Search Results (37)

Background/Objectives: Patients with unresectable hepatocellular carcinoma (uHCC) refractory or intolerant to immune checkpoint inhibitor (ICI)-based regimens represent a growing yet therapeutically underserved population with limited treatment options. We investigated the efficacy, safety, and mechanistic underpinnings of lenvatinib combined with New FP hepatic arterial infusion chemotherapy (LEN–New FP) in this challenging clinical setting. Methods: We retrospectively analyzed 14 consecutive patients with uHCC treated with LEN–New FP between April 2022 and March 2025. Tumor response was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Proper hepatic artery (PHA) diameter was serially measured on angiography as an exploratory assessment of vascular remodeling, and tumor vascularity was semi-quantitatively evaluated using a 4-point angiographic scoring system (Tumor Vascularity Score [TVS]). Results: The cohort comprised BCLC stage B/C (7/7), mALBI grade 1–2b, and 13 of 14 patients with prior ICI-containing therapy. The objective response rate and disease control rate were 85.7% and 100%, including two complete responses. Median overall survival was 22.8 months from LEN–New FP initiation (median follow-up: 15.1 months) and 36.2 months from first-line initiation; median intrahepatic progression-free survival was 10.4 months. A total of 11 of 14 patients (78.6%) transitioned to subsequent therapies, including four curative-intent conversions. PHA narrowing was observed in 10 of 13 evaluable patients (76.9%), with no clear association with hepatic function deterioration. TVS decreased in 10 of 12 evaluable patients (83.3%), with reduction observed in 90.0% of PR/CR cases. Conclusions: LEN–New FP achieved sustained intrahepatic tumor control and encouraging survival in aggressive uHCC, including ICI-refractory or -intolerant disease. The concordant reduction in PHA diameter and tumor vascularity score provides angiographic evidence of VEGFR inhibition-mediated vascular remodeling, offering mechanistic insight into the synergistic antitumor effects of this regimen and supporting LEN–New FP as a promising multimodal strategy within the evolving landscape of HCC treatment. Full article

Background: The role of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) management has evolved over recent years. Although it appears that the overall number of procedures is declining, international guidelines now endorse TACE beyond the Barcelona Clinic Liver Cancer (BCLC) intermediate stage, and multiple TACE platforms allow patient-tailored treatments. In this context, degradable starch microspheres TACE (DSM-TACE) may be valuable when the goal is to preserve liver function and spare healthy parenchyma. This study reports multicenter retrospective Italian data to assess the efficacy and safety of DSM-TACE with EmboCept^® in patients with early-to advanced-stage HCC, and to evaluate whether procedural selectivity (superselective vs. lobar) influences outcomes. Methods: This retrospective multicenter study included 201 patients initially; after applying exclusion criteria, 187 patients (334 HCC nodules) treated across eight centers (2014–2024) were analyzed. Treatment indications were discussed in multidisciplinary tumor boards in all centers. Superselective DSM-TACE was performed in 48 patients (66 nodules, 19.8%), while 139 patients (268 nodules, 80.2%) underwent a lobar approach. Repeated sessions were performed on demand and recorded for lobar treatments. Tumor response was assessed using mRECIST criteria at 1, 3–6, 6–9, and 9–12 months; adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). efficacy and safety outcomes were compared according to the DSM-TACE approach. Results: In terms of safety, analysis confirmed the overall good tolerability of DSM-TACE, with no grade ≥ 3 adverse events and no major complications or procedure-related deaths. No significant differences were observed in post-embolization syndrome (PES) rates between groups. With regard to efficacy, for the entire cohort, the overall response rate (ORR) was 70% at 1 month, 31.6% at 3–6 months, 20.5% at 6–9 months, and 13.5% at 9–12 months, while the disease control rate (DCR) was 91.4% at 1 month, 69% at 3–6 months, 38.6% at 6–9 months, and 27% at 9–12 months. At intermediate follow-up, superselective DSM-TACE achieved higher ORR than lobar treatment at 3–6 months (53.8% vs. 26.4%; p = 0.009) and 6–9 months (43.8% vs. 15.3%; p = 0.009). Per-nodule analysis confirmed this advantage at 3–6 months (ORR = 66.7% vs. 31.3%; p = 0.0008). Conclusions: DSM-TACE with EmboCept^® provides favorable tumor control and a good safety profile in routine clinical practice. A superselective approach is associated with improved response at intermediate follow-up compared with lobar strategy, supporting DSM-TACE as a flexible therapeutic option for localized HCC. Full article

