Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression.

Background: The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation.

Methods: Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy.

The Prognostic Impact of Circulating Tumour DNA in Melanoma Patients Treated with Systemic Therapies-Beyond Mutant Detection.

In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection.

Detection of splicing variants in plasma-derived cell-free nucleic acids and extracellular vesicles of melanoma patients failing targeted therapy therapies.

The analysis of plasma circulating tumour nucleic acids provides a non-invasive approach to assess disease burden and the genetic evolution of tumours in response to therapy. splicing variants are known to confer melanoma resistance to BRAF inhibitors. We developed a test to screen cell-free RNA (cfRNA) for the presence of splicing variants.

Circulating Tumor DNA Predicts Outcome from First-, but not Second-line Treatment and Identifies Melanoma Patients Who May Benefit from Combination Immunotherapy.

Purpose: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment.

Experimental Design: Plasma circulating tumor DNA (ctDNA) was quantified in 125 samples collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- ( = 32) or second-line ( = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy ( = 66). An external validation cohort included 128 patients commencing ICI therapies in the first- ( = 77) or second-line ( = 51) settings.

Role of Serum Vascular Endothelial Growth Factor (VEGF) as a Potential Biomarker of Response to Immune Checkpoint Inhibitor Therapy in Advanced Melanoma: Results of a Pilot Study.

The development of biomarkers predictive of response to immune checkpoint inhibitor (ICI) therapies in advanced melanoma is an area of great interest in oncology. Our study evaluated the potential role of serum vascular endothelial growth factor (VEGF) as a predictive biomarker of clinical benefit and response to treatment with ICIs. Pre-treatment peripheral blood samples were obtained from advanced melanoma patients undergoing ICI therapy as monotherapy or in combination at two tertiary care hospitals in Western Australia.

PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study.

Background: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

Methods: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy.

Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells.

Background: Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application.

Methods: Here we compared two microfluidic devices for the recovery of circulating melanoma cells.

A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision.

Purpose: To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi.

Methods: We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years.

Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies.

Background: A significant number of melanoma patients experience recurrence to distant sites, despite having had surgical treatment of the primary lesion, with curative intent. Monitoring of patients for early evidence of disease recurrence would significantly improve management of the disease, allowing timely therapeutic intervention. Circulating tumor DNA (ctDNA) is becoming a well-recognized biomarker for monitoring malignancies and has, in a few studies, been shown to signify disease recurrence earlier than conventional methods.

Locus-specific concordance of genomic alterations between tissue and plasma circulating tumor DNA in metastatic melanoma.

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.

Correlation between circulating tumour DNA and metabolic tumour burden in metastatic melanoma patients.

Background: Circulating tumour DNA (ctDNA) may serve as a measure of tumour burden and a useful tool for non-invasive monitoring of cancer. However, ctDNA is not always detectable in patients at time of diagnosis of metastatic disease. Therefore, there is a need to understand the correlation between ctDNA levels and the patients' overall metabolic tumour burden (MTB).

Droplet Digital PCR for Mutation Detection in Formalin-Fixed, Paraffin-Embedded Melanoma Tissues: A Comparison with Sanger Sequencing and Pyrosequencing.

The identification of somatic mutations is crucial for guiding therapeutic decisions about personalized melanoma treatment. However, genetic analysis of tumors is usually performed on limited and often low-quality DNA from tumors with low tumor cellularity and high tumor heterogeneity. Different mutation-detection platforms exist, with varying analytical sensitivities.

Sensitive droplet digital PCR method for detection of promoter mutations in cell free DNA from patients with metastatic melanoma.

Background: Currently mainly mutant circulating tumor DNA (ctDNA) is utilized to monitor patients with melanoma. promoter mutations are common in various cancers and found in up to 70% of melanomas, including half of wild-type cases. Therefore, a sensitive method for detection of promoter mutations would increase the number of patients that could be monitored through ctDNA analysis.

Improving health Professional's knowledge of hepatitis B using cartoon based learning tools: a retrospective analysis of pre and post tests.

Background: Hepatitis B serology is complex and a lack of knowledge in interpretation contributes to the inadequate levels of screening and referral for highly effective hepatitis antiviral treatments. This knowledge gap needs to be addressed so that current and future healthcare professionals are more confident in the detection and assessment of hepatitis B to improve the uptake of treatment and reduce long-term complications from the disease. Cartoons have been used effectively as a teaching tool in other settings and were considered as a potentially useful teaching aid in explaining hepatitis B serology.

Development of a simplified method of human semen storage for the testing of sperm DNA fragmentation using the Halosperm G2 test kit.

Objective: To develop a simple, convenient, and stable storage method for semen before DNA fragmentation testing.

Design: Experimental cross-sectional study.

Setting: Fertility clinic.