Journal article

Longitudinal Monitoring of ctDNA in Patients with Melanoma and Brain Metastases Treated with Immune Checkpoint Inhibitors

Jenny H Lee, Alexander M Menzies, Matteo S Carlino, Ashleigh C McEvoy, Shahneen Sandhu, Alison M Weppler, Russell J Diefenbach, Sarah-Jane Dawson, Richard F Kefford, Michael J Millward, Zeyad Al-Ogaili, Thien Tra, Elin S Gray, Stephen Q Wong, Richard A Scolyer, Georgina Long, Helen Rizos

CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2020

Abstract

PURPOSE: Brain involvement occurs in the majority of patients with metastatic melanoma. The potential of circulating tumor DNA (ctDNA) for surveillance and monitoring systemic therapy response in patients with melanoma brain metastases merits investigation. EXPERIMENTAL DESIGN: This study examined circulating BRAF, NRAS, and c-KIT mutations in patients with melanoma with active brain metastases receiving PD-1 inhibitor-based therapy. Intracranial and extracranial disease volumes were measured using the sum of product of diameters, and response assessment performed using RECIST. Longitudinal plasma samples were analyzed for ctDNA over the first 12 weeks of treatment (threshold 2.5 copies/mL p..

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Grants

Awarded by National Health and Medical Research Council


Awarded by cancer council grant


Funding Acknowledgements

We thank the Melanoma biobank across Royal Prince Alfred Hospital, Melanoma Institute Australia, Westmead Hospital, Peter MacCallum Cancer Centre, and Sir Charles Gairdner Hospitals and the clinicians who contributed patients. This work was supported by the National Health and Medical Research Council (grant numbers 1093017, 1130423, 1107126, and 1117911), cancer council grant (1100249). R.J. Diefenbach was supported in part by a donation to Melanoma Institute Australia from the Clearbridge Foundation.