Abstract 1691: The landscape of intra-tumor heterogeneity (ITH) and its association with actionable mutation and blood tumor mutation burden (bTMB) in patients with non-small cell lung cancer (NSCLC) assessed by circulating tumor DNA (ctDNA)

Background: ITH, which is caused by subpopulations of cells with distinct genomic alterations within the same tumor is known to have an impact on the biological profile and natural history of the tumor. However, assessment of ITH is mostly done tissue-based. Herein, we investigated the correlation of ITH assessed by ctDNA with bTMB and the presence of actionable mutations. Method: Blood samples were collected from consecutive 53 patients with NSCLC seen at Northwestern Memorial Hospital. For each sample, SNV, indel, and CNV results generated by sequencing of all plasma ctDNA (Guardant360) were formatted for PyClone. ITH scores were calculated using the number of clusters identified in the sample divided by the number of variants detected in the sample. Result: bTMB was evaluable for 22 patients (41%). 7 patients (13%) had actionable mutations associated with FDA-approved therapies. Cluster number was positively correlated with bTMB (Pearson r 0.69, p-value 0.0004, CI 0.38 to 0.86) and was negatively correlated with the presence of actionable mutations (median 2 vs 5, p-value 0.01). ITH scores were not significantly correlated with bTMB (Pearson r 0.03, p-value 0.89, CI -0.39 to 0.44). Conclusion: Higher cluster number was inversely correlated with the presence of actionable mutations and positively correlated with bTMB. Our study illustrates the importance of utilizing liquid biopsy to assess ITH with tissue-based ITH in clinics for a better understanding of the biological profile of tumor. Citation Format: Leeseul Kim, Yeun Ho Lee, Hye Sung Kim, Horyun Choi, Jinah Kim, Young Kwang Chae. The landscape of intra-tumor heterogeneity (ITH) and its association with actionable mutation and blood tumor mutation burden (bTMB) in patients with non-small cell lung cancer (NSCLC) assessed by circulating tumor DNA (ctDNA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1691.