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University of British Columbia
Lesion volume Estimation from PET without Requiring Segmentation
Francois Benard, M.D.
fbenard@bccrc.ca
Molecular imaging techniques provide valuable information about the presence of specific drug targets on cancer cells, and are useful in cancer clinical trials and clinical practice to provide an early assessment of tumor response to chemotherapy. In clinical trials involving new anti-cancer drugs, tumor size and activity can be measured/monitored using imaging methods such as computed tomography (CT), which looks at the appearance of organs, and positron emission tomography (PET), which measures tumor function based on the accumulation of radioactive drugs, or radiotracers. While randomized Phase III Clinical Trials are often designed to use progression free survival or overall survival as the primary endpoint, objective measurements of tumor response remain essential in phase II trials to speed up the drug discovery process. Recently, the use of free circulating tumor DNA (ctDNA) has been proposed as a potential cancer detection tool or to monitor patients for treatment response and relapse, identifying those mutations specific to a patient’s cancer.
This project is working on improving existing methods to measure tumor volume and accurately measure the accumulation of PET radiotracers, and relate the total viable tumor mass to the amount of circulating tumor DNA (ctDNA) present in the blood. The presence of specific DNA mutations (from both ctDNA as well as biopsy material) will be correlated with the lack of early response by PET/CT imaging, to see if the data from both approaches can improve the ability to identify which patients are likely to respond, or be resistant to, a particular treatment.
The accuracy of PET/CT in measuring radiotracer uptake in tumors of various shapes or sizes in comparison to ctDNA / genomic biomarkers from sequencing data will be improved. A series of templates to integrate PET/CT results will be developed, facilitating prospective collection of minable data sets from clinical trials as well as retrospective analysis. Next, the relationship between ctDNA levels and image-based indicators of tumor burden as a function of response to treatment in a series of patients enrolled in ongoing clinical trials will be examined. Finally, whether the integration of genomic data with the assessment of early response(s) to therapy can improve/accelerate the detection of treatment resistance in patients with metastatic cancers will be investigated. It is proposed that the integration of information about the presence of pre-existing mutations in a diverse clonal subpopulation of cancer cells and early treatment response assessment will improve the ability to predict which cancers will be responsive/resistant to treatment. Taken together, genomic predictors of disease resistance/response with early assessment of therapeutic efficacy by PET/CT imaging will be integrated. It is anticipated that there will be a considerable improvement in the ability to identify those patients who will benefit from systemic therapies, thus sparing patients with resistant disease unnecessary toxicity, directing them more quickly towards more beneficial treatments.
Laboratory URL: http://molonc.bccrc.ca/benard-lab/
