Alpha-fetoprotein Response Research Articles

Prognosis predictors of hepatocellular carcinoma after hepatectomy following conversion therapy

BackgroundHepatectomy is the optimal treatment for less than 20% patients with hepatocellular carcinoma (HCC). A combination of hepatic artery infusion chemotherapy and systemic therapy-based conversion therapy provides a chance of resection for those with unresectable HCC. Yet, the prognosis for those successfully conversion resection is still unknown. The study is to determine the factors predicted prognosis of patients after conversion hepatic resection. MethodsA total of 343 HCC patients underwent hepatectomy following conversion therapy from August 2018 to April 2023. Univariate and multivariate analysis were used to screen for independent factors affecting patients’ prognosis. ResultsOne hundred and fifty-seven (45.8%) patients developed recurrence or metastasis at a median time of 16.7 months (95% CI 12.4-21.0 months) from hepatectomy. Univariate and multivariate analysis identified tumor number, alpha fetoprotein (AFP) response, tumor response, and successful downstaging were independent recurrent-free survival related predictors. Albumin bilirubin (ALBI) score and AFP response were independent death related predictors. ConclusionsClinical parameters reflecting the depth of conversion therapy response, were promising in predicting prognosis for HCC patients after conversion hepatic resection.

Alpha-fetoprotein and des-gamma-carboxy prothrombin can predict the objective response of patients with hepatocellular carcinoma receiving durvalumab plus tremelimumab therapy.

Durvalumab plus tremelimumab (Durva/Treme) combined immunotherapy is the first-line therapy recommended for unresectable hepatocellular carcinoma (HCC). Since sequential therapy is more effective in improving prognosis, tumor markers have been used as predictive biomarkers for response to systemic therapy. This study aimed to investigate the predictive ability of objective response (OR) by tumor markers for Durva/Treme therapy against HCC. In this multicenter study, 110 patients with HCC who received Durva/Treme therapy were retrospectively enrolled. The OR rate was 15.5%. To aid early decision-making regarding OR, we evaluated the predictors contributing to OR in two steps: before (first step) and 4 weeks after (second step) treatment induction. Changes in tumor markers (alpha-fetoprotein [AFP] and des-gamma-carboxy prothrombin [DCP]) from baseline to 4 weeks after treatment (ΔAFP/ΔDCP) were included as the input factors. In the first step, multivariable analysis identified only the baseline AFP level (odds ratio 3.497, p = 0.029) as a predictor of OR. Patients with AFP ≥ 400 ng/mL had a significantly higher OR rate than those with < 400 ng/mL (28.2 vs. 8.5%, p = 0.011), and there was no significant difference in progression-free survival (PFS) between the two groups. When AFP/DCP response was defined as a ≥10% reduction from baseline, multivariable analysis showed that AFP response (odds ratio 6.023, p = 0.042) and DCP response (odds ratio 11.657, p = 0.006) were both independent predictors of OR in the second step. The PFS of patients with AFP or DCP response was significantly longer than that of patients without AFP or DCP response. The study demonstrated that the use of AFP and DCP can predict the OR of patients with HCC receiving Durva/Treme therapy.

Hepatic Arterial Infusion Chemotherapy Combined Lenvatinib and PD-1 Inhibitor Showed Improved Survival for Infiltrative Hepatocellular Carcinoma: A Multicenter Cohort Study.

Lenvatinib and programmed cell death protein-1 (PD-1) inhibitor on infiltrative hepatocellular carcinoma (HCC) have obtained demonstrated efficacy and still need improvement. Hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC. This study aimed to compare the efficacy of HAIC combined Lenvatinib and PD-1 inhibitor versus Lenvatinib combined PD-1 inhibitor for infiltrative HCC. A total of 232 patients were enrolled. There were 114 patients received Lenvatinib combined PD-1 inhibitor (Len+PD-1 group) and 118 patients received HAIC combined Lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1 group). Overall survival (OS), progression-free survival (PFS) and safety of patients were compared between the two groups by propensity score-matching (PSM). The 6-, 12-, and 24-month OS rates were 93.8%, 65.1% and 13.4% in Len+PD-1 group, and 100%, 77.3% and 32.1% in HAIC+Len+PD-1 group, respectively. The 3-, 6-, and 12-month PFS rates were 86.4%, 45.7% and 14.1% in Len+PD-1 group, and 95.1%, 59.3% and 25.9% in HAIC+Len+PD-1 group, respectively. The HAIC+Len+PD-1 group had obviously better survival than the Len+PD-1 group both in OS (P=0.002) and PFS (P=0.004). Subgroup analysis revealed that OS in patients with metastasis was improved with HAIC+Len+PD-1 treatment. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. In addition, HAIC+Len+PD-1 group showed manageable adverse events (AEs). Patient with infiltrative HCC, HAIC+Len+PD-1 treatment had longer OS and PFS than Len+PD-1 treatment. Early AFP response was an effective indicator of better survival and tumor response to therapy.

