Background: Radiological response dynamics may provide prognostic information beyond conventional response categories in patients with unresectable hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab. Building upon findings from the IMbrave150 trial, we evaluated the prognostic significance of depth of response (DpR), duration of response (DoR), and time to response (TTR) in a real-world cohort. Methods: This retrospective multicenter study included 183 treatment-naïve patients with unresectable HCC treated with atezolizumab plus bevacizumab between November 2020 and September 2024. Tumor response was assessed according to mRECIST. Associations of DpR, DoR, and TTR with overall survival (OS) and progression-free survival (PFS) were evaluated using landmark analyses and time-dependent Cox analyses. Results: Deeper tumor response, longer DoR, and ≥50% reductions in serologic biomarker correlated with improved survival. Patients who achieved an early response (≤2 months) tended to have less favorable survival outcomes than those with a later response. Multivariate analysis confirmed DoR (HR= 0.40; 95% CI: 0.30-0.55; P < 0.001) and DpR (HR=0.45; 95% CI:0.38-0.55; P < 0.001) as independent predictors for improved OS, while early response independently predicted worse OS (HR=1.64; 95%CI: 1.26-2.15; P < 0.001). Similar trends were observed for PFS. Exploratory analyses suggested a potential association between conversion surgery and prolonged OS. Conclusions: DpR and DoR were independently associated with survival outcomes in patients with unresectable HCC receiving atezolizumab plus bevacizumab, extending and validating previous findings from IMbrave150 in a real-world setting. The prognostic significance of TTR and conversion surgery warrants further prospective investigation.
Introduction:While immunotherapy has emerged as a promising treatment option, no reliable predictive biomarker has been established for immunotherapy in hepatocellular carcinoma (HCC). In this study, we used genetic analyses to verify the prognostic significance of tumor mutation burden (TMB) in HCC and to search for other cancer characteristics related to prognosis. Methods:Patients with HCC who received a combined therapy of atezolizumab and bevacizumab were prospectively enrolled between July 2020 and April 2023. Circulating tumor DNA analysis was performed using next-generation sequencing before immunotherapy (baseline) and 3 weeks after initiation of immunotherapy (follow-up), from which we retrieved non-synonymous baseline, follow-up, vanished (detected only at baseline), and acquired (detected only at follow-up) variants. Gene sets related to cancer hallmarks and representative oncogenic pathways were curated. Results:Forty-two patients were enrolled in this study. Higher TMB was not correlated with better prognosis. Instead, it showed an inverse relationship, with higher baseline TMB significantly associated with shorter progression-free survival (PFS) (median 2.73 vs. 9.17 months, p = 0.04). Among other cancer characteristics, acquired variants in the Wnt/β-catenin (PFS: p = 1.14 × 10-4; overall survival [OS]: p = 0.004) and ATP-dependent chromatin remodeling (PFS: p = 0.002; OS: p = 0.006) pathways were significantly correlated with worse prognosis. Conclusion:In HCC, TMB is not a reliable predictive biomarker for immunotherapy. Instead, the emergence of acquired genetic variants in the Wnt/β-catenin and chromatin remodeling pathways act as a key driver of resistance.
