha fetoprotein > 200 ng/mL (p = 0.013). The presence of ≥5 HCC tumors on initial imaging was associated with a worse local tumor progression-free survival (LTPFS) on multivariate analysis (p = 0.002). No single genetic mutation was associated with shorter TVDT. Conclusion: Patients with HCC exhibiting rapid growth, defined as shorter TVDT, may be associated with worse overall survival following TAE. Rapid tumor growth does not seem to be correlated with a single genetic mutation.

Malignant bile duct obstruction (MBDO) can occur in patients with both primary liver cancers and metastatic disease and can be a cause of significant morbidity. Laboratory abnormalities or symptoms often prompt decompression to lower bilirubin for chemotherapy, treat cholangitis, and divert bile to treat a leak or alleviate pruritus. Intervention may also be undertaken to perform biopsy or provide access to intraductal therapies such as brachytherapy, photodynamic therapy, or radiofrequency ablation. There are multiple ways to achieve biliary decompression including percutaneous procedures performed by interventional radiologists, endoscopic procedures performed by advanced endoscopists, and biliary bypass performed by hepatobiliary surgeons. Which approach is undertaken depends on several factors including the performance status, life expectancy, level of obstruction, anatomy, and patient preference. Every intervention has inherent risks as well as potential benefits, and a review of these complex patients by a multidisciplinary team ensures all options are considered. Finally, some cases require the technique and expertise of more than one specialty to achieve the desired outcome. This article highlights the importance of a multidisciplinary team in dealing with MBDOs.

The aim of this study was to evaluate associations between TP53 status and outcomes after transarterial embolization (TAE) for the treatment of patients with hepatocellular carcinoma (HCC). This single-institution study included patients from 1/2014 to 6/2022 who underwent TAE of HCC and genomic analysis of tumoral tissue. The primary outcome was overall survival (OS) with relation to TP53 status, and the secondary outcome was the time to progression. Survival analysis was performed using the Kaplan–Meier method. The time to progression with death or the last patient contact without progression as competing risks were used to obtain a cumulative incidence function, and the association with TP53 status was evaluated using the Gray test. In total, 75 patients (63 men) with a median age of 70.0 (IQR 62.0–76.3) years were included. Of these, 26/75 (34.7%) patients had TP53-mutant HCC. Patients with TP53-mutant HCC had a significantly worse median OS of 15.2 (95% CI, 9.5–29.3) months, versus 31.2 (95% CI, 21.2–52.4) months as the median OS (p = 0.023) for TP53 wild-type HCC. Competing risk analysis showed a shorter time to local hepatic progression (at the site of the previously treated tumor) after TAE in patients with TP53-mutant HCC. The cumulative incidences of local progression at 6 and 12 months for TP53-mutant HCC were 65.4% and 84.6%, versus 40.8% and 55.1% for TP53 wild-type HCC (p = 0.0072). A TP53 mutation may predict a worse overall survival and a shorter time to local progression in HCC patients treated with TAE.

Background/Objectives: The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). Methods: In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. Results: Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child–Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. Conclusions: This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection.

The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112–444, range), and 18/21 (85.7%) patients received 112–140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4–61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3–58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8–27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.

Purpose: Evaluate safety and feasibility of simultaneous biliary drainage (BD) and portal vein embolization (PVE) prior to hepatectomy in hilar cholangiocarcinoma (HCCA) patients. Methods: From January 2010 to June 2022, patients with potentially surgically resectable HCCA who underwent preoperative PVE and BD were analyzed. Type of initial BD, time interval between BD and PVE, changes in future liver remnant (FLR), time interval between BD, PVE and resection, and complications were recorded. Patients were divided into 3 groups based on the BD-PVE interval: Group A: simultaneous BD and PVE or within 7 days (d), n = 6; Group B: d ≥ 7 to ≤ 30, n = 7; Group C: d > 30, n = 14). Primary endpoints were post-PVE complications, FLR change, and resection rate. Secondary endpoints were Clavien-Dindo ≥ 3, Grade B/C Post Hepatectomy Liver Failure (PHLF) and 90 days mortality rate. Results: A total of 27 patients (mean age = 64.4 +/- 11.2 years) underwent both BD and PVE prior to hepatectomy. Mean degree of hypertrophy at 4-6 weeks post-PVE was 10.4 +/- 3.7% with no significant difference between the 3 groups (p > 0.05). Resection was 67% in Group A, and 57% and 36% in groups B and C respectively (p < 0.05). Time to surgery was 38.5 +/- 12 days in Group A, and 60 and 147 days in groups B and C respectively (p = 0.002). No major post PVE SIR complication was reported in group A. Overall rate of Grade III/IV Clavien-Dindo complication was 61.5% with no difference among the three groups (50%, 75%, and 60%; groups A, B and C, respectively). Overall PHLF Grade B/C was reported in 46.2% of patients. No patients in Group A demonstrated Grade B/C PHLF. Conclusion: Simultaneous BD and PVE is safe and reduces the time to surgery, which may help contribute to a higher rate of surgical resection.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide accounting for over 800,000 new cases in 2018, with the highest incidence in Asia and Africa where hepatitis B is the most common risk factor. In Europe, Japan, and the United States, hepatitis C chronic alcohol abuse and non-alcoholic fatty liver disease are more common risk factors. Five-year survival is low, less than 20% worldwide. HCC is a particularly challenging disease to treat because therapeutic options and prognosis must also consider hepatitis or cirrhosis independent of the malignancy. Locoregional therapies (LRT) including ablation, arterially directed therapy and external beam radiation are the preferred treatments for patients with good performance status, unresectable disease limited to the liver and preserved liver function. In practice, patients with portal vein tumor thrombus and limited extrahepatic disease may also be considered candidates for LRT. There are several guidelines developed by expert panels provide recommendations on treating this challenging disease including the Barcelona Clinic Liver Cancer, European Association for the Study of the Liver, European Society for Medical Oncology, American Association for the Study of the Liver Diseases, and the National Comprehensive Cancer Network. The purpose of this paper is to review the guidelines as they are applied clinically in regions with high incidence of HCC.