Background: Selective internal radiation therapy (SIRT) with yttrium-90 microspheres has become an established locoregional treatment for hepatocellular carcinoma (HCC). Nevertheless, real-world data on clinical outcomes, including efficacy, safety, and prognostic determinants, remain limited. Methods: This study retrospectively analysed 56 patients with radiologically and/or histologically confirmed HCC who underwent SIRT at a tertiary referral centre. Baseline demographics, clinical information, tumour characteristics, procedural data, and follow-up outcomes were recorded. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included radiological response (mRECIST), histological necrosis, and treatment-related toxicity. Prognostic pathways were explored using structural equation modelling (SEM). Results: The mean age at the beginning of SIRT was 65.0 ± 11.6 years; most patients were male (87.5%) and had preserved liver function (mean ALBI −2.9 ± 0.4). BCLC staging distribution was 50% stage A, 32.1% stage B, and 17.9% stage C. According to mRECIST criteria at 6 months, 15.2% achieved complete response (CR), 47.8% partial response (PR), 30% stable disease (SD), and 7% progressive disease (PD). Median OS was 19 months (12–32) for BCLC stage A, 28 months (3–42) for stage B, and 19 months (12–56) for stage C (log-rank p = 0.743). SEM identified diffuse tumour morphology as the most significant predictor of poor prognosis. Radical treatments were performed in 28% of patients, including four liver transplants and ten resections. Adverse events occurred in 11 patients, of which 7 were Clavien–Dindo grade I and 4 were grade II. Conclusions: In this real-world HCC group, SIRT provided durable tumour control and survival with excellent tolerability. Full article

Background: Glypican-3 (GPC3) is overexpressed in most hepatocellular carcinoma (HCC) tissues but is absent in normal adult liver. We evaluated whether tumor GPC3 expression is associated with clinical outcomes in patients with advanced HCC treated with atezolizumab–bevacizumab (AB). Methods: We conducted a single-center retrospective cohort study of 139 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who received AB between January 2022 and August 2025. Tumor GPC3 expression was assessed by immunohistochemistry. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Baseline characteristics were largely balanced between GPC3-positive (n = 87) and GPC3-negative (n = 52) groups. Median OS was significantly shorter in patients with GPC3-positive tumors than in those with GPC3-negative tumors (p = 0.006). In multivariable analysis, GPC3 positivity remained independently associated with higher mortality (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.05–3.00; p = 0.033), along with Child–Pugh class B. PFS did not differ significantly between the groups (p = 0.712). ORR was lower in GPC3-positive tumors than in GPC3-negative tumors (approximately 17–18% vs. ~32%; p = 0.023). Membranous GPC3 localization was associated with inferior OS compared with cytoplasmic or absent expression (p = 0.025). Conclusions: Tumor GPC3 expression was associated with decreased OS and lower ORR among AB-treated patients with advanced HCC, suggesting potential clinical relevance and may help in risk stratification. Full article

Background: Atezolizumab plus bevacizumab is the standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). Immune-related liver injury (IrLI) is common; however, the association between IrLI severity and patient outcomes remains unknown. This study aimed to investigate the prognostic value of irLI in such patients. Methods: One hundred and sixteen patients who fulfilled the IMBrave150 inclusion criteria were enrolled. IrLI was defined as an increase in serum ALT and/or AST levels attributed to treatment and was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: A total of 61 patients (52.6%) developed any grade of irLI, with a median onset time of 1.7 months. Multivariate analysis revealed that grade II ALBI (hazard ratio [HR] = 2.003, p = 0.028) and BCLC stage C (HR = 3.876, p = 0.016) were associated with worse OS and PFS (HR = 1.327, p = 0.044 and HR = 1.790, p = 0.039, respectively), whereas grade 2 irLI was associated with better OS (HR = 0.223, p = 0.046) and PFS (HR = 0.244, p = 0.011). Patients with grade 2 irLI showed better median OS (not reached) than those without irLI (16.7 months), those with grade 1 (17.5 months), and those with grade ≥ 3 (7.3 months) (overall log-rank p = 0.037). Furthermore, patients with grade 2 irLI demonstrated significantly enhanced PFS (not reached) compared to those without irLI (5.7 months), grade 1 (4.6 months), or grade ≥ 3 (2.3 months), with an overall log-rank p = 0.010. In addition, patients with grade 2 irLI had the highest disease control rate (overall p = 0.053). Conclusion: In patients with uHCC treated with Ate/Bev, moderate elevation of liver enzymes (grade 2 irLI) was associated with significantly improved survival and tumor control. Full article