Background:The PRISM study is a nationwide, multicenter, prospective observational study in Japan evaluating the real-world efficacy and safety of systemic therapies for unresectable hepatocellular carcinoma (HCC). HCC patients starting systemic therapy are prospectively enrolled, enabling assessment of outcomes and tolerability across treatment lines. By capturing all patients treated in routine practice, the study is expected to provide a clear picture of the actual treatment outcomes in Japan. Methods:We analyzed the first 1,000 patients enrolled between July 2020 and July 2022, focusing on outcomes of first-line therapy and subsequent patterns. Data on demographics, tumor stage, liver function, regimens, survival, and adverse events (AEs) were prospectively collected and centrally monitored. Survival was estimated by Kaplan-Meier method, and tumor responses were assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). Results:Of 935 evaluable patients, 82.8% received atezolizumab + bevacizumab (Atezo+Bev) and 15.2% lenvatinib as first-line therapy. Median overall survival and progression-free survival were 21.8 and 7.7 months for Atezo+Bev, respectively, and 20.8 and 6.7 months for lenvatinib, with overall survival numerically longer than that reported in pivotal clinical trials, while progression-free survival remained comparable. Objective response rates were 29.6% (RECIST) and 35.0% (mRECIST) for Atezo+Bev, 24.6% and 35.2% for lenvatinib, and 0% and 6.3% for sorafenib by RECIST and mRECIST, respectively. Grade ≥3 treatment-related AEs occurred in 21.6% and 22.9%, with safety profiles consistent with prior reports. Approximately 50% of patients received second-line therapy, most often lenvatinib after Atezo+Bev and vice versa, with a median progression-free survival of ∼4 months; later-line regimens yielded even shorter benefit. Conclusion:The PRISM study confirms the real-world reproducibility of Atezo+Bev and lenvatinib in Japan, demonstrating their feasibility across diverse patient populations. Ongoing follow-up and subgroup analyses, particularly in special populations, are expected to help optimize long-term outcomes.
Introduction:This study aimed to compare the real-world effectiveness and safety of hepatic resection versus stereotactic body radiation therapy (SBRT) as initial local treatments for Barcelona Clinic Liver Cancer (BCLC) stage 0 hepatocellular carcinoma (HCC). Methods:We retrospectively analyzed 537 treatment-naïve patients with single HCC measuring ≤2 cm who underwent hepatic resection (n = 450) or SBRT (n = 87) between January 2015 and December 2023. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between treatment groups. Overall survival (OS) and disease-free survival (DFS) were evaluated using weighted Cox proportional hazards models, while competing-risk models estimated the cumulative incidence of overall and intrahepatic recurrence. Treatment-related adverse events (TRAEs) and longitudinal changes in liver function were also assessed. Results:At baseline, patients in the SBRT group were significantly older, had a higher comorbidity burden, and exhibited poorer liver function compared to those in the resection group. Over a median follow-up of 56.8 months (range, 8.3-117.0), the unadjusted 3-year OS rates were 98.8% for resection versus 92.3% for SBRT (hazard ratio [HR] 3.15; p = 0.002), and 3-year DFS rates were 80.9% versus 64.9%, respectively (HR 1.58; p = 0.026). However, the IPTW-adjusted analysis demonstrated comparable outcomes between treatment groups, with 3-year rates of OS at 98.9% versus 96.2% (HR 1.15; p = 0.775), DFS at 79.1% versus 74.1% (HR 1.06; p = 0.851), and overall recurrence at 20.9% versus 20.2% (HR 0.96; p = 0.906) for resection and SBRT, respectively. Grade ≥3 TRAEs occurred in 31 patients (6.9%) in the resection group and none in the SBRT group. Liver function remained well preserved in both treatment groups. Conclusion:After adjusting for baseline imbalances, SBRT achieved survival outcomes comparable to hepatic resection as initial local therapy, while maintaining an excellent safety profile. These findings suggest that SBRT may serve as a viable alternative for patients with BCLC stage 0 HCC who are suboptimal surgical candidates.
