Liver Cancer最新文献

Introduction: It is challenging to diagnose liver masses in the context of a rough liver background using computed tomography and magnetic resonance imaging. Perfluorobutane CEUS microbubble, an ultrasound (US) contrast agent, has a unique phase called the Kupffer phase. This study aimed to explore whether the diagnostic ability of Kupffer-CEUS is affected by the rough liver background.

Methods: A prospective analysis was conducted on patients with access to histological pathology of FLLs and liver parenchyma from 23 centers between August 2020 and March 2021. Kupffer-CEUS was performed on 552 patients, who were divided into two groups (normal and abnormal) based on the pathological results of liver parenchyma, and the abnormal group was further divided into four groups (sight liver fibrosis, serious liver fibrosis, fatty liver, mixed). Kupffer-CEUS was divided into vascular phase and vascular and Kupffer phase.

Results: In Kupffer-CEUS, differences in diagnostic efficiency of FLLs between normal and abnormal liver backgrounds were not statistically significant. However, in patients with abnormal liver backgrounds, the specificity (57.45% vs. 74.47%, p = 0.008) and accuracy (89.81% vs. 96.92%, p < 0.001) of the vascular phase in distinguishing malignant from benign lesions were statistically lower than those of the vascular and Kupffer phase (V&KP). Subgroup analysis revealed that the sensitivity, specificity, and accuracy of V&KP in screening FLLs were all higher than those of vascular phase, except for the accuracy in patients with serious liver fibrosis (98.51% vs. 94.06, p < 0.001).

Conclusion: This study indicated that although there is no obvious restriction on the choice of Kupffer-CEUS methods when diagnosing liver masses in patients with normal or abnormal liver backgrounds, Kupffer phase CEUS can effectively reduce the misdiagnosis of FLLs. Particularly for patients with serious liver fibrosis, contrast-enhanced US combined with the Kupffer phase can provide a more accurate diagnosis than conventional contrast-enhanced ultrasonography.

Introduction: Accurately predicting the outcomes of conversion therapy among patients with initially unresectable hepatocellular carcinoma (uHCC) remains a challenge. Clinical complete response (cCR) has been proposed as a predictor of prognosis. However, information on its prognostic value in these patients is limited. We aimed to explore the prognostic value of cCR in patients with uHCC following conversion therapy and identify predictors of cCR.

Methods: We included 241 patients with uHCC who underwent transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) as first-line treatment. The prognostic value of cCR, predictive factors of cCR, and the relationship between cCR and pathological complete response (pCR) were analyzed.

Results: The cCR rate of the 241 patients included was 17.4%. Patients with cCR showed better overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) than those without. cCR was an independent risk factor for OS (hazard ratio [HR]: 0.11, 95% confidence interval [CI]: 0.03-0.42, p = 0.001) and PFS (HR: 0.29, 95% CI: 0.15-0.56, p < 0.001). Serum α-fetoprotein levels ≥400 ng/mL (odds ratio [OR]: 0.47, 95% CI: 0.22-0.95, p = 0.040) and extrahepatic metastasis (OR: 0.13, 95% CI: 0.01-0.62, p = 0.046) were independent negative predictors of cCR. A total of 107 patients (44.4%) underwent conversion surgery. Among these patients, cCR was associated with better OS (p = 0.009) and recurrence-free survival (p = 0.007). cCR was significantly correlated with pCR (Φ = 0.61, p < 0.001). Albumin levels ≥35 g/L (OR: 0.12, 95% CI: 0.02-0.69, p = 0.018) and cCR (OR: 30.32, 95% CI: 9.19-128.00, p < 0.001) were independent predictors of pCR.

Conclusion: cCR after triple therapy has an excellent long-term survival advantage and is significantly related to pCR. cCR may be a surrogate marker for predicting prognosis and pCR in patients with uHCC receiving triple therapy.

Introduction: Atezolizumab-bevacizumab (Atezo-Bev) has become the standard first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). However, data on subsequent treatment after Atezo-Bev failure are lacking. We aimed to investigate the efficacy and safety of regorafenib for uHCC progression after first-line Atezo-Bev.

Methods: This investigator-initiated, single-arm, phase 2 trial involved two academic centers in Korea. Eligibility criteria included a diagnosis of HCC, prior treatment with at least 2 cycles of Atezo-Bev, and Child-Pugh A liver function. Eligible patients received regorafenib 160 mg once daily for 3 weeks of every 4-week cycle (i.e., 3 weeks on, 1 week off) until progressive disease or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate, disease control rate according to RECIST v1.1, overall survival (OS), and treatment-related adverse events.

