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12 2023 JCO Precision Oncology


11 2023 Cancer Research and Treatment


10 2023

Practical Utility of Liquid Biopsy for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer

Abstract Background: Assessment of genomic alterations in castration-resistant prostate cancer (CRPC) patients has become an important process for treatment decisions, but traditional tissue-based evaluation can be challenging.   Methods: To evaluate the clinical utility of liquid biopsy for the evaluation of genomic alterations in CRPC, we have prospectively collected plasma samples fr|om patients being treated for clinically confirmed CRPC. The cell-free DNA (cfDNA) extracted fr|om the plasma samples were analyzed using AlphaLiquid®100-HRR panel. Available archival tumor tissue samples were also collected and analyzed using the same panel.   Results: Plasma samples fr|om a total of 87 patients were included in this study. Somatic mutations fr|om cfDNA were detected in 78 (89.7%) of all 87 CRPC patients. Somatic mutations were detectable regardless of the presence of overt metastasis, or concomitant treatment given at the time of plasma sample collection. 23 patients were found to have known deleterious mutations in HRR genes fr|om their cfDNA. 11 patients were additionally found to have possibly pathogenic mutations calculated by pathogenicity prediction algorithm. Archival tissue samples were available in 33 (37.9%) of the patients, 31 fr|om prostate and 2 fr|om metastatic bone lesions, collected a median of 2 years before the blood sample collection. Tissue sequencing was able to yield an NGS result in only 51.5% of the tissue samples. The general sensitivity of cfDNA for detecting somatic mutations discovered fr|om tissues was 71.8%, but important somatic/germline mutations in HRR genes were found in higher concordance (100%).Conclusions:Liquid biopsy can be a reasonable substitute for tissue biopsy in CRPC patients for evaluating genomic alterations.



9 2022 Clinical Epigenetics


8 2022

Dynamic changes in longitudinal circulating tumour DNA profile during metastatic colorectal cancer treatment

BackgroundCirculating tumour DNA (ctDNA) has been spotlighted as an attractive biomarker because of its easy accessibility and real-time representation of tumour genetic profile.  However, the clinical utility of longitudinal ctDNA monitoring has not been clearly defined.MethodsSerial blood samples were obtained fr|om metastatic colorectal cancer patients undergoing first-line chemotherapy.  ctDNA was sequenced using a targeted next-generation sequencing platform which included 106 genes.  Changes in ctDNA profile and treatment outcome were comprehensively analysed.ResultsA total of 272 samples fr|om 62 patients were analysed. In all, 90.3% of patients had detectable ctDNA mutation before treatment.  ctDNA clearance after chemotherapy was associated with longer progression-free survival which was independent of radiological response (adjusted hazard ratio 0.22, 95% confidence interval 0.10–0.46).  Longitudinal monitoring was able to detect ctDNA progression which preceded radiological progressive disease (PD) in 58.1% (median 3.3 months).  Diverse resistant mutations (34.9%) and gene amplification (7.0%) at the time of PD were discovered.  For 16.3% of the PD patients, the newly identified mutations could be potential candidates of targeted therapy or clinical trial.ConclusionctDNA profile provided a more accurate landscape of tumour and dynamic changes compared to radiological evaluation.  Longitudinal ctDNA monitoring may improve personalised treatment decision-making.

British Journal of Cancer