Liver Cancer最新文献

Introduction: The high response rates observed with immunotherapy may allow downstaging to curative treatment in hepatocellular carcinoma (HCC). We aimed to investigate the factors associated with curative treatment receipt after immunotherapy and its outcomes.

Methods: HCC patients who received immunotherapy as a first-line treatment during 2017-2020 were identified from the US National Cancer Database. Patients were classified into two groups: immunotherapy with subsequent curative treatment (resection, transplantation, and local ablation) and immunotherapy without curative treatment. Multivariable Cox regression analysis was performed to determine factors associated with OS, followed by propensity score (PS) matching and inverse probability of treatment weighting (IPTW)-adjusted analysis.

Results: Of the 4,329 HCC patients (median age 66 years, 81% male, 33% T4, 22% N1, and 32% M1 stage) who received immunotherapy as a first-line treatment, 138 (3.2%) received subsequent curative treatment after immunotherapy, with a median interval of 3.0 months between the two treatments. Curative treatment receipt was independently associated with care in an academic health system (odds ratio: 3.40, 95% CI: 1.68-7.38). OS was significantly longer in those with curative treatment conversion (hazard ratio [HR]: 0.15, 95% CI: 0.11-0.22), including after PS matching (HR: 0.20, 95% CI: 0.13-0.30) and IPTW-adjusted (HR: 0.19, 95% CI: 0.11-0.31) analyses. The median survival was not reached versus 10 months for those with and without subsequent curative treatment.

Conclusion: Curative treatment conversion after immunotherapy was infrequent but was associated with significantly improved survival. Care at an academic center increases the probability of receiving subsequent curative treatment and favorable outcomes.

Background: Atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre) are standard first-line therapies for unresectable hepatocellular carcinoma (HCC). However, predictive biomarkers to guide treatment selection remain undefined. In this study, we aimed to evaluate the prognostic utility of a modified tumor marker (mTM) score, incorporating alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), for selecting between Atez/Bev and Dur/Tre and in stratifying treatment outcomes of unresectable HCC.

Methods: We conducted a multicenter retrospective study of 1,313 patients with unresectable HCC treated with either Atez/Bev (n = 1,157) or Dur/Tre (n = 156). The mTM score was defined based on baseline AFP (≥100 ng/mL) and DCP (≥100 mAU/mL), assigning one point to each elevated marker. Patients were categorized as mTM low (score 0) or mTM high (score 1-2). Survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards models, with inverse probability of treatment weighting applied for confounder adjustment.

Results: Among the mTM low patients, Atez/Bev was associated with significantly longer progression-free survival (PFS) (11.5 vs. 4.4 months, p < 0.001) and overall survival (30.6 vs. 17.0 months, p = 0.023) than Dur/Tre. In contrast, in mTM high patients, PFS was comparable between Atez/Bev and Dur/Tre (6.6 vs. 6.5 months, p = 0.873). However, in patients with DCP >400 mAU/mL, Dur/Tre was associated with improved PFS.

Conclusion: The mTM score is a clinically relevant biomarker for treatment stratification in unresectable HCC. Atez/Bev may be preferable in mTM low patients, whereas Dur/Tre may provide greater benefit in those with elevated DCP levels. Prospective validation is warranted to refine the optimal cutoff values for clinical implementation.

Introduction: The tumor microenvironment (TME) plays a critical role in determining the clinical outcomes in patients with intrahepatic cholangiocarcinoma (iCCA). This study investigates the prognostic significance of CD8+ T cells and regulatory T cells (Tregs) in tumor-infiltrating lymphocytes (TILs) and their relationship to histopathological features.

Methods: Immunofluorescence analysis was conducted on a cohort of 34 resected iCCA cases to assess CD8+ T cell and Treg densities. Statistical correlations with survival and immune and histopathological features were examined. Validation was performed on an independent cohort of 95 iCCA pre-neoadjuvant therapy (NAT) biopsy specimens to assess the prognostic power of the immune and histopathological features to survival and NAT response.

Results: In the cohort of resected iCCA cases, immunofluorescence revealed that increased CD8+ T-cell infiltration is associated with improved survival (p = 0.018), underscoring their role in anti-tumor immunity. Conversely, higher density of Tregs is linked to poorer survival (p = 0.038), suggesting its tumor-promoting, immunosuppressive effects. Intriguingly, CD8+ T cells and Tregs are associated with distinct histopathological features, with CD8+ T cells correlating with dense tumor-infiltrating lymphocytes (TILs, Pearson's R = 0.498; p = 0.004) and Tregs being more prevalent in regions of tumor budding (TB, Pearson's R = 0.382; p = 0.029). These observations were validated in an independent pre-NAT cohort (n = 95), whereby higher TIL density, particularly increased CD8+ T cells and reduced Treg, and lower TB predict favorable response to NAT, as shown by improved overall and disease-free survival.

Conclusion: These findings provide critical insights for stratifying patients and highlight the potential for optimizing immune-targeted therapies in patients with iCCA.

