Liver Cancer最新文献

Introduction: In the realm of oncology, the pinnacle of therapeutic success is achieving a state where the patient is entirely free of cancer, i.e., "cancer free." This benchmark should not only apply to early-stage malignancies but should also be the standard aim for advanced-stage diseases, including hepatocellular carcinoma (HCC). However, there is a glaring gap in the research landscape concerning the understanding of what cancer-free status truly means for advanced-stage HCC. Our study sheds light on the profound implications of reaching a cancer-free by radiologic assessments in patients with advanced-stage HCC.

Methods: We established a database tracking the full clinical course of all patients with HCC (from 2003 to 2022). We identified the initial instances of macrovascular invasion or extrahepatic spread. We defined radiologic cancer-free (rCF) as cases in which no recurrence was observed for at least 2 months following curative treatment or complete response to systemic therapies. The frequency of achieving rCF status was investigated, categorized by patients' background.

Results: We identified 795 patients with advanced-stage HCC. The rCF rate was 8.7%. Patients who achieved rCF status had significantly better prognoses compared to those who did not (p < 0.001). In the decision tree analysis, the number of tumors ≥8 was the strongest factor, making it difficult to achieve rCF status. Analysis of stage progression patterns revealed varying background characteristics at the time of advanced-stage diagnosis, with discrepancies in rCF rates.

Conclusions: Despite the low rate of achieving rCF status, the prognostic impact was significant. Patients with certain tumor characteristics had a higher likelihood of achieving rCF status. The distribution of tumor conditions varies based on the pattern of progression, which affects the likelihood of achieving an rCF status.

Introduction: Immune checkpoint inhibitors (ICIs) are fundamental in treating advanced hepatocellular carcinoma (HCC). Considering previous reports implied varied responses among patient subgroups, such as patients with different hepatitis etiologies, we planned this meta-analysis to identify specific populations that might derive greater survival benefits from ICIs as a first-line treatment.

Methods: We conducted a comprehensive search in PubMed and the Cochrane Library for phase III clinical trials comparing ICIs and multikinase inhibitors (MKIs) as first-line therapies for advanced HCC. We extracted and synthesized hazard ratios (HRs) for overall survival across different patient subgroups mainly using the random-effect model.

Results: Our analysis included nine phase III trials involving ICIs, either alone or in combination with other treatments, compared with MKIs. The synthesized HRs for patients with hepatitis B virus, hepatitis C virus, and nonviral etiologies were 0.74, 0.77, and 0.86, respectively, showing no significant differences (p = 0.13). Such finding remained when we only analyzed clinical trials with positive results. HRs consistently favored ICIs across various demographics such as age, sex, geographic region, performance status, alpha-fetoprotein levels, and disease stage or extent. Notably, patients with extrahepatic spread showed a trend toward better outcomes (HR 0.73) compared to those without (HR 0.85, p = 0.07).

Conclusion: The efficacy of ICIs as a first-line treatment for advanced HCC was consistent across diverse patient subgroups, regardless of hepatitis etiology or other demographic factors. These findings do not support using these characteristics to determine the use of ICI therapy in advanced HCC.

Introduction: Immunotherapy is the first-line treatment for intermediate-advanced stage hepatocellular carcinoma (HCC), although its outcomes vary. This study aimed to identify imaging biomarkers of immunotherapy susceptibility linked to gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and immune phenotypes, particularly immune-excluded phenotypes, with a tumor immune barrier.

Methods: We performed immunohistochemical staining with a CD8⁺ antibody, and samples were classified into immune-inflamed, -intermediate, -excluded, and -ignored phenotypes. We assessed EOB-MRI findings obtained from 104 patients who underwent hepatectomy for HCC and evaluated the relationship between MRI findings and immune phenotype. Spatial transcriptome analysis of tumor tissues in each immune phenotype was performed to characterize the MRI findings. For validation, we analyzed the treatment effect on 60 nodules in another cohort of 27 patients who received combined immunotherapy using anti-programmed death-ligand 1 and anti-vascular endothelial growth factor (VEGF) antibodies.

Results: HCCs with rim arterial phase hyperenhancement (APHE) (odds ratio [OR] 17.3, p = 0.009), peritumoral enhancement in the arterial phase (OR: 8.6, p < 0.004), and intermediate intensity on the hepatobiliary phase (HBP) measured with a visual 3-point scale (OR: 28.2, p = 0.002) were associated with immune-excluded phenotype, where tumors tended to be larger and of the single nodular type with extranodular growth and confluent multinodular rather than the simple nodular type. Spatial transcriptome analysis revealed a spatial relationship among cytotoxic T lymphocytes, VEGF signals, and cancer-associated fibroblasts at the tumor-invasive margins in this phenotype. From the validation study, nodules with any one of these three imaging findings had a significantly prolonged time to-nodular progression (p = 0.007, median not reached vs. 226 days).

Conclusion: HCCs with rim APHE, peritumoral enhancement in arterial phase, and intermediate intensity on HBP with visual 3-point scale could be non-invasive biomarkers to predict the immune-excluded phenotype with the tumor immune barrier. These HCCs were most likely to respond to combined immunotherapy.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complications of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment, and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient's general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements, and economic cost.

Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the "Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023)."

