Background:
While liquid biopsies are convenient and robust, they also have limitations that must be recognized for optimal use.The amount of circulating tumor DNA (ctDNA) shed into a patient’s blood depends on the type and stage of cancer, as well the patient’s current treatment.
In a patient where a lot of ctDNA had been shed into the bloodstream, Foundation Medicine’s comprehensive liquid biopsy-based molecular profiling test will indicate that the patient has an elevated tumor fraction. This elevated tumor fraction can be useful in treatment decision making.
Study Details:
In this study, researchers hypothesized that genomic biomarkers, such as tumor fraction, in ctDNA may identify patients who have poorer overall survival with second generation novel hormonal therapy. 494 pre-treatment blood samples from IMbassador250, a prospective phase III international trial for men with metastatic castrate resistant prostate cancer (mCRPC), were submitted for comprehensive genomic profiling using FoundationOne Liquid CDx.
Researchers detected elevated tumor fraction using a novel algorithm that incorporates aneuploidy as well as tumor-derived short variant signal. A pre-specified tumor fraction cutoff of ≥ 2% was defined as high.
The tumor fraction-high group had significantly shorter overall survival than tumor fraction-low group. Focusing on the patients with a tumor fraction ≥ 2%, exploratory analysis observed less favorable outcomes when AR amplification was detected, while individual AR mutations were not strongly associated with overall survival.
Why This Matters:
In this cohort, tumor fraction < 2% at baseline is strongly associated with favorable overall survival on second generation novel hormonal therapy compared to patients with tumor fraction ≥ 2%. Tumor fraction alone has comparable discriminatory ability to anticipate overall survival compared to all available clinical features combined and adds significant prognostic power when combined with clinical features in this setting. AR amplifications, but not mutations, were also associated with poor prognosis.
View the full publication on ASCO.org.