Dataset Information

Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC.

ABSTRACT:

Background and aims

Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for large hepatocellular carcinoma (HCC). However, post-HAIC prognosis can vary in different patients due to tumor heterogeneity. Herein, we established two nomogram models to assess the survival prognosis of patients after HAIC combination therapy.

Methods

A total of 1082 HCC patients who underwent initial HAIC were enrolled between February 2014 and December 2021. We built two nomogram models for survival prediction: the preoperative nomogram (pre-HAICN) using preoperative clinical data and the postoperative nomogram (post-HAICN) based on pre-HAICN and combination therapy. The two nomogram models were internally validated in one hospital and externally validated in four hospitals. A multivariate Cox proportional hazards model was used to identify risk factors for overall survival (OS). The performance outcomes of all models were compared by area under the receiver operating characteristic curve (AUC) analysis with the DeLong test.

Results

Multivariable analysis identified larger tumor size, vascular invasion, metastasis, high albumin-bilirubin grade, and high alpha-fetoprotein as indicators for poor prognosis. With these variables, the pre-HAICN provided three risk strata for OS in the training cohort: low risk (5-year OS, 44.9%), middle risk (5-year OS, 20.6%), and high risk (5-year OS, 4.9%). The discrimination of the three strata was improved significantly in the post-HAICN, which included the above-mentioned factors and number of sessions, combination with immune checkpoint inhibitors, tyrosine kinase inhibitors, and local therapy (AUC, 0.802 versus 0.811, p < 0.001).

Conclusions

The nomogram models are essential to identify patients with large HCC suitable for treatment with HAIC combination therapy and may potentially benefit personalized decision-making.

Lay summary

Hepatic arterial infusion chemotherapy (HAIC) provides sustained higher concentrations of chemotherapy agents in large hepatocellular carcinoma (HCC) by hepatic intra-arterial, result in better objective response outperformed the intravenous administration. HAIC is significantly correlated with favorable survival outcome and obtains extensive support in the effective and safe treatment of intermediate advanced-stage HCC. In view of the high heterogeneity of HCC, there is no consensus regarding the optimal tool for risk stratification before HAIC alone or HAIC combined with tyrosine kinase inhibitors or immune checkpoint inhibitors treatment in HCC. In this large collaboration, we established two nomogram models to estimate the prognosis and evaluate the survival benefits with different HAIC combination therapy. It could help physicians in decision-making before HAIC and comprehensive treatment for large HCC patients in clinical practice and future trials.

SUBMITTER: Yao W

PROVIDER: S-EPMC10126656 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC.

Yao Wang W Wei Ran R Jia Jia J Li Wang W Zuo Mengxuan M Zhuo Shuqing S Shi Ge G Wu Peihong P An Chao C

Therapeutic advances in medical oncology 20230417

<h4>Background and aims</h4>Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for large hepatocellular carcinoma (HCC). However, post-HAIC prognosis can vary in different patients due to tumor heterogeneity. Herein, we established two nomogram models to assess the survival prognosis of patients after HAIC combination therapy.<h4>Methods</h4>A total of 1082 HCC patients who underwent initial HAIC were enroll ...[more]

PMID: 37113732

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Project description:Background and aimThe prediction models of postoperative survival for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) have not been well established. The study objective was the development of nomograms to predict disease recurrence and overall survival (OS) in these patients.MethodsData were obtained from 1046 HBV-related MVI-positive HCC patients who had undergone curative resection from January 2014 to December 2017. The study was approved by the Eastern Hepatobiliary Surgery Hospital and Jinling Hospital ethics committee, and patients provided informed consent for the use of their data. Nomograms for recurrence and OS were created by Cox regression model in the training cohort (n=530). The modes were verified in an internal validation cohort (n= 265) and an external validation cohort (n= 251).ResultsThe nomograms of recurrence and OS based on preoperative serological indicators (HBV-DNA, neutrophil-lymphocyte ratio, a-fetoprotein), tumor clinicopathologic features (diameter, number), surgical margin and postoperative adjuvant TACE achieved high C-indexes of 0.722 (95% confidence interval [CI], 0.711-0.732) and 0.759 (95% CI, 0.747-0.771) in the training cohort, respectively, which were significantly higher than conventional HCC staging systems (BCLC, CNLC, HKLC).The nomograms were validated in the internal validation cohort (0.747 for recurrence, 0.758 for OS) and external validation cohort(0.719 for recurrence, 0.714 for OS) had well-fitted calibration curves. Our nomograms accurately stratified patients with HBV-HCC with MVI into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. Prediction models for recurrence-free survival (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-RFS/) and OS (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-OS/) were constructed.ConclusionsThe two nomograms showed good predictive performance and accurately distinguished different recurrence and OS by the nomograms scores for HBV-HCC patients with MVI after resection.

