Liver Cancer最新文献

Introduction: Hepatocellular carcinoma (HCC) has a high recurrence rate even after curative resection. Although the tumor mutational burden (TMB) has emerged as a potential biomarker for survival outcomes in HCC, its clinical significance remains unclear.

Methods: A retrospective analysis of 204 patients who underwent an initial liver resection was performed. Patients were classified into TMB-high (≥4.8 mutations/Mb) or TMB-low groups based on whole-exome sequencing. We assessed relapse-free survival (RFS), overall survival (OS), and performed subgroup analyses focusing on patients without recurrence within the first two postoperative years. Gene expression profiling and mutational signature analyses were also conducted.

Results: Patients with TMB-high tumors showed significantly shorter RFS compared to the TMB-low group (median 24.2 vs. 37.1 months; p = 0.008), whereas OS was not significantly different. Multivariate analysis identified TMB-high status as an independent prognostic factor for RFS (hazard ratio [HR], 1.72; p = 0.011). In the subgroup without early recurrence, TMB-high status was the only independent factor associated with late recurrence (HR, 2.45; p = 0.005). TMB-high tumors correlated with advanced liver fibrosis and specific somatic mutations (CTNNB1, TTN, MUC16). Additionally, mutational signatures associated with chronic inflammation and alcohol consumption were enriched in the TMB-high group.

Conclusion: High TMB is associated with shorter RFS in HCC, particularly among patients with long-term follow-up, indicating an increased risk for multicentric recurrence. TMB may serve as a valuable prognostic biomarker for recurrence risk stratification. The associations between TMB, liver fibrosis, and inflammation suggest potential therapeutic strategies targeting the hepatic microenvironment to reduce recurrence risk in patients undergoing liver resection for HCC.

Background: Multi-biomarker panels have shown promise to improve hepatocellular carcinoma (HCC) surveillance in patients with chronic liver disease; however, we lack comparative data on their relative performance for early-stage HCC detection.

Methods: We conducted a systematic review of PubMed, Ovid MEDLINE, and Embase databases from January 2010 to November 2024 to identify studies evaluating the performance of three commercially available blood-based biomarker panels (GALAD, GAAD, and ASAP) for HCC surveillance. Pooled estimates were calculated using the DerSimonian and Laird method for a random-effects model.

Results: Of 44 eligible studies (n = 33,100 patients) examining HCC surveillance, 37 studies evaluated GALAD, 12 GAAD, and 11 ASAP. Pooled sensitivities of the biomarker panels for early-stage HCC ranged from 70.1% to 74.1%, with pooled specificities ranging from 83.3% to 87.2%. Among studies directly comparing biomarker panels, sensitivity for early-stage HCC did not significantly differ for GALAD versus GAAD (RR 0.96, 95% CI: 0.80-1.15) or GALAD versus ASAP (RR 1.12, 95% CI: 0.79-1.60). The pooled sensitivity of GALAD for early-stage HCC was higher than that of ultrasound among studies directly comparing the two (79.0% [95% CI: 62.2-89.6] versus 73.3% [95% CI: 45.4-90.1], respectively); however, this difference was not statistically significant (RR 1.09, 95% CI: 0.78-1.51). Studies were limited by inclusion of patients with non-cirrhotic liver disease, varying biomarker cutoffs across studies, and high statistical heterogeneity (I ² >50%) for pooled estimates.

Conclusion: Multi-biomarker panels including GALAD, GAAD, and ASAP demonstrate promising performance for early-stage HCC detection, supporting their prospective validation for HCC surveillance.

Objectives: The main objectives of this research are to evaluate the outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) who received transcatheter arterial chemoembolization (TACE)/hepatic artery infusion chemotherapy (HAIC)-based combination therapy and to investigate the effects of liver resection following comprehensive conversion therapy on the short-term benefits and long-term survival of these patients.

Materials and methods: A total of 301 initially unresectable HCC patients who received TACE/HAIC-based combination therapy between January 2019 and December 2021 were retrospectively reviewed. The study analyzed the conversion rate to resection, changes in tumor burden after treatment, and the survival outcomes.

Results: The study found that 20.9% (63/301) of initially unresectable HCC patients were able to undergo liver resection. The conversion resection rate among all patients was 38.2% (29/76) and 17.3% (23/132) for those with Barcelona Clinic Liver Cancer (BCLC) stage A and C. Patients who underwent surgery achieved promising outcomes with a pathological complete response (pCR) rate of 31.7% (20/63) and a 100% R0 resection rate. Kaplan-Meier survival analysis showed that patients who had successful surgery after conversion therapy had significantly longer median overall survival (OS) (not reached vs. 58.5 months) and progression-free survival (PFS) (42.83 months vs. 9.7 months) compared to those who did not (both p < 0.05). Additionally, patients achieving radiographic complete response (CR) had significantly better OS and PFS than those who did not. Multivariable logistic regression analysis showed that age (OR = 0.95, p < 0.001), positive HBsAg expression (OR = 0.34, p = 0.011), and alpha-fetoprotein levels ≥400 (OR = 0.49, p = 0.045), ECOG PS score of 1 (OR = 0.43, p = 0.038), BCLC stage B (OR = 0.23, p < 0.001) and stage C (OR = 0.44, p = 0.045), systemic inflammation response index (OR = 0.73, p = 0.018) were independent predictors for successful conversion surgery (all p < 0.05).

Conclusion: Patients with initially unresectable HCC can achieve promising curative effects and conversion resection rates with TACE/HAIC-based comprehensive therapy. More importantly, patients who undergo liver resection following conversion resection had significantly better long-term survival.