Hepatocellular carcinoma (HCC), which accounts for approximately 75-85% of primary liver cancers, ranks 4th in newly diagnosed cases among various types of cancer in China, and is the 2nd leading cause of cancer-related mortality, thereby posing a significant threat to the life and health of the Chinese population. Since the publication of the "Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China" in June 2017, which were updated by the China's National Health Commission in December 2019 and December 2021, additional high-quality evidence from researchers worldwide regarding the diagnosis, staging, and treatment of HCC has emerged, necessitating another update to the guidelines. The new edition (2024 Edition) was written by more than 120 multidisciplinary experts in the field of HCC in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of HCC. The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with HCC, as proposed in the "Healthy China 2030: A Vision for Health Care."

Introduction: Previous studies on preoperative predictors of microvascular invasion (MVI) in intrahepatic cholangiocarcinoma (ICCA) have presented inconsistent results. This study aimed to identify preoperative clinical and magnetic resonance imaging (MRI) factors that can predict MVI in ICCA and to evaluate their prognostic utility using a multicenter cohort.

Methods: A multicenter cohort of 446 patients who underwent preoperative MRI and surgical resection for ICCA at six tertiary referral institutions between 2009 and 2018 was analyzed for clinical, pathologic, and MR imaging characteristics. Univariable and multivariable logistic regression analyses were performed to identify significant predictors of pathologically confirmed MVI, which were subsequently used to stratify patients into low-, intermediate-, and high-risk groups based on the number of predictors identified. Kaplan-Meier survival analysis and log-rank test were conducted to assess long-term survival and early recurrence among the three groups.

Results: Among the 446 patients (mean age, 63.0 ± 9.9 years; 277 men), 234 (52.5%) had MVI on pathology. Independent predictors of MVI included serum carbohydrate antigen 19-9 levels (≥80 U/mL; odds ratio [OR]: 2.68, 95% confidence interval [CI]: 1.64-4.37, p < 0.001), tumor size (≥4 cm; OR: 1.60, 95% CI: 1.01-2.54, p = 0.046), tumor multiplicity (OR: 2.84, 95% CI: 1.58-5.12, p < 0.001), and arterial phase peritumoral enhancement (OR: 2.83, 95% CI: 1.81-4.42, p < 0.001). Stratifying patients by MVI risk - low (no predictors), intermediate (1-3 predictors), and high (4 predictors) - revealed a significant decrease in both recurrence-free and overall survival rates (p < 0.001), along with a corresponding increase in early recurrence rates (p < 0.001) as the risk level increased.

Conclusion: Risk stratification utilizing four key predictors can effectively assess the risk of MVI in ICCA and is associated with postoperative outcomes.

Background and aims: As systemic therapy for hepatocellular carcinoma (HCC) rapidly advances, eight treatment regimens are currently approved in Japan. However, the limited settings of phase III clinical trials necessitate large-scale real-world data to evaluate effective treatment sequences. To address this, we established a nationwide registry called the Hepatoma Registry of Integrating and Aggregating Electronic Health Record (HERITAGE).

Approach and results: HERITAGE, associated with a nationwide follow-up survey by the Japan Liver Cancer Association, included cases where first-line systemic therapy commenced between April 2015 and December 2022. We collected data on treatment regimens, patient demographics, effectiveness, and duration and assessed changes in regimens, trends in patient characteristics, efficacy per regimen, and cross-resistance in combinations of first- and second-line treatments. The study enrolled over 8,000 treatment lines from 5,525 cases. Chronological analysis revealed a progression in first-line treatments from sorafenib to lenvatinib and then to atezolizumab plus bevacizumab. These regimens were frequently reused in second and subsequent lines. There was an increase in older patients and those with nonviral etiologies and robust liver function. Treatments were generally initiated at earlier disease stages. Cross-resistance studies indicated that responses to second-line treatments were significantly influenced by the efficacy of first-line therapies, particularly in tyrosine kinase inhibitor sequences.

Conclusions: Through establishing a comprehensive registry, this study unveiled evolving patterns in treatment regimens and shifts in patient demographics for systemic HCC therapy in Japan.

Introduction: Particle therapy (PT) for intrahepatic cholangiocarcinoma is expected to provide good local control. However, it is difficult to compare PT with the current standard treatment modalities, surgery, and chemotherapy. Therefore, we conducted a meta-analysis and systematic review of the literature to compare PT with surgery and drug therapy.

Methods: A meta-analysis was performed using studies from 2010 to 2024 in which PT or surgery or drug therapy was performed for intrahepatic cholangiocarcinoma. 40 articles (7 PT, 13 surgery, 19 drug therapy, one surgery, and drug therapy) were selected based on used of radial surgery or first-line drug therapy. PT was basically for unresectable cases, and 80% of drug therapy cases had distant metastases.

