AUTHOR=Botrus Gehan , Uson Junior Pedro Luiz Serrano , Raman Puneet , Kaufman Adrienne E. , Kosiorek Heidi , Yin Jun , Fu Yu , Majeed Umair , Sonbol Mohamad Bassam , Ahn Daniel H. , Chang Isabela W. , Drusbosky Leylah M. , Dada Hiba , Starr Jason , Borad Mitesh , Mody Kabir , Bekaii-Saab Tanios S. TITLE=Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.794009 DOI=10.3389/fonc.2021.794009 ISSN=2234-943X ABSTRACT=Background

Plasma-based circulating cell-free tumor DNA (ctDNA) genomic profiling by next-generation sequencing (NGS)is an emerging diagnostic tool for pancreatic cancer (PC). The impact of detected genomic alterations and variant allele fraction (VAF) in tumor response to systemic treatments and outcomes is under investigation.

Methods

Patients with advanced PC who had ctDNA profiled at time of initial diagnosis were retrospectively evaluated. We considered the somatic alteration with the highest VAF as the dominant clone allele frequency (DCAF). ctDNA NGS results were related to clinical demographics, progression-free survival (PFS) and overall survival (OS).

Results

A total of 104 patients were evaluated. Somatic alterations were detected in 84.6% of the patients. Patients with ≥ 2 detectable genomic alterations had worse median PFS (p < 0.001) and worse median OS (p = 0.001). KRAS was associated with disease progression to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (p < 0.001) and worse median OS (p = 0.002). TP53 was associated with worse median PFS (p = 0.02) and worse median OS (p = 0.001). The median DCAF was 0.45% (range 0-55%). DCAF >0.45% was associated with worse median PFS (p<0.0001) and median OS (p=0.0003). Patients that achieved clearance of KRAS had better PFS (p=0.047), while patients that achieved clearance of TP53 had better PFS (p=0.0056) and OS (p=0.037).

Conclusions

Initial detection of ctDNA in advanced PC can identify somatic alterations that may help predict clinical outcomes. The dynamics of ctDNA are prognostic of outcomes and should be evaluated in prospective studies.