Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy

被引:11
作者
Chan, Wei Yen [1 ,2 ]
Lee, Jenny H. [1 ,3 ]
Stewart, Ashleigh [1 ,2 ]
Diefenbach, Russell J. [1 ,2 ]
Gonzalez, Maria [2 ]
Menzies, Alexander M. [2 ,4 ,5 ]
Blank, Christian [6 ,7 ,8 ]
Scolyer, Richard A. [2 ,4 ,9 ,10 ,11 ]
Long, Georgina V. [2 ,4 ,5 ,9 ]
Rizos, Helen [1 ,2 ]
机构
[1] Macquarie Univ, Fac Med Hlth & Human Sci, Sydney, NSW, Australia
[2] Univ Sydney, Melanoma Inst Australia, Sydney, NSW, Australia
[3] Chris Obrien Lifehouse, Dept Med Oncol, Sydney, NSW, Australia
[4] Univ Sydney, Fac Med & Hlth, Sydney, NSW, Australia
[5] Royal North Shore & Mater Hosp, Dept Med Oncol, Sydney, NSW, Australia
[6] Netherlands Canc Inst NKI, Dept Med Oncol, Amsterdam, Netherlands
[7] Leiden Univ, Med Ctr LUMC, Dept Med Oncol, Leiden, Netherlands
[8] Univ Clin Regensburg UKR, Dept Hematol & Med Oncol, Regensburg, Germany
[9] Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia
[10] Royal Prince Alfred Hosp, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia
[11] NSW Hlth Pathol, Sydney, NSW, Australia
基金
英国医学研究理事会;
关键词
Circulating tumour DNA; Stage III melanoma; Neoadjuvant therapy; Recurrence risk; SURVIVAL; ADJUVANT; IPILIMUMAB;
D O I
10.1186/s13046-024-03153-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundNeoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy. MethodsPlasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system. ResultsPre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management. ConclusionPost-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.
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页数:9
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