Liver Cancer最新文献

Introduction: Intermediate-stage hepatocellular carcinoma (HCC) derives limited benefit from transarterial chemoembolization (TACE), which has led to introduction of the concept of "TACE-unsuitable HCC." Drug therapy may be more beneficial, but intrahepatic lesion control tends to be a problem. Particle therapy including proton beam therapy (PBT) provides high local control (LC) with minimal toxicity, even in advanced cases. On this study, we retrospectively assessed the efficacy and safety of PBT in patients with TACE-unsuitable previously untreated HCC.

Methods: Between 2010 and 2018, 202 patients underwent definitive PBT for previously untreated HCC. TACE-unsuitable HCC was defined as one or more of the following; cases exceeding up-to-seven criteria, of ALBI grade 2-3, non-simple nodular type or presence of macroscopic vascular invasion (MVI). Overall survival (OS), LC, progression-free rate (PFR), and time to progression (TTP) were analyzed by the Kaplan-Meier method. Risk factor analysis was performed using a Cox regression model. Adverse events were evaluated based on CTCAE v. 5.0.

Results: TACE-unsuitable criteria were present in 165 cases. The median follow-up time was 3.35 years. The 3-year OS was 62.9%, 3-year PFR was 42.4%, and 3-year LC was 89.3%. In multivariate analysis, there were significant associations of ECOG PS, ALBI, and tumor size with OS; and of sex and tumor size with TTP; but no factors related to LC. Two cases had acute adverse events of dermatitis grade 3; and 7 cases had chronic adverse events, including 4 cases of gastrointestinal bleeding grade 3, and one each of hemobilia, pleural effusion, and erosive dermatitis.

Conclusion: PBT for TACE-unsuitable previously untreated HCC, which can be a noninferior treatment option if the number of tumors is limited, but suppression of out-of-field recurrence is needed for further prolongation of survival.

Background: Laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC) is increasing. To evaluate the efficacy of LH for small HCC (≤3 tumors within ≤3 cm), we compared short- and long-term outcomes between LH, open hepatectomy (OH), and radiofrequency ablation (RFA) as an ancillary study of the prospective multicenter study "Efficacy of SUrgery vs. Radio Frequency ablation on primary hepatocellular carcinoma" (SURF trial).

Methods: The study population comprised patients enrolled in the SURF trial. Primary endpoints were recurrence-free survival (RFS) and overall survival (OS). Secondary endpoints were short-term outcomes and the relation between tumor conditions and prognosis for each treatment. RFS and OS were adjusted by inverse probability of treatment-weighting analysis.

Results: Of 398 patients included in the study, 38 underwent LH (LH group), 139 underwent OH (OH group), and 221 underwent RFA (RFA group). RFS and OS did not differ significantly between groups. Five-year RFS and OS rates in the LH, OH, and RFA groups were 50%, 41.6%, and 41.8% (p = 0.89) and 85.2%, 80.1%, and 80.1% (p = 0.83), respectively. Postoperative complication rates (Clavien-Dindo classification ≥III) in the LH, OH, and RFA groups were 22.5%, 23.2%, and 4.2%, respectively (p < 0.01). Median postoperative hospital stays in the LH, OH, and RFA groups were 11, 13, and 7 days (p < 0.01), respectively. OH was selected significantly more frequently than RFA when patients had the following factors: maximum tumor diameter >2 cm (OR = 3.13; 95% CI = 1.72-5.69), proximity to major vessels (OR = 2.08; 95% CI = 1.01-4.30), and good liver function (OR = 0.46; 95% CI = 0.22-0.93). There was no significant difference in prognosis between tumor conditions and each treatment.

Conclusions: Survival rates after LH for early HCC were not significantly different from those of OH and RFA. However, LH is a feasible and effective treatment for early HCC with a wide variety of tumor conditions.

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.