Prognostic Value of Alpha-Fetoprotein in Unresectable Hepatocellular Carcinoma Treated with Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

ASSESSEMENT IN PERFORMANCE OF LI-RADS ALGORITHM IN DETECTING TREATMENT RESPONSE OF HEPATOCELLULAR CARCINOMA AFTER TRANS-ARTERIAL CHEMOEMBOLIZATION

Background:Trans-arterial hemoembolization (TACE) usually indicated for unresectable hepatocellular carcinoma (HCC) on purpose as a bridging, downstaging or palliative treatment. Liver Imaging Reporting and Data Systems Treatment Response (LR-TR) was created to evaluate each lesion post-TACE, which has localized and is suitable for determining whether the tumor is still viable or Non-viable. Purpose: To assess the completion of LI-RADS version 2018 on computer tomography in the evaluation of HCC after TACE. Materials and Methods: A retrospective cross-sectional study involved 58 patients with hepatocellular carcinoma (HCC) who underwent treatment base TACE from June 2021 – September 2022. The clinical situation, AFP levels, and computer tomography (CT) of the patient after treatment were analyzed. The Radiologist evaluated pre- and post-treatment CT findings using LR-TR category, appropriately. The pooled sensitivity, specificity, and accuracy correclated between LR-TR with standard reference. Results: A total 58 patients with HCC (M/F: 13:1, mean age 56.9±11.0 years). For demonstrating the treatment response after first TACE on CT, Non-viable resulted in 32.8%(19/58), and LR-TR Viable was 67.2%(39/58), sensitivity value of 90% (36/40), specificity value of 83.3% (15/18), positive predictor value of 16.7% (3/18), a negative predictor value of 10% (4/40), accuracy value of 87.9% (51/58). The performance status response- AFP response- imaging response correlation was not statistically different, p= 0.552 and p=0.647. Conclusion: Using LR-TR on CT detects treatment response of HCC post-TACE was useful, and high sensitivity, specificity, and accuracy.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma.

The efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus programmed cell death protein-1 (PD-1) for unresectable hepatocellular carcinoma (HCC) have rarely been evaluated and it is unknown which factors are related to efficacy. To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC. This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022. Overall survival (OS) and progression-free survival (PFS) were determined. The objective response rate (ORR) and disease control rate (DCR) were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors. Additionally, the prognostic factors affecting the clinical outcome were assessed. One hundred and two patients were enrolled with a median follow-up duration of 12.63 months. The median OS was 26.43 months (95%CI: 17.00-35.87), and the median PFS was 10.07 months (95%CI: 8.50-11.65). The ORR and DCR were 61.76% and 81.37%, respectively. The patients with Barcelona Clinic Liver Cancer Classification (BCLC) B stage, early neutrophil-to-lymphocyte ratio (NLR) response (decrease), or early alpha-fetoprotein (AFP) response (decrease > 20%) had superior OS and PFS than their counterparts. This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC. The patients with BCLC B-stage disease with early NLR response (decrease) and early AFP response (decrease > 20%) may achieve better clinical outcomes with this triple therapy.

A Real-World Experience on a Chinese Population of Patients With Unresectable Hepatocellular Carcinoma Treated With Nivolumab.

