Genomic analysis of circulating tumor DNA (ctDNA) to identify potentially targetable alterations is increasingly used in the clinical management of patients with advanced cancer. Beyond tumor profiling, ctDNA analysis also can enable calculation of circulating tumor fraction (TF). While most prognostic models in metastatic cancer are tumor-type specific and require significant patient-level data, quantification of TF in ctDNA has the potential to serve as a pragmatic, tumor-agnostic prognostic tool.
In this study, researchers used the Flatiron Health-Foundation Medicine Clinico-Genomic Database to assess whether the quantification of ctDNA shed using a TF biomarker, based on widely available commercial liquid biopsy testing, could offer robust prognostic information for patients with advanced cancer across multiple tumor types (metastatic castration-resistant prostate cancer, metastatic breast cancer, advanced non-small cell lung cancer, and metastatic colorectal cancer).
Why this matters
The study found plasma ctDNA TF is a pragmatic, independent prognostic biomarker across four advanced cancers with potential to guide clinical discussions around expected treatment outcomes. An immediate application of these data could be in the analysis of clinical trial cohorts, as quantification of TF within a trial population and comparison to real-world cohorts could characterize whether an enrolled population is representative of the expected clinical presentation of the disease. Additionally, prospective study of TF-guided risk stratification to guide therapeutic choice is now being incorporated into some clinical trials.
With further prospective validation, ctDNA TF could be used to inform discussion of escalation and de-escalation of cancer therapy based on patient-level tumor biology.