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
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract