Blood levels of a protein called CA-125 are currently used to gauge treatment response in women receiving chemotherapy for high grade serous ovarian cancer (HGSOC). However, CA-125 levels don’t change rapidly enough to guide treatment changes after one or two cycles of chemotherapy. In the new study, researchers measured levels of ctDNA carrying mutations in the gene TP53, which are detected in 99% of patients with HGSOC. 318 blood samples from 40 HGSOC patients, taken before, during, and after standard-of-care treatment were analyzed. CT images of the patients’ tumors were collected, as well as data on the progression of their cancers.
The fraction of mutated TP53 in ctDNA (TP53MAF) was correlated with volume of disease as measured by CT scan (Pearson r=0.59, p<0.001), and—unlike CA-125—pre-treatment TP53MAF levels were also correlated with each patient’s time to progression. While CA-125 took 84 days to reflect the full extent of changes after chemotherapy, changes were reflected in TP53MAF in a median of just 37 days. In patients being treated for a relapse, a decrease in TP53MAF of more than 60% was associated with a longer time to progression, while a decrease of 60% or less was associated with poor response to chemotherapy and a time to progression of less than 6 months. The study was limited by small sample size, heterogeneity of treatments, and its retrospective design; larger, prospective trials with uniform treatments are now needed to confirm the findings.
“These findings have strong potential for clinical utility owing to the ease of assaying DNA in plasma and the low cost and speed of ctDNA testing,” the authors say. “Having very early information on response would empower patients and physicians to test alternative treatment options and have high utility in trials that link biomarkers to targeted therapy.”