Results: Forty patients were enrolled from December 2021 through May 2023. The median follow-up duration was 10.1 months (95% confidence interval [CI]: 8.3-12.0). The median PFS was 3.5 months (95% CI: 3.0-3.9). The median OS was 10.5 months (95% CI: 7.1-13.8), and the 6-month OS rate was 65.0%. The objective response rate and disease control rate were 10.0% and 82.5%, respectively. The most common grade 3-4 treatment-related adverse event was thrombocytopenia (5.0%). When stratified according to time to progression on prior Atezo-Bev (first quartile [<2.3 months] vs. second to fourth quartiles [≥2.3 months]), patients with longer time to progression on prior Atezo-Bev had better OS (15.0 vs. 3.6 months, p < 0.001), objective response rate (13.3% vs. 0%, p = 0.009), and a tendency toward better PFS with regorafenib (3.8 vs. 2.5 months; p = 0.054).

Conclusion: Second-line regorafenib was effective for treating uHCC progression after first-line Atezo-Bev. The efficacy and safety outcomes from our study were consistent with those observed in the pivotal phase 3 RESORCE trial, which included sorafenib-tolerant/-progressed patients.

Introduction: Patients born with congenital porto-systemic shunts have been shown to have a high risk of benign and malignant liver tumors in otherwise healthy livers. This study aimed to evaluate the genetic landscape of liver tumors in patients with congenital porto-systemic shunts (CPSS) and correlate genotype with histological findings.

Methods: Nodules from patients with CPSS and sporadic pediatric focal nodular hyperplasia (FNH) or FNH-like nodules were evaluated histologically and sequenced for a panel of 50 genes using next-generation sequencing.

Results: Thirty-eight nodules from 17 patients with CPSS were histologically classified as hepatoblastomas (n = 2), hepatocellular carcinomas (n = 4), HNF-1α-inactivated hepatocellular adenomas (HCAs) (n = 2), β-catenin-activated HCAs (n = 5), unclassified HCAs (n = 9), and FNH-like nodules (n = 16). CTNNB1 variants were detected in 26/38 nodules (68%) across different histological categories (2/2 hepatoblastomas, 4/4 HCCs, 10/16 HCAs, 10/16 FNH-like nodules), but not in sporadic FNH or FNH-like nodules (0/10). Less frequent variants were identified in APOB, GNAS, HNF1A, SERPINA1, MAML2, PTCH1, G6PC, KMT2C, DICER1, AXIN1, IL6ST and the promoter region of TERT. Germline variants were identified in AXIN1, HFE, SERPINA1, and ZNF521. CTNNB1 variants affecting amino acid positions 32 and 33 are more common in malignant tumors. Multiple CTNNB1 variants were identified in 6/7 (86%) of patients with multiple nodules, but no intratumoral variation was found.

Discussion: CPSS is strongly associated with nodules containing variants in CTNNB1, irrespective of the histological category. Areas in background liver containing these variants were also identified, and different variants could be identified in individual patients. The high proportion of CTNNB1 variants may explain the higher malignant potential of benign tumors found in CPSS.

Introduction: In the phase 3 RESORCE trial, regorafenib prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC) whose disease progressed on prior sorafenib. The prospective, observational REFINE study aimed to evaluate the safety and effectiveness of regorafenib in a broader population of patients in real-world clinical practice, including patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, Child-Pugh B liver status, and sorafenib intolerance.

Methods: This international, prospective, multicenter study (NCT03289273) enrolled patients with uHCC for whom the decision to treat with regorafenib was made by their physician before enrollment, according to the local health authority-approved label. The primary aim was to evaluate the safety of regorafenib, including the incidence of treatment-emergent adverse events (TEAEs) and dose modifications due to TEAEs.

Results: Of the 1,028 patients enrolled, 1,005 initiated regorafenib and were eligible for analysis. Median age was 66 years (range 21-94); most patients were male (83%), Child-Pugh A (61%), and had an ECOG PS of 0 or 1 (82%) at study entry. Overall, 47%, 11%, and 40% of patients initiated regorafenib at 160, 120, and 80 mg/day, respectively. Median treatment duration was 3.7 months (range 1 day to 38.9 months). Dose modifications and permanent discontinuation of regorafenib due to TEAEs occurred in 45% and 31% of patients, respectively. The most common drug-related TEAEs were hand-foot skin reaction (31%), diarrhea (26%), and fatigue (15%). Median OS was 13.2 months (95% confidence interval 11.6, 14.8).