Introduction:Atezolizumab plus bevacizumab (Atezo+Bev) is the most widely used first-line treatment for unresectable hepatocellular carcinoma (HCC), while lenvatinib remains a standard alternative. Previous studies suggest limited efficacy of Atezo+Bev in patients with HCC exhibiting a CRAFITY score of 2 (CRP ≥1 mg/dL and AFP ≥100 ng/mL). We conducted an international collaborative study to compare the efficacy of Atezo+Bev and lenvatinib stratified by the baseline CRAFITY score. Methods:We retrospectively analyzed 994 patients who initiated Atezo+Bev or lenvatinib as first-line therapy for unresectable HCC between September 2017 and March 2024 across 11 hospitals in Japan and 13 hospitals in Taiwan. Patients were categorized by baseline CRAFITY score, and progression-free survival (PFS) and overall survival (OS) were compared between treatment groups. Results:The median age of the patients was 71 years, and 770 (77.5%) were male. The baseline CRAFITY score was 0 in 375 patients (37.7%), 1 in 402 patients (40.4%), and 2 in 217 patients (21.8%). In patients with a CRAFITY-0 score, median PFS (10.8 vs. 9.4 months; p = 0.548) and OS (21.1 vs. 29.3 months; p = 0.074) did not differ significantly between Atezo+Bev and lenvatinib. Similar findings were observed in CRAFITY-1 patients, with median PFS of 6.0 vs. 6.1 months (p = 0.943) and OS of 12.7 vs. 15.1 months (p = 0.168). In contrast, among CRAFITY-2 patients, lenvatinib was associated with significantly longer PFS (2.3 vs. 4.4 months; hazard ratio, 0.66; p = 0.017), while OS did not differ significantly between treatments (5.7 vs. 9.1 months; hazard ratio, 0.90; p = 0.586). A significant interaction was observed between CRAFITY score (0/1 vs. 2) and treatment regimen (Atezo+Bev vs. lenvatinib) for PFS (p = 0.002). Consistent findings were observed in adjusted analyses. Conclusion:Lenvatinib was associated with significantly longer PFS than Atezo+Bev in patients with a baseline CRAFITY score of 2. The CRAFITY score may be useful for identifying patients in whom lenvatinib could be considered as a first-line option, and prospective validation is warranted.
Introduction:Prior studies suggest that per- and polyfluoroalkyl substances (PFAS) may increase risk of liver disease including hepatocellular carcinoma (HCC) via changes in hepatic lipid, amino acid, and glucose metabolism. However, whether PFAS promotes HCC among individuals with cirrhosis has not been examined. We examined associations of PFAS exposure and risk of HCC among patients with cirrhosis. Methods:In this nested case-control study, pre-diagnostic serum PFAS concentrations were measured using liquid chromatography-tandem mass spectrometry in 47 male patients with cirrhosis who developed incident HCC (cases) and 47 sex- and race/ethnicity-matched male cirrhosis patients who did not progress to HCC (controls). We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using conditional logistic regression. Results:All cases and controls were male, and there were no differences in the distributions of age and race/ethnicity between matched cases and controls. Most cases and controls (81%) had hepatitis C virus, and 85% were overweight/obese. Higher levels of perfluorooctanoic acid-type compounds, including L-perfluorooctanoic acid (OR, 1.63; 95% CI: 1.00-2.74), perfluorodecanoic acid (OR, 2.16; 95% CI: 1.00-5.12), perfluorononanoic acid (OR, 4.26; 95% CI: 1.84-11.9), and perfluoroundecanoic acid (OR, 3.18; 95% CI: 1.27-8.77), were associated with increased risk of HCC. Similarly, higher levels of perfluorooctane sulfonate (PFOS) were associated with higher HCC risk but only in patients with HCV (total PFOS, OR, 1.81; 95% CI: 1.08-4.00). Conversely, higher perfluorobutanesulfonic acid levels were associated with lower risk of HCC, and there was no significant association between perfluoroethylcyclohexane sulfonate level and HCC risk. Conclusions:Exposure to higher PFAS levels was associated with an increased risk of HCC among patients with cirrhosis. These preliminary findings need to be confirmed in large studies and may provide a new insight into the mechanisms of environmental-associated HCC.
