Principal Investigator

Laura
Beretta
Awardee Organization

University Of Tx Md Anderson Can Ctr
United States

Fiscal Year
2024
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Early Detection of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related death in the United States. To address the magnitude of this problem, it is critically important to identify those at high risk for HCC and institute effective surveillance strategies for early diagnosis. Liver cirrhosis is the main risk factor for HCC. Biannual ultrasound and α-fetoprotein remains the surveillance modality most frequently used in patients with cirrhosis, despite very low sensitivity and specificity. Our goals are to identify a blood-based model for risk stratification in patients with cirrhosis, as well as an integrated blood-based and liver imaging model to optimize early HCC detection in high-risk patients. During the first grant period, we developed a multi-center prospective cohort of patients with cirrhosis under contrast MRI surveillance. Such cohort provides a unique opportunity to study blood biomarkers and imaging features on clinical material from patients rigorously classified as having a very early disease in a surveillance setting. Longitudinal collection of paired blood samples and MRIs from these patients is particularly valuable in assessing how early blood markers and imaging features become positive during the period when lesions are observed to obtain a diagnosis of HCC. To date, 912 cirrhotic patients have been enrolled and 2590 paired blood samples and MRIs have been collected. During follow-up, 63 patients developed HCC and 212 patients had detectable lesion(s). In parallel, we have identified in plasma and exosomes, proteins and metabolites for HCC risk prediction and early detection. We also developed quantitative imaging and artificial intelligence (AI)-based methods to analyze imaging scans of patients with liver cancers. We demonstrated how voxel-wise enhancement pattern mapping (EPM) can improve the contrast-to-noise ratio in CT scans. We extended this finding to MRIs for patients with HCC, including patients in our prospective cohort. Differences in EPM signals from prediagnostic MRIs to diagnostic MRIs may improve early detection and lesion characterization. Our AI-based tools complement the EPM algorithm by providing high-throughput tools to process the thousands of MRIs from our patient cohort in an efficient and accurate manner. In this competing renewal, we will extend the existing cohort and further evaluate the performance of these novel blood and liver MRI markers. We will determine longitudinal changes and evaluate their capacity to detect preclinical disease. We will identify the panel of markers that best predict HCC development and that could therefore have utility in risk assessment and early detection of HCC. This proposal achieves in one study two major goals: i) early detection and ii) characterization of tumors when biomarker becomes positive. The impact is multiple: spare patients from unnecessary imaging tests; identify high-risk patients and trigger the decision to perform MRI for surveillance instead of ultrasound; detect lesions at an early stage allowing for curative treatment. Together, these clinical applications would significantly reduce the cost of HCC surveillance and improve survival of HCC patients.

Publications

  • Wahid KA, Cardenas CE, Marquez B, Netherton TJ, Kann BH, Court LE, He R, Naser MA, Moreno AC, Fuller CD, Fuentes D. Evolving Horizons in Radiotherapy Auto-Contouring: Distilling Insights, Embracing Data-Centric Frameworks, and Moving Beyond Geometric Quantification. ArXiv. 2023 Oct 16. PMID: 37904737
  • Khan IM, Gjuka D, Jiao J, Song X, Wang Y, Wang J, Wei P, El-Serag HB, Marrero JA, Beretta L. A Novel Biomarker Panel for the Early Detection and Risk Assessment of Hepatocellular Carcinoma in Patients with Cirrhosis. Cancer prevention research (Philadelphia, Pa.). 2021 Jun;14(6):667-674. Epub 2021 Mar 8. PMID: 33685927
  • Jiao J, Sanchez JI, Saldarriaga OA, Solis LM, Tweardy DJ, Maru DM, Stevenson HL, Beretta L. Spatial molecular and cellular determinants of STAT3 activation in liver fibrosis progression in non-alcoholic fatty liver disease. JHEP reports : innovation in hepatology. 2022 Nov 22;5(2):100628. doi: 10.1016/j.jhepr.2022.100628. eCollection 2023 Feb. PMID: 36687470
  • Jiao J, Niu W, Wang Y, Baggerly K, Ye Y, Wu X, Davenport D, Almeda JL, Betancourt-Garcia MM, Forse RA, Stevenson HL, Watt GP, McCormick JB, Fisher-Hoch SP, Beretta L. Prevalence of Aflatoxin-Associated TP53R249S Mutation in Hepatocellular Carcinoma in Hispanics in South Texas. Cancer prevention research (Philadelphia, Pa.). 2018 Feb;11(2):103-112. Epub 2017 Oct 31. PMID: 29089331
  • Wahid KA, Fuentes D. Weak Supervision, Strong Results: Achieving High Performance in Intracranial Hemorrhage Detection with Fewer Annotation Labels. Radiology. Artificial intelligence. 2024 Jan;6(1):e230598. PMID: 38294326
  • Jiao J, Kwan SY, Sabotta CM, Tanaka H, Veillon L, Warmoes MO, Lorenzi PL, Wang Y, Wei P, Hawk ET, Almeda JL, McCormick JB, Fisher-Hoch SP, Beretta L. Circulating Fatty Acids Associated with Advanced Liver Fibrosis and Hepatocellular Carcinoma in South Texas Hispanics. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Sep;30(9):1643-1651. Epub 2021 Jun 21. PMID: 34155064
  • Sanchez JI, Jiao J, Kwan SY, Veillon L, Warmoes MO, Tan L, Odewole M, Rich NE, Wei P, Lorenzi PL, Singal AG, Beretta L. Lipidomic Profiles of Plasma Exosomes Identify Candidate Biomarkers for Early Detection of Hepatocellular Carcinoma in Patients with Cirrhosis. Cancer prevention research (Philadelphia, Pa.). 2021 Oct;14(10):955-962. Epub 2021 Jul 12. PMID: 34253566
  • Jiao J, Watt GP, Stevenson HL, Calderone TL, Fisher-Hoch SP, Ye Y, Wu X, Vierling JM, Beretta L. Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors. Hepatology communications. 2018 Apr 27;2(6):718-731. doi: 10.1002/hep4.1187. eCollection 2018 Jun. PMID: 29881823

Clinical Trials

Study Name Clinical Trial ID
Contrast Enhanced Ultrasound With Lumason in Detecting Liver Cancer in Participants With Cirrhosis NCT03407001