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
3190 - GI101, a novel triple-targeting bispecific CD80-IgG4-IL2variant fusion protein, elicits synergistic anti-tumor effects in preclinical models
Presenter: Jae Chan Park
Session: Poster Display session 3
Resources:
Abstract
4062 - Phase 1b, open-label, dose-escalation study of M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced solid tumors
Presenter: Julius Strauss
Session: Poster Display session 3
Resources:
Abstract
5777 - THOR-707, a novel not-alpha IL-2, promotes all key immune system anti-tumoral actions of IL-2 without eliciting vascular leak syndrome (VLS)
Presenter: Marcos Milla
Session: Poster Display session 3
Resources:
Abstract
5047 - A phase I clinical trial of malignant pleural mesothelioma treated with locally delivered autologous anti-FAP-targeted CAR T-cells
Presenter: Alessandra Curioni
Session: Poster Display session 3
Resources:
Abstract
1679 - HPV16 E6-specific TCR-T armored with checkpoint blockade in the treatment of cervical cancer
Presenter: Paul Bryson
Session: Poster Display session 3
Resources:
Abstract
1133 - the Mutant Neoantigen Specific T Cell Is a Personalized Immunotherapy in Refractory Solid Tumor
Presenter: Qi Song
Session: Poster Display session 3
Resources:
Abstract
3338 - NY-ESO-1 and LAGE1A –an emerging target for cell therapies in solid tumours
Presenter: Ioanna Eleftheriadou
Session: Poster Display session 3
Resources:
Abstract
3089 - Targeting myeloid-derived suppressor cells and T cells: combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model
Presenter: Mikael Sodergren
Session: Poster Display session 3
Resources:
Abstract
5991 - Master Checkpoint Cbl-b Inhibition: Anti-tumor Efficacy in a Murine Colorectal Cancer Model Following siRNA-based Cell Therapy
Presenter: Kathrin Thell
Session: Poster Display session 3
Resources:
Abstract
5007 - Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy
Presenter: Miren Zuazo
Session: Poster Display session 3
Resources:
Abstract