Liver Cancer最新文献

Introduction: Treatment options for intermediate-stage hepatocellular carcinoma (HCC) include transarterial radioembolization (TARE) and systemic treatment. Currently, in the absence of contraindications, first-line systemic therapies include combinations of immune checkpoint inhibitors with anti-angiogenic agents or different checkpoint inhibitors. Combinations of TARE and systemic treatment are being investigated for synergistic effects due to a boosting of the immune response. However, a high hepatopulmonary shunt (HPS) fraction - abnormal passage of blood from the hepatic vasculature to the pulmonary circulation resulting from the formation of abnormal vasculature within the tumor - precludes some patients from receiving TARE due to the risk of nontarget lung radiation. Here, we present a case in which treatment of a patient with atezolizumab and bevacizumab led to a significant reduction in HPS, enabling locoregional treatment of the tumor while the tumor did not respond to systemic treatment alone according to the mRECIST criteria.

Case presentation: Here, we report the case of a patient with intermediate-stage HCC who received systemic treatment with atezolizumab and bevacizumab due to a high HPS fraction of 42% precluding him from treatment with radioembolization. Despite eventually showing tumor progression to systemic treatment based on clinical and radiological evaluation, the lung shunt fraction was markedly reduced by the systemic treatment to only 3.4%, enabling successful treatment of the tumor with radioembolization.

Conclusion: The anti-angiogenic effects of bevacizumab may reduce HPS in patients with intermediate-stage HCC, thereby extending the utility of TARE. In patients who do not respond to systemic treatment and who are amenable to treatment with TARE due to tumor stage, repeated measurements of HPSF might be considered after treatment with bevacizumab.

Background: Hepatocellular carcinoma (HCC) associated with metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly identified in non-cirrhosis livers, representing a distinct clinical challenge. Unlike other etiologies, up to 50% of MASLD-related HCC arises without cirrhosis, conferring a significantly elevated risk and bypassing the traditional cirrhosis-carcinoma sequence.

Summary: This review delineates the unique pathogenesis of non-cirrhotic MASLD-HCC, focusing on the interplay between metabolic dysregulation, chronic inflammation, and a characteristic immunosuppressive tumor microenvironment (TME). We synthesize evidence on how immune dysregulation - particularly involving dysfunctional CD8+ T cells and an altered myeloid compartment - facilitates hepatocarcinogenesis independent of advanced fibrosis. The roles of genetic susceptibility (e.g., PNPLA3 and TM6SF2 variants), gut-liver axis disruption, and distinct molecular traits are also examined. We further evaluate emerging biomarkers for risk stratification and discuss the implications of the non-cirrhotic MASH immune contexture for responses to immunotherapy.

Key messages: Non-cirrhotic MASLD-HCC is a distinct oncogenic entity driven by metabolic-immune interplay. Its recognition necessitates a shift in clinical paradigm: (1) surveillance strategies must incorporate metabolic and genetic risk factors beyond cirrhosis; (2) the unique TME may predict immunotherapy efficacy, urging etiology-specific trial design; and (3) a precision oncology framework integrating molecular subtyping and biomarker profiling is essential for early detection and tailored management of this growing patient population.

Hepatocellular carcinoma (HCC) surveillance is recommended using a combination of abdominal ultrasound plus alpha-fetoprotein (AFP) in patients with chronic hepatitis B or cirrhosis from any etiology. However, this strategy is limited by suboptimal sensitivity for early-stage HCC, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease. Phase 2 and phase 3 biomarker studies have reported the promise of novel blood-based biomarkers, including AFP, des-gamma-carboxy prothrombin, and lens culinaris agglutinin-reactive AFP (AFP-L3). Biomarker panels, such as the GALAD score, GAAD, and ASAP combine these biomarkers plus age and gender into biomarker panels. A panel of 10 experts from Asia and the USA convened to discuss the clinical utility of these biomarkers for detecting early-stage HCC. The experts agreed that biomarker panels have shown higher sensitivity than each individual biomarker and showed promise for early-stage HCC detection, particularly in those with a high proportion of patients with obesity and MASLD and geographies with insufficient access to high-quality ultrasound. However, biomarkers require prospective validation in clinical utility trials demonstrating net benefit in patients with cirrhosis, and implementation may face challenges including widespread access to testing, broader insurance coverage, and improving awareness among physicians and patients.

Introduction: Subgroups of people with unresectable hepatocellular carcinoma (uHCC) are often excluded from clinical trials due to adverse prognostic factors. The SIERRA (NCT05883644) study assesses the efficacy and safety of STRIDE (Single Tremelimumab Regular Interval Durvalumab) in clinically relevant subgroups of uHCC with poorer prognosis, including participants with more decompensated hepatic function, worse performance status, or more advanced disease than the HIMALAYA (NCT03298451) study.

Methods: SIERRA is a phase 3b, single-arm, multicenter study that enrolled participants with uHCC with: Child-Pugh (CP) class of B7 or B8 with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, without main trunk portal vein thrombosis (PVT) (CP B7/B8 cohort); CP class A with ECOG PS 2, without main trunk PVT (ECOG PS 2 cohort); or CP class A with ECOG PS 0-1 with evidence of chronic main trunk PVT (Vp4 cohort). Participants received STRIDE (tremelimumab 300 mg plus durvalumab 1,500 mg once followed by durvalumab 1,500 mg every 4 weeks). This preplanned early safety analysis occurred once ∼60 participants had been followed for ≥6 months (data cutoff: September 27, 2024). Co-primary endpoints are incidence of grade 3/4 adverse events (AEs) possibly related to study treatment (PRAEs) within 6 months of treatment initiation and objective response rate. The study is ongoing.

Results: This analysis included 98 participants (CP B7/B8 cohort, n = 35; ECOG PS 2 cohort, n = 44; Vp4 cohort, n = 19). Median (Q1-Q3) number of cycles of durvalumab was 4.0 (2.0-8.0). Incidence of grade 3/4 PRAEs occurring within 6 months of treatment was 19.4% (95% confidence interval, 12.1-28.6) overall. Incidence of serious AEs was 32.7%. PRAEs, leading to death, occurred in 2.0% of participants.

Conclusion: The safety profile of STRIDE was manageable and consistent with the HIMALAYA study in participants with poorer prognosis than in HIMALAYA.

Background: Recurrence rates following thermal ablation for hepatocellular carcinoma (HCC) remain high, but the patterns of recurrence and post-recurrence outcomes are not well characterized. This study aimed to investigate the recurrence patterns and long-term post-recurrence survival (PRS) in patients with HCC after thermal ablation to inform post-recurrence treatment strategy.

Methods: A retrospective analysis was conducted on 824 patients who underwent thermal ablation for HCC between 2007 and 2023. Recurrence patterns and factors influencing PRS in patients with recurrence within and beyond the Milan criteria were evaluated. An independent cohort of 198 patients served as an external validation cohort for the prognostic models.

Results: During a median follow-up of 54.5 months, 536 patients experienced HCC recurrence, with 83.8% within and 16.2% beyond Milan criteria. For patients with recurrence within Milan criteria, early recurrence, recurrent tumor size, AFP, ALBI grade, and FIB-4 score were independent predictors of PRS. In patients with recurrence beyond Milan criteria, diabetes mellitus, macrovascular invasion, AFP, ALBI grade, and FIB-4 score independently predicted PRS. Based on PRS predictors, a risk model stratified patients with recurrence within Milan criteria into four risk groups, with median PRS of 103.7, 65, 48.7, and 28.6 months, respectively (p < 0.001). For recurrence beyond Milan criteria, a separate risk model classified patients into three risk groups, showing median PRS of 70.1, 24.7, and 8.1 months, along with probabilities of successful downstaging of 66.7%, 39.3%, and 0%, respectively (p < 0.001). The external validation results showed that both the Milan-in and Milan-out models demonstrated significant discriminative performance in the validation cohort.

Conclusions: PRS in patients with recurrent HCC after thermal ablation is significantly influenced by recurrence patterns, tumor characteristics, and host factors. These findings may guide post-recurrence treatment strategies and optimize the timing of salvage liver transplantation.

Purpose: This study aimed to compare the outcomes of proton radiotherapy alone versus its combination with immuno-oncology agents (Proton-IO) or tyrosine kinase inhibitors (Proton-TKI) in patients with intermediate- to advanced-stage hepatocellular carcinoma (HCC).

Methods: We retrospectively reviewed the medical records of 137 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC treated with proton radiotherapy at Linkou Chang Gung Memorial Hospital between 2020 and 2023. Patients were stratified into three groups: proton radiotherapy alone (n = 64), Proton-IO (n = 44), and Proton-TKI (n = 29). The most frequently used immuno-oncology agents were atezolizumab-bevacizumab (n = 33) and pembrolizumab (n = 5). Tyrosine kinase inhibitors (TKIs) included lenvatinib (n = 16) and sorafenib (n = 13).

Results: With a median follow-up of 30 months, patients in the Proton-IO group were significantly associated with higher 2-year overall survival (OS) rates compared with those receiving Proton-TKI or proton radiotherapy alone (77.0% vs. 47.2% vs. 52.7%; p = 0.002). Proton-IO was also associated with significantly longer time to progression (TTP) and distant metastasis-free survival (DMFS) (2-year TTP: 50.5% vs. 28.1% vs. 24.2%, p = 0.003; 2-year DMFS: 83.4% vs. 61.1% vs. 67.2%, p = 0.027). No significant differences in 2-year local control rates were observed among the treatment groups (97.7% vs. 92.9% vs. 86.8%; p = 0.230). Multivariate analysis identified Proton-IO as an independent predictor of improved OS (p < 0.001), TTP (p < 0.001), and DMFS (p = 0.004). Grade 3-4 upper gastrointestinal (UGI) bleeding was observed in 2 (1.5%) patients (proton monotherapy, n = 1; Proton-IO, n = 1). There were no significant differences among the groups in the incidence of grade ≥3 UGI bleeding, liver toxicity, colitis, rib fractures, or hematologic adverse events.

Conclusion: In BCLC stage B/C HCC, proton radiotherapy combined with immunotherapy was significantly associated with higher OS, TTP, and DMFS without an increase in grade ≥3 toxicity compared with proton radiotherapy alone or Proton-TKIs.

Introduction: Immunotherapy is an attractive strategy for downstaging/bridging treatment of hepatocellular carcinoma (HCC) before liver transplantation (LT). This multicentre study reports the feasibility and effectiveness of LT following immunotherapy in a French HCC cohort.

Methods: Clinical, biological, and radiological data were collected at the start and end of immunotherapy, and before LT. Outcomes were evaluated through radiological response post-immunotherapy, recurrence risk (R3-alpha-fetoprotein [AFP] score) on explanted livers, and post-LT complications, aiming to assess primary LT success, overall and disease-free survival.

Results: Twenty-one HCC patients (17 males; median age 62 years [57-64]) were included in the study. Fourteen (66.7%) patients were BCLC-B, and sixteen (76.2%) received atezolizumab/bevacizumab (median 8.5 cycles [4.7-14]). At the end of immunotherapy, 57.1% met Milan-in criteria, and 95.2% had AFP score ≤2 (p = 0.002). The median interval from last immunotherapy to LT was 5.1 (2.7-9.3) months. All but 3 patients received standard immunosuppression. Explant pathology showed residual tumours in 71.4%, with 47.6% at high recurrence risk according to R3-AFP score. Two patients experienced allograft rejection, and one (4.8%) had HCC recurrence post-LT. Early adverse events occurred in 6 (28.5%) patients, leading to 5 (23.8%) deaths. At 12 months, 71.4% were alive without HCC recurrence. Lower overall survival was linked to pre-LT Child-Pugh B class, absence of prior HCC treatment, fewer than 5 immunotherapy cycles, and early post-LT complications.

Conclusion: LT following immunotherapy is feasible in selected HCC patients, although caution is warranted due to the potential but manageable rejection risk. However, high early mortality warrants further investigation in larger prospective series.

Introduction: This study aimed to evaluate the effect of sandwiching on-demand transcatheter arterial chemoembolization (TACE) during atezolizumab (Atezo) and bevacizumab (Bev) therapy on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC).

Methods: We retrospectively analyzed 398 patients who started Atezo/Bev therapy between October 2020 and April 2024. Overall, 245 patients were included: 51 in the ABC-TACE sandwich group and 194 in the Atezo/Bev alone group. Propensity score matching was performed to balance baseline characteristics, resulting in 49 matched patients per group. OS and PFS were analyzed using the Kaplan-Meier methods, with landmark analysis to adjust for immortal time bias. Multivariate analysis identified independent predictors of OS and PFS.

Results: The ABC-TACE sandwich group had significantly longer OS (median, not reached vs. 21.0 months, p < 0.05) and PFS (18.7 months vs. 11.2 months, p < 0.05) than the Atezo/Bev alone group. Landmark analysis showed prolonged OS at multiple time points in the ABC-TACE sandwich group (p < 0.05, p < 0.05, p = 0.078). TACE independently contributed to both OS and PFS. No significant differences in adverse events were observed between the groups. No deterioration in the Child-Pugh score was observed before and after TACE (p = 0.976).

Conclusion: Sandwiching TACE during Atezo/Bev therapy may improve survival outcomes for unresectable HCC.

Introduction: Liver function deterioration after transarterial chemoembolization (TACE) may preclude systemic therapy. The JIVROSG-1302 PRESIDENT study, a prospective, randomized controlled trial, showed a significantly higher local complete response rate with selective conventional TACE (cTACE) than with selective TACE using drug-eluting beads (DEB-TACE). However, this study did not assess the changes in liver function after selective TACE. The purpose of this study, JIVROSG-2001 PRESIDENT-ALBI, was to evaluate the change in liver function after selective TACE for unresectable hepatocellular carcinoma (HCC) using the same patient cohort.

Methods: The primary endpoint was ALBI grade deterioration rate after 3 months of TACE compared to DEB-TACE and cTACE. Secondary endpoints included the ALBI grade and score change and the identification of risk factors associated with liver function deterioration.

Results: A total of 197 patients with unresectable HCC were enrolled in this study. The ALBI grade deterioration rate at 3 months was 11% for the DEB-TACE group and 6% for the cTACE group, with no significant difference (p = 0.203). The mean ALBI score deterioration at 1 and 3 months was 0.06 and 0.02, respectively, and no notable deterioration in liver function was observed. The risk factors for ALBI score deterioration 1 month after selective TACE included large tumor diameter, high number of treated tumors, and treated vessels.

Conclusions: Selective TACE, whether DEB-TACE or cTACE, did not significantly impair the liver function. Even with selective TACE, larger tumors, multiple tumors, and a large number of treated blood vessels were associated with worsening liver function 1 month after TACE.