Scimex: Levels of circulating tumor DNA (ctDNA) detected in a blood test are correlated with the size of ovarian cancers and can predict a patient’s response to treatment or time to disease progression, according to a retrospective study of cancer patients’ blood samples published in PLOS Medicine by Nitzan Rosenfeld and James Brenton of Cancer Research UK Cambridge Institute and colleagues.
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
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.”