Identifying biomarkers associated with disease-free survival in stage I non–small cell lung cancer.

Authors

null

Christopher W. Seder

Rush University Medical Center, Chicago, IL

Christopher W. Seder , Hita Moudgalya , Andrew E. Donaldson , Kayla Viets Layng , Elizabeth Mauer , Janakiraman Subramanian , Cristina L. Fhied , Nicole Geissen , Gillian Alex , Justin Karush , Michael J. Liptay , Jeffrey Allen Borgia

Organizations

Rush University Medical Center, Chicago, IL, Tempus Labs, Chicago, IL, Hanna Cancer Assocs, Knoxville, TN

Research Funding

Other

Background: Patients with early stage, non-small cell lung cancer (NSCLC) with solitary pulmonary lesions ≤4 cm typically have favorable outcomes. However, disease recurrence impacts up to 30% of patients, leading to either additional surgical or systemic interventions. New methods to risk stratify patients based on clinical and molecular parameters may improve our ability to select cases that would benefit from more frequent surveillance or enrollment in clinical trials evaluating systemic therapy. Methods: We retrospectively analyzed data from 179 patients with early stage (T1a-2aN0M0) NSCLC from a single institution. All patients had anatomic resection, negative margins, and systematic nodal sampling. Clinical and demographic data were abstracted from patient charts and tumor samples were molecularly profiled using the Tempus xT solid tumor assay (DNA-seq of 595-648 genes at 500x coverage, whole exome-capture RNA-seq). Pathogenic alterations (single nucleotide variants and insertion/deletions) and RNA expression were examined. Bivariate Cox-proportional Hazards models were used to assess the association of individual clinical, demographic, and molecular variables with recurrence-free survival, defined as the time from surgery until recurrence or death. Results: Our dataset included 166 stage IA1-3 patients and 13 stage IB patients, of which 36 patients experienced a recurrence or death event after surgery. Clinical and DNA-seq data was available for all patients, and RNA expression data was available for 172 patients. Across all patients, the most common somatically mutated genes were TP53 (33% of tumors) and KRAS (16% of tumors), consistent with previous studies. Increasing log10-RNA expression for NTRK1 (HR: 5.95; 95% CI, 1.16-30.4; p = 0.027) and CD274 (PD-L1) (HR: 7.88; 95% CI, 1.61-38.6; p = 0.013) and decreasing log10-RNA expression for EGFR (HR: 0.24; 95% CI, 0.05-1.21; p = 0.071) and ERBB2 (Her2) (HR: 0.20; 95% CI, 0.04-0.97; p = 0.042) were associated with increased risk of recurrence or death. Conclusions: Increased expression of NTRK1 and CD274 (PD-L1) and decreased expression of EGFR and ERBB2 (Her2) were associated with a increased risk for recurrence following surgery. This may have mechanistic implications for heightened tumor aggressiveness and/or metastatic potential. Future work will expand our cohort and validate our findings in a broader set of early-stage NSCLC patients.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Track

Lung Cancer

Sub Track

Local-Regional Non–Small Cell Lung Cancer

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 8543)

DOI

10.1200/JCO.2022.40.16_suppl.8543

Abstract #

8543

Poster Bd #

170

Abstract Disclosures