Background/Objectives: Inflammation-based markers have emerged as potential prognostic tools in hepatocellular carcinoma (HCC), but comparative data with classical prognostic factors in untreated HCC are limited. This study aimed to evaluate and compare the prognostic performance of inflammatory and conventional markers using Harrell’s concordance index (C-index). Methods: This retrospective study included 250 patients with untreated HCC. Prognostic variables included age, BCLC stage, Child–Pugh classification, Milan criteria, MELD score, AFP, albumin, Charlson comorbidity index, and the inflammation-based markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), Systemic Inflammation Response Index (SIRI), and Systemic Immune-inflammation Index (SIII). Survival was analyzed using Cox regression. Predictive performance was assessed using the C-index, Akaike Information Criterion (AIC), and likelihood ratio tests. Results: Among the classical markers, BCLC showed the highest predictive performance (C-index: 0.717), while NLR ranked highest among the inflammatory markers (C-index: 0.640), above the MELD score and Milan criteria. In multivariate analysis, NLR ≥ 2.3 remained an independent predictor of overall survival (HR: 1.787; 95% CI: 1.264–2.527; p < 0.001), along with BCLC stage, albumin, Charlson index, and Milan criteria. Including NLR in the model modestly improved the C-index (from 0.781 to 0.794) but significantly improved model fit (Δ–2LL = 10.75; p = 0.001; lower AIC). Conclusions: NLR is an accessible, cost-effective, and independent prognostic marker for overall survival in untreated HCC. It shows discriminative power comparable to or greater than most conventional predictors and may complement classical stratification tools for HCC. Full article

Background: Transarterial radioembolization (TARE) with Yttrium-90 microspheres is an established therapy for unresectable hepatocellular carcinoma (HCC). However, its clinical efficacy compared to transarterial chemoembolization (TACE) remains unclear. Methods: We retrospectively reviewed 279 consecutive patients undergoing TARE (n = 104) or TACE (n = 175) at four tertiary centers. Patients with metastatic disease, locally advanced HCC, or Child–Pugh (CP) C were excluded. Data on treatment, adverse events, survival outcomes (median overall survival [mOS], and objective response rates [by modified Response Evaluation Criteria in Solid Tumors; mRECIST]) were collected. Results: The median follow-up of the cohort was 27 months (IQR 13–50), the mean age was 67.6 ± 10.1 years, and 207 (74.2%) were male. The cohort was balanced in age, performance status, CP class, and HCC etiology. Maximum tumor diameter was significantly larger in the TARE cohort compared to the TACE cohort (4.4 vs. 3.1 cm, p < 0.001), including within the BCLC 0/A (4.2 vs. 2.7 cm, p = 0.001) and BCLC B (5.0 vs. 4.0 cm, p = 0.049) subgroups. The mOS was longer with TACE (37 vs. 22 months; hazard ratio [HR] 1.65, 95% CI: 1.19–2.29, p = 0.002). In BCLC 0/A patients, TACE yielded longer mOS (60 vs. 25 months; HR 2.35, 95% CI: 1.17–4.69; p = 0.016). In BCLC B, mOS was longer with TACE (32 vs. 20 months), but was not statistically significant (HR 1.39, 95% CI: 0.96–2.03, p = 0.080). In BCLC 0/A, complete response rates were higher with TACE (43.2% vs. 34.3%, p = 0.012). Hepatic decompensation was more frequent with TARE- (26.0%) than with TACE-treated patients (13.7%, p = 0.010). Conclusions: TACE demonstrated superior survival outcomes over TARE, particularly in early-stage disease. These results advocate for a more nuanced selection of embolization therapies in these patients. Full article

