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Full-Text Articles in Medicine and Health Sciences

Circulating Tumor Dna Reflects Uveal Melanoma Responses To Protein Kinase C Inhibition, John J. Park, Russell J. Diefenbach, Natalie Byrne, Georgina V. Long, Richard A. Scolyer, Elin S. Gray, Matteo S. Carlino, Helen Rizos Jan 2021

Circulating Tumor Dna Reflects Uveal Melanoma Responses To Protein Kinase C Inhibition, John J. Park, Russell J. Diefenbach, Natalie Byrne, Georgina V. Long, Richard A. Scolyer, Elin S. Gray, Matteo S. Carlino, Helen Rizos

Research outputs 2014 to 2021

The prognosis for patients with UM is poor, and recent clinical trials have failed to prolong overall survival (OS) of these patients. Over 95% of UM harbor activating driver mutations, and this allows for the investigation of ctDNA. In this study, we investigated the value of ctDNA for adaptive clinical trial design in metastatic UM. Longitudinal plasma samples were analyzed for ctDNA in 17 metastatic UM patients treated with PKCi-based therapy in a phase 1 clinical trial setting. Plasma ctDNA was assessed using digital droplet PCR (ddPCR) and a custom melanoma gene panel for targeted next generation sequencing (NGS). Baseline …


Liquid Biopsy In Ovarian Cancer Using Circulating Tumor Dna And Cells: Ready For Prime Time?, Du-Bois Asante, Leslie Calapre, Melanie Ziman, Tarek M. Meniawy, Elin S. Gray Jan 2020

Liquid Biopsy In Ovarian Cancer Using Circulating Tumor Dna And Cells: Ready For Prime Time?, Du-Bois Asante, Leslie Calapre, Melanie Ziman, Tarek M. Meniawy, Elin S. Gray

Research outputs 2014 to 2021

Liquid biopsies hold the potential to inform cancer patient prognosis and to guide treatment decisions at the time when direct tumor biopsy may be impractical due to its invasive nature, inaccessibility and associated complications. Specifically, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have shown promising results as companion diagnostic biomarkers for screening, prognostication and/or patient surveillance in many cancer types. In ovarian cancer (OC), CTC and ctDNA analysis allow comprehensive molecular profiling of the primary, metastatic and recurrent tumors. These biomarkers also correlate with overall tumor burden and thus, they provide minimally-invasive means for patient monitoring during clinical …


Locus‐Specific Concordance Of Genomic Alterations Between Tissue And Plasma Circulating Tumor Dna In Metastatic Melanoma, Leslie Calapre, Tindaro Giardina, Cleo Robinson, Anna L. Reid, Zeyad Al-Ogaili, Michelle R. Pereira, Ashleigh C. Mcevoy, Lydia Warburton, Nicholas K. Hayward, Muhammad A. Khattak, Tarek M. Meniawy, Michael Millward, Benhur Amanuel, Melanie R. Ziman, Elin S. Gray Feb 2019

Locus‐Specific Concordance Of Genomic Alterations Between Tissue And Plasma Circulating Tumor Dna In Metastatic Melanoma, Leslie Calapre, Tindaro Giardina, Cleo Robinson, Anna L. Reid, Zeyad Al-Ogaili, Michelle R. Pereira, Ashleigh C. Mcevoy, Lydia Warburton, Nicholas K. Hayward, Muhammad A. Khattak, Tarek M. Meniawy, Michael Millward, Benhur Amanuel, Melanie R. Ziman, Elin S. Gray

Research outputs 2014 to 2021

Circulating tumor DNA (ctDNA) may serve as a surrogate to tissue biopsy for noninvasive identification of mutations across multiple genetic loci and for disease monitoring in melanoma. In this study, we compared the mutation profiles of tumor biopsies and plasma ctDNA from metastatic melanoma patients using custom sequencing panels targeting 30 melanoma-associated genes. Somatic mutations were identified in 20 of 24 melanoma biopsies, and 16 of 20 (70%) matched-patient plasmas had detectable ctDNA. In a subgroup of seven patients for whom matching tumor tissue and plasma were sequenced, 80% of the mutations found in tumor tissue were also detected in …


Circulating Tumour Dna (Ctdna) As A Biomarker In Metachronous Melanoma And Colorectal Cancer- A Case Report, Leslie Calapre, Lydia Warburton, Michael Millward, Elin S. Gray Jan 2019

Circulating Tumour Dna (Ctdna) As A Biomarker In Metachronous Melanoma And Colorectal Cancer- A Case Report, Leslie Calapre, Lydia Warburton, Michael Millward, Elin S. Gray

Research outputs 2014 to 2021

Background: Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker for monitoring disease status of patients with advanced cancers. The presence of ctDNA in the blood is a result of biological processes, namely tumour cell apoptosis and/or necrosis, and can be used to monitor different cancers by targeting cancer-specific mutation. Case presentation: We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer. The kinetics of ctDNA derived from each cancer type were monitored targeting BRAF …


Circulating Tumour Dna: A Non-Invasive Biomarker For Melanoma, Ashleigh Cavell Mcevoy Jan 2018

Circulating Tumour Dna: A Non-Invasive Biomarker For Melanoma, Ashleigh Cavell Mcevoy

Theses: Doctorates and Masters

Cutaneous melanoma accounts for 90% of all skin cancer deaths (Balch et al., 2010) and is responsible for 3.6% of deaths from cancer in Australia (Australian Institute of Health and Welfare, 2016). Whilst early detection and successful surgical removal of primary melanomas have improved survival rates (DeSantis et al., 2014), approximately 30% of these patients will have disease recurrence at some point in their lives (Soong et al., 1992; Soong et al., 1998). This is despite being considered disease free following treatment, which may have included surgical removal of the primary and/or its metastasis/es, radiation and/or systemic therapy. Whilst the …


Circulating Tumor Dna To Monitor Treatment Response And Detect Acquired Resistance In Patients With Metastatic Melanoma, Elin S. Gray, Helen Rizos, Anna L. Reid, Suzanah Boyd, Michelle Pereira, Johnny Lo, Varsha Tembe, James Freeman, Jenny Lee, Richard Scolyer, Kelvin Siew, Chris Lomma, Adam Cooper, Muhammad Khattak, Tarek Meniawy, Georgina Long, Matteo Carlino, Michael Millward, Mel R. Ziman Jan 2015

Circulating Tumor Dna To Monitor Treatment Response And Detect Acquired Resistance In Patients With Metastatic Melanoma, Elin S. Gray, Helen Rizos, Anna L. Reid, Suzanah Boyd, Michelle Pereira, Johnny Lo, Varsha Tembe, James Freeman, Jenny Lee, Richard Scolyer, Kelvin Siew, Chris Lomma, Adam Cooper, Muhammad Khattak, Tarek Meniawy, Georgina Long, Matteo Carlino, Michael Millward, Mel R. Ziman

Research outputs 2014 to 2021

Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab). Baseline ctDNA levels were evaluated relative to treatment response and progression-free survival (PFS). Tumor-associated ctDNA was …