Background: In the open-label, phase 3 REFLECT trial, lenvatinib had noninferior overall survival (OS) to sorafenib, as well as improved progression-free survival (PFS) and objective response rate (ORR) in patients with unresectable hepatocellular carcinoma (uHCC). We report post hoc safety and efficacy in older patients. Methods: In REFLECT (NCT01761266), patients with histologically/cytologically confirmed uHCC were randomized 1:1 to lenvatinib (12 mg/day [bodyweight ≥60 kg] or 8 mg/day [bodyweight <60 kg]) or sorafenib 400 mg twice daily in 28-day cycles. In this analysis, OS, PFS, ORR, and safety were evaluated in patients aged ≥65 and ≥75 years. Efficacy was evaluated per modified Response Evaluation Criteria in Solid Tumors by masked independent imaging review. Results: By data cutoff (November 13, 2016), 401 patients (208 receiving lenvatinib, 193 receiving sorafenib) were aged ≥65 years; of them, 125 (58 receiving lenvatinib, 67 receiving sorafenib) were aged ≥75 years. In the age ≥65 group, median OS was 14.6 months (95%CI: 13.0−18.7) in the lenvatinib arm and 13.4 months (95%CI: 11.6−16.3) in the sorafenib arm (hazard ratio [HR]: 0.844; 95%CI: 0.664−1.074); the OS HR was 0.807 (95%CI: 0.634−1.028) after adjusting for baseline alpha-fetoprotein. Median PFS was 7.4 months (95%CI: 5.6−9.1) with lenvatinib and 5.4 months (95%CI: 3.6−5.5) with sorafenib (HR: 0.571; 95%CI: 0.432−0.755). ORRs were 42.8% (95%CI: 36.1−49.5) with lenvatinib and 14.5% (95%CI: 9.5−19.5) with sorafenib. The most frequent treatment-emergent adverse events (TEAEs) were hypertension (47.3%) in the lenvatinib arm and palmar-plantar erythrodysesthesia syndrome (50.8%) in the sorafenib arm. The incidence of grade ≥3 TEAEs was 82.1% and 72.5% in the lenvatinib and sorafenib arm, respectively. Similar results were observed in patients aged ≥75 years. Conclusions: Consistent with the overall REFLECT population, older patients in the lenvatinib arm generally showed improved efficacy versus the sorafenib arm, supporting lenvatinib as an option for older patients with uHCC.
Introduction:The recently adopted nomenclature of steatotic liver disease (SLD) introduces new diagnostic categories, including metabolic dysfunction-associated steatotic liver disease (MASLD), the intermediate metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-associated liver disease (ALD). However, their specific impact on the outcomes of hepatocellular carcinoma (HCC) remains unclear. This study aimed to evaluate how alcohol consumption influences prognosis in patients with SLD-related HCC. Methods:We analyzed data from 2,864 HCC patients enrolled in the nationwide ITA.LI.CA database (2008-2022), stratifying those with SLD based on alcohol intake into MASLD, MetALD, and ALD. A comparator group with hepatitis B virus (HBV)-related HCC was also included. Multivariable Cox regression and competing risk analyses were employed to assess survival and cause-specific mortality. Results:Among SLD-related HCC, MASLD accounted for 47.1%, ALD 18.7%, and MetALD 7.2%. Patients with ALD showed the poorest liver function, more advanced tumor stage, and the highest mortality risk. Alcohol use progressively worsened prognosis from MASLD to ALD. MetALD and ALD were both associated with increased liver failure- and extrahepatic-related deaths compared to MASLD. In multivariable models, tumor burden, liver decompensation, and alcohol intake were significant predictors of mortality. Notably, metabolic comorbidities impacted prognosis predominantly in MetALD and ALD, suggesting an interaction between alcohol and systemic metabolic dysfunction. Conclusion:Alcohol consumption exerts a dose-dependent detrimental effect on clinical outcomes in SLD-related HCC. These findings support a distinct prognostic stratification for HCC patients with MetALD and ALD, reinforcing the need for alcohol abstinence in individuals with metabolic liver disease.
Introduction:Transarterial chemoembolization (TACE) is the standard treatment for unresectable, nonmetastatic hepatocellular carcinoma (HCC). Although adding systemic therapies (TACE + S) is hypothesized to mitigate TACE-induced angiogenesis and enhance efficacy, the definitive clinical advantage of TACE + S over TACE monotherapy, particularly with respect to overall survival (OS), remains uncertain. We aimed to comprehensively evaluate the efficacy and safety of this combination using a rigorous meta-analysis and trial sequential analysis (TSA). Methods:We systematically searched major databases for randomized controlled trials (RCTs) comparing TACE + S versus TACE alone or TACE plus placebo in patients with unresectable HCC without macrovascular invasion or extrahepatic metastasis. The primary outcome was OS; secondary outcomes included progression-free survival, time to progression (TTP), objective response rate (ORR), and adverse events (AEs). TSA was employed to assess the statistical reliability of findings and the adequacy of the cumulative evidence across all outcomes. Results:A total of 10 RCTs comprising 2,296 patients were included. Compared with TACE alone/placebo, TACE + S demonstrated a statistically significant improvement in OS (hazard ratio [HR] = 0.83, 95% CI: 0.73-0.95, p = 0.008), with TSA confirming the statistical reliability of the evidence. TACE + S also significantly improved TTP based on mRECIST (HR = 0.63, 95% CI: 0.54-0.74, p < 0.001) and ORR by RECIST 1.1 (relative risk = 1.44, 95% CI: 1.22-1.70, p < 0.001). Subgroup analysis showed a more pronounced OS benefit in patients with HBV-related HCC (HR = 0.69, p = 0.009). However, the combination strategy was associated with a significantly higher incidence of both all-grade and grade ≥3 treatment-related AEs, though no treatment-related deaths were reported. Conclusion:In patients with unresectable, nonmetastatic HCC, the combination of TACE and systemic therapy provides superior OS, more favorable tumor control, and delayed disease progression compared with TACE monotherapy. These significant benefits are particularly pronounced in the HBV-associated HCC population. While the increased risk of AEs is notable, this approach remains a viable option, underscoring the necessity for careful patient selection and proactive management strategies.
Background: The liver presents a fundamental paradox: it possesses unparalleled regenerative capacity yet demonstrates exquisite cancer susceptibility under chronic injury, with 85-90% of hepatocellular carcinoma (HCC) arising from chronic liver disease. Despite decades of research, the field lacks a unifying framework explaining this contradiction. Summary: We propose that HCC arises not from regeneration failing but from regeneration succeeding too long. The identical molecular pathways that safely restore hepatic mass after acute injury become carcinogenic when activated for decades rather than weeks—duration determines destiny. Living donor hepatectomy (60% resection) demonstrates zero cancer risk despite maximal proliferation because activation lasts only 2-4 weeks. Conversely, chronic HCV infection triggers identical responses monthly for 25-30 years, yielding 40-60% cumulative HCC incidence. When regeneration persists chronically, seven corruptions progressively accumulate: Division Trap (mutational accumulation), Selection Engine (clonal expansion), Memory Lock (epigenetic cementing), Physical Prison (mechanical oncogenesis), Immune Betrayal (tolerance induction), Termination Failure (brake inactivation), and Senescence Trap (SASP-mediated promotion). These develop in parallel and interact synergistically. Clinical evidence validates stage-dependent reversibility: HCV cure at F0-F1 achieves >95% cancer prevention, while cure at F4 cirrhosis provides 70% risk reduction despite irreversible corruptions. Taiwan's HBV vaccination program demonstrates >80% cancer reduction sustained over 40 years when chronic injury is prevented entirely. Key Messages: Duration of pathway activation—not pathway identity—determines whether regeneration remains safe or becomes carcinogenic. Understanding HCC pathways as regenerative pathways stuck "ON" enables rational therapeutic strategies through corruption-specific targeting. Early intervention prevents >95% of cancers; even late intervention at cirrhosis achieves 70% benefit. The regeneration paradox transforms HCC from mysterious misfortune into predictable consequence, enabling precision prevention and treatment.
