Therapeutic Actionability of Circulating Cell-Free DNA Alterations in Carcinoma of Unknown Primary. JCO Precis Oncol 2021;5
Date
11/16/2021Pubmed ID
34778692Pubmed Central ID
PMC8585281DOI
10.1200/PO.21.00011Abstract
UNLABELLED: Cancer of unknown primary (CUP) is a metastatic disease with unidentifiable primary tumor. Somatic alterations can be assessed noninvasively via liquid biopsies interrogating cell-free DNA (cfDNA).
METHODS: We evaluated 1,931 patients with CUP with a cfDNA next-generation sequencing panel (73-74 genes).
RESULTS: Overall, 1,739 patients (90%) had ≥ 1 cfDNA alteration. We then explored alteration actionability (per the levels of evidence from the OncoKB database); 825 patients (47.4% of 1,739) had level 1, level 2, or resistance/R1 alterations. Among 40 clinically annotated patients with CUP who had cfDNA evaluated, higher degrees of matching treatment to alterations (Matching Score > 50% v ≤ 50%) was the only variable predicting improved outcome: longer median progression-free survival (10.4 v 2.5 months; P = .002), overall survival (13.4 v 5.7 months; P = .07, trend), and higher clinical benefit rate (stable disease ≥ 6 months/partial response/complete response; 83% v 25%; P = .003).
CONCLUSION: In summary, cfDNA frequently reveals strong level-of-evidence actionable alterations in CUP, and high degrees of matching to therapy correlates with better outcomes.
Author List
Kato S, Weipert C, Gumas S, Okamura R, Lee S, Sicklick JK, Saam J, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Cell-Free Nucleic Acids
Cohort Studies
Female
High-Throughput Nucleotide Sequencing
Humans
Liquid Biopsy
Male
Middle Aged
Molecular Targeted Therapy
Neoplasms, Unknown Primary
Survival Rate
Young Adult
