Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival

Frontiers in Oncology

卷:11

Pedro Luiz Serrano Uson Junior¹  Heidi Kosiorek³  Adrienne E. Kaufman³  Gehan Botrus³  Daniel H. Ahn³  Isabela W. Chang³  Puneet Raman³  Mohamad Bassam Sonbol³  Tanios S. Bekaii-Saab³  Kabir Mody⁴  Umair Majeed⁴  Jun Yin⁴  Jason Starr⁴  Yu Fu⁵  Leylah M. Drusbosky⁵  Hiba Dada⁵  Mitesh Borad⁶ 

[1] Center for Personalized Medicine, Hospital Israelita Albert Einstein, Sao Paulo, Brazil;

[2] Center of individualized Medicine, Mayo Clinic, Rochester, MN, United States;

[3] Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, United States;

[4] Division of Oncology, Mayo Clinic, Jacksonville, FL, United States;

[5] Guardant Health, Inc., Redwood City, CA, United States;

[6] Mayo Clinic Cancer Center, Phoenix, AZ, United States;

关键词: circulating tumor DNA;    ctDNA;    KRAS;    TP53;    pancreatic cancer;   

DOI  :  10.3389/fonc.2021.794009

来源: DOAJ

【 摘 要 】

BackgroundPlasma-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.MethodsPatients 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).ResultsA 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).ConclusionsInitial 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.

【 授权许可】

Unknown