Results: Forty selected articles found 1-3-year OS rates (PT vs. surgery vs. drug therapy) of 70.7% (95% CI: 64.2-76.1%) vs. 78.6% (74.2-82.3%) (p = 0.1198) vs. 49.0% (43.4-54.4%) (p = 0.0001); 47.1% (40.9-53.0%) vs. 56.3% (48.8-63.1%) (p = 0.1265) vs. 25.3% (19.7-31.3%) (p = 0.0011); and 36.6% (27.0-46.3%) vs. 46.8% (41.7-51.6%) (p = 0.1213) vs. 14.7% (8.3-22.7%) (p = 0.0021), respectively. And the 1-3-year local control rates for PT were 89.4% (95% CI: 81.3-94.1%), 74.6% (63.0-83.1%) and 67.1% (51.4-78.7%), respectively. Meta-regression analysis was performed using modality (PT vs. surgery vs. drug therapy), male: female ratio, and median age as risk factors. The results showed no significant difference between surgery and PT, but drug therapy showed significantly lower 1- and 2-year OS rates and median survival time, and a trend toward lower 3-year OS.

Conclusion: The results of this analysis suggest that PT for intrahepatic cholangiocarcinoma may be one of the standard treatments in unresectable cases and in combination with drug therapy.

Metastatic liver tumors (MLTs) are the most common type of malignant liver tumors, primarily because the liver is a frequent target organ for metastasis. Metastatic cancer is generally considered a systemic disease, so the mainstay of treatment should be systemic therapies, including chemotherapy, targeted therapies, and immunotherapy. Currently, it is believed that a multimodal approach, combining local and systemic treatments, can improve tumor control and potentially prolong patient survival. Local treatments, in addition to surgery, include ablation therapy as one of the options. Ablation therapy has its limitations and advantages for local tumor control but can also be combined with other locoregional treatments such as surgical resection, transarterial embolization, and stereotactic body radiotherapy to manage appropriate subsets of patients. Ablation of hepatocellular carcinoma has been performed for many years. In recent years, the number of MLTs cases treated with ablation has been increasing. However, the characteristics of primary liver tumors and MLTs, as well as their responses to ablation therapy, are distinct. At present, there is no established international guideline specifically for the ablation treatment of MLTs. The consensus guidelines developed by the Taiwan Academy of Tumor Ablation (TATA) represent evidence-based medical statements. These guidelines are created and reviewed by an expert team including hepatologists, medical oncologists, radiation oncologists, and intervention radiologists through comprehensive medical literature searches, discussions, and voting. The process adheres to evidence-based standards, such as evaluating levels of evidence and grading recommendations. Furthermore, the guidelines are finalized through thorough discussions among all experts and by calculating voting consistency. In cases where clinical evidence is unclear or lacking, expert opinions are also incorporated. Additionally, the guidelines provide recommendations on the future development of ablation therapy for MLTs.

Introduction: Intermediate-stage hepatocellular carcinoma (HCC) presents varying tumor burdens. For patients unsuitable for transcatheter arterial chemoembolization (TACE) due to high tumor burden, recent guidelines recommend systemic therapy. This study evaluates the efficacy and safety of atezolizumab plus bevacizumab for TACE-unsuitable patients with unresectable intermediate-stage HCC beyond up-to-seven criteria.

Methods: This prospective, phase II, single-arm, non-blinded study enrolled TACE-naïve patients with unresectable intermediate-stage HCC beyond up-to-seven criteria, Child-Pugh A, no previous systemic therapy, and ECOG Performance Status score of 0-1 from 35 sites in Japan. Patients received atezolizumab 1,200 mg and bevacizumab 15 mg/kg every 3 weeks. The primary endpoint was the 6-month progression-free survival (PFS) rate by modified RECIST (mRECIST). Key secondary endpoints included the objective response rate (ORR) and safety. Exploratory endpoints examined individual changes in tumor size, comparison by inverse probability weighting (IPW) of data with retrospective historical data of TACE-treated patients, and conversion rate to a curative intent therapy.

Results: In total, 74 patients were enrolled from December 2020 to September 2021 (median follow-up, 15.1 months). The 6-month PFS rate by mRECIST was 66.8% (90% CI: 56.8, 75.0), and the lower limit of the 90% CI exceeded the pre-specified threshold of 55%. ORR by mRECIST was 40.5%. After treatment with atezolizumab plus bevacizumab, 10 patients, including 5 patients who had a tumor burden beyond the up-to-11 criteria at baseline, were able to transition to curative intent therapy. PFS by mRECIST by IPW was 9.2 months with atezolizumab plus bevacizumab versus 5.7 months with TACE (hazard ratio 0.67, p = 0.029). Adverse events (AEs), mostly hypertension, proteinuria, and malaise, were common. AEs requiring corticosteroids occurred in 10 patients (13.5%).

Conclusion: Atezolizumab plus bevacizumab appears beneficial as first-line treatment for TACE-unsuitable patients with unresectable intermediate-stage unresectable HCC beyond up-to-seven criteria. Future strategies utilizing multimodal approaches may further improve outcomes.