For unresectable hepatocellular carcinoma (HCC), nivolumab (anti-programmed death receptor-1 (PD-1)) is used as non-curative interventions. The aim of the study was to focus on the real-world experience of nivolumab applied to patients with HCC. Unresectable HCC patients receiving nivolumab treatments at Taichung Veterans General Hospital, from June 2018 to May 2020, were recruited. Exclusion criteria were Child-Pugh stage C, poor performance status, a lack of compliance or intolerable to drug treatments. The tumor radiological responses and survival outcomes of enrolled patients were collected and analyzed. Among a total of 57 patients, most of them were classified as Child-Pugh stage A (70.2%) and Barcelona Clinic Liver Cancer (BCLC) stage C (66.7%). Nivolumab was given to 14 (24.6%) as the primary-line, and 43 patients (75.4%) as the secondary-line systemic treatments. The mean therapeutic duration was 6.5 months. Objective response rate (ORR) was 24.6%, and disease control rate (DCR) was 42.1%. The overall median progression-free survival (PFS) was 5.8 months (95% confidence interval (CI): 1.1 - 10.6), and overall survival (OS) was 11.5 months (95% CI: 4.3 - 17.8). Immune-related adverse event (IRAE) was 8.8%. Presence of alpha-fetoprotein (AFP) response (a decline in AFP ≥ 10% from baseline) during therapy predicted the tumor radiological response (to objective response: hazard ratio (HR): 4.89, 95% CI: 1.14 - 21.00; to disease control: HR: 4.71, 95% CI: 1.32 - 16.81). Those with tumor radiological responses showed longer PFS and OS. Decline in AFP during therapy has a predicting role on HCC radiological responses to nivolumab. Achieving radiological responses had better survival outcomes.

Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy for hepatocellular carcinoma patients with portal vein tumor thrombus.

Patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) present a poor prognosis. Current systemic therapies offer limited benefits. Hepatic artery infusion chemotherapy (HAIC) is a local regional treatment for advanced HCC, particularly in selected patients such as patients with PVTT or high intrahepatic tumor burden. The purpose of this study is to retrospectively evaluate the efficacy and safety of HAIC combined with anti-PD-1 immunotherapy for HCC patients with PVTT, and explore factors related to survival prognosis, providing clues for treatment decisions for HCC patients. This is a single-center retrospective study conducted over 2 years on consecutive PVTT patients receiving HAIC combined anti-PD-1 antibodies. The primary endpoint was overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors affecting OS. Treatment-associated adverse events were evaluated as well. A total of 119 patients were analyzed. The median OS and PFS were 14.9 months and 6.9 months. A total of 31.1% of grade 3-4 adverse events were reported, with elevated transaminase and total bilirubin being the most common. The independent variables correlated with survival include treatment-related alpha-fetoprotein (AFP) response, the presence of extrahepatic organ metastasis, absolute value of platelet (PLT), neutrophil-to-lymphocyte ratio, and combined usage of tyrosine kinase inhibitors (TKIs). In HCC patients with PVTT, combination therapy with HAIC and anti-PD-1 antibodies might be a promising therapy. The efficacy and safety of this combination protocol on patients with HCC complicated by PVTT warrants further investigation prospectively, especially in combination with TKIs.

Favorable AFP response is associated with longer HCC patients' waitlist and post-transplant survival

Favorable AFP response is associated with longer HCC patients' waitlist and post-transplant survival

Development and Assessment of Nomogram Based on AFP Response for Patients with Unresectable Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan-Meier analysis with the log-rank test was used to compare different risk groups. The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02-4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02-11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18-0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice.

Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy.

Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy. This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration >50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991-45.950, p<0.001; high-DCP group: OR: 17.853; 95% CI: 4.478-71.179, p<0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p<0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p<0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p<0.001). After 6 weeks of triple therapy, an AFP or DCP reduction of >50% predicts better treatment outcomes in uHCC patients.

Reclassification of therapeutic response of unresectable hepatocellular carcinoma to anti-angiogenic therapy and immunotherapy using alpha RECIST.

