Nearly 50% of pregnant participants with abnormal cell-free DNA sequencing results were found to have undiagnosed cancers, according to an ongoing study published in The New England Journal of Medicine. The research builds on the success of cell-free DNA screening in prenatal care, which has reduced invasive diagnostic procedures like amniocentesis by 50-70% worldwide.
Conducted at the National Institutes of Health, researchers explored the incidental detection of maternal cancer through cell-free DNA (cfDNA) sequencing, a method commonly used for prenatal screening. The study aimed to identify sequencing patterns and biomarkers that could help detect occult cancers in participants who received unusual or nonreportable cfDNA results. The study enrolled 107 participants (mean age 33, range 19-53) who were either pregnant or up to 2 years postpartum, with 89 participants pregnant at the time of cancer screening.
Participants underwent a standardized cancer-screening protocol after receiving abnormal cfDNA results from 12 commercial laboratories in North America. The screening included whole-body magnetic resonance imaging (MRI), laboratory tests, serum tumor markers, fecal occult blood testing, and physical examinations.
Cancer was present in 52 of the 107 participants (48.6%), with lymphoma being the most common diagnosis (31 participants, 59.6%). Of these lymphoma cases, 20 were Hodgkin's lymphoma and 11 were non-Hodgkin's lymphoma. Other diagnoses included colorectal cancer (9 participants, 17.3%), breast cancer (4 participants, 7.7%), cholangiocarcinoma, adrenocortical carcinoma, non-small-cell lung cancer, pancreatic cancer, Ewing's sarcoma, and renal carcinoma. Among the 20 participants with solid tumors, 2 had stage 1 disease, 5 had stage 2 or 3 disease, and 13 had stage 4 disease, with 13 participants eligible for potentially curative treatment. The study revealed that 29 of the 52 participants (55.8%) with cancer were asymptomatic, while 13 (25%) exhibited symptoms that were attributed to pregnancy or other causes.
The research demonstrated that whole-body MRI had a high sensitivity of 98.0% and specificity of 88.5% in detecting occult cancer. Physical examination and laboratory tests were of limited use in identifying cancer. The standardized research cfDNA sequencing revealed 49 participants with a combination of chromosomal gains and losses across multiple chromosomes, 47 of whom (95.9%) had cancer. In contrast, sequencing patterns showing only chromosomal gains or losses were associated with nonmalignant conditions such as fibroids.
The median time between initial clinical sequencing and cancer screening was 9.6 weeks, ranging from 2.0 to 114.6 weeks. The study noted several limitations, including subjective grouping of cfDNA sequencing patterns, lack of prespecified hypotheses or analyses, inability to directly compare research and original clinical sequencing results, and variable follow-up periods for participants with ongoing concerns for cancer.
The findings suggest that whole-body MRI is an effective tool in the follow-up of patients with nonreportable cfDNA results, highlighting the importance of timely cancer screening. The study demonstrates the potential for cfDNA sequencing to identify participants at risk for occult cancer and emphasizes the need for further research in this area.
Full disclosures can be found in the published study.