BACKGROUND AND AIMS: Transarterial chemoembolisation (TACE) is considered the standard-of-care for patients with intermediate-stage hepatocellular carcinoma (HCC), despite several patients exhibit features that may be associated with suboptimal outcome of treatment– also referred to as TACE-unsuitable. In this study our aim was to provide real-world evidence that patients who are considered TACE-unsuitable may receive greater benefit by systemic therapy than by TACE. METHODS: This study analysed 1,150 patients with TACE-unsuitable HCC, defined according to Asia-Pacific Primary Liver Cancer Expert criteria. Patients were initially treated with TACE (n=842), sorafenib (n=96), lenvatinib (n=62), or atezolizumab/bevacizumab (n=47). Overall survival (OS) was the primary endpoint. Inverse Probability of Treatment Weighting was applied to adjust for baseline differences. RESULTS: Compared to TACE, atezolizumab/bevacizumab reduced mortality risk [Hazard Ratio (HR): 0.47, 95% Confidence Interval (95%CI): 0.27–0.80; p=0.008), lenvatinib was neutral (HR 0.62, 95%CI: 0.35–1.08; p=0.091), and sorafenib was associated with increased mortality (HR 1.85, 95%CI: 1.28–2.65; p=0.001). OS at 24-month was 60.2% for TACE, 31.9% for sorafenib, 68.3% for lenvatinib, and 70.5% for atezolizumab/bevacizumab (p<0.0001). The disease control rate was 53.2% with TACE, 47.9% with sorafenib, 67.8% with lenvatinib (p=0.030 versus TACE; p=0.025 versus sorafenib), and 75.6% with atezolizumab/bevacizumab (p<0.001 versus TACE; p<0.001 versus sorafenib). CONCLUSIONS: In TACE-unsuitable patients, systemic treatment with atezolizumab/bevacizumab and, to a lesser extent, with lenvatinib, is associated with improved outcome compared to TACE. These findings support a paradigm shift in the initial management of intermediate-stage HCC favouring the early use of systemic therapy in appropriately selected patients.
Introduction:Beta-blockers reduce portal hypertension; however, evidence comparing carvedilol and propranolol in patients with hepatocellular carcinoma (HCC) is lacking. We aimed to compare the clinical outcomes of carvedilol versus propranolol in patients with HCC. Methods:Using the Korean National Health Insurance Service database (2009-2023), we identified 11,124 patients with newly diagnosed HCC who were prescribed either carvedilol (n = 2,457) or propranolol (n = 8,667) within 180 days of diagnosis. The primary outcome was all-cause mortality, and the secondary outcome was hepatic decompensation. Multivariable Cox regression and 1:2 PS matching were used as primary analytical approaches, with sensitivity analyses restricted to 6-month survivors and a new-user design. Results:During a median follow-up of 1.5 years, carvedilol use was associated with a significantly lower risk of hepatic decompensation (adjusted hazard ratio [aHR] 0.67; 95% confidence interval [CI] 0.62-0.72) and all-cause mortality (aHR 0.84; 95% CI 0.79-0.90) compared to propranolol. In the 1:2 PS-matched cohort (n = 5,922), these associations remained consistent for both decompensation (HR 0.68; 95% CI 0.63-0.74) and mortality (HR 0.84; 95% CI 0.78-0.90). These benefits were consistent across various subgroups, and in sensitivity analysis excluding early death within 6 months from diagnosis and using a new-user design. Conclusion:In patients with HCC, carvedilol was associated with better survival and lower risk of hepatic decompensation than propranolol. Carvedilol may be the preferred beta-blocker over propranolol in the setting of HCC.
