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Poster Display session 3

3696 - Ultra-sensitive detection of circulating tumor DNA identifies patients in high risk of recurrence in early stages melanoma

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Melanoma

Presenters

Filip Janku

Citation

Annals of Oncology (2019) 30 (suppl_5): v760-v796. 10.1093/annonc/mdz268

Authors

F. Janku1, H.J. Huang2, I. Treskova3, K. Pivovarcikova4, S.G. Call2, F. Meric-Bernstam2, M. Pesta5, J. Polivka6

Author affiliations

  • 1 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2 Department Of Investigational Cancer Therapeutics (phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 3 Department Of Plastic Surgery, Charles University Hospital Pilsen, Pilsen/CZ
  • 4 Department Of Pathology, Charles University Hospital Pilsen, Pilsen/CZ
  • 5 Biomedical Center, Charles University Faculty of Medicine in Pilsen, Pilsen/CZ
  • 6 Biomedical Center, Charles University Faculty of Medicine in Pilsen, 32300 - Pilsen/CZ

Resources

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Abstract 3696

Background

Up to 70% of patients with resected high-risk melanoma develop disease recurrence within 5 years. Adjuvant immunotherapy or targeted therapy can reduce the recurrence rate below approximately 60%; however, it is at the cost of possible toxicity including long-term side effects. We hypothesize that detection of plasma-derived circulating tumor DNA (ctDNA) from patients with resected melanoma can identify patients in high-risk of disease recurrence.

Methods

We developed an ultrasensitive and specific droplet digital PCR – based method (Bio-Rad) to detect BRAFV600E-mutated ctDNA in pre-amplified cell-free DNA with sensitivity up to 1 mutant copy in the wild-type background. Plasma samples from patients with surgically resectable melanoma and BRAFV600E mutation in tumor tissue were collected on the day of surgery and during follow-up visits for BRAFV600E ctDNA detection. Results were correlated with clinical outcomes.

Results

Total of 23 patients with resectable melanoma (stage 1, n = 7; stage 2, n = 9; stage 3, n = 6; stage 0, n = 1) with BRAFV600E mutation in tumor tissue were enrolled. BRAFV600E-mutated ctDNA was detected in 11 (48%) patients before surgery and in 8 (35%) patients after surgery. Patients with ctDNA in samples collected after surgery had more disease recurrences (4/8, 50% vs. 0/11, 0%; P = 0.02) and shorter disease-free survival than patients without ctDNA in samples collected after surgery (P = 0.03).

Conclusions

Our early data demonstrate that ultrasensitive droplet digital PCR method can detect ctDNA in patients with resectable melanoma and that patients with detectable ctDNA in blood samples collected after surgery have superior disease-free survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Sabine Family Foundation (Filip Janku), the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy (Filip Janku), the Institution Research Grant MD Anderson (Filip Janku), Rising Tide Foundation for Cancer Research (Filip Janku), the National Institute of Health through MD Anderson Cancer Center (P30 CA016672), MH CZ—DRO (Faculty Hospital Plzen—FNPl, 00669806), by the Charles University Research Fund (Progres Q39), and by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic.

Disclosure

F. Janku: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): BioMed Valley Discoveries; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Plexxikon; Advisory / Consultancy, Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Piqur; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Asana; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: IFM Therapeutics; Advisory / Consultancy: Synlogic; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Trovagene; Advisory / Consultancy: Immunomet; Non-remunerated activity/ies, instrument loan: BioRad. All other authors have declared no conflicts of interest.

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