NLCECA score: a serum inflammatory-tumor biomarker score to predict survival of advanced perihilar cholangiocarcinoma after hepatic arterial infusion chemotherapy
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ABSTRACT:
SUBMITTER: Fu S
PROVIDER: S-EPMC10891088 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Cholangiocarcinoma (CCA) is the second most common primitive liver cancer. Despite recent advances in the surgical management, the prognosis remains poor, with a 5-year survival rate of less than 5%. Intrahepatic CCA (iCCA) has a median survival between 18 and 30 months, but if deemed unresectable it decreases to 6 months. Most patients have a liver-confined disease that is considered unresectable because of its localization, with infiltration of vascular structures or multifocality. The peculiar dual blood supply allows the delivery of high doses of chemotherapy via a surgically implanted subcutaneous pump, through the predominant arterial tumor vascularization, achieving much higher and more selective tumor drug levels than systemic administration. The results of the latest studies suggest that adequate and early treatment with the combination approach of hepatic arterial infusion (HAI) and systemic (SYS) chemotherapy is associated with improved progression-free and overall survival than SYS or HAI alone for the treatment of unresectable iCCA. Current recommendations are limited by a lack of prospective trials. Individualization of chemotherapy and regimens based on selective targets in mutant iCCA are a focus for future research. In this paper we present a comprehensive review of the studies published to date and ongoing trials.
| S-EPMC8228250 | biostudies-literature
Project description:Despite the availability of molecularly targeted agents for advanced hepatocellular carcinoma (aHCC), these are limited to compensated cirrhotic patients, and concerns about decreased hepatic functional reserve (HFR) and unknown adverse events, which may affect long-term survival, remain unaddressed. In this study, we enrolled 96 aHCC patients treated with bimonthly hepatic arterial infusion chemotherapy (B-HAIC) with cisplatin or sorafenib monotherapy (oral sorafenib 400 mg twice daily) not only to demonstrate its efficacy and significance but also to indicate preferable candidates by setting a response-related biomarker. Differences in treatment had no significant effect on overall survival (OS). The response rate in patients treated with B-HAIC was relatively higher than those treated with sorafenib. HFR was well maintained over the treatment course with B-HAIC, while it was significantly impaired with sorafenib. By employing multivariate analysis, we found negative trends between progression-free survival (PFS) periods and serum levels of alpha fetoprotein as well as des-gamma-carboxy prothrombin (DCP). In addition, a logistic regression analysis of the relationship between serum DCP levels and PFS periods over 420 days (14 months) showed that the PFS periods of patients with higher DCP was significantly shorter than those of patients with lower DCP (p = 0.02). Subsequently, the present study demonstrated the efficacy and safety of B-HAIC and identified a predictor of unpreferable patients. Based on these results, B-HAIC might be an alternative treatment after the implementation of new molecularly targeted therapies.
| S-EPMC7914951 | biostudies-literature
Project description:BackgroundIntrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA.MethodsLocally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration.ResultsBetween May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumor tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination.ConclusionFOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.
| S-EPMC10880187 | biostudies-literature
Project description:BackgroundA post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA.MethodsWe retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center.ResultsIn total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p < 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0-13.6%) in the gem-cis group versus 34.3% (95% CI 28.1-41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19-0.39).ConclusionsThis study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.
| S-EPMC10695893 | biostudies-literature
Project description:BackgroundPatients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA.Patients and methodsA literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures.ResultsAfter removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0-39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively.ConclusionHAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials.
| S-EPMC9356931 | biostudies-literature
Project description:BACKGROUND:Hepatic arterial infusion chemotherapy (HAIC) is frequently used to treat advanced hepatocellular carcinoma (HCC) in Asian countries. However, there is a lack of evidence supporting the use of HAIC. SUMMARY:Many studies report high response rates in patients with advanced HCC receiving HAIC, and clinical responses translate to survival benefits. Therefore, prediction of an antitumor response is important in selecting appropriate treatments. There are no proven post-sorafenib therapeutic measures or procedures for HCC patients with poor liver function, and HAIC is one of the few options for patients in these situations. Despite studies showing its effectiveness, the use of HAIC for treatment of advanced HCC is unclear because convincing data from large-scale randomized clinical trials are lacking. For HAIC to become a standard treatment for HCC, such trials must establish its efficacy compared with other HCC therapies; prediction of antitumor response in HAIC may aid trial design, and a multi-center, open-labelled, randomized clinical trial of HAIC in advanced HCC is currently in progress. Optimization of HCC treatment protocols and regimens is also required. KEY MESSAGE:We think that both HAIC and sorafenib are effective treatments for advanced HCC, and this review presents evidence supporting this contention.
| S-EPMC4608627 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA. Locally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration. Between May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumour tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination. FOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.
2024-02-06 | GSE255058 | GEO
Project description:Background: Systemic chemotherapy (SC) remains the only first-line treatment for unresectable intrahepatic cholangiocarcinoma (iCCA). Hepatic arterial infusion chemotherapy (HAIC) has been recently proven to be effective in managing hepatocellular carcinoma (HCC). Hence, our study aims to investigate the safety and efficacy of HAIC in treating unresectable iCCA patients. Methods: We reviewed 146 patients with unresectable iCCA who had received HAIC or SC between March 2016 and March 2022 in a retrospective manner. Outcomes of patients and safety were compared between the HAIC and SC groups. Results: There were 75 and 71 patients in the HAIC and SC groups, respectively. The median OS in the HAIC and SC groups was 18.0 and 17.8 months (p = 0.84), respectively. The median PFS in the HAIC and SC groups was 10.8 and 11.4 months (p = 0.59), respectively. However, the HAIC group had significantly longer intrahepatic progression-free survival (IPFS) than the SC group (p = 0.035). The median IPFS in the HAIC and SC groups was 13.7 and 11.4 months, respectively. According to the OS (p = 0.047) and PFS (p = 0.009), single-tumor patients in the HAIC group appeared to benefit more. In addition, the overall incidence of adverse events (AEs) was lower in the HAIC group than that in the SC group. Conclusion: Our study revealed that HAIC was a safe and effective therapeutic regimen for unresectable iCCA with better intrahepatic tumor control when compared to SC. Meanwhile, patients with single tumor were more likely to benefit from HAIC than SC.
| S-EPMC10508288 | biostudies-literature
Project description:Background & aimsHepatic arterial infusion chemotherapy (HAIC) is an option for treating advanced hepatocellular carcinoma (HCC). Because of the poor prognosis in HAIC non-responders, it is important to identify patients who may benefit from continuous HAIC treatment; however, there are currently no therapeutic assessment scores for this identification. Therefore, we aimed to establish a new therapeutic assessment score for such patients.MethodsWe retrospectively analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP) and/or des-gamma-carboxy prothrombin (DCP) levels and analyzed various parameters for their possible use as predictors of response and survival. AFP and DCP responses were assessed after half a course of HAIC (2 weeks); a positive-response was defined as a reduction of ≥ 20% from baseline.ResultsMultivariate analysis identified DCP response (odds ratio 16.03, p < 0.001) as an independent predictor of treatment response. In multivariate analysis, Child-Pugh class A (hazard ratio [HR] 1.99, p = 0.018), AFP response (HR 2.17, p = 0.007), and DCP response (HR 1.90, p = 0.030) were independent prognostic predictors. We developed an Assessment for Continuous Treatment with HAIC (ACTH) score, including the above 3 factors, which ranged from 0 to 3. Patients stratified into two groups according to this score showed significantly different prognoses (≤ 1 vs. ≥ 2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003).ConclusionsThe ACTH score may be useful in the therapeutic assessment of HCC patients receiving HAIC.
| S-EPMC4439162 | biostudies-literature
Project description:AimsTo compare the effectiveness, safety, and survival outcomes in patients with infiltrative hepatocellular carcinoma (HCC) who underwent hepatic arterial infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE).MethodsA total of 160 patients with infiltrative HCCs who underwent initial TACE (n = 68) and HAIC (n = 92) treatment from January 2016 to March 2020. We applied the propensity score matching (PSM) to adjust for potential imbalances. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were compared between two groups. Multivariate analysis was evaluated through the forward stepwise Cox regression model and β coefficients was applied for the nomogram construction.ResultsThe median follow-up duration for the study population was 20.8 months. After PSM, the median OS and PFS in the HAIC group were significantly higher than those in the TACE group (OS, 13.3 vs 10.8 months; p = 0.043; PFS, 7.8 vs 4.0 months; p = 0.035) and the ORR and DCR in the HAIC group were significantly higher than those in the TACE group (ORR, 34.8% vs 11.8%; p = 0.001; DCR, 54.3% vs 36.8%; p = 0.028). A nomogram model comprising albumin-bilirubin grade, treatment responses, sessions, and treatment modalities, showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.789; validation set, C-index of 0.757), which outperformed other staging systems and conventional indices.ConclusionHAIC improve significantly survival compared to TACE in patients with infiltrative HCC. A prospective randomized trial is ongoing to confirm this finding.
| S-EPMC8716800 | biostudies-literature