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The Prognostic Impact of Circulating Tumour DNA in Melanoma Patients Treated with Systemic Therapies-Beyond BRAF Mutant Detection.
Marsavela, Gabriela; Johansson, Peter A; Pereira, Michelle R; McEvoy, Ashleigh C; Reid, Anna L; Robinson, Cleo; Warburton, Lydia; Khattak, Muhammad A; Meniawy, Tarek M; Amanuel, Benhur; Millward, Michael; Hayward, Nicholas K; Ziman, Melanie R; Gray, Elin S; Calapre, Leslie.
Afiliação
  • Marsavela G; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
  • Johansson PA; QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.
  • Pereira MR; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
  • McEvoy AC; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
  • Reid AL; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
  • Robinson C; Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, Western Australia 6009, Australia.
  • Warburton L; School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
  • Khattak MA; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
  • Meniawy TM; Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6010, Australia.
  • Amanuel B; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
  • Millward M; School of Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia.
  • Hayward NK; Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia 6150, Australia.
  • Ziman MR; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia.
  • Gray ES; Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6010, Australia.
  • Calapre L; School of Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia.
Cancers (Basel) ; 12(12)2020 Dec 16.
Article em En | MEDLINE | ID: mdl-33339135
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. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors (76%, p = 0.0149). Decreasing ctDNA levels within 12 weeks of treatment was strongly concordant with treatment response (Cohen's k = 0.798, p < 0.001) and predictive of longer progression free survival. Notably, a slower kinetic of ctDNA decline was observed in patients treated with immunotherapy compared to those on BRAF/MEK inhibitors. Whole exome sequencing of ctDNA was also conducted in 9 patients commencing anti-PD-1 therapy to derive tumour mutational burden (TMB) and neoepitope load measurements. The results showed a trend of high TMB and neoepitope load in responders compared to non-responders. Overall, our data suggest that changes in ctDNA can serve as an early indicator of outcomes in metastatic melanoma patients treated with systemic therapies and therefore may serve as a tool to guide treatment decisions.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article