School of Medicine and Health Sciences Poster Presentations

Title

A comparison of circulating free DNA from the blood and urine of patients with non-small cell lung cancer (NSCLC).

Document Type

Poster

Abstract Category

Cancer/Oncology

Keywords

liquid biopsy, non-small cell lung cancer (NSCLC), circulating free DNA (cfDNA), personalized medicine

Publication Date

Spring 5-1-2019

Abstract

Background: Circulating free DNA (cfDNA) can be found in the blood of most cancer patients. Its detection and molecular analysis provides a less invasive way to monitor response to anticancer therapies as there is growing evidence supporting that cfDNA correlates well with tumor bulk. This study explores whether mutated cfDNA can be detected in the urine of patients with established NSCLC. Design: This study was undertaken as part of the NORA clinical trial, a phase II clinical trial exploring the efficacy of metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy and subsequent concomitantly with radiotherapy (RT) in patients with NSCLC. Patients: Patients involved in this study had locally invasive (stage III) or metastatic (stage IV) NSCLC. Patients had previously-identified mutations in the EGFR gene that had been confirmed by solid biopsy or measured by blood liquid biopsy. Common deletions included del(6223), del(6225), del(6254), or del(6255), which sensitizes the tumor to TKI's like erlotinib and gefitinib; T790M, which sensitizes the tumor to osimertinib; or L858R. Patients had consented to be a part of the study, and had provided paired blood and urine samples in at least one consultation. Inclusion and exclusion criteria for the trial are included at clinicaltrials.gov. Methods: Patient blood was extracted and urine was collected using standard procedures. At the time of experimentation, blood was separated into plasma and DNA was extracted and analyzed using digital PCR (dPCR). The results of the assay were reported as the ratio of mutant to wild-type DNA molecules. Exosomes were isolated from corresponding urine samples using an in-house procedure, and DNA was subsequently isolated from exosomes. Similarly, dPCR was performed on urine-isolated DNA samples and analyzed as a ratio of mutant DNA to wild-type. Results: At the time of writing, 45 patients had contributed 70 pairs of serial paired samples, and 10 had appreciable levels of mutated cfDNA in the blood sample. We were unable to measure mutated cfDNA in any corresponding urine samples. Conclusion: Although our results did not bear fruit, further studies should be conducted with different methodologies to attempt to detect mutated DNA in the urine of these patients. Clinicaltrials.gov Identifier: NCT02709720

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Presented at Research Days 2019.

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A comparison of circulating free DNA from the blood and urine of patients with non-small cell lung cancer (NSCLC).

Background: Circulating free DNA (cfDNA) can be found in the blood of most cancer patients. Its detection and molecular analysis provides a less invasive way to monitor response to anticancer therapies as there is growing evidence supporting that cfDNA correlates well with tumor bulk. This study explores whether mutated cfDNA can be detected in the urine of patients with established NSCLC. Design: This study was undertaken as part of the NORA clinical trial, a phase II clinical trial exploring the efficacy of metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy and subsequent concomitantly with radiotherapy (RT) in patients with NSCLC. Patients: Patients involved in this study had locally invasive (stage III) or metastatic (stage IV) NSCLC. Patients had previously-identified mutations in the EGFR gene that had been confirmed by solid biopsy or measured by blood liquid biopsy. Common deletions included del(6223), del(6225), del(6254), or del(6255), which sensitizes the tumor to TKI's like erlotinib and gefitinib; T790M, which sensitizes the tumor to osimertinib; or L858R. Patients had consented to be a part of the study, and had provided paired blood and urine samples in at least one consultation. Inclusion and exclusion criteria for the trial are included at clinicaltrials.gov. Methods: Patient blood was extracted and urine was collected using standard procedures. At the time of experimentation, blood was separated into plasma and DNA was extracted and analyzed using digital PCR (dPCR). The results of the assay were reported as the ratio of mutant to wild-type DNA molecules. Exosomes were isolated from corresponding urine samples using an in-house procedure, and DNA was subsequently isolated from exosomes. Similarly, dPCR was performed on urine-isolated DNA samples and analyzed as a ratio of mutant DNA to wild-type. Results: At the time of writing, 45 patients had contributed 70 pairs of serial paired samples, and 10 had appreciable levels of mutated cfDNA in the blood sample. We were unable to measure mutated cfDNA in any corresponding urine samples. Conclusion: Although our results did not bear fruit, further studies should be conducted with different methodologies to attempt to detect mutated DNA in the urine of these patients. Clinicaltrials.gov Identifier: NCT02709720