Abstract 1376
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 type | Stage | Somatic mutation | Epigenetic pattern | Total number | Recurrence+, n (%) | Site of recurrence |
---|---|---|---|---|---|---|
Adenocarcinoma | stage 1 | ctDNA- | methylation- | 9 | 1 (11) | Lung |
n = 17 | methylation+ | 6 | 2 (33.3) | Stump, bone | ||
ctDNA+ | 2 | 1 (50) | lung | |||
stage 2 | ctDNA- | methylation- | 0 | 0 (0) | ||
n = 2 | methylation+ | 0 | 0(0) | |||
ctDNA+ | 1 | 1 (100) | multiple | |||
stage 3 | ctDNA- | methylation- | 0 | 0 (0) | ||
n = 4 | methylation+ | 2 | 0 (0) | |||
ctDNA+ | 2 | 2 (100) | brain, multiple | |||
Sqaumous cell carcinoma | stage1 | ctDNA- | methylation- | 0 | 0 (0) | |
n = 7 | methylation+ | 3 | 0 (0) | |||
ctDNA+ | 4 | 1 (25) | multiple | |||
stage2 | ctDNA- | methylation- | 0 | 0 (0) | ||
n = 9 | methylation+ | 0 | 0 (0) | |||
ctDNA+ | 9 | 2 (22.2) | multiple, lung | |||
stage3 | ctDNA- | methylation- | 0 | 0 (0) | ||
n = 4 | methylation+ | 1 | 0 (0) | |||
ctDNA+ | 3 | 1 (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.
Resources from the same session
4290 - Characterization of the mechanism of action and efficacy of MEN1611 (PA799), a novel PI3K inhibitor, in breast cancer preclinical models.
Presenter: Alessio Fiascarelli
Session: Poster Display session 3
Resources:
Abstract
2167 - Neat-1: culprit lnRNA tying PIG-C, MSLN, CD80 in TNBC
Presenter: Nada Hussein
Session: Poster Display session 3
Resources:
Abstract
1829 - A novel RAF/MEK inhibitor CH5126766 in phase 1 clinical trial has an effectiveness in the combination with eribulin for the treatment of triple negative breast cancer
Presenter: Hisako Ono
Session: Poster Display session 3
Resources:
Abstract
4357 - Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer
Presenter: Eva Galan-Moya
Session: Poster Display session 3
Resources:
Abstract
5163 - Preclinical Evaluation targeting both IGF1R and IR in Triple Negative Breast Cancer
Presenter: Alex Eustace
Session: Poster Display session 3
Resources:
Abstract
832 - Monospecific antibody targeting of CDH11 inhibits epithelial-to-mesenchymal transition and represses cancer stem cell-like phenotype by up-regulating miR-335 in metastatic breast cancer, in vitro and in vivo.
Presenter: Jia-Hong Chen
Session: Poster Display session 3
Resources:
Abstract
3781 - Pharmacological screening with Chk1 inhibitors identify synergistic agents to overcome resistance to platinums in basal breast and ovarian cancer
Presenter: Ana Lucia Sanabria
Session: Poster Display session 3
Resources:
Abstract
3275 - Comparison of 11 circulating miRNAs and CA125 kinetics in ovarian cancer during first line treatment: data from the randomized CHIVA trial (a GINECO-GCIG study)
Presenter: Patrick Robelin
Session: Poster Display session 3
Resources:
Abstract
3391 - Inhibiting Ehmt2 and Ezh2 histone methyltransferases alters the immune microenvironment in a Trp53-/- murine ovarian cancer model
Presenter: Pavlina Spiliopoulou
Session: Poster Display session 3
Resources:
Abstract
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract