Refining prognosis in patients with hepatocellular carcinoma through incorporation of metabolic imaging biomarkers

Takeuchi, Satoshi; Rohren, Eric M.; Abdel-Wahab, Reham; Xiao, Lianchun; Morris, Jeffrey S.; Macapinlac, Homer A.; Hassan, Manal M.; Kaseb, Ahmed O.

doi:10.1007/s00259-016-3583-2

Cited by 10 publications

(6 citation statements)

References 27 publications

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“…A non-invasive method is required to provide standardized patient selection to ensure their suitability for LT. Previous studies demonstrated that 18 F FDG PET/CT is a powerful prognostic marker for patients with HCC following LT, and it was found to be strongly correlated with pathological characteristics of tumors, such as microvascular invasion No 3 0 3 Yes 87 29 58 NA 3 1 2 and differentiation (12,26,27). In addition to FDG, other PET radioactive tracers, such as labeled choline and acetate, are frequently used in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Predicting tumor recurrence using metabolic indices of 18F‑FDG PET/CT prior to orthotopic liver transplantationfor hepatocellular carcinoma

Ding

Wei

et al. 2020

Oncol Lett

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The present study analyzed the ability of metabolic burden indices from 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) to predict tumor recurrence following orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). Seven major metabolic indices were measured by 18 F-FDG PET/CT in 93 patients with HCC, prior to OLT. The Mann-Whitney U test was then used to predict the association of metabolic indices, including the maximum standardized uptake value (SUVmax), tumor-to-mediastinum SUV ratio, tumor-to-normal-liver SUV ratio, SUV normalized to lean body mass metabolic tumor volume (MTV), total lesion glycolysis (TLG) and uptake-volume product (UVP), with the recurrence risk. The Deauville-like scoring system was used to quantify the recurrence risk. Univariate and multivariable Cox regression models were performed to determine survival rate. The results showed that Deauville-like score (PET-negative vs.-positive), MTV (cutoff value, 13.36), TLG (cutoff value, 62.21) and UVP (cutoff value, 66.60) had high prediction performance for tumor recurrence (P<0.05). TLG had the highest receiver operating characteristics area under the curve of 0.725. Among the clinical factors, high level of α-fetoprotein (AFP, ≥144 ng/ml), Milan criteria, tumor number (>3), involvement of both right and left lobes, and tumor size (>5 cm) were found to be significant predictors of tumor recurrence. Patients in the low metabolic group had longer recurrence-free survival (RFS) times compared with those in the high metabolic group, regardless of whether they met the Milan criteria or not. AFP, uptake-volume product according the SUV mean of mediastinum (UVP-M), Milan criteria, lymph node metastasis, and the number of tumors were significant prognostic factors for RFS (P<0.05) in both univariate and multivariate survival analyses. Additionally, the MVI was a significant prognostic factor based on univariate survival analyses. Overall, the present study demonstrated the metabolic burden indices measured by PET/CT, Deauville-like score, MTV, TLG and UVP as significant prognostic factors in patients with HCC following OLT. The combination of metabolic indices measured by PET/CT and the existing criteria, such as the Milan criteria, may play an important role in evaluating the suitability of OLT in specific patients.

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Section: Discussionmentioning

confidence: 99%

Predicting tumor recurrence using metabolic indices of 18F‑FDG PET/CT prior to orthotopic liver transplantationfor hepatocellular carcinoma

Ding

Wei

et al. 2020

Oncol Lett

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“…With regards to energy metabolism, cancers can also turn to aerobic glycolysis (ie. the Warburg phenomenon), which can potentially be monitored by FDG PET/CT(39). In contrast to the favorable association between tumor FCh uptake and survival, tumor FDG uptake has been associated with a worse prognosis in HCC(39).…”

