It may now be easier to avoid unnecessary biopsies in patients with medullary thyroid carcinoma with somatic RET M918T mutations, according to Texas researchers who studied the use of a new liquid biopsy for managing this patient population.
They reported their findings at the 86th Annual Meeting of the American Thyroid Association (ATA).
“Our assay is able to detect in a patients’ blood any DNA that is derived from the patient’s tumor. The assay does this by specifically searching for a somatic mutation present only in tumor cells RET M918T, the most common mutation found in patients with sporadic medullary thyroid carcinoma,” said study investigator Gilbert Cote, PhD, professor at the University of Texas MD Anderson Cancer Center in Houston.
Dr Cote and his colleagues from MD Anderson Cancer Center and the School of Health Professions assessed the utility of liquid biopsy technology instead of tumor biopsy to detect a mutation present in about 40% of sporadic medullary thyroid carcinoma.
The team found elevated detection of the mutation in plasma-derived tumor DNA samples in 32% of patients with direct tumor analysis. In addition, the presence of elevated expression of the mutated gene in cell-free DNA (cfDNA) was strongly associated with a higher risk of death.
The Bio-Rad QX200™ Droplet Digital™ PCR system was able to identify RET M918T cfDNA in 18 of 47 patients with medullary thyroid carcinoma (38%) with somatic M918T mutation detected by tissue biopsy. The researchers reported that 13 patients had RET M918T cfDNA allelic fraction levels that exceeded 1%, which was the value chosen to segregate the cohort for survival analysis. The study confirmed previous work suggesting that calcitonin doubling time of less than 6 months was significantly associated with worst survival.
“There are 2 major take-home messages from our study. First, when we are able to detect mutant tumor DNA in the blood, we found a 100% concordance with the mutation being present in the tumor. Therefore, the test can be used when no tumor tissue is available for mutation testing. Second, we found that the level of circulating tumor DNA was associated with progressing cancer and ultimately patient survival,” Dr Cote told Endocrinology Advisor.
In patients with a known RET M918T mutation, the test can be used to complement other biomarkers such as serum calcitonin, with the advantage of looking at a single time point in the patient’s history, according to Dr Cote. He said this is especially important when patients are started on new treatments. This assay provides 1 measure of determining if the therapy is effective.
In this current study, TNM Classification of Malignant Tumor stage was not associated with calcitonin doubling time or M918T cfDNA allelic fraction.
Dr Cote said these findings warrant further investigation. These current study findings are also highly relevant, he noted, because they were made possible by the National Cancer Institute funding in the first ever thyroid cancer SPORE grant. He said he hopes that trials like these will lead to significant clinical advances over the next 3 to 5 years.
Disclosures: Dr Cote reports no financial relationships or commercial interests.
- Cote GJ, Evers C, Hu M, et al. Poster 74. Liquid biopsy of cfDNA as a predictor of survival in medullary thyroid carcinoma patients with somatic RET M918T mutations. Presented at: American Thyroid Association Annual Meeting; September 21-25, 2016; Denver, Colorado.