Search Results (85)

Objective: Tumor progression is regulated by systemic immune status, nutritional metabolism, and the inflammatory microenvironment. This study aims to investigate inflammatory–nutritional biomarkers associated with metachronous liver metastasis (MLM) in colorectal cancer (CRC) and develop a machine learning model for accurate prediction. Methods: This study enrolled 680 patients with CRC who underwent curative resection, randomly allocated into a training set (n = 477) and a validation set (n = 203) in a 7:3 ratio. Feature selection was performed using Boruta and Lasso algorithms, identifying nine core prognostic factors through variable intersection. Seven machine learning (ML) models were constructed using the training set, with the optimal predictive model selected based on comprehensive evaluation metrics. An interactive visualization tool was developed to interpret the dynamic impact of key features on individual predictions. The partial dependence plots (PDPs) revealed a potential dose–response relationship between inflammatory–nutritional markers and MLM risk. Results: Among 680 patients with CRC, the cumulative incidence of MLM at 6 months postoperatively was 39.1%. Multimodal feature selection identified nine key predictors, including the N stage, vascular invasion, carcinoembryonic antigen (CEA), systemic immune–inflammation index (SII), albumin–bilirubin index (ALBI), differentiation grade, prognostic nutritional index (PNI), fatty liver, and T stage. The gradient boosting machine (GBM) demonstrated the best overall performance (AUROC: 0.916, sensitivity: 0.772, specificity: 0.871). The generalized additive model (GAM)-fitted SHAP analysis established, for the first time, risk thresholds for four continuous variables (CEA > 8.14 μg/L, PNI < 44.46, SII > 856.36, ALBI > −2.67), confirming their significant association with MLM development. Conclusions: This study developed a GBM model incorporating inflammatory-nutritional biomarkers and clinical features to accurately predict MLM in colorectal cancer. Integrated with dynamic visualization tools, the model enables real-time risk stratification via a freely accessible web calculator, guiding individualized surveillance planning and optimizing clinical decision-making for precision postoperative care. Full article

Background: Hepatocellular carcinoma (HCC) with hepatic vein invasion (HVI) is classified as advanced stage and palliative management is the primary treatment option. This study compared the long-term outcomes of curative and non-curative treatments in patients of HCC with HVI. Methods: Data were obtained from a retrospective multicenter cohort of the Korean Primary Liver Cancer Registry. We reviewed 18,315 patients newly diagnosed with HCC between 2008 and 2019. After propensity score matching based on the albumin-bilirubin (ALBI) score; tumor number, and tumor size, clinical outcomes were compared between the curative group (n = 42, 29.0%) undergoing surgical resection or local ablation and the non-curative group (n = 103, 71.0%) receiving other treatments. Results: Tumor burdens such as tumor number, maximum tumor size, levels of alpha-fetoprotein (AFP), and protein induced by absence of vitamin K or antagonist-II did not differ significantly between the groups (p = 0.672, p = 0.143, p = 0.153 and p = 0.651, respectively). In long-term outcomes, the overall survival (OS) and cancer-specific survival (CSS) were significantly better in the curative group compared to the non-curative group (p < 0.001, both). Multivariate analysis indicated that non-curative treatment, ALBI grade ≥ 2, and AFP ≥ 400 ng/mL were common risk factors for OS and CSS. Conclusions: Curative-intent treatment has the potential to significantly enhance long-term outcomes in selected patients of HCC with HVI who preserved liver function and performance status. Full article

Objective: To evaluate the prognostic value of pre-therapeutic inflammatory markers before transarterial chemoembolization with degradable starch microspheres (DSM-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: A total of 155 patients (81% male, median age: 68 years) who underwent first-time DSM-TACE between 07/13 and 06/22 were included in the study. Inflammatory indices were dichotomized using median values. Cox proportional hazard model for univariate (UVA) and multivariate (MVA) analyses (hazard ratio; 95% CI, p-value) and Kaplan–Meier analyses (overall survival (OS) in months; 95% CI; log-rank test) were performed. Results: The median OS of the study cohort was 15.9 (12.9–20) months with a median survival according to BCLC stages A (12%), B (41%), and C (47%) of median not reached, 19.3 (15.3–27), and 7.2 (4.5–9.0) months, respectively (p < 0.0001). In the UVA, several inflammatory markers on OS were statistically significant with the systemic inflammatory response index (SIRI; ≤median (2.04) HR: 0.41 (0.19–0.89); p = 0.024) and the lymphocyte to monocyte ratio (LMR; >median (1.82) HR: 0.44 (0.2–0.9); p = 0.025) remaining statistically significant in MVA together with the BCLC stage (p = 0.0001), ALBI grade (p = 0.016), hepatic tumor burden (≤25% vs. >25%; p = 0.006), and largest HCC lesion (≤5.5 cm vs. >5.5 cm; p = 0.008). In subgroup analysis, patients with elevated LMR and reduced SIRI exhibited significantly prolonged overall survival (OS) in both BCLC B (p < 0.0001) and Child–Pugh A (p = 0.021) subgroups. Conclusion: The findings suggest that SIRI and LMR may serve as valuable tools in identifying BCLC B and Child–Pugh A patients who could potentially benefit better from DSM-TACE treatment. Nevertheless, further research is recommended to confirm these findings and to provide more comprehensive insights. Full article

