Anti-PD-1 combined sorafenib versus anti-PD-1 alone in the treatment of advanced hepatocellular cell carcinoma: a propensity score-matching study.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching. RESULTS: There were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28. CONCLUSIONS: This is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.

Early prediction of 1-year tumor response of hepatocellular carcinoma with lipiodol deposition pattern through post-embolization cone-beam computed tomography during conventional transarterial chemoembolization.

OBJECTIVE: To evaluate whether parenchyma-to-lipiodol ratio (PLR) and lesion-to-lipiodol ratio (LLR) on C-arm cone-beam computed tomography (CBCT) can predict 1-year tumor response in patients with hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (cTACE). METHODS: This retrospective analysis included 221 HCC target lesions within up-to-seven criteria in 80 patients who underwent cTACE with arterial-phase CBCT and unenhanced CBCT after cTACE from 2015 to 2018. PLR and LLR of every tumor slice were obtained through mean density division of liver parenchyma and tumor enhancement with intratumoral lipiodol deposition. The cutoff values (COVs) of maximal PLR and LLR of every tumor were analyzed using Youden's index. The reliability of COV, correlations between the related parameters, and 1-year progression were assessed through interobserver agreement and multivariate analysis. COV validity was verified using the chi-square test and Cramer's V coefficient (V) in the validation cohort. RESULTS: Standard COVs of PLR and LLR were 0.149 and 1.4872, respectively. Interobserver agreement of COV for PLR and LLR was near perfect (kappa > 0.9). Multivariate analysis suggested that COV of PLR is an independent predictor (odds ratio = 1.23532×1014, p = 4.37×10-7). COV of PLR showed strong consistency, correlation with 1-year progression in prediction model (V = 0.829-0.776; p < 0.0001), and presented as an effective predictor in the validation cohort (V = 0.766; p < 0.0001). CONCLUSION: The COV of PLR (0.149) assessed through immediate post-embolization CBCT is an objective, effective, and approachable predictor of 1-year HCC progression after cTACE. KEY POINTS: • The maximal PLR value indicates the least lipiodol-distributed region in an HCC tumor. The maximal LLR value indicates the least lipiodol-deposited region in the tumor due to incomplete lipiodol delivery. PLR and LLR are concepts like signal-to-noise ratio to characterize the lipiodol retention pattern objectively to predict 1-year tumor progression immediately without any quantification software for 3D image analysis immediately after cTACE treatment. • COV of PLR can facilitate the early prediction of tumor progression/recurrence and indicate the section of embolized HCC, providing the operator's good targets for sequential cTACE or combined ablation. • The validation cohort in our study verified standard COVs of PLR and LLR. The validation process was more convincing and delicate than that of previous retrospective studies.

Less barium enema, more colonoscopy: A 12-year nationwide population-based study in Taiwan.

BACKGROUND: Colorectal cancer (CRC) is the second most common and third most fatal cancer in Taiwan. To reduce incidence and mortality rates from cancer, including CRC, the Health Promotion Administration in Taiwan initiated the National Program on Cancer Prevention in 2005. For patients who have a positive fecal occult blood test, colonoscopy is recommended, and double-contrast barium enema (BE) is reserved as an alternative for those who cannot receive colonoscopy. In addition, single-contrast BE is sometimes used in pediatrics to evaluate colonic condition. This study evaluated the usage trends of BE and colonoscopy in Taiwan. METHODS: Data from the National Health Insurance Research Database from 2001 to 2013 were used in this study. Patients who received BE and colonoscopy were identified using the procedure codes of the National Health Insurance program. Age-standardized, yearly rates of BE and colonoscopy procedures were calculated. RESULTS: According to the data, the total number of colonoscopies increased 3.7-fold from 2001 to 2013. The compound annual growth rates for BE and colonoscopy were -5.36% and 10.47%, respectively, during the same period. The compound annual growth rates for BE and colonoscopy were -3.89% and 11.64% from 2005 to 2009, and -11.36% and 9.82% from 2010 to 2013, respectively. BE was conducted significantly more frequently than colonoscopy in patients who were aged <12 years and in female patients. CONCLUSION: Professional association guidelines, national cancer prevention programs, patient and physician preferences, and increasing awareness and knowledge of CRC may all contribute to the increasing use of colonoscopy and the dramatic decline in the use of BE in Taiwan.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma.

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Objective Measurement of Arterial Flow Before and After Transcatheter Arterial Chemoembolization: A Feasibility Study Using Quantitative Color-Coding Analysis.

PURPOSE: To quantitatively measure the hemodynamic change of hepatic artery before and after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) by quantitative color-coding analysis (QCA). MATERIALS AND METHODS: This prospective study registered 64 consecutive HCC patients who underwent segmental or subsegmental TACE with epirubicin and lipiodol at level 2 or 3 of the subjective angiographic chemoembolization endpoint. QCA was used to determine the maximal density time (T(max)) of selected intravascular region of interest (ROI). Relative T(max) (rT(max)) was defined as the T(max) at the selected ROI minus the time of contrast medium spurting from the catheter tip. The rT(max) of hepatic arteries was analyzed before and after embolization. RESULTS: The pre- and post-treatment rT(max) of the landmarks at the treated segmental artery were 1.96 ± 0.48 and 3.14 ± 1.77 s, p < 0.001. According to the treated lobe, 30 patients were treated for the right lobe alone, and 8 patients were treated for the left lobe alone. The pre- and post-rT(max) of treated segmental artery were 2.06 ± 0.54, 3.34 ± 1.63 s, p < 0.001 and 1.89 ± 0.45, 2.68 ± 1.46 s, p = 0.12, respectively. The rT(max) of the proximal lobar hepatic arteries or proper hepatic artery had no significant change before and after TACE. CONCLUSIONS: The QCA is feasible to quantify embolization endpoints by comparing the rT(max) in selected hepatic arteries before and after TACE. The rT(max) of treated segmental artery was significant prolonged after optimized procedures.

Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC).

Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate-stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non-response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long-term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.