Evolution of the genomic landscape of circulating tumor DNA (ctDNA) in metastatic prostate cancer over treatment and time
| Autor: | Benjamin L. Maughan, Erin B. Bailey, Andrew W. Hahn, Roberto Nussenzveig, Julia A. Batten, David D. Stenehjem, Emma Carroll, Neeraj Agarwal |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Time Factors Concordance Circulating Tumor DNA Cohort Studies 03 medical and health sciences Prostate cancer 0302 clinical medicine Internal medicine medicine Biomarkers Tumor Over treatment Humans Liquid biopsy Neoplasm Metastasis business.industry Genome Human Disease progression Liquid Biopsy High-Throughput Nucleotide Sequencing Prostatic Neoplasms DNA Neoplasm Genomics Middle Aged medicine.disease Prognosis Combined Modality Therapy 030104 developmental biology Circulating tumor DNA 030220 oncology & carcinogenesis Genomic Profile business After treatment Follow-Up Studies |
| Zdroj: | Cancer treatment and research communications. 19 |
| ISSN: | 2468-2942 |
| Popis: | Background Targeted therapies have shown promise for men with metastatic castration-resistant prostate cancer (mCRPC). Due to the difficulty with obtaining tumor tissue in bony metastases, liquid biopsies are a promising alternative to guide treatment selection. While concurrent tissue next-generation sequencing (tNGS) and liquid biopsy has high concordance, it is unknown whether the genomic landscape of metastatic prostate cancer (mPC) changes over time or treatment. Herein, we hypothesize that the genomic landscape of mPC evolves with new treatments and/or time between tests. Patients and Methods Men with mPC from the University of Utah with matched tNGS and liquid biopsy were included. Clinical data was collected retrospectively. Exonic regions from 69 genes covered by both platforms were included for analysis. Paired t tests were used to assess number of genomic alterations (GAs) between testing platforms. Number of alterations was assessed by time and number of treatments between testing by multivariate nonparametric trend tests. Results 101 men with mPC were eligible and included. In men with no new treatments and ≤ 1 year between tests, a similar number of GAs were detected in both tests (2.0 vs. 2.2). In contrast, men with ≥ 1 new treatment between tests had significantly more GAs after treatment (5.0 vs. 2.4, p = 0.005). Total number of GAs was correlated with number of new treatments between testing (p = 0.003) and not time between testing (p = 0.76). Conclusion The genomic landscape of mPC evolves with subsequent therapies. This finding suggests that contemporary tumor genomic profile upon disease progression may optimize guidance towards subsequent therapy selection. |
| Databáze: | OpenAIRE |
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