Background/objectives: The real-world survival of patients with unresectable hepatocellular carcinoma (uHCC) treated with lenvatinib has been explored retrospectively with a small sample size. We conducted a prospective observational 2-year extension study (510 study) of a 1-year observational post-marketing study of lenvatinib (504 study) to evaluate the long-term overall survival (OS) of patients with uHCC treated with lenvatinib and associated factors with a large sample size. Methods: Patients with uHCC included (July 2018 to January 2019) in the 504 study and who consented were eligible for the 510 study and were followed for up to 3 years after lenvatinib treatment initiation. Using the data from the 504 study and 510 study of the 504 study analysis set, we estimated the OS, the time from the first lenvatinib dose to all-cause death by the Kaplan–Meier method (ClinicalTrials.Gov Registration ID, 504 study: NCT03663114; 510 study: NCT04008082). Results: The 703 patients included in the analysis were followed for a median period (min, max) of 12.5 months (0.1, 44.8). The median OS (95% confidence interval) was 16.6 months (15.4, 18.5). OS was significantly (p < 0.05) associated with bile duct invasion (hazard ratio [HR]: 1.621), portal vein invasion (HR: 1.365), ≥ 4 intrahepatic lesions (HR: 1.437), extrahepatic lesions (HR: 1.357), Child–Pugh B/C (HR: 1.515), mALBI Grade 2a (HR: 1.331), and Grade ≥ 2b (HR: 1.811). Conclusions: This large-scale, prospective, real-world study demonstrated a long OS, comparable to that reported in the global Phase III REFLECT trial. More advanced-stage tumors and worse hepatic function have been suggested as OS-associated factors, consistent with previous reports. Full article

Background: Muscle depletion (MD) is a critical factor that influences clinical outcomes in patients with hepatocellular carcinoma (HCC). Although its role in cancer prognosis is recognized, its integration into widely used prognostic systems remains underexplored. This study aimed to evaluate the prognostic impact of MD on overall survival (OS) in HCC patients and to improve existing noninvasive prognostic models by incorporating MD-related metrics. Methods: A retrospective analysis was conducted on 1072 HCC patients treated at Taipei Tzu Chi Hospital between January 2006 and December 2016. All patients had follow-up data and computed tomography (CT) scans at vertebral level L3 for MD evaluation. Independent prognostic factors for OS were identified using Cox proportional hazards models, and the predictive performance of various prognostic models was assessed through the area under the receiver operating characteristic curve (AUROC). Results: The key independent predictors of OS in HCC patients included hepatitis B virus infection, hepatitis C virus infection, liver cirrhosis, tumor size, serum alpha-fetoprotein levels, and MD-related metrics (psoas muscle-to-spine ratio, psoas muscle-to-vertebral ratio, and myosteatosis). Among existing models, the Barcelona Clinic Liver Cancer (BCLC) stage, the Child–Turcotte–Pugh (CTP) class, and the albumin–bilirubin (ALBI) grade demonstrated robust predictive performance for OS. However, incorporating MD significantly improved the predictive accuracy of these models, with the MD–BCLC model showing the highest AUROC (0.804, 95% CI: 0.777–0.832, p < 0.001). Conclusions: MD is an independent and significant prognostic predictor for patients with HCC. Integrating MD metrics into established systems, particularly the BCLC staging system, markedly improves OS prediction, providing a more comprehensive tool for clinical decision-making in the management of HCC. Full article

Background/Objectives: Radiofrequency ablation (RFA) is an important local treatment for hepatocellular carcinoma (HCC). This study aimed to evaluate the characteristics of tumor recurrence after RFA and analyze predictors of tumor recurrence and survival in patients with HCC. Methods: We retrospectively reviewed data from treatment-naïve patients with HCC who underwent RFA for HCC treatment between 2008 and 2017 at four tertiary hospitals in South Korea. Results: A total of 636 patients with HCC treated with RFA were enrolled in the study. The mean age was 66.3 ± 10.4 years, with 75.0% of patients being male. Most patients (96.7%) had underlying liver cirrhosis, and viral hepatitis (types B and C) accounted for most cases. The average maximum tumor size was 2.2 ± 0.9 cm, with 84.3% of tumors being single lesions. During the follow-up period, 331 patients experienced recurrence, with 95.5% of cases being intrahepatic and one-fifth occurring at the RFA site. Most patients underwent RFA or transarterial chemoembolization as subsequent therapy for recurrence. Multivariate analysis revealed that age, the albumin–bilirubin (ALBI) grade, and Child–Pugh class B status were independent factors associated with tumor recurrence. Only the ALBI grade was significantly associated with mortality. Additionally, the ALBI grade differentiated between recurrence-free survival and overall survival in the Kaplan–Meier survival curve. Conclusions: The ALBI grade was independently associated with tumor recurrence and prognosis in patients with HCC following RFA. This grading system can help clinicians identify high-risk patients, optimize treatment strategies, and enhance patient care. Full article

