Abstract
Inter-lesional heterogeneity indices on FDG PET/CT correlate with ctDNA oncogenic pathway activation in progressive colorectal cancer
The Journal of nuclear medicine (1978), Vol.66(Suppl 1), 251833
06/01/2025
Abstract
Introduction: Increased intra-lesional heterogeneity is shown to be correlated with increased tumor aggressiveness and drug resistance. Oncogenic pathway activation is a process where the altered proto-oncogenes lead to the advantageous growth of cancer cells and thus cancer progression. We hypothesize increased inter-lesional heterogeneity as investigated on FDG PET/CT can indicate oncogenic pathway activation in poly-metastatic progressive colorectal cancer patients (selected as an exploratory clinical model). Methods: Fifteen metastatic and recently progressed colorectal cancer patients were evaluated using whole-body FDG PET/CT (Biograph Vision, Siemens Healthineers) and simultaneous whole exome sequencing of ctDNA at the start of new line of therapy. All metastatic lesions were segmented using gradient technique (PET edge, MIM Software), and intra-lesional heterogeneity indices were summarized across the body to using previously published method (EJNMMI Rep. 2024 Nov 30;8(1):39). We investigated correlations between cancer pathway-level mutational patterns and quantitative PET imaging features by developing a computational pipeline in the RStudio environment using a combination of 'tidyverse' and base R (version 4.3.2) packages that summarizes multiple regions of interest per patient and calculates correlations between binary mutation status and key imaging measurements. Heatmaps were prepared with 'ggplot2'." Results: Several indices of inter-lesional heterogeneity summarized across all lesions in the body were significantly correlated with oncogenic pathway activation (p-value <0.05 in all cases; however, correction of the p-values for multiple testing indicated the need for a larger sample size). Correlations pairs and r-values include: (MYC, Max Total SUV & Max TLG, r=0.6); (Cell cycle, Max Total SUV & Max TLG, r=0.6); (TP53, NOTCH, RTK-RAS, PI13K, Cell-Cycle with Mean SUV max, r=0.6-0.7); (TP53, PI3K, Cell-cycle with Mean SUV Mean, r=0.6-0.8), (Cell-cycle, Mean SUV Min, r=0.7); (WNT, TP53, NOTCH, RTK-RAS, TGF-Beta, PI3K with Mean Standard Deviation SUV, r=0.6-0.7); (MYC, Max Total SUV & Max TLG, r=0.6); (Cell cycle, Max Total SUV & Max TLG, r=0.6), (TP53, NOTCH, RTK-RAS, PI13K, Cell-Cycle with Mean SUV max, r=0.6-0.7); (TP53, PI3K, Cell-cycle with Mean SUV Mean, r=0.6-0.8); (Cell-cycle, Mean SUV Min, r=0.7); (WNT, TP53, NOTCH, RTK-RAS, TGF-Beta, PI3K with Mean Standard Deviation of SUV, r=0.6-0.7). Conclusions: Inter-lesional heterogeneity on FDG PET/CT appears to be associated with activation of oncogenic pathways in these colorectal cancer patients. These findings will be further confirmed in larger cohorts, including transcriptome analysis. Advancements in this area can shed light on the biologic correlates of PET radiomic features and pave the way for multi-omics facilitated precision advanced cancer management.
Details
- Title: Subtitle
- Inter-lesional heterogeneity indices on FDG PET/CT correlate with ctDNA oncogenic pathway activation in progressive colorectal cancer
- Creators
- Ahmad Shariftabrizi - University of IowaSaima Sharif - University of IowaMichael Chimenti - University of IowaArman RahmimNoami Fei - University of IowaFereshteh YousefiriziMichael Graham - University of IowaTobias HeckelSaeed AshrafiniaIsabelle PhilippShazia Naseem - University of IowaJessica Sieren - University of IowaBruce SpottiswoodeAli Kamen
- Resource Type
- Abstract
- Publication Details
- The Journal of nuclear medicine (1978), Vol.66(Suppl 1), 251833
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Publisher
- Society of Nuclear Medicine
- Language
- English
- Date published
- 06/01/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Hematology, Oncology, and Blood & Marrow Transplantation; Radiation Oncology; Internal Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9984927213802771
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