Format

Send to

Choose Destination
Ann Oncol. 2019 Mar 12. pii: mdz075. doi: 10.1093/annonc/mdz075. [Epub ahead of print]

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

Lee JH1,2, Saw RP2,3,4, Thompson JF2,3,4, Lo S2,4, Spillane AJ2,5, Shannon KF2,6, Stretch J2, Howle J7, Menzies AM2,4,5, Carlino MS2,4,7, Kefford RF1,2,7, Long GV2,4,5, Scolyer RA2,4,8, Rizos H1,2.

Author information

1
Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia.
2
Melanoma Institute Australia, NSW, Australia.
3
Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, NSW, Australia.
4
Sydney Medical School, The University of Sydney, NSW, Australia.
5
Northern Sydney Cancer Centre, Royal North Shore Hospital, NSW, Australia.
6
Chris O'Brien Lifehouse, NSW, Australia.
7
Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, NSW, Australia.
8
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW, Australia.

Abstract

BACKGROUND:

The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease relapse and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.

PATIENTS AND METHODS:

ctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence free survival (DM-RFS) and melanoma specific survival (MSS).

RESULTS:

The detection of ctDNA in the discovery and validation cohort was 34% and 33% respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactose dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery (hazard ratio (HR) 2.11 p < 0.01) and validation cohort (HR 2.29, p = 0.04) and remained significant in a multivariable analysis (HR 1.85, p = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.

CONCLUSION:

Pre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III subclass. This biomarker may have an important role in prognosis and stratifying patients for adjuvant treatment.

KEYWORDS:

adjuvant; circulating tumor DNA; melanoma; stage III; survival

PMID:
30860590
DOI:
10.1093/annonc/mdz075

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center