Principal Investigator

Samir M
Hanash
Awardee Organization

University Of Tx Md Anderson Can Ctr
United States

Fiscal Year
2023
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Clinical Validation Center for Lung Cancer Early Detection

The lung cancer early detection CVC has two main goals: Specific Aim 1 is to develop a bloodbased biomarker panel for personalized risk assessment, modeled for its cost effectiveness. To this effect, substantial validation work in phase 3 studies has been done using retrospective longitudinal cohorts to test the performance of a four-marker protein panel (4MP) as a means to determine lung cancer risk and need for CT screening. The goal moving forward is to test the 4MP alone and in combinations with other types of markers in the screening setting, using lung cancer screening cohorts available to the CVC. The resulting marker panel, in combination with subject characteristics, would identify subjects who are currently not eligible based on USPSTF criteria that would benefit from CT screening based on their risk, ultimately leading to a utility trial for which a concept has been presented at a recent EDRN scientific meeting. The utility trial concept also includes as an objective to test the value of biomarkers in informing subjects who are currently eligible but not decided to undergo CT screening, about their risk through a decision sharing process. Specific Aim 2 will test the use of biomarkers and AI for interpretation of CT images and to personalize the screening frequency and duration. Sub Aim 1 is intended to validate the macrovasculature surrounding a nodule (vessel number) previously developed as a biomarker, in an independent screening cohort. Sub Aim 2 is intended to develop a validated integrative computational model for improved early lung cancer detection that includes bloodbased biomarkers, CT features such as emphysema, presence or absence of a nodule, small airways and subject characteristics for interpretation of CT images and to determine screening frequency. The model will be subjected to a cost effectiveness analysis compared to current lung cancer screening guidelines. The CVC represents a multi-institution, multi-investigator effort with expertise in cancer biomarkers and statistics; pulmonology and lung cancer; epidemiology; radiomics, bioinformatics and artificial intelligence; and clinical trial design, simulation modeling and cost-effectiveness analysis. The CVC brings in substantial accomplishments in biomarker discovery and validation related to lung cancer screening and in CT image analysis. In pursuit of its aims, the CVC has access to samples from a multitude of cohorts for validation studies.

Publications

  • Seif El Dahan K, Reczek A, Daher D, Rich NE, Yang JD, Hsiehchen D, Zhu H, Patel MS, Bayona Molano MDP, Sanford N, Gopal P, Parikh ND, Yopp AC, Singal AG. Multidisciplinary care for patients with HCC: a systematic review and meta-analysis. Hepatology communications. 2023 Apr 26;7. (5). doi: 10.1097/HC9.0000000000000143. eCollection 2023 May 1. PMID: 37102768
  • Pu J, Gezer NS, Ren S, Alpaydin AO, Avci ER, Risbano MG, Rivera-Lebron B, Chan SY, Leader JK. Automated detection and segmentation of pulmonary embolisms on computed tomography pulmonary angiography (CTPA) using deep learning but without manual outlining. Medical image analysis. 2023 Oct;89:102882. Epub 2023 Jul 14. PMID: 37482032
  • Gezer NS, Bandos AI, Beeche CA, Leader JK, Dhupar R, Pu J. CT-derived body composition associated with lung cancer recurrence after surgery. Lung cancer (Amsterdam, Netherlands). 2023 May;179:107189. Epub 2023 Apr 8. PMID: 37058786
  • Iyer K, Ren S, Pu L, Mazur S, Zhao X, Dhupar R, Pu J. A Graph-Based Approach to Identify Factors Contributing to Postoperative Lung Cancer Recurrence among Patients with Non-Small-Cell Lung Cancer. Cancers. 2023 Jul 3;15. (13). PMID: 37444581
  • Irajizad E, Fahrmann JF, Marsh T, Vykoukal J, Dennison JB, Long JP, Do KA, Feng Z, Hanash S, Ostrin EJ. Mortality Benefit of a Blood-Based Biomarker Panel for Lung Cancer on the Basis of the Prostate, Lung, Colorectal, and Ovarian Cohort. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Sep 20;41(27):4360-4368. Epub 2023 Jun 28. PMID: 37379494
  • Ren S, Beeche CA, Iyer K, Shi Z, Auster Q, Hawkins JM, Leader JK, Dhupar R, Pu J. Graphical modeling of causal factors associated with the postoperative survival of esophageal cancer subjects. Medical physics. 2024 Mar;51(3):1997-2006. Epub 2023 Jul 31. PMID: 37523254
  • Pu J, Bandos A, Yu T, Wang R, Yuan JM, Herman J, Wilson D. Pulmonary circulatory system characteristics are associated with future lung cancer risk. Medical physics. 2023 Dec 30. Epub 2023 Dec 30. PMID: 38159298