Conclusion: The results of the real-world REFINE study confirmed the safety and effectiveness of regorafenib in a broad population of patients with uHCC. Of patients who received standard regorafenib dosing in REFINE, safety and efficacy findings were consistent with those reported in the RESORCE trial.

Introduction: Adjuvant immune checkpoint inhibitors (ICIs) may improve recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC). This study evaluated the effects of adjuvant ICI treatment duration on RFS and overall survival (OS) among patients with HCC at high risk of recurrence.

Methods: The RFS and OS of patients from three centers who received either adjuvant ICI therapy or active surveillance after curative hepatic resection between January 1, 2019, and December 31, 2023, were analyzed. Further analysis was performed to evaluate the effects of ICI treatment duration on RFS and OS.

Results: A total of 1,271 patients were included, of whom 1,032 (81.2%) received active surveillance and 239 (18.8%) received adjuvant ICI therapy. The median RFS in the adjuvant therapy cohort was 22.6 months (95% CI 18.3-26.9), significantly higher than the RFS of 19.1 months (95% CI 16.4-21.4) in the active surveillance cohort (HR 0.79; 95% CI 0.66-0.95; p = 0.019). The median OS was not reached for either group, but OS tended to be better in the adjuvant therapy cohort than in the active surveillance group (HR 0.72, 95% CI 0.54-0.94; p = 0.010). Similar results were obtained after propensity score matching. Among patients who received adjuvant ICI therapy, those who received it for longer than 6 months had slightly higher RFS (HR 0.66; 95% CI 0.42-1.04; p = 0.071) and OS (HR 0.59; 95% CI 0.30-1.17; p = 0.128) than those who received it for up to 6 months.

Conclusions: Adjuvant ICI therapy significantly improves the prognosis of patients with HCC at high risk of recurrence after curative resection. Six months of adjuvant ICI treatment may be insufficient.

Background: CD8⁺ T cells are critical for the oncogenesis and progression of the hepatocellular carcinoma (HCC) tumor microenvironment, receiving antigen signals from antigen-presenting cells and directly contributing to antitumor responses.

Summary: CD8⁺ T cells mediate immunogenic cell death, facilitate immune signal transmission, and play a significant role in various treatments, including surgery, transarterial chemoembolization, and immunotherapy. Extensive research on the role of CD8⁺ T cells within the HCC microenvironment has shown considerable progress. Immunometabolic targets on CD8⁺ T cells have demonstrated potential in combination with immunotherapies for HCC; however, they have not yet reached the clinical trial stage.

Key messages: This review provides a comprehensive overview of recent research on immune and immunometabolic targets of CD8⁺ T cells within the HCC microenvironment. By highlighting advances and potential mechanisms, this review aims to support the development of effective clinical strategies in this field.

Introduction: The phase 3 LEAP-002 study (NCT03713593) of advanced hepatocellular carcinoma (HCC) suggested improved antitumor activity of lenvatinib plus pembrolizumab versus lenvatinib alone with manageable safety, although overall survival (OS) and progression-free survival (PFS) did not reach prespecified statistical significance. This post hoc analysis assessed efficacy and safety in Japanese patients.

Methods: Patients with advanced HCC without prior systemic treatment were randomly assigned 1:1 to receive 8 mg (body weight <60 kg) or 12 mg (body weight ≥60 kg) oral lenvatinib once daily plus 200 mg intravenous pembrolizumab or placebo every 3 weeks for up to 35 cycles. Dual primary end points were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary end points were objective response rate, disease control rate, duration of response, and time to progression per RECIST v1.1 by BICR and safety.

Results: Overall, 80 patients were enrolled in Japan (lenvatinib plus pembrolizumab, n = 39; lenvatinib plus placebo, n = 41). Median time from randomization to database cutoff (June 21, 2022) was 34.1 months (range: 26.9-39.6). Median OS was 31.4 months (95% CI: 21.2- not reached) for lenvatinib plus pembrolizumab and 21.4 months (95% CI: 14.4-25.4) for lenvatinib plus placebo (hazard ratio [HR] = 0.55 [95% CI: 0.31-0.96]). Median PFS for lenvatinib plus pembrolizumab was 10.4 months (95% CI: 6.2-18.5) and 6.5 months (95% CI: 6.0-8.3) for lenvatinib plus placebo (HR = 0.54 [95% CI: 0.32-0.90]). Grade 3 or 4 treatment-related adverse events occurred in 26 patients (67%) in the lenvatinib plus pembrolizumab group and 24 patients (59%) in the lenvatinib plus placebo group.

Conclusion: In Japanese patients enrolled in LEAP-002, findings were consistent with the global population where OS and PFS trended toward improvement; a similar safety profile was observed.