To assess the therapeutic response of HCC to antiangiogenic therapy plus immunotherapy by integrating RECIST 1.1 and alpha-fetoprotein (AFP) response at the 6th week to predict overall survival (OS). This retrospective study included 150 and 214 patients with HCC who received combination therapy in training and validation cohorts. The medical images and AFP levels obtained at baseline and 6th week were collected. AFP response stratification: partial response (PR): AFP% ≥ 75% decline; stable disease (SD): AFP% < 75% decline and ≤ 10% elevation; progressive disease (PD): AFP% > 10% elevation. The alpha-RECIST was: PR: RECIST 1.1-PR or AFP-PR; PD: AFP-PD or RECIST 1.1-PD and does not satisfy AFP-PR; SD: neither PR nor PD. OS was compared using Kaplan-Meier curves. The predictive ability of various criteria was evaluated using the concordance index and time-dependent area under the receiver-operating characteristic curve. RECIST 1.1 achieved significant OS stratification (p = 0.020) for AFP < 20ng/mL. For AFP ≥ 20ng/mL, alpha-RECIST showed better performance than RECIST 1.1, mRECIST, and AFP response according to C-index (0.73 vs 0.66 vs 0.68 vs 0.69). The National Cancer Center (NCC) strategy utilized RECIST 1.1 for AFP < 20ng/mL and alpha-RECIST for AFP ≥ 20ng/mL and showed better performance than RECIST 1.1, mRECIST and AFP response according to C-index (0.73 vs 0.67 vs 0.69 vs 0.64). The performances of alpha-RECIST and NCC Strategy were confirmed in the validation cohort (C-index = 0.77 and 0.74). The alpha-RECIST and NCC Strategy achieved better survival stratification in patients with HCC under combination therapy in the AFP ≥ 20ng/mL group and the whole cohort compared to the RECIST 1.1, mRECIST, and AFP response. The alpha-RECIST and National Cancer Center strategy are optimal methods for determining therapeutic response to a combination of anti-angiogenic therapy plus immunotherapy and facilitating accurate prognostic stratification for HCC in the AFP ≥ 20ng/mL group and the whole cohort, which may help oncologists for early identification of responders and progression at 6weeks and clinical decision-making. • RECIST 1.1 is indicated for patients with baseline alpha-fetoprotein (AFP) < 20ng/mL. • For patients with baseline AFP ≥ 20ng/mL, integrating RECIST 1.1 and AFP response (alpha-RECIST) may aid in the early identification of survival benefits and progression definition prior to the administration of additional efficacious drugs. • The National Cancer Center strategy is an optimal stratified strategy for determining therapeutic response to a combination of anti-angiogenic therapy and immunotherapy for HCC based on baseline AFP levels.

Alpha-Fetoprotein Response after First Transarterial Chemoembolization (TACE) and Complete Pathologic Response in Patients with Hepatocellular Cancer.

Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change after the first TACE in the prediction of complete tumor necrosis. The study comprised 101 patients with HCC who underwent liver transplantation (LT) after TACE in the period between January 2011 and December 2020. The ΔAFP was defined as the difference between the AFP value before the first TACE and AFP either before the second TACE or the LT. The receiver operator characteristics (ROC) curves were used to identify an optimal cut-off value. Complete tumor necrosis was found in 26.1% (18 of 69) and 6.3% (2 of 32) of patients with an initial AFP level under and over 100 ng/mL, respectively (p = 0.020). The optimal cut-off value of ΔAFP for the prediction of complete necrosis was a decline of ≥10.2 ng/mL and ≥340.5 ng/mL in the corresponding subgroups. Complete tumor necrosis rates were: 62.5% (5 of 8) in patients with an initial AFP < 100 ng/mL and decline of ≥10.2 ng/mL; 21.3% (13 of 61) in patients with an initial AFP < 100 ng/mL and decline of <10.2 ng/mL; 16.7% (2 of 12) in patients with an initial AFP > 100 ng/mL and decline of ≥340.5 ng/mL; and null in 20 patients with an initial AFP > 100 ng/mL and decline of <340.5 ng/mL, respectively (p = 0.003). The simple scoring system, based on the initial AFP and AFP decline after the first treatment, distinguished between a high, intermediate and low probability of complete necrosis, with an area under the ROC curve of 0.699 (95% confidence intervals 0.577 to 0.821, p = 0.001). Combining the initial AFP with its change after the first treatment enables early identification of the efficacy of TACE.

Factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment: A real-world experience.

The aim of this study was to investigate the factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment. We conducted a retrospective study using a multi-institutional electronic medical records database in Taiwan. We included advanced HCC patients newly receiving ramucirumab as second-line or beyond systemic therapy between January 2016 and February 2022. The clinical outcomes were median progression-free survival (PFS) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), overall survival (OS) and adverse events. We applied Kaplan-Meier methods to estimate median PFS and OS. Uni-variable and multi-variable Cox regression models were applied to identify the prognostic factors. We included 39 ramucirumab naive users with a median age of 65.5 (IQR: 57.0-71.0) years and treatment time of 5.0 (3.0-7.0) cycles, of whom 82.1% were male and 84.6% were Barcelona Clinic Liver Cancer (BCLC) stage C. After median follow-up time of 6.0 months, 33.3% of patients' AFP level had decreased more than 20% within 12 weeks. The median PFS and OS were 4.1 months and non-reach, respectively. Moreover, tumor burden beyond the up-to-11 criteria (HR: 2.95, 95% CI: 1.04-8.38) and a decrease in estimated glomerular filtration rate of more than 10% within 12 weeks (HR: 0.31, 0.11-0.88) were significantly related to PFS in the multi-variable analysis. No patient discontinued ramucirumab during the treatment on account of side effects. Ramucirumab was an effective treatment option with good AFP response for advanced HCC patients in real-world experience. Tumor burden beyond the up-to-11 criteria and a decrease in estimated glomerular filtration rate were independent predictive factors for progression-free survival.

Real-world experience with atezolizumab plus bevacizumab in the management of non-resectable hepatocellular carcinoma refractory to first-line systemic therapy: Review of literature.

e16189 Background: Hepatocellular carcinoma is the fifth most common cancer worldwide and the third leading cause of cancer-associated deaths. In 2020, the positive results of the IMbrave 150 trial and FDA (Food and Drug Administration) approval subsequently revolutionized the management of non-resectable hepatocellular carcinoma as the first-line treatment. However, their role as second-line therapy in people refractory to systemic therapy needs to be better studied. We perform a comprehensive literature review evaluating outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Methods: We performed a comprehensive literature search of PubMed, Embase, and Cochrane, evaluating the outcomes of atezolizumab plus bevacizumab in patients refractory to first-line systemic therapy. Results: Conclusions: Atezolizumab plus Bevacizumab is Safe and effective in the patient’s refractory to prior systemic therapy. However, when used as a second-line therapy, patients tend to have lower Median Odds of survival and Median progression-free survival. The outcome also changes with the type of prior systemic chemotherapy, with initial hyper-progression reported with prior therapy with lenvatinib. The AFP response at six weeks could be a predictive indicator of disease progression. [Table: see text]

Blood biomarkers predict outcomes in patients with hepatocellular carcinoma treated with immune checkpoint Inhibitors: A pooled analysis of 44 retrospective sudies.

We conducted the first meta-analysis to identify the predictive significance of baseline blood biomarkers (such as neutrophil to lymphocyte ratio (NLR), early alpha-fetoprotein (AFP) response, albumin-bilirubin (ALBI), AFP, platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), protein induced by vitamin K absence II (PIVKA-II), and lymphocyte to monocyte ratio (LMR)) in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs). Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by November 24, 2022. Clinical outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and hyperprogressive disease (HPD). A total of 44 articles with 5322 patients were included in this meta-analysis. The pooled results demonstrated that patients with high NLR levels had significantly poorer OS (HR: 1.951, P<0.001) and PFS (HR: 1.632, P<0.001), lower ORR (OR: 0.484, P<0.001) and DCR (OR: 0.494, P=0.027), and higher HPD (OR: 8.190, P<0.001). The patients with high AFP levels had shorter OS (HR: 1.689, P<0.001) and PFS (HR: 1.380, P<0.001), and lower DCR (OR: 0.440, P<0.001) than those with low AFP levels, however, there was no difference in ORR (OR: 0.963, P=0.933). We also found that early AFP response was correlated with better OS (HR: 0.422, P<0.001) and PFS (HR: 0.385, P<0.001), higher ORR (OR: 7.297, P<0.001) and DCR (OR: 13.360, P<0.001) compared to non-responders. Besides, a high ALBI grade was significantly related to shorter OS (HR: 2.440, P=0.009) and PFS (HR: 1.373, P=0.022), lower ORR (OR: 0.618, P=0.032) and DCR (OR: 0.672, P=0.049) than those with an ALBI grade 1. The NLR, early AFP response, and ALBI were useful predictors of outcomes in HCC patients treated with ICIs.

Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee.

Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. Thirty-six eligible patients enrolled on study. The median age at enrollment was 27months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648ng/mL and the median AFP following two VIT cycles was 19,262ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). VIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.

AFP Response to Locoregional Therapy Can Stratify the Risk of Tumor Recurrence in HCC Patients after Living Donor Liver Transplantation

(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.

Association between early response of alpha-fetoprotein and treatment efficacy of systemic therapy for advanced hepatocellular carcinoma: A multicenter cohort study from China.

Alpha-fetoprotein (AFP) is a well-identified biomarker in hepatocellular carcinoma (HCC). However, only limited AFP-related studies have evaluated its early response to systemic therapy. This study was performed with the aim of assessing the value of early AFP response in predicting overall survival (OS) and progression-free survival (PFS) in advanced HCC patients receiving systemic therapy. This cohort study included HCC patients with baseline AFP ≥ 200 ng/ml and no prior treatment history. A > 20% decline in the serum AFP level from baseline to the first follow-up (i.e., 4~6 weeks after treatment) was defined as an early AFP response. Patient demographic information, clinical characteristics, radiological response, and survival rates were compared between patients with early AFP response and patients without early AFP response. We further utilized multivariate Cox regression to seek characteristics related to OS and PFS. Among 154 patients, 69 patients (44.8%) showed an early AFP response. The disease control rate (76.8 vs. 54.1%; P = 0.003) and objective response rate (38.4 vs. 11.8%; P = 0.001) were significantly higher in patients with an early AFP response. By performing multivariate analysis, early AFP response remained a prognostic factor for longer PFS (HR 0.546; 95% CI 0.371-0.804; P = 0.002) and longer OS (HR 0.529; 95% CI 0.335-0.834; P = 0.006). An early AFP response is correlated with longer overall survival and progression-free survival for advanced HCC patients receiving systemic therapy. Moreover, an early AFP response is an independent prognostic factor for longer OS and PFS.

The prognostic role of early tumor shrinkage in patients with hepatocellular carcinoma undergoing immunotherapy

BackgroundEarly tumor shrinkage (ETS) has been identified as a promising imaging biomarker for patients undergoing immunotherapy for several cancer entities. This study aimed to validate the potential of ETS as an imaging biomarker for patients undergoing immunotherapy for hepatocellular carcinoma (HCC).MethodsWe screened all patients with HCC that received immunotherapy as the first or subsequent line of treatment at our tertiary care center between 2016 and 2021. ETS was defined as the reduction in the sum of the sizes of target lesions, between the initial imaging and the first follow-up. The ETS was compared to the radiologic response, according to the modified response evaluation criteria in solid tumors (mRECIST). Furthermore, we evaluated the influence of ETS on overall survival (OS), progression-free survival (PFS), and the alpha-fetoprotein (AFP) response.ResultsThe final analysis included 39 patients with available cross-sectional imaging acquired at the initiation of immunotherapy (baseline) and after 8–14 weeks. The median ETS was 5.4%. ETS was significantly correlated with the response according to mRECIST and with the AFP response. Patients with an ETS ≥10% had significantly longer survival times after the first follow-up, compared to patients with < 10% ETS (15.1 months vs. 4.0 months, p = 0.008). Additionally, patients with both an ETS ≥10% and disease control, according to mRECIST, also had significantly prolonged PFS times after the initial follow-up (23.6 months vs. 2.4 months, p < 0.001).ConclusionETS was strongly associated with survival outcomes in patients with HCC undergoing immunotherapy. Thus, ETS is a readily assessable imaging biomarker that showed potential for facilitating a timely identification of patients with HCC that might benefit from immunotherapy.