Key messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality; it ranks as the second most common cause of cancer deaths in China. Most HCC patients are first diagnosed at an advanced stage. In recent years, targeted therapy combined with immunotherapy has become the preferred regimen for systemic treatment of intermediate-advanced HCC, while targeted therapy combined with immunotherapy plus local treatment could further improve the efficacy in many clinical studies. To better guide the clinical treatment for effective and safe combination therapy, our interdisciplinary panel on the treatment of intermediate-advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, interventional radiologists, and traditional Chinese medicine physicians have formulated this consensus based on current clinical studies and clinical medication experience for reference. The consensus contained 15 recommendations, including the applicable population and management, local treatment selection, conversion strategy, treatment strategy after tumor progression and management of common adverse reactions.

Introduction: Proteinuria presents a challenging complication during systemic therapy for hepatocellular carcinoma (HCC). This study aims to identify risk factors for proteinuria in patients with HCC treated with atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic treatment.

Methods: A retrospective analysis was conducted on 622 consecutive patients with unresectable HCC who received Atezo/Bev or LEN as first-line systemic treatment between October 2013 and October 2022. Cumulative incidence of proteinuria was estimated using Kaplan-Meier curves and compared using log-rank tests. Risk factors for proteinuria were identified using Cox proportional-hazard models, along with propensity score-matched and subgroup analyses.

Results: Among 367 patients treated with Atezo/Bev and 255 with LEN, the cumulative incidence of proteinuria at 12 months was 27.5%. In the multivariable analysis, Atezo/Bev treatment (adjusted HR [aHR]: 1.57; 95% CI: 1.03-2.42), diabetes (aHR: 1.64; 95% CI: 1.03-2.61), hypertension (aHR: 2.27; 95% CI: 1.04-4.97), Child-Pugh class B (aHR: 3.43; 95% CI: 1.34-8.78), macrovascular invasion (MVI; aHR: 1.58; 95% CI: 1.04-2.38), and an estimated glomerular filtration rate ≤60 mL/min/1.73 m² (aHR: 3.21; 95% CI: 1.84-5.62) were identified as risk factors for proteinuria. A higher risk of proteinuria in Atezo/Bev patients compared with LEN was consistently observed in the PS-matched cohort, particularly pronounced in subgroups with MVI (HR: 2.84; 95% CI: 1.23-6.54) compared with those without MVI (HR: 1.31; 95% CI: 0.69-2.47).

Conclusions: Patients treated with Atezo/Bev as first-line systemic treatment for HCC exhibited a higher risk of proteinuria compared with those with LEN, particularly when accompanied by MVI.

Introduction: Nodal metastases (lymph node metastasis [LNM]) are one of the major determinants of prognosis following surgery for intrahepatic cholangiocarcinoma (ICC). Previous studies investigating the correlation between clinical-radiological features and the probability of LNM include patients undergoing inadequate nodal sampling. Aim of this study was to develop a model to predict the risk of LNM in patients undergoing adequate lymphadenectomy using preoperative clinical and radiological features.

Methods: Patients undergoing radical surgery for ICC with adequate lymphadenectomy at seven Italian Centers between 2000 and 2023 were collected and divided into a derivation and a validation cohort. Logistic regression and dominance analysis were applied in the derivation cohort to identify variables associated with LNM at pathology. The final coefficients were derived from the model having the highest c-statistic in the derivation cohort with the lowest number of variables included (parsimony). The model was then tested in the external validation cohort, and the linear predictor was divided into quartiles to generate four risk categories.

Results: A total of 693 patients were identified. Preoperative CA 19-9, clinically suspicious lymph nodes at radiology, patients' age, and tumor burden score were significantly associated with LNM. These factors were included in a model (https://aicep.website/calculators/) showing a c-statistic of 0.723 (95% CI: 0.680, 0.766) and 0.771 (95% CI: 0.699, 0.842) in the derivation and validation cohort, respectively. A progressive increase of pathological lymph node positivity across risk groups was observed (29.9% in low-risk, 45.1% in intermediate-low risk, 51.5% in intermediate-high risk, and 87.3% in high-risk patients; p = 0.001).

Conclusions: A novel model that combines preoperative CA 19-9, clinically suspicious lymph nodes at radiology, patients' age, and tumor burden score was developed to predict the risk of LNM before surgery. The model exhibited high accuracy and has the potential to assist clinicians in the management of patients who are candidate to surgery.

Introduction: Despite its prognostic impact, nutritional status has not yet been integrated into the assessment of hepatocellular carcinoma (HCC). This study investigated the association between geriatric nutritional risk index (GNRI) and overall survival (OS) in patients with HCC using a nationwide registry.

Methods: Data from the Korea Central Cancer Registry between 2008 and 2019 were analyzed. We explored the integration of the GNRI with the albumin-bilirubin (ALBI) grade for prognostic stratification. Restricted cubic spline regression was used to assess the association between GNRI and survival, stratified by ALBI grade.

Results: Among the 16,416 treatment-naïve HCC patients, the ALBI grades were distributed as follows: grade 1, 7,409; grade 2, 7,445; and grade 3, 1,562. Patients were categorized according to Barcelona Clinic Liver Cancer (BCLC) stages: 5,132 stage 0/A, 2,608 stage B, 5,289 stage C, and 968 stage D. The median OS for all patients was 3.1 years (95% CI: 3.0-3.2) and significantly differed with the inclusion of ALBI grade and GNRI (p < 0.001). The effect of combining ALBI grade and GNRI was further evaluated for each BCLC stage. This risk stratification showed a significant correlation with OS for each BCLC stage (all p < 0.001), except for stage D (p = 0.082). Multivariate analysis revealed that a combination of favorable ALBI grade and high GNRI score was independently associated with decreased mortality risk.

Conclusion: The GNRI was significantly correlated with OS across ALBI grades and BCLC stages. Integrating the GNRI into the ALBI grade may enhance risk stratification for patients with HCC.