Detection of circulating tumor DNA (ctDNA) and early changes in ctDNA levels are predictive of systemic treatment outcomes in patients with advanced solid tumors, according to research published in JCO Precision Medicine.
The findings provide proof of the “feasibility and value of using ctDNA dynamics to monitor therapeutic response in patients with advanced cancers,” the researchers wrote.
For this study, the researchers analyzed ctDNA in serial blood samples taken from 204 patients. The patients had gastrointestinal tract tumors (46.5%), melanoma (14.6%), breast cancer (11.9%), gynecologic cancers (8.1%), lung cancer (4.6%), head and neck cancers (3.5%), gliomas (1.9%), and other cancers (8.8%).
The patients received a total of 260 systemic therapies between 2012 and 2019. Blood samples were collected at baseline, mid-treatment, first restaging, and then whenever possible throughout treatment.
In all, 67.4% of patients had ctDNA detected at baseline, 66.3% had detectable ctDNA mid-treatment, and 60.4% had detectable ctDNA at first restaging.
Patients who did not achieve a response to treatment had higher rates of ctDNA detection than patients who did respond. This was true at the mid-treatment time point (70.9% vs 33.3%; P =.001) and at first restaging (66.4% vs 11.8%; P <.001) but not at baseline.
Patients whose disease progressed during treatment had higher rates of ctDNA detection than patients without progression. This was true at baseline (77.4% vs 60.2%; P =.007), mid-treatment (77.5% vs 58.4%; P =.009), and at first restaging (79% vs 47.8%; P <.001).
Patients with detectable ctDNA had a shorter median time to treatment failure than those without detectable ctDNA at baseline (11 weeks vs 16 weeks; P =.001), mid-treatment (10 weeks vs 18 weeks; P <.001), and first restaging (10 weeks vs 24 weeks; P <.001).
The researchers also found that non-responders were more likely to have positive delta values at mid-treatment (40.9% vs 11.1%; P =.009) and at first restaging (47.4% vs 0; P =.001). Delta values were defined as the difference in variant allele frequency between 2 time points. Positivity was defined as any value above 0 and was used to determine the possibility of using longitudinal ctDNA monitoring to predict treatment outcomes.
Patients with disease progression were also more likely to have positive delta values at mid-treatment (46.5% vs 29.4%; P =.033) and at first restaging (61.8% vs 27.1%; P =.001).
In addition, the median time to treatment failure was significantly shorter for patients with positive delta values at mid-treatment (9 weeks vs 15 weeks; P =.014) and at first restaging (9 weeks vs 15 weeks; P =.002).
“Detection of ctDNA and early dynamic changes in its quantity can predict the clinical outcomes of systemic therapies in patients with advanced solid tumors,” the researchers concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Gouda MA, Huang HJ, Piha-Paul SA, et al. Longitudinal monitoring of circulating tumor DNA to predict treatment outcomes in advanced cancers. JCO Precis Oncol. 2022;6:e2100512. doi:10.1200/PO.21.00512