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Proffered paper session - Translational research

3299 - Circulating tumour DNA analysis predicts relapse following resection in stage II and III melanoma


20 Oct 2018


Proffered paper session - Translational research


Translational Research

Tumour Site



Lavinia Tan


Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269


L. Tan1, S.K. Sandhu1, R. Lee2, J. Li3, J. Callahan4, J. Raleigh3, A. Hatzimihalis3, P. Middlehurst2, M. Henderson5, M. Shackleton6, A. Haydon6, D. Gyorki5, D. Oudit7, R.J. Hicks4, P. Lorigan8, G.A. McArthur1, R. Marais2, S.Q. Wong3, S. Dawson1

Author affiliations

  • 1 Medical Oncology, Peter MacCallum Cancer Center, 3000 - Melbourne/AU
  • 2 Molecular Oncology Group, Cancer Research UK Manchester Institute, M20 4BX - Manchester/GB
  • 3 Cancer Research, Peter MacCallum Cancer Center, 3000 - Melbourne/AU
  • 4 Nuclear Medicine, Peter MacCallum Cancer Center, 3000 - Melbourne/AU
  • 5 Surgical oncology, Peter MacCallum Cancer Center, 3000 - Melbourne/AU
  • 6 Medical Oncology, The Alfred Hospital, 3004 - Melbourne/AU
  • 7 Surgical oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 8 Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB


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Abstract 3299


Adjuvant immunotherapy and BRAF-targeted therapies have shown improved relapse-free survival (RFS) in patients (pts) with resected melanoma. There is a critical need to develop biomarkers to stratify pts based on risk of relapse given the cost and toxicities with these therapies.


Droplet digital PCR was used to detect known mutations in circulating tumour DNA (ctDNA) from 112 pts with resected stage II-III melanoma who consented to prospective serial plasma and risk-adapted F-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) monitoring. External validation was performed in a prospective independent cohort.


In 92/112 pts who did not receive adjuvant therapy, 55/92 (60%) pts relapsed at a median follow-up of 21 months. Plasma samples were available in 67/92 pts at baseline and 59/92 pts postoperatively (median 2 weeks post surgery). ctDNA was detected at baseline and postoperatively in 21/67 (31%) pts and 15/59 (25%) pts respectively. 19/21 and 14/15 pts with ctDNA detected at baseline and the postoperative visit relapsed. Detection of ctDNA predicted patients at high risk of relapse at baseline (RFS hazard ratio [HR] 4.7; 95% confidence interval [CI] 2.3-9.6; p < 0.0001) and postoperatively (HR 9.3; 95% CI 4-22; p < 0.0001). Inferior distant metastasis-free survival (DMFS) was associated with ctDNA detection at baseline (HR 5.3; 95% CI 2.5-11; P < 0.0001) and postoperatively (HR 14; 95% CI 5.4-37; P < 0.0001). These findings were validated in an independent cohort. Postoperative ctDNA detection remained an independent predictor of both RFS (HR 8; 95% CI 3-20; P < 0.0001) and DMFS (HR 11; 95% CI 4-30; P < 0.0001) after adjustment for disease stage and BRAF mutation status. In 20/112 pts who received adjuvant therapy, 3/18 pts with a postoperative plasma sample had detectable ctDNA. Serial plasma samples were available in 2 of 3 cases and showed clearance of ctDNA post immunotherapy. At a median follow-up of 7 months, none of the pts with detectable ctDNA who received adjuvant therapy have relapsed.


Detection of ctDNA at baseline and after surgical resection in two independent prospective cohorts identifies pts with stage II/III melanoma at highest risk of relapse with potential to guide adjuvant therapy decisions.

Clinical trial identification

Legal entity responsible for the study

Peter MacCallum Cancer Centre.


National Health and Medical Research Council, Cancer Research UK, Wellcome Trust.

Editorial Acknowledgement


S.K. Sandhu: Honorarium: Merck, Bristol-Myers Squibb. M. Shackleton: Travel support: BMS, Merck; Consultancy: BMS, Merck, MSD; Honoraria: BMS, Merck, MSD Research support: BMS. A. Haydon: Advisory board: Novartis, MSD. D. Gyorki: Advisory board: Amgen; Honorarium: Amgen. P. Lorigan: Consultancy/ Advisory work: Amgen, GSK, Roche, BMS, Merck, Novartis; Speaker bureau: Merck, BMS, Novartis, Roche; Support for travel: Merck, BMS, Roche. R. Marais: Research funding: Basilea Pharmaceuticals. All other authors have declared no conflicts of interest.

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