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Combined genomic and epigenomic assessment of cell-free circulating tumor DNA (cfDNA) for cancer diagnosis and recurrence-risk assessment in early-stage lung cancer

Date

30 Sep 2019

Session

Poster Display session 3

Presenters

Junghee Lee

Citation

Annals of Oncology (2019) 30 (suppl_5): v25-v54. 10.1093/annonc/mdz239

Authors

J. Lee1, I. Kim2, J.H. Cho1, H.K. Kim1, J. Lee3, S. Lee4, M. Shultz2, A. Jaimovich2, J. Odegaard2, S. Olsen2, A. Talasaz2, J. Kim1

Author affiliations

  • 1 Department Of Thoracic And Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 06351 - Seoul/KR
  • 2 Guardant Health, Inc., 94063 - Redwood City/US
  • 3 Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 06351 - Seoul/KR
  • 4 Division Of Hematology-oncology, Department Of Medicine, Samsung Medical Center, Seoul/KR
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Background

Circulating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or recurrence prediction in early stage lung cancer patients.

Methods

We analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing assay incorporating somatic and epigenomic analysis, and a bioinformatic classifier to filter non-tumor derived variants.Table: 111P

Cell typeStageSomatic mutationEpigenetic patternTotal numberRecurrence+, n (%)Site of recurrence
Adenocarcinomastage 1ctDNA-methylation-91 (11)Lung
n = 17methylation+62 (33.3)Stump, bone
ctDNA+21 (50)lung
stage 2ctDNA-methylation-00 (0)
n = 2methylation+00(0)
ctDNA+11 (100)multiple
stage 3ctDNA-methylation-00 (0)
n = 4methylation+20 (0)
ctDNA+22 (100)brain, multiple
Sqaumous cell carcinomastage1ctDNA-methylation-00 (0)
n = 7methylation+30 (0)
ctDNA+41 (25)multiple
stage2ctDNA-methylation-00 (0)
n = 9methylation+00 (0)
ctDNA+92 (22.2)multiple, lung
stage3ctDNA-methylation-00 (0)
n = 4methylation+10 (0)
ctDNA+31 (33.3)Mediastinal LNs

Results

Somatic mutation analysis alone detected ctDNA in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 67% (37/55). ctDNA detection rate varied by pathological subtypes; using combined approach, ctDNA was detected in all squamous cell carcinoma patients, while only 55% (12/22) in adenocarcinoma (ADC) (p=0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, within 2 years of follow-up, pre-operative ctDNA status was correlated with tumor recurrence after resection; among 17 stage I ADC patients, three of eight (38%) ctDNA-positive cases showed recurrence, while only one of nine (11%) ctDNA-negative cased did (p=0.29). Interestingly, patients with somatic mutation in their ctDNA have shown higher recurrence rate.

Conclusions

Utilizing a plasma-only sequencing assay incorporating somatic genomic and epigenomic analysis, ctDNA detection rate in early stage lung cancer (stage I-III) can far outperform the detection rate of somatic sequence variant detection alone. And, the presence of pre-operative ctDNA in patients with early stage lung adenocarcinoma may identify those who are more likely to have disease recurrence.

Legal entity responsible for the study: Guradant Health, Inc.

Clinical trial identification

Editorial acknowledgement

Funding

Guardant Health, Redwood City, CA, USA.

Disclosure

I. Kim: Full / Part-time employment, Officer / Board of Directors: Guardant Health. M. Shultz: Officer / Board of Directors: Guardant Health. A. Jaimovich: Officer / Board of Directors: Guardant Health. J. Odegaard: Officer / Board of Directors: Guardant health, Inc. S. Olsen: Officer / Board of Directors: Guardant Health, Inc. A. Talasaz: Officer / Board of Directors: Guardant health. J. Kim: Research grant / Funding (self): Guardant health, Inc. All other authors have declared no conflicts of interest.

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