Background:Management of advanced hepatocellular carcinoma (HCC) has evolved rapidly in recent years. Following the publication of the IMbrave150 study in 2020, which established atezolizumab-bevacizumab as first-line therapy, multiple systemic therapies have been approved and incorporated into global clinical guidelines. However, outcomes remain suboptimal in high-risk cases (e.g., extensive tumor burden, macrovascular invasion). Summary:This review examines the role of hepatic arterial infusion chemotherapy (HAIC) in the context of modern systemic therapy for advanced HCC. A literature search (2020-2025) was conducted employing a PICO framework (Patients: advanced HCC; Intervention: HAIC; Comparison: any or no alternative therapy; Outcomes: efficacy and safety). HAIC is a regional chemotherapy approach delivered via the hepatic artery, allowing high intratumoral drug concentration with manageable systemic toxicity. It is popularly used in East Asia and has demonstrated promising survival benefits in patients with portal vein tumor thrombosis (PVTT) or large tumors - subgroups where systemic therapies or transarterial chemoembolization frequently fail. HAIC is an integral modality for advanced HCC, especially for patients with extensive liver tumors or PVTT. It provides critical bridge-to-curative options by downsizing tumors and improving systemic treatment effects. To integrate HAIC into global practice, standardization of techniques, patient selection, biomarkers, and confirmatory trials in non-Asian populations is needed. HAIC can change the standard of care by improving outcomes in patient subsets poorly served by current therapies. Key Messages:Paradigm shift to synergy: HAIC has transitioned from a palliative locoregional tool to a central pillar of "triple therapy" (HAIC + tyrosine kinase inhibitor + immune checkpoint inhibitor), leveraging immunogenic cell death to improve systemic treatment efficacy. Superiority in high-risk subsets: This modality demonstrates exceptional survival benefits in patients with high tumor burden and major PVTT (Vp4 PVTT) - subgroups where standard systemic monotherapies frequently fail. A bridge to cure: HAIC-based combination regimens significantly increase conversion-to-surgery rates by inducing rapid tumor necrosis and downstaging, thereby providing curative opportunities for initially unresectable patients. Global standardization needs: Future adoption relies on international consensus to standardize delivery protocols and biomarker-driven model validation for precise patient selection.
Introduction:Patients with early-stage hepatocellular carcinoma (HCC) are eligible for potentially curative treatments, yet these therapies are underused in clinical practice. Methods:We conducted a retrospective cohort study of patients with treatment-naïve, early-stage HCC (within Milan criteria) seen between January 2010 and July 2021 at two US health systems. Barriers to curative treatment were identified through review of medical records. We used univariable and multivariable logistic regression to identify factors associated with curative treatment receipt. Results:Among 629 eligible patients with early-stage HCC (median age 60 years; 72.3% male), 396 (63.0%) received curative treatment. In multivariable analysis, evaluation at a tertiary care center was associated with higher odds of curative treatment (OR 2.95, 95% CI: 1.98-4.47). In contrast, having Medicaid (OR 0.27, 95% CI: 0.14-0.53), being enrolled in a county-based subsidy program (OR 0.31, 95% CI: 0.16-0.58), or being uninsured (OR 0.24, 95% CI: 0.11-0.50) were associated with lower odds of curative treatment compared to private insurance. Other factors inversely associated with curative treatment included multifocal disease (OR 0.49, 95% CI: 0.31-0.75), increasing tumor size (continuous: OR 0.73, 95% CI: 0.60-0.88), and worse liver function (Child-Pugh B vs. A: OR 0.27, 95% CI: 0.18-0.40; Child-Pugh C vs. A: OR 0.13, 95% CI: 0.07-0.24). Common barriers to liver transplantation included lack of insurance, medical comorbidities, and psychosocial challenges. Common barriers to resection and ablation included comorbidities and unfavorable tumor location, respectively. Conclusion:Underuse of curative treatment for early-stage HCC is mediated by tumor-specific, clinical, and system-level factors, underscoring a need for multilevel interventions to address identified barriers.
