Liver Cancer最新文献

Introduction: IMbrave150 established first-line atezolizumab plus bevacizumab as a global standard of care for unresectable hepatocellular carcinoma (HCC). We report exploratory analyses of associations between overall survival (OS) and depth of response (DpR) or duration of response (DoR).

Methods: IMbrave150 was a phase III randomized study of atezolizumab plus bevacizumab versus sorafenib in patients with unresectable HCC. DpR was defined as maximum tumor shrinkage from baseline based on the sum of longest diameters per independent review facility (IRF)-assessed RECIST 1.1. DoR was defined as time from first complete/partial response by IRF-assessed RECIST 1.1 until progression or death. Associations between OS and DpR or DoR were evaluated by scatterplot in both arms; OS and PFS were evaluated by DpR in atezolizumab plus bevacizumab-treated patients. To minimize immortal time bias, the DpR analysis included patients who survived ≥6 months.

Results: Of 312 and 140 patients with baseline measurable disease in the atezolizumab plus bevacizumab and sorafenib arms, respectively, 264 and 99 surviving ≥6 months were included in the DpR analysis, and 97 and 18 in the DoR analysis. Tumor shrinkage occurred in 230/312 (74%) patients in the atezolizumab plus bevacizumab arm and 76/140 (54%) in the sorafenib arm; their mean (SD) DpR was -42.5% (32.4%) and -25.0% (21.9%), respectively. Atezolizumab plus bevacizumab-treated ≥6-month survivors with DpR <0% had improved OS versus those with DpR ≥0% (HR: 0.29; 95% CI: 0.19-0.44). Those with deeper responses (DpR -100% to -60%) had longer OS than those with DpR ≥20% (unstratified HR: 0.08; 95% CI: 0.03-0.21). In scatterplots, DpR and DoR were generally associated with OS in both arms; interpretation was limited by censored patients.

Conclusions: DpR and DoR to atezolizumab plus bevacizumab and sorafenib were associated with OS in patients with unresectable HCC. More longer, deeper responses occurred with atezolizumab plus bevacizumab.

Globally, the incidence and associated mortality of primary liver cancer have been steadily increasing. Currently, 80% of cases are found in Asia. Curative resection is applicable in only 20% of patients; therefore, various nonsurgical treatment modalities have been developed. Image-guided percutaneous liver tumor ablation is regarded as the best option for treating early-stage hepatocellular carcinoma (HCC). However, skills and knowledge in ablation can vary among operators. Furthermore, Asia has the highest number of ablation procedures for HCC and the largest number of doctors performing ablation worldwide. Thus, the Asian Conference on Tumor Ablation has developed guidelines for HCC. These guidelines will discuss indications, pre-ablative diagnosis and planning, techniques, peri-ablative management, evaluation of therapeutic effectiveness, complications, post-ablative follow-up, prevention of recurrence, and treatment of recurrence for HCC.

Introduction: Adoptive cell therapy derived from autologous tumor-infiltrating lymphocytes (TILs) has demonstrated promising therapeutic efficacy in several cancers. However, its possible synergistic effects with anti-PD-1 therapy in advanced hepatocellular carcinoma (aHCC) remain unexplored. This study aimed to investigate the efficacy of TIL infusion combined with anti-PD-1 therapy for aHCC.

Case presentation: Referring to the current protocol of our clinical trial (NCT03658785), 2 patients with HCC at BCLC stage C were enrolled to receive autologous TIL infusion combined with anti-PD-1 therapy. They underwent unplanned palliative tumor resection to alleviate pain caused by tumor rupture prior to receiving TIL infusion plus anti-PD-1 therapy. Long-term outcomes and treatment-related adverse events were evaluated. Throughout the entire treatment process, both patients experienced only mild symptoms. Notably, both patients achieved complete responses to the treatment and have remained tumor-free for 2 and 4 years, respectively.

Conclusion: Autologous TIL infusion combined with anti-PD-1 therapy is a safe and feasible strategy for patients with aHCC. Palliative hepatectomy with maximal tumor burden reduction may significantly improve its efficacy and even results in cure for aHCC patients.

Introduction: Hepatocellular carcinoma (HCC) has a high incidence rate and is often asymptomatic in its early stages. Combination therapies using immune checkpoint inhibitors (ICIs) have demonstrated survival benefits and high objective response rates, offering hope for conversion surgery in patients with initially unresectable HCC. We aimed to investigate the oncological outcomes of conversion surgery compared to those with continuing systemic treatment alone in patients who responded well to ICI-based therapy, as well as the surgical outcomes associated with conversion surgery.

Methods: We consecutively enrolled patients diagnosed with HCC between January 1, 2019, and February 1, 2024. These patients received treatment with ICIs combined with either anti-vascular endothelial growth factor antibodies or tyrosine kinase inhibitors. Tumor response and resectability were assessed every 2 months. Patients who responded positively and met the criteria for conversion surgery were included.

Results: Among 613 patients with initially unresectable HCC, 128 achieved conversion and met the surgical resection criteria during combination therapy. Of these, 54 continued nonsurgical comprehensive treatment, 74 underwent conversion surgery, and 57 continued their original treatment post-surgery. The median follow-up time was 24.1 and 42.5 months for the surgery and non-surgery groups, respectively. The median progression-free survival (PFS) was 29.4 months in the surgery group versus 11.2 months in the non-surgery group (p < 0.0001, hazard ratio [HR] = 0.39 [0.24-0.63]). The median OS was not reached in the surgery group, compared to 25.4 months in the non-surgery group (p < 0.0001, HR = 0.26 [0.14-0.46]). Multivariate Cox regression analysis indicated that conversion surgery was independently associated with improved OS and PFS (p < 0.001), and continuing the original treatment post-surgery significantly influenced OS and recurrence-free survival.

Conclusion: Conversion surgery after meeting the surgical criteria during immunotherapy provides significant prognostic benefits for patients with initially unresectable HCC, demonstrating high safety and R0 resection rates. For those undergoing conversion surgery, promptly resuming the original treatment after surgery is necessary.

[This corrects the article DOI: 10.1159/000528034.].

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.