S. Zhang2, T. Boyle1,2, C. Williams1,2, S. Antonia1,2, A. Chiappori1,2, J. Gray1,2, T. Tanvetyanon1,2, B. Creelan1,2, E. Haura1,2, M. Shafique1,2, J. Fontaine1,2, J. Cox1,2, F. Kaszuba1,2, R. Keenan1,2, V. Nair1,2, E. Toloza1,2 1Moffitt Cancer Center And Research Institute,Tampa, FL, USA 2University Of South Florida College Of Medicine,Tampa, FL, USA
Introduction: Liquid biopsy of peripheral blood circulating tumor DNA (ctDNA) and protein can capture genetic and proteomic data that represents the molecular state of tumors. We sought to investigate whether liquid biopsy can correlate histopathologic factors, treatment, or outcomes with ctDNA mutations and proteomic signatures.
Methods: We retrospectively analyzed data from all non-small cell lung cancer (NSCLC) patients who underwent liquid biopsy analysis of ctDNA and proteins on peripheral blood samples from August 2016 to June 2018. The ctDNA analysis detected presence of targetable mutations, and proteomic analysis grouped patients into Good or Poor status. Patients with proteomic Poor were excluded. Liquid biopsy results were then correlated with histopathologic factors, such as tumor histology, grade of differentiation, tumor (T) status, nodal (N) status, metastasis (M) status, pathologic stage (pStage), and treatment. Student’s t-test, Kruskal-Wallis test, or Chi-square test were used to compare these factors between groups, and Kaplan-Meier curves were used to compare survival. Statistical differences were significant at p≤0.05.
Results: Of 522 patients analyzed by liquid biopsy, 62 (11.9%) proteomic-Poor patients were excluded. Of 460 (88.1%) proteomic-Good patients, 376 (81.7%) were mutation-negative [mutation(-)], and 84 (18.3%) were mutation-positive [mutation(+)]. Mean age were similar between mutation(-) and mutation(+) groups (83.4 yr vs. 67.5 yr; p=0.462). Mean primary tumor size differed between mutation(-) and mutation(+) groups (3.0 cm vs. 4.7 cm; p=0.002). Histology (i.e. adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma, etc.) differed between the two groups, with mutation(-) patients having proportionately more squamous histology (p<0.01). Tumor grade of differentiation, N status, M status, and pStage differed between mutation(-) and mutation(+) groups, with the mutation(+) group having more patients with poorly-differentiated (G3) tumors (p<0.01), N2 and N3 status (p<0.01), M1 status (p<0.01), and pStage III and IV cancers (p< 0.01). Treatment differed between mutation(-) and mutation(+) groups, with the mutation(-) group more likely to have surgery or radiation and the mutation(+) group more likely to receive systemic therapy (p<0.01). In Kaplan-Meier survival analysis, the mutation(-) group had 1-year overall survival (1-yr OS) of 88.5% compared to a 1-yr OS of 45.2% for the mutation(+) group (p<0.01).
Conclusion: A commercially-available peripheral blood liquid biopsy kit identified NSCLC patients as mutation(-) or mutation(+) by ctDNA analysis and as Good status by proteomic analysis. While age did not correlate with mutation status, mutation(+) patients had larger tumors, more poorly-differentiated tumors, more N2 and N3 status, more distant metastases, and higher pStaged cancers, required systemic therapy more often, and had worse 1-yr OS than mutation(-) patients.