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

被引：9

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

共 50 条

[31] Higher proportions of CD39+tumor-resident cytotoxic T cells predict recurrence-free survival in patients with stage III melanoma treated with adjuvant immunotherapy [J].

Attrill, Grace Heloise ;

Owen, Carina N. ;

Ahmed, Tasnia ;

Vergara, Ismael A. ;

Colebatch, Andrew J. ;

Conway, Jordan W. ;

Nahar, Kazi J. ;

Thompson, John F. ;

da Silva, Ines Pires ;

Carlino, Matteo S. ;

Menzies, Alexander M. ;

Lo, Serigne ;

Palendira, Umaimainthan ;

Scolyer, Richard A. ;

Long, Georgina, V ;

Wilmott, James S. .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2022, 10 (06)

[32] Surgical removal of the index node marked using magnetic seed localization to assess response to neoadjuvant immunotherapy in patients with stage III melanoma [J].

Schermers, B. ;

Franke, V. ;

Rozeman, E. A. ;

van de Wiel, B. A. ;

Bruining, A. ;

Wouters, M. W. ;

van Houdt, W. J. ;

ten Haken, B. ;

Muller, S. H. ;

Bierman, C. ;

Ruers, T. J. M. ;

Blank, C. U. ;

van Akkooi, A. C. J. .

BRITISH JOURNAL OF SURGERY, 2019, 106 (05) :519-522

[33] Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma [J].

Rozeman, E. A. ;

Hoefsmit, E. P. ;

Reijers, I. L. M. ;

Saw, R. P. M. ;

Versluis, J. M. ;

Krijgsman, O. ;

Dimitriadis, P. ;

Sikorska, K. ;

van de Wiel, B. A. ;

Eriksson, H. ;

Gonzalez, M. ;

Torres Acosta, A. ;

Grijpink-Ongering, L. G. ;

Shannon, K. ;

Haanen, J. B. A. G. ;

Stretch, J. ;

Ch'ng, S. ;

Nieweg, O. E. ;

Mallo, H. A. ;

Adriaansz, S. ;

Kerkhoven, R. M. ;

Cornelissen, S. ;

Broeks, A. ;

Klop, W. M. C. ;

Zuur, C. L. ;

van Houdt, W. J. ;

Peeper, D. S. ;

Spillane, A. J. ;

van Akkooi, A. C. J. ;

Scolyer, R. A. ;

Schumacher, T. N. M. ;

Menzies, A. M. ;

Long, G. V. ;

Blank, C. U. .

NATURE MEDICINE, 2021, 27 (02) :256-+

[34] IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma [J].

Reijers, Irene L. M. ;

Rao, Disha ;

Versluis, Judith M. ;

Menzies, Alexander M. ;

Dimitriadis, Petros ;

Wouters, Michel W. ;

Spillane, Andrew J. ;

Klop, Willem M. C. ;

Broeks, Annegien ;

Bosch, Linda J. W. ;

Lopez-Yurda, Marta ;

van Houdt, Winan J. ;

Rawson, Robert V. ;

Grijpink-Ongering, Lindsay G. ;

Gonzalez, Maria ;

Cornelissen, Sten ;

Bouwman, Jasper ;

Sanders, Joyce ;

Plasmeijer, Elsemieke ;

Elshot, Yannick S. ;

Scolyer, Richard A. ;

van de Wiel, Bart A. ;

Peeper, Daniel S. ;

van Akkooi, Alexander C. J. ;

Long, Georgina V. ;

Blank, Christian U. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2023, 220 (05)

[35] Circulating Tumour DNA in Advanced Melanoma Patients Ceasing PD1 Inhibition in the Absence of Disease Progression [J].

Warburton, Lydia ;

Calapre, Leslie ;

Pereira, Michelle R. ;

Reid, Anna ;

Robinson, Cleo ;

Amanuel, Benhur ;

Ziman, Mel ;

Millward, Michael ;

Gray, Elin .

CANCERS, 2020, 12 (11) :1-11

[36] Response prediction and risk stratification of patients with rectal cancer after neoadjuvant therapy through an analysis of circulating tumour DNA [J].

Liu, Wenyang ;

Li, Yifei ;

Tang, Yuan ;

Song, Qianqian ;

Wang, Jingjing ;

Li, Ning ;

Chen, Silin ;

Shi, Jinming ;

Wang, Shulian ;

Li, Yexiong ;

Jiao, Yuchen ;

Zeng, Yixin ;

Jin, Jing .

EBIOMEDICINE, 2022, 78

[37] Impact of Adjuvant Immunotherapy on Overall Survival in a Contemporary Cohort of Patients with Stage III Melanoma [J].

Sharon, Cimarron E. E. ;

Tortorello, Gabriella N. N. ;

Ma, Kevin ;

Sinnamon, Andrew J. J. ;

Mitchell, Tara C. C. ;

Karakousis, Giorgos C. C. ;

Miura, John T. T. .

ANNALS OF SURGICAL ONCOLOGY, 2023, 30 (09) :5329-5332

[38] Neoadjuvant immunotherapy for patients with resectable stage III/IV cutaneous melanoma - A Swedish retrospective real-world study (NEO-MEL) [J].

Nelson, Axel ;

Krabbe, Ellen ;

Bjorkstrom, Karl ;

Huibers, Anne ;

Jovanovic, Braslav ;

Blank, Christian U. ;

Ullenhag, Gustav J. ;

Helgadottir, Hildur ;

Ny, Lars ;

Bagge, Roger Olofsson .

EUROPEAN JOURNAL OF CANCER, 2025, 224

[39] 18F-FDG PET/CT During Neoadjuvant Targeted Therapy in Prior Unresectable Stage III Melanoma Patients Can (Early) Metabolic Imaging Predict Histopathologic Response or Recurrence? [J].

van der Hiel, Bernies ;

Blankenstein, Stephanie A. ;

Aalbersberg, Else A. ;

Wondergem, Maurits ;

Stokkel, Marcel P. M. ;

van de Wiel, Bart A. ;

Klop, W. Martin C. ;

van Akkooi, Alexander C. J. ;

Haanen, John B. .

CLINICAL NUCLEAR MEDICINE, 2022, 47 (07) :583-589

[40] Pretreatment SUVmax value to predict outcome in patients with stage III NSCLC receiving concurrent chemoradiotherapy [J].

Yaprak, Gokhan ;

Ozcelik, Melike ;

Gemici, Cengiz ;

Seseogullari, Ozgur .

NORTHERN CLINICS OF ISTANBUL, 2019, 6 (02) :129-133

← 1 2 3 4 5 →