Section: Discussionmentioning

confidence: 99%

“…the Warburg phenomenon), which can potentially be monitored by FDG PET/CT(39). In contrast to the favorable association between tumor FCh uptake and survival, tumor FDG uptake has been associated with a worse prognosis in HCC(39). Although FDG uptake was not investigated in the present study, previous diagnostic trials comparing FDG PET/CT and FCh PET/CT for HCC revealed discordance between these tracers (ie.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics Associates Molecular Features with 18F-Fluorocholine PET/CT Imaging Phenotype and Its Potential Relationship to Survival in Hepatocellular Carcinoma

et al. 2019

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Studies involving transcriptomics have revealed multiple molecular subtypes of hepatocellular carcinoma (HCC). PET/CT has also identified distinct molecular imaging subtypes, including those with increased and decreased choline metabolism as measured by tissue uptake of the radiopharmaceutical 18F-fluorocholine. Gene signatures reflecting the molecular heterogeneity of HCC may identify the biological and clinical significance of these imaging subtypes. In this study, 41 patients underwent 18F-fluorocholine PET/CT followed by tumor resection and gene expression profiling. Over- and under-expressed components of previously published gene signatures were evaluated for enrichment between tumors with high and low 18F-fluorocholine uptake using gene set analysis. Significant gene sets were enumerated by false discovery rate (FDR) based on phenotype permutation. Associations with overall survival were analyzed by univariate and multivariate proportional hazards regression. Ten gene sets related to HCC were significantly associated with high tumor 18F-fluorocholine uptake at FDR q < 0.05, including those from 3 different clinical molecular classification systems and 2 prognostic signatures for HCC that showed predictive value in the study cohort. Tumor avidity for 18F-fluorocholine was associated with favorable characteristics based on these signatures, with lower mortality based on survival analysis (hazard ratio 0.36, 95% confidence interval 0.14 to 0.95). Tumors demonstrating high 18F-fluorocholine uptake were also enriched for genes involved in oxidative phosphorylation, fatty acid metabolism, peroxisome, bile acid metabolism, xenobiotic metabolism, and adipogenesis. These results provide a pathobiological framework to further evaluate 18F-fluorocholine PET/CT as a molecular and prognostic classifier in HCC.

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“…They can quantify tumor metabolic process for further analysis ( 5 , 19 ). Standardized uptake values (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG) are sensitive prognosis biomarkers for cancer documented in the literature ( 20–22 ). By the development of modern technologies, a large number of metabolic biomarkers in different tumors are measured and reported with potential applications in cancer diagnosis, treatment and prognosis ( 23 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

CMBD: a manually curated cancer metabolic biomarker knowledge database

et al. 2021

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The pathogenesis of cancer is influenced by interactions among genes, proteins, metabolites and other small molecules. Understanding cancer progression at the metabolic level is propitious to the visual decoding of changes in living organisms. To date, a large number of metabolic biomarkers in cancer have been measured and reported, which provide an alternative method for cancer precision diagnosis, treatment and prognosis. To systematically understand the heterogeneity of cancers, we developed the database CMBD to integrate the cancer metabolic biomarkers scattered over literatures in PubMed. At present, CMBD contains 438 manually curated relationships between 282 biomarkers and 76 cancer subtypes of 18 tissues reported in 248 literatures. Users can access the comprehensive metabolic biomarker information about cancers, references, clinical samples and their relationships from our online database. As case studies, pathway analysis was performed on the metabolic biomarkers of breast and prostate cancers, respectively. ‘Phenylalanine, tyrosine and tryptophan biosynthesis’, ‘phenylalanine metabolism’ and ‘primary bile acid biosynthesis’ were identified as playing key roles in breast cancer. ‘Glyoxylate and dicarboxylate metabolism’, ‘citrate cycle (TCA cycle)’, and ‘alanine, aspartate and glutamate metabolism’ have important functions in prostate cancer. These findings provide us with an understanding of the metabolic pathway of cancer initiation and progression. Database URL: http://www.sysbio.org.cn/CMBD/

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Refining prognosis in patients with hepatocellular carcinoma through incorporation of metabolic imaging biomarkers

Cited by 10 publications

References 27 publications

Predicting tumor recurrence using metabolic indices of 18F‑FDG PET/CT prior to orthotopic liver transplantationfor hepatocellular carcinoma

Predicting tumor recurrence using metabolic indices of 18F‑FDG PET/CT prior to orthotopic liver transplantationfor hepatocellular carcinoma

Transcriptomics Associates Molecular Features with 18F-Fluorocholine PET/CT Imaging Phenotype and Its Potential Relationship to Survival in Hepatocellular Carcinoma

CMBD: a manually curated cancer metabolic biomarker knowledge database

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