Introduction: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains dismal. Although systemic therapy is the standard of care, its effectiveness is limited. This study aimed to compare the efficacy and safety of transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with systemic therapy versus systemic therapy alone in patients with HCC and PVTT. Methods: We retrospectively analyzed 478 patients newly diagnosed with HCC and PVTT between January 2021 and December 2024. Propensity score matching (PSM) was used to balance baseline characteristics. Outcomes compared between the combination therapy group (TACE/HAIC plus targeted therapy and immunotherapy, n = 374) and the systemic therapy group (n = 104) included overall survival (OS), progression-free survival (PFS), tumor response, and adverse events. Results: After PSM (184 vs. 102 patients), the combination therapy group showed significantly longer median OS (15.7 vs. 5.9 months; hazard ratio [HR] = 0.524, 95% confidence interval [CI]: 0.391-0.702; p < 0.001) and PFS (7.0 vs. 3.6 months, HR = 0.732, 95% CI: 0.558-0.959; p = 0.024). The disease control rate was also higher in the combination therapy group (43.5% vs. 27.5%, p = 0.007). Subgroup analyses revealed pronounced survival benefits in patients with Vp4 PVTT and those with Child-Pugh B liver function. Although adverse events were more frequent in the combination therapy group, the incidence of grade 3-4 toxicities was generally comparable between the two groups. Conclusion: In HCC patients with PVTT, combining TACE or HAIC with systemic therapy significantly improves survival outcomes compared to systemic therapy alone, with acceptable safety. This multimodal approach offers a promising treatment strategy, particularly for patients with advanced PVTT or impaired liver function.
Liver transplantation (LT) provides the best long-term survival outcomes for patients with liver cancer. As a result, the field of transplant oncology has grown greatly over the past few decades, and many centers have expanded their criteria to allow increased access to LT for liver malignancies. Center-level guidelines and practices in transplant oncology significantly vary across the world, leading to debate regarding the best course of treatment for this patient population. An international consensus conference was convened by the International Liver Transplantation Society and the International Liver Cancer Association on February 1-2, 2024, in Valencia, Spain, to establish a more universal consensus regarding LT for oncologic indications. The conference followed the Delphi process, followed by external expert review. Consensus statements were accepted regarding patient assessment and waitlisting criteria, pretransplant treatment (including immunotherapy) and downstaging, living donor LT, post-LT patient management, and patient- and caregiver-related outcomes. The multidisciplinary participants in the consensus conference provided up-to-date recommendations regarding the selection and management of patients with liver cancer being considered for LT. Although participants deferred to center protocols in many cases, there was great interest in safely expanding access to LT for patients with larger tumor burden and biologically amenable lesions.
Introduction:Accurate imaging diagnosis is essential for evaluating liver transplantation (LT) eligibility in hepatocellular carcinoma (HCC) patients. This study investigated whether pre-transplant imaging assessment using the Liver Imaging Reporting and Data System (LI-RADS) and Asia-Pacific guideline-based criteria could effectively predict long-term prognosis when determining LT eligibility. Methods:From a prospective registry, we analyzed 1,094 patients with a preoperative HCC diagnosis who had dynamic CT available within 1 month before LT. LT eligibility was assessed with Milan criteria (MC) and Up-to-Seven criteria (UTS). Imaging evaluation was performed using the LI-RADS, Asian Pacific Association for the Study of the Liver, Japan Society of Hepatology, and Korean Liver Cancer Association-National Cancer Center guidelines. We compared HCC-related mortality using competing risk analysis, overall survival, and prognostic performance between imaging-based and pathologic assessments. Results:The cohort comprised 158 (14.4%) anti-HCC treatment naïve patients and 936 (85.6%) patients who received anti-HCC treatments in the pre-LT setting. No significant difference in HCC-related mortality was observed between patients meeting imaging-based MC and pathological MC (5-year HCC-related mortality: 8.6-8.7% vs. 6.6%; all p > 0.05). Prognostic performance, assessed by 5-year area under the precision-recall curve and integrated Brier score, showed no significant differences between imaging-based MC and pathological MC groups (all p > 0.05). Similar results were observed for overall survival, UTS-based analyses, and pre-LT treatment subgroup analyses. Concordance between imaging-based MC and pathology-based MC was 84.0-84.4%. Conclusion:Although some discordance between imaging-based and pathology-based LT eligibility criteria was observed, pre-transplant imaging provided prognostic stratification comparable to pathology. Given that comprehensive pathological assessment is unattainable before LT, imaging-based evaluation using both LI-RADS and Asia-Pacific guidelines represents a practical and clinically relevant approach for determining LT eligibility.