Introduction: The potential for curative conversion with immunotherapy-based systemic treatment used with noncurative intent in patients with hepatocellular carcinoma (HCC) remains debated. This study aimed to provide a reliable epidemiological snapshot of response patterns to atezolizumab plus bevacizumab (AB) therapy, with a focus on curative conversion rates.

Methods: Patients with HCC undergoing first-line noncurative AB or lenvatinib (LENV, used as reference) from 2019 to 2023 were included, using centre-level aggregate data from a broad international consortium. The primary endpoint was the curative conversion rate, differentiating potential conversion (PC) - when objective response (OR) resulted in a consistent decrease in tumour burden and alpha-fetoprotein levels - from actual conversion (AC), when OR led to curative treatment. Secondary endpoints included OR, under-conversion (UC; [PC - AC]/OR) rates, and crude survival rates of AC patients. A meta-analytic approach was employed to analyse aggregate data.

Results: Forty-eight international centres treating 2,379 patients with HCC with a noncurative intent (1,401 with AB and 978 with LENV) were included. A significant discrepancy was observed between PC (16% and 13% for AB and LENV, p = 0.03) and AC rates (3% for both AB and LENV, p = 0.14). UC rates remained similarly high (40% and 36% for AB and LENV, p = 0.93), despite differing OR rates (29% and 24% for AB and LENV, p = 0.01). Subgroup and meta-regression analyses did not identify any clear treatment, centre, or patient patterns that explained the high UC rate. The 3-year survival rate for the 72 patients who underwent a curative conversion after AB was 93%.

Conclusions: Although patients treated with AB achieved higher OR and PC rates than those treated with LENV, AC remained similarly low, highlighting a potentially worrisome UC phenomenon in real life, also with novel immunotherapy-based combinations.

Introduction: The optimal imaging modality and diagnostic criteria for accurately detecting and characterizing subcentimeter hepatocellular carcinoma (HCC) remain uncertain, and this study aims to compare performance of gadoxetic acid-enhanced MRI (EOB-MRI) and extracellular contrast agent-enhanced MRI (ECA-MRI) in detecting and characterizing subcentimeter HCC.

Methods: A total of 1,022 patients at risk of HCC (mean age, 53.80 ± 11.24, 732 men) with 1,210 subcentimeter hepatic lesions were retrospectively included. Lesion detection rate and HCC characterization performance were calculated and compared between EOB-MRI and ECA-MRI sets using generalized estimating equation method.

Results: Consensually, EOB-MRI demonstrated significantly higher sensitivity for detecting subcentimeter hepatic lesions compared to ECA-MRI (0.995 vs. 0.953, p < 0.001). EOB-MRI and ECA-MRI showed comparable performance in characterizing subcentimeter HCC based on typical vascular pattern (sensitivity, 0.382 vs. 0.457, p = 0.064; specificity 0.941 vs. 0.933, p = 0.462). After applying modified criteria, the sensitivities (EOB-MRI: 0.382 vs. 0.812, p < 0.001; ECA-MRI: 0.457 vs. 0.574, p < 0.001) were significantly increased on both MRIs by consensus reading, while specificities did not differ a lot (EOB-MRI: 0.859 vs. 0.941, p = 0.012; ECA-MRI: 0.894 vs. 0.933, p = 0.084). And compared with ECA-MRI, EOB-MRI exhibited significantly higher sensitivity (0.812 vs. 0.574, p < 0.001) based on modified criteria, without a substantial loss of specificity (0.859 vs. 0.894, p = 0.162).

Conclusion: EOB-MRI with modified criteria exhibited superior detection and characterization performance of subcentimeter HCC when compared with ECA-MRI in patients at risk of HCC, thus offering clinicians more opportunities to accurately identify high-risk subcentimeter lesions.

Introduction: The necessity of surgical resection for hepatocellular carcinoma (HCC) patients who achieve clinical complete response (CR) following triple therapy (transarterial chemoembolization, targeted therapy, and immunotherapy) remains controversial. Thus, this study aimed to compare survival outcomes between surgical resection and nonsurgical management in these patients.

Methods: Between January 2018 and March 2024, 127 HCC patients who achieved clinical CR (cCR) following triple therapy were retrospectively included in this study. Patients were stratified into two groups based on whether they underwent surgical resection: the surgical resection group (n = 62) and the nonsurgical resection group (n = 65). Clinical characteristics, imaging findings, pathological results, and long-term outcomes were compared. Propensity score matching (PSM) was performed to mitigate the effect of potential confounders.

Results: In the surgical group, 44 of 62 patients (70.9%) achieved pathological CR. The overall postoperative complication rate was 24.2%, with severe complications (grade III-IV) recorded in 8.1% of patients. After PSM, 55 matched pairs were included. One-, two-, and three-year overall survival (OS) rates following cCR were 96.0%, 90.8%, and 90.8% in the surgical group, compared to 91.3%, 85.8%, and 73.1% in the nonsurgical group (p = 0.013). Additionally, one-, two-, and three-year recurrence-free survival (RFS) rates were 81.5%, 74.6%, and 74.6% in the surgical group, compared to 81.1%, 53.5%, and 35.7% in the nonsurgical group (p = 0.020). Finally, multivariate analysis identified surgical resection as an independent prognostic factor for both OS (hazard ratio [HR], 0.266; 95% confidence interval [CI], 0.087-0.817; p = 0.021) and RFS (HR, 0.457; 95% CI, 0.228-0.914; p = 0.027).

Conclusion: For HCC patients achieving cCR after triple therapy, surgical resection may confer significant survival benefits and should therefore be considered as an optional treatment method.

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.