Objectives: The principal objective of this study was to assess the predictive efficacy of the global immune–nutrition–inflammation index (GINI) and the albumin–bilirubin (ALBI) score among patients receiving chemoradiotherapy for esophageal cancer. Methods: A retrospective analysis was conducted on 46 patients who received definitive or neoadjuvant radiotherapy for esophageal cancer at our institution. Blood samples were collected from these patients prior to the initiation of radiotherapy to measure the biomarkers, including the C-reactive protein (CRP), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), the global immune–nutrition–inflammation index (GINI), and the albumin–bilirubin (ALBI) grade. The predictive significance of these biomarkers for progression-free survival (PFS) and overall survival (OS) was evaluated using both univariate and multivariate Cox regression analyses. Results: The median follow-up time for this study was 19.5 months (range: 2.6–166.3 months). Univariate analysis revealed that the platelet count (p = 0.003) and monocyte count (p = 0.04) were significant predictors of PFS. In the multivariate analysis, only the platelet count (p = 0.005) remained an independent predictor of PFS. Univariate analysis demonstrated that the neutrophil count (p = 0.04), lymphocyte count (p = 0.01), NLR (p = 0.005), PLR (p = 0.004), CRP (p = 0.02), ALBI grade (p = 0.01), and GINI (p = 0.005) were significant predictors of OS. Multivariate analysis identified the GINI as a predictor of OS, approaching statistical significance (p = 0.08). Conclusion: The results of our study indicate that the pretreatment GINI and ALBI grades are significantly and independently associated with the OS rates in patients with esophageal cancer who are undergoing chemoradiotherapy. Full article

Background: There is a strong correlation between systemic inflammation intensity and clinical presentation, disease progression, and survival during liver cirrhosis decompensation. This study aimed to evaluate the prognostic performance of blood-based biomarkers as meta-inflammation markers, including NLR, PLR, LMR, INPR, MPR, ALBI, FIB4, and APRI, in predicting hospital mortality in patients with acute decompensation of alcohol-related liver cirrhosis. Methods: Data from 411 patients with their first onset of acute decompensation were analyzed, forming two groups: deceased and survived during hospitalization. Generalized partial least squares regression analysis was applied to explore the effects of surrogate indicators on mortality rates, using mortality rate as the dependent variable. Root Mean Square Error, Akaike’s, and Bayesian information criteria determined that four components accounted for most of the variance. Results: Variables with significant negative contributions to the outcome prediction (ranked by standardized regression coefficients) were encephalopathy grade, total bilirubin, Child–Turcotte–Pugh score, MELD, NLR, MPV, FIB4, INR, PLR, and ALT. Coefficient sizes ranged from −0.63 to −0.09, with p-values from 0 to 0.018. Conclusions: NLR, PLR, and FIB4 significantly contribute to hospital mortality prediction in patients with acute decompensation of alcohol-related liver cirrhosis. Conversely, some variables used to predict liver disease severity, including INPR, APRI, LMR, and ALBI score, did not significantly contribute to hospital mortality prediction in this patient population. 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

To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532–1.450–2.361 (p for trend 0.037), 1.057–1.691–3.364 (p for trend 0.004), 1.176–0.686–0.281 (p for trend 0.002), 0.639–0.759–1.820 (p for trend 0.462), 1.030–0.959–0.147 (p for trend 0.011), and 0.697–0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592–1.073–2.811 (p for trend 0.255), 1.161–1.282–4.324 (p for trend 0.03), 0.965–0.781–0.655 (p for trend 0.095), 0.737–0.623–2.147 (p for trend 0.153), 1.061–0.832–0.800 (p for trend 0.391), and 1.412–0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects. Full article