Project description:BACKGROUND:CpG island methylator phenotype (CIMP), a common biological phenomenon characterized by a subset of concurrently methylated genes, can have an influence on the progression of multiple cancers. However, the potential mechanism of CIMP in hepatocarcinogenesis and its clinical relevance remains only partially understood. METHODS:We used a methylation array from the cancer genome atlas (TCGA) to stratify HCC patients into different CIMP subtypes, and evaluated their correlation with clinical characteristics. In addition, mutation, CNV, and transcriptome profiles were also utilized to evaluate the distinctive genomic patterns correlated with CIMP. Finally, a CIMP-associated prognostic model (CPM) was trained and validated using four independent datasets. FINDINGS:A subgroup of patients was identified as having CIMP-H, which was associated with worse OS and DFS. Gene enrichment analysis indicated that the terms "liver cancer with EPCAM up", "tumor invasiveness up", "methyltransferase complex", and "translational initiation" were enriched in CIMP-H subgroup. Notably, somatic mutation analysis indicated that CIMP-H patients presented with a higher mutation burden of BRD4, DDIAS and NOX1. Moreover, four CPM associated genes could significantly categorize patients into low- and high-risk groups in the training dataset and another 3 independent validation datasets. Finally, a nomogram incorporating a classifier based on four mRNAs, pathological M stage and CIMP status was established, which showed a favorable discriminating ability and might contribute to clinical decision-making for HCC. INTERPRETATION:Our work highlights the potential clinical application value of CPM in predicting the overall survival of HCC patients and the mechanisms underlying the role of CIMP in hepatocarcinogenesis. FUND: This work was supported by the State Key Project on Infectious Diseases of China (2018ZX10723204-003), the National Nature Science Foundation of China (Nos. 81874065, 81500565, 81874149, 81572427, and 81401997), the Hepato-Biliary-Pancreatic Malignant Tumor Investigation Fund of Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province (CXPJJH11800001-2018356).

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Project description:Introduction: Reliable biomarkers are in need to predict the prognosis of hepatocellular carcinoma (HCC). Whilst recent evidence has established the critical role of copper homeostasis in tumor growth and progression, no previous studies have dealt with the copper-related genes (CRGs) signature with prognostic potential in HCC. Methods: To develop and validate a CRGs prognostic signature for HCC, we retrospectively included 353 and 142 patients as the development and validation cohort, respectively. Copper-related Prognostic Signature (Copper-PSHC) was developed using differentially expressed CRGs with prognostic value. The hazard ratio (HR) and the area under the time-dependent receiver operating characteristic curve (AUC) during 3-year follow-up were utilized to evaluate the performance. Additionally, the Copper-PSHC was combined with age, sex, and cancer stage to construct a Copper-clinical-related Prognostic Signature (Copper-CPSHC), by multivariate Cox regression. We further explored the underlying mechanism of Copper-PSHC by analyzing the somatic mutation, functional enrichment, and tumor microenvironment. Potential drugs for the high-risk group were screened. Results: The Copper-PSHC was constructed with nine CRGs. Patients in the high-risk group demonstrated a significantly reduced overall survival (OS) (adjusted HR, 2.65 [95% CI, 1.83-3.84] and 3.30, [95% CI, 1.27-8.60] in the development and validation cohort, respectively). The Copper-PSHC achieved a 3-year AUC of 0.74 [95% CI, 0.67-0.82] and 0.71 [95% CI, 0.56-0.86] for OS in the development and validation cohort, respectively. Copper-CPSHC yield a 3-year AUC of 0.73 [95% CI, 0.66-0.80] and 0.72 [95% CI, 0.56-0.87] for OS in the development and validation cohort, respectively. Higher tumor mutation burden, downregulated metabolic processes, hypoxia status and infiltrated stroma cells were found for the high-risk group. Six small molecular drugs were screened for the treatment of the high-risk group. Conclusion: Copper-PSHC services as a promising tool to identify HCC with poor prognosis and to improve disease outcomes by providing potential clinical decision support in treatment.

Dataset Information

Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC.

Background and aims

Methods

Results

Conclusions

Lay summary

Publications

Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC.

Similar Datasets

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