Background/Objectives: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) was updated in 2022 to refine patient stratification, particularly in patients with intermediate-stage (BCLC B) HCC. Although transarterial chemoembolization (TACE) remains a key treatment for these patients, there is no prognostic model for survival outcomes based on the pretreatment factors of patients who meet the updated 2022 BCLC indications for TACE. The aim of this study was to develop a pretreatment risk model predicting overall survival (OS) in patients with intermediate-stage HCC and reclassified as candidates for TACE according to the updated 2022 BCLC criteria. Methods: This retrospective study included 658 HCC patients treated with first-line TACE according to the updated BCLC 2022 guidelines. Pretreatment factors such as the Child–Pugh score, tumor burden (up-to-11 criteria), bilobar tumor involvement, and serum alpha-fetoprotein (AFP) levels were analyzed. Cox proportional hazards models were used to identify significant predictors of OS, with these factors subsequently incorporated into a risk prediction model. Results: Significant predictors of OS included Child–Pugh score ≥ 7, bilobar tumor involvement, beyond up-to-11 criteria, and AFP ≥ 400 ng/mL. A risk model was developed using these factors, stratifying patients into low-, intermediate-, and high-risk groups. The median OS in the low-, intermediate-, and high-risk groups was 53, 35, and 21 months, respectively. Conclusions: The proposed pretreatment risk prediction model may be useful for predicting OS and guiding TACE candidacy in intermediate-stage HCC patients based on the updated 2022 BCLC guidelines. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Barcelona Clinic Liver Cancer (BCLC) guidelines recommend antiangiogenic agents with immune checkpoint inhibitors as first-line therapy for advanced HCC. We present our experience of treating HCC patients with Atezolizumab–Bevacizumab, their response rates, adverse events, survival, and response and survival predictors. Methods: This retrospective analysis included HCC patients diagnosed at All India Institute of Medical Sciences, New Delhi, India between July 2021 and April 2024 and receiving at least one dose of Atezolizumab–Bevacizumab. The primary outcome was overall response rate (ORR), comprising complete response (CR) and partial response (PR), as per mRECIST criteria. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and predictors of response and survival. Results: Sixty-three patients were analyzed {mean age: 56.0 + 12.7 years; 82.5% males}. Forty-three (68.2%) patients had BCLC stage C HCC. Thirty-five (55.5%) patients belonged to Child–Pugh class A and 28 (44.5%) belonged to Child–Pugh class B. At 1 year, OS was 39% and PFS was 27%. Among 43 patients with data for radiological response, ORR was 48.8% (CR—9.3% and PR—39.5%) and DCR was 62.7% with stable disease (SD) in 13.9% of patients. PD occurred in 37.2% of patients. AFP response predicted radiological response, while Child–Pugh class and BCLC stage predicted survival. Adverse events were reported in 49.2% of patients. Conclusions: Our study shows slightly lower survival than previous studies with Child–Pugh class being the most important determinant of survival. AFP response predicts radiological response and not survival. Full article

Objective: This study aimed to investigate the prognostic value of preoperative myosteatosis and the albumin–bilirubin (ALBI) grade in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) and develop a robust prognostic score based on these factors. Methods: Patients with HCC who underwent TACE between January 2009 and December 2020 were included. Multivariate Cox regression analysis identified prognostic factors. CT-based body composition parameters were acquired from baseline abdominal CT images at the level of the third lumbar vertebra. A prognostic score (Myo-ALBI) was developed based on the presence of preoperative myosteatosis and the ALBI grade, and its prognostic value was evaluated. Results: Of 446 patients, 63% were male, and the mean age was 62.4 years. Preoperative myosteatosis was present in 41.5% of patients. The BCLC stages were mostly B (67.9%). Multivariate analysis shows that preoperative myosteatosis, ALBI grade 2, and ALBI grade 3 were independent prognostic factors. The Myo-ALBI grade was incorporated into a prognostic model, including alpha-fetoprotein and up-to-seven criteria, to generate a nomogram. The C-index of the nomogram based on the Myo-ALBI grade (0.743) was significantly higher than the non-Myo-ALBI nomogram (0.677), the up-to-seven criteria (0.653), the ALBI grade (0.616), and the Child–Pugh class (0.573) (all p < 0.05). The t-ROC curve for the nomogram was consistently superior to the other models throughout the observation period in all patients and the BCLC-B subgroup. Conclusions: The combination of preoperative CT-derived myosteatosis and ALBI grade enhances prognostication for patients with unresectable HCC undergoing TACE. The Myo-ALBI nomogram constructed in this study could support individualized prognosis prediction, assisting in treatment decision-making for HCC patients. Full article

