Principal Investigator

Anna S.F.
Lok
Awardee Organization

University Of Michigan At Ann Arbor
United States

Fiscal Year
2022
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

NOVEL STRATEGIES TO IMPROVE LIVER CANCER SURVEILLANCE UPTAKE AND EARLY DETECTION

This proposal is submitted in response to RFA-CA-17-025. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and one of the few cancers with increasing incidence in the United States. Survival of patients with HCC is poor because most patients are diagnosed at late stages when treatment options are limited. HCC surveillance can detect cancers early and improve survival but it is inconsistently implemented. Not all liver nodules detected on surveillance imaging are malignant, these indeterminate nodules require follow up imaging to determine if they are HCC. This proposal assembles a team of specialists with complementary expertise in liver diseases, liver cancer, radiology, engineering, statistics, and information technology. The goals are to: (1) Improve HCC surveillance uptake in patients with cirrhosis by leveraging electronic medical records to remind healthcare providers and patients when they are due for screening tests; (2) Leverage analytic morphomics and machine learning to increase the detectability of HCC at an early stage; and (3) Increase detectability of HCC at an early stage using tagged HCC-specific peptides. We have worked closely together for many years and have participated/led many NIH funded clinical research networks. We have expertise and experience to carry out the proposed studies and will collaborate with other centers in the Liver Center Network to validate the methods/models we develop. We will also enroll patients with cirrhosis and collect data and specimens and provide access to existing well characterized data and specimen repositories that include both prevalent and incident HCC for Trans-Network studies. We are confident we will be able to contribute to this Liver Cancer Network and to early detection of HCC in multiple ways.

Publications

  • Benhammou JN, Rich NE, Cholankeril G, Zhang P, Zeng W, Rao S, Tayob N, National Cancer Institute’s Translational Liver Consortium Early-Career Working Group, Li W, Wu X, Feng S, Fujiwara N, Meng X, Zhu S, Zaidi S. DETECT: Development of Technologies for Early HCC Detection. Gastroenterology. 2022 Jul;163(1):21-27. Epub 2022 Mar 23. PMID: 35339460
  • Parikh ND, Tayob N, Singal AG. Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era? Journal of hepatology. 2023 Jan;78(1):207-216. Epub 2022 Sep 8. PMID: 36089157
  • Yokoo T, Masaki N, Parikh ND, Lane BF, Feng Z, Mendiratta-Lala M, Lee CH, Khatri G, Marsh TL, Shetty K, Dunn CT, Al-Jarrah T, Aslam A, Davenport MS, Gopal P, Rich NE, Lok AS, Singal AG. Multicenter Validation of Abbreviated MRI for Detecting Early-Stage Hepatocellular Carcinoma. Radiology. 2023 Apr;307(2):e220917. Epub 2023 Jan 24. PMID: 36692401
  • Singal AG, Tayob N, Mehta A, Marrero JA, El-Serag H, Jin Q, Saenz de Viteri C, Fobar A, Parikh ND. GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis. Hepatology (Baltimore, Md.). 2022 Mar;75(3):541-549. Epub 2021 Dec 17. PMID: 34618932
  • Tayob N, Lok ASF, Feng Z. A multivariate parametric empirical Bayes screening approach for early detection of hepatocellular carcinoma using multiple longitudinal biomarkers. Statistics in medicine. 2022 Jun 15;41(13):2338-2353. Epub 2022 Feb 23. PMID: 35199349
  • Singal AG, Lok AS, Feng Z, Kanwal F, Parikh ND. Conceptual Model for the Hepatocellular Carcinoma Screening Continuum: Current Status and Research Agenda. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Jan;20(1):9-18. Epub 2020 Sep 19. PMID: 32961340
  • Singal AG, Hoshida Y, Pinato DJ, Marrero J, Nault JC, Paradis V, Tayob N, Sherman M, Lim YS, Feng Z, Lok AS, Rinaudo JA, Srivastava S, Llovet JM, Villanueva A. International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma. Gastroenterology. 2021 Jun;160(7):2572-2584. Epub 2021 Mar 9. PMID: 33705745
  • Wang M, Singal AG, Parikh N, Kono Y, Marrero J, Mehta A. A Biomarker Panel Based upon AFP, Fucosylated Kininogen and PEG-Precipitated IgG Is Highly Accurate for the Early Detection Hepatocellular Carcinoma in Patients with Cirrhosis in Phase II and Phase III Biomarker Evaluation. Cancers. 2022 Dec 2;14. (23). PMID: 36497452
  • Fujiwara N, Fobar AJ, Raman I, Li QZ, Marrero JA, Parikh ND, Singal AG, Hoshida Y. A Blood-Based Prognostic Liver Secretome Signature Predicts Long-term Risk of Hepatic Decompensation in Cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 May;20(5):e1188-e1191. Epub 2021 Mar 13. PMID: 33727162
  • Singal AG, Zhang E, Narasimman M, Rich NE, Waljee AK, Hoshida Y, Yang JD, Reig M, Cabibbo G, Nahon P, Parikh ND, Marrero JA. HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis. Journal of hepatology. 2022 Jul;77(1):128-139. Epub 2022 Feb 6. PMID: 35139400
  • Singal AG, Parikh ND, Shetty K, Han SH, Xie C, Ning J, Rinaudo JA, Arvind A, Lok AS, Kanwal F, Translational Liver Cancer Investigators. Natural History of Indeterminate Liver Nodules in Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study. The American journal of gastroenterology. 2024 Nov 1;119(11):2251-2258. Epub 2024 Apr 30. PMID: 38686922
  • Fujiwara N, Kobayashi M, Fobar AJ, Hoshida A, Marquez CA, Koneru B, Panda G, Taguri M, Qian T, Raman I, Li QZ, Hoshida H, Sezaki H, Kumada H, Tateishi R, Yokoo T, Yopp AC, Chung RT, Fuchs BC, Baumert TF, Marrero JA, Parikh ND, Zhu S, Singal AG, Hoshida Y. A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis. Med (New York, N.Y.). 2021 Jul 9;2(7):836-850.e10. Epub 2021 Apr 21. PMID: 34318286
  • Tan Y, Zhu J, Gutierrez Reyes CD, Lin Y, Tan Z, Wu Z, Zhang J, Cano A, Verschleisser S, Mechref Y, Singal AG, Parikh ND, Lubman DM. Discovery of Core-Fucosylated Glycopeptides as Diagnostic Biomarkers for Early HCC in Patients with NASH Cirrhosis Using LC-HCD-PRM-MS/MS. ACS omega. 2023 Mar 21;8(13):12467-12480. doi: 10.1021/acsomega.3c00519. eCollection 2023 Apr 4. PMID: 37033807
  • McMahon B, Cohen C, Brown RS Jr, El-Serag H, Ioannou GN, Lok AS, Roberts LR, Singal AG, Block T. Opportunities to address gaps in early detection and improve outcomes of liver cancer. JNCI cancer spectrum. 2023 May 2;7. (3). PMID: 37144952