Background: The therapeutic options for hepatocellular carcinoma (HCC) have greatly expanded recently, and current first-line therapies include sorafenib, lenvatinib, and atezolizumab-bevacizumab. The aim of this study was to investigate the therapeutic efficacy of sequential systemic treatments after progressing to the first-line agent in patients with unresectable HCC. Methods: Data were collected from subjects with HCC, BCLC stage B or C, who received first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab from September 2020 to December 2022. The patients who progressed after first-line therapy were evaluated according to individual clinical status in order to decide whether or not to accept sequential therapy. The clinical baseline characteristics and overall survival (OS) of enrolled patients were collected and further analyzed. Results: Among the 127 enrolled patients, percentage of sequential therapy was 67.9%, 21.6%, and 37.5% in those with tumor progression after first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab, respectively. Acceptance of sequential therapy (HR 0.46, p = 0.041) and presentation of ALBI grade I (HR 0.36, p = 0.002) had a significantly positive impact on OS. Pre-treatment ALBI grade had a significant impact on the decision to accept sequential therapy in patients with progressed HCC. Conclusions: The patients who were able to undergo sequential therapy had a better survival outcome compared to those who received only one agent, and the pre-treatment ALBI level might be regarded as a cornerstone tool to assess survival outcomes in patients undergoing treatment for HCC. Full article

Background: The ability of the survival nomogram developed in the EACH study and albumin–bilirubin (ALBI) grade to predict the survival of advanced hepatocellular carcinoma (HCC) patients receiving oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) remains unvalidated. Here, we comprehensively evaluated these prognostic tools. Methods: The survival nomogram and ALBI grade of each patient were assessed, and the area under the receiver operating curve (AUROC) and Harrell’s C-index for the risk classification model were calculated. Results: Overall, 76 HCC patients who received FOLFOX4 between August 2017 and June 2023 were included. The survival nomogram classified patients into low-, intermediate-, and high-risk groups, with a median overall survival (OS) of 9.82, 10.64, and 3.70 months, respectively (p = 0.23). The AUROC was 0.621 and Harrell’s C-index was 0.589. However, the ALBI grade categorized all patients into grade 1, 2, and 3, with a median OS of 9.82, 6.83, and 1.58 months, respectively (p = 0.00024). The AUROC was 0.663 and Harrell’s C-index was 0.663. Conclusion: The ALBI grade can be a potential prognostic tool. However, the survival nomogram does not provide clear discrimination. Therefore, FOLFOX4 should be an option for patients with ALBI grade 1 who cannot receive immunotherapy or targeted therapy. Additional prospective studies with a larger cohort are warranted to validate the survival nomogram and ALBI grade as prognostic tools. Full article

Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child–Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50–13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82–9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19–11.82) and the median PFS was 6.50 months (95% CI, 3.93–9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations. Full article

The Prognostic Nutritional Index (PNI) is widely recognized as a screening tool for nutrition. We retrospectively examined the impact of PNI in patients with chronic liver disease (CLD, n = 319, median age = 71 years, 153 hepatocellular carcinoma (HCC) patients) as an observational study. Factors associated with PNI < 40 were also examined. The PNI correlated well with the albumin–bilirubin (ALBI) score and ALBI grade. The 1-year cumulative overall survival rates in patients with PNI ≥ 40 (n = 225) and PNI < 40 (n = 94) were 93.2% and 65.5%, respectively (p < 0.0001). In patients with (p < 0.0001) and without (p < 0.0001) HCC, similar tendencies were found. In the multivariate analysis, hemoglobin (p = 0.00178), the presence of HCC (p = 0.0426), and ALBI score (p < 0.0001) were independent factors linked to PNI < 40. Receiver operating characteristic (ROC) curve analysis based on survival for the PNI yielded an area under the ROC curve of 0.79, with sensitivity of 0.80, specificity of 0.70, and an optimal cutoff point of 42.35. In conclusion, PNI can be a predictor of nutritional status in CLD patients. A PNI of <40 can be useful in predicting the prognosis of patients with CLD. Full article

The severity of liver functional reserve is an important prognostic predictor in hepatocellular carcinoma (HCC). The albumin–bilirubin (ALBI), easy (EZ)-ALBI, platelet-albumin–bilirubin (PALBI), platelet–albumin (PAL) score, and MELD 3.0 score are used to evaluate the severity of liver dysfunction. However, their prognostic role in HCC patients, specifically with renal insufficiency (RI), is unclear. We aimed to investigate the predictive accuracy of the five models in these patients. A total of 1120 newly diagnosed HCC patients with RI were enrolled. A multivariate Cox proportional analysis was used to identify independent predictors associated with survival. In the Cox model, older age, an α-fetoprotein ≥20 ng/mL, vascular invasion, a medium and high tumor burden score, poor performance status, a higher ALBI grade, an EZ-ALBI grade, a PALBI grade, a PAL grade, and MELD 3.0 score were all independently associated with decreased overall survival (all p < 0.001). Among the five liver reserve models, the ALBI grade is the best surrogate marker to represent liver functional reserve in terms of outcome prediction. The albumin-based liver reserve models (ALBI, EZ-ALBI, PALBI, and PAL) and MELD 3.0 are all feasible prognostic markers to indicate liver injury, specifically in HCC patients with RI. Among them, the ALBI grade is the most robust tool for survival prediction in these patients. Full article