Background/Objectives: The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). Methods: In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. Results: Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child–Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. Conclusions: This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection. Full article

This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes. Full article

Background: Introduced in the latest BCLC 2022, endovascular trans-arterial radioembolization (TARE) has an important role in the treatment of unresectable hepatocellular carcinoma (HCC) as a “bridge” or “downstaging” of disease. The evolution of TARE technology allows a more flexible and personalized target treatment, based on the anatomy and vascular characteristics of each HCC. The flex-dose delivery program is part of this perspective, which allows us to adjust the dose and its radio-embolizing power in relation to the size and type of cancer and to split the therapeutic dose of Y90 in different injections (split-bolus). Methods: From January 2020 to January 2022, we enrolled 19 patients affected by unresectable HCC and candidates for TARE treatment. Thirteen patients completed the treatment following the flex-dose delivery program. Response to treatment was assessed using the mRECIST criteria with CT performed 6 and 9 months after treatment. Two patients did not complete the radiological follow-up and were not included in this retrospective study. The final cohort of this study counts eleven patients. Results: According to mRECIST criteria, six months of follow-up were reported: five cases of complete response (CR, 45.4% of cases), four cases of partial response (PR, 36.4%), and two cases of progression disease (PD, 18.2%). Nine months follow-up reported five cases of complete response (CR, 45.4%), two cases of partial response (PR, 18.2%), and four cases of progression disease (PD, 36.4%). No intra and post-operative complications were described. The average absorbed doses to the hepatic lesion and to the healthy liver tissue were 319 Gy (range 133–447 Gy) and 9.5 Gy (range 2–19 Gy), respectively. Conclusions: The flex-dose delivery program represents a therapeutic protocol capable of “saving” portions of healthy liver parenchyma by designing a “custom-made” treatment for the patient. Full article

Background: Hepatocellular carcinoma (HCC) accounts for 75% of primary liver tumors. Controlling risk factors associated with its development and implementing screenings in risk populations does not seem sufficient to improve the prognosis of these patients at diagnosis. The development of a predictive prognostic model for mortality at the diagnosis of HCC is proposed. Methods: In this retrospective multicenter study, the analysis of data from 191 HCC patients was conducted using machine learning (ML) techniques to analyze the prognostic factors of mortality that are significant at the time of diagnosis. Clinical and analytical data of interest in patients with HCC were gathered. Results: Meeting Milan criteria, Barcelona Clinic Liver Cancer (BCLC) classification and albumin levels were the variables with the greatest impact on the prognosis of HCC patients. The ML algorithm that achieved the best results was random forest (RF). Conclusions: The development of a predictive prognostic model at the diagnosis is a valuable tool for patients with HCC and for application in clinical practice. RF is useful and reliable in the analysis of prognostic factors in the diagnosis of HCC. The search for new prognostic factors is still necessary in patients with HCC. Full article

Background: Intermediate-stage hepatocellular carcinoma (BCLC B HCC) occurs in a heterogeneous group of patients and can be addressed with a wide spectrum of treatments. Consequently, survival significantly varies among patients. In recent years, several subclassification systems have been proposed to stratify patients’ prognosis. We analyzed and compared these systems (Bolondi, Yamakado, Kinki, Wang, Lee, and Kim criteria) in patients undergoing systemic therapy. Methods: We considered 171 patients with BCLC B HCC treated with sorafenib as first-line systemic therapy in six Italian centers from 2010 to 2021 and retrospectively applied the criteria of six different subclassification systems. Results: Except for the Yamakado criteria, all the subclassification systems showed a statistically significant correlation to overall survival (OS). In the postestimation analysis, the Bolondi criteria (OS of subgroups 22.5, 11.9, and 6.6 mo, respectively; C-index 0.586; AIC 1338; BIC 1344) and the Wang criteria (OS of subgroups 20.6, 11.9, and 7.0, respectively; C-index 0.607; AIC 1337; BIC 1344) presented the best accuracy. Further analyses of these two subclassification systems implemented with the prognostic factor of alpha-fetoprotein (AFP) > 400 ng/mL have shown an increase in accuracy for both systems (C-index 0.599 and 0.624, respectively). Conclusions: Intermediate-stage subclassification systems maintain their predictive value also in the setting of systemic therapy. The Bolondi and Wang criteria showed the highest accuracy. AFP > 400 ng/mL enhances the performance of these systems. Full article