The advent of immune ICI has remarkably improved survival in advanced melanoma patients in the last decade. Long term responders following 2 years of treatment with immunotherapy go on to surveillance with frequent radiological imaging every 3-6 months up to 5-10 years. This not only exposes patients with a relatively low risk of recurrence to significant amounts of ionising radiation, but also increases the burden and cost on already stretched radiology departments. Therefore, this study aims to assess the feasibility and patient experience of using ctDNA with minimally invasive liquid biopsy assays as a biomarker for detecting disease relapse or progression at the point of radiological progression. Data from this pilot study will help to design a future validation study for establishing optimal liquid biopsy for surveillance in advanced melanoma patients.
This prospective study will measure ctDNA in a simple plasma sample and using a dried blood spot assay, collected at the time of radiological disease progression. We will investigate the use of tumour informed and tumour naïve approaches, assessing targeted sequencing, copy number variations using whole genome low depth sequencing, fragmentomics and methylation as potential methods to improve molecular recurrence detection. We will also collect urine samples to investigate the use of cfDNA to detect relapse in the brain, which has been noted to be more challenging to detect using ctDNA in the blood than other sites of relapse. In addition, we will investigate the use of novel immunophenotyping technology through a collaboration with MelioHealth (IMU) in the same setting. The IMU platform combines high resolution cellular analysis and machine learning to enable high-content, high-throughput and real-time cellular immunophenotyping from less than 2ml of whole blood. We hypothesize that disease relapse following immunotherapy may detectably trigger a patient's immune system memory, which may be particularly important for those patients who do not shed ctDNA.
Study Type
OBSERVATIONAL
Enrollment
100
The Royal Marsden
Chelsea, London, United Kingdom
Proportion of patients with measurable ctDNA at the point of radiological disease progression
Proportion positive of ctDNA assays vs. standard imaging including CT, MRI or PET scans depending upon site of disease relapse
Time frame: 1 year
Patient acceptance of liquid biopsy measured by proportion of enrolled patients to those invited to participate in the study
Patient satisfaction with using liquid biopsy for each assay measured by a question on satisfaction (Yes/No/Undecided)
Time frame: 1 year
Cost of standard imaging pathway and additional cost of using liquid biopsy testing
To assess the cost of standard imaging pathway and additional cost of using liquid biopsy testing
Time frame: 1 year
Proportion of patients with positive tests in the different liquid biopsy assays to detect disease relapse
To assess the sensitivity of different liquid biopsy assays, including plasma vs blood spot for measuring ctDNA at point of disease progression
Time frame: 1 year
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