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

被引：2

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

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2024年 / 43卷 / 01期

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.

引用

页数：9

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