Radiation and Cancer Biology

SS 03 - Biology 1 - Innovative Biologic Approaches to Improve Risk Stratification and Treatment Outcomes

23 - Association of Circulating Tumor Cells (CTCs) and Genomic Signatures in Prostate Cancer Patients

Sunday, October 21
1:25 PM - 1:35 PM
Location: Room 008

Association of Circulating Tumor Cells (CTCs) and Genomic Signatures in Prostate Cancer Patients
A. Pollack1, T. M. Giret1, F. M. Chinea1, D. Kwon1, T. Udayakumar1, R. J. Cote1, J. Stortz2, L. Lam2, E. Davicioni2, C. Buerki2, M. C. Abramowitz1, and R. Stoyanova1; 1University of Miami, Miami, FL, 2GenomeDx Biosciences, Vancouver, BC, Canada

Purpose/Objective(s): Intermediate and high-risk prostate cancer patients who are candidates for radiotherapy (RT) are very heterogeneous. Genomic classifiers add to clinical-pathologic risk factors and have the potential to become integral to risk stratification. Since circulating tumor cells (CTCs) are determinate of metastasis and genomic predictors of CTCs are not yet understood in this population, we investigated the associations of CTC counts with several genomic classifiers in patients enrolled in a randomized Phase II radiotherapy clinical trial (BLaStM, NCT02307058).

Materials/Methods: CTCs were enumerated in blood samples from 31 patients using a microfilter system. The number of single CTCs, CTC clusters and their sum were recorded. Several gene signatures were investigated. Decipher® (metastatic risk), PORTOS (predictor of RT response) and PAM50 (predictor hormone response, which includes gene expression-based "intrinsic" subtypes: luminal A, luminal B, HER2-enriched, and basal-like), were quantified in tissue obtained by MRI-Ultrasound fused biopsies. A high-density gene expression microarray processed at a biosciences laboratory was used. A Poisson regression model with demographic and disease characteristics variables (PSA, Gleason Score (GS), T stage, %tumor in biopsies, age, race/ethnicity) were used in the univariable analysis (UVA). Multivariable analysis (MVA) included the statistically significant variables, where each biomarker was examined, along with chosen covariates for association with CTC counts in a one-at-a-time manner.

Results: CTCs were evident in over 70% of patients tested. The single cell and cluster median values in 8 mL of blood were 33 (range 0-343) and 4 (range 0-26). In MVA, several of the signatures were associated with total CTC number (single cells and clusters). When the biopsy core containing the highest Gleason score (GS) and %tumor were analyzed, the significant relationships included PORTOS (RR 6.00; p<0.001), PAM50_basal (RR 2.21; p<0.001), and Decipher (RR 1.16; p=0.048). Since multiple biopsies were analyzed for gene expression, when the cores with the highest signature value were selected, PORTOS surged (RR=47.10; p<0.0001) in the MVA. Despite the relatively small sample size, the results indicate a strong signal related to radiation sensitivity. NCCN risk categories were not significantly related to CTC counts or gene signatures.

Conclusion: Determinants of prostate cancer lethality in intermediate to high-risk prostate cancer are poorly understood. Our results show an association between tumor gene expression alterations and CTC number, indicating that genes linked to radiation sensitivity have a role in early metastatic risk.

Author Disclosure: A. Pollack: Research Grant; Radiation Therapy Oncology Group, Varian Medical Systems. Honoraria; Mayo Clinic, City of Hope. Consultant; Medivation. Travel Expenses; Radiation Therapy Oncology Group, Mayo Clinic, Rio Oncology, Varian Medical Systems Inc, IBA Proton Therapy, City of Hope. T.M. Giret: None. F.M. Chinea: None. D. Kwon: None. T. Udayakumar: None. R.J. Cote: None. L. Lam: None. E. Davicioni: Stock; GemomeDx. CEO; GenomeDx. M.C. Abramowitz: None. R. Stoyanova: None.

Alan Pollack, MD, PhD

University of Miami Sylvester Comprehensive Cancer Center

Disclosure:
Employment
University of Miami Miller School of Medicine: Chair and Professor of Radiation Oncology: Employee; University of Miami School of Medicine: Chair and Professor of Radiation Oncology: Employee

Compensation
City of Hope: Honoraria, Travel Expenses; Radiation Therapy Oncology Group: Research Grants, Travel Expenses; Varian: Research Grants; Varian Medical Systems: Research Grants

Biography:
Dr. Pollack is Professor and Chair of the Department of Radiation Oncology at the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine. He obtained a Ph.D. in Microbiology and Immunology from the University of Miami and later graduated from the University of Miami Miller School of Medicine’s Ph.D. to M.D. program. He did an internal medicine internship at Jackson Memorial Hospital in Miami, before doing a residency in radiation oncology at U.T.-M.D. Anderson Cancer Center in Houston. While at M.D. Anderson, Dr. Pollack attained the rank of Professor, was Director of the Residency Training Program and was a co-leader of the GU group before assuming the Chair in Radiation Oncology position at Fox Chase Cancer Center in Philadelphia in 2001. He held that position for 7 years before returning to Miami as Chair and Professor of Radiation Oncology in 2008. He became interim Deputy Director of Sylvester in 2017. Dr. Pollack’s research interests have centered on the management of prostate cancer with radiotherapy, the role and length of androgen deprivation therapy, radiation dose escalation, radiation fractionation, small molecule/gene/viral vector targeted therapy, and tissue biopsy, liquid biopsy and imaging markers of outcome.

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