دورية أكاديمية
The prognostic impact of circulating tumour dna in melanoma patients treated with systemic therapies—beyond braf mutant detection
| العنوان: | The prognostic impact of circulating tumour dna in melanoma patients treated with systemic therapies—beyond braf mutant detection |
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| المؤلفون: | 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 |
| المصدر: | Research outputs 2014 to 2021 |
| بيانات النشر: | Edith Cowan University, Research Online, Perth, Western Australia |
| سنة النشر: | 2020 |
| المجموعة: | Edith Cowan University (ECU, Australia): Research Online |
| مصطلحات موضوعية: | [RSTDPub], BRAF, Circulating tumour DNA (ctDNA), Immunotherapy, Melanoma, Neoantigen load, Response, Targeted therapy, Tumour mutational burden, Diseases, Immunology and Infectious Disease, Life Sciences, Medicine and Health Sciences, Rehabilitation and Therapy |
| الوصف: | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://ro.ecu.edu.au/ecuworkspost2013/9379Test; https://ro.ecu.edu.au/cgi/viewcontent.cgi?article=10386&context=ecuworkspost2013Test |
| الإتاحة: | https://ro.ecu.edu.au/ecuworkspost2013/9379Test https://ro.ecu.edu.au/cgi/viewcontent.cgi?article=10386&context=ecuworkspost2013Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.BD9BBEB2 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |