A personalized, tumor-informed circulating tumor DNA assay demonstrated 100% specificity and 75% sensitivity for detecting cancer recurrence after liver transplantation in patients with hepatocellular carcinoma or cholangiocarcinoma, according to a prospective, single-center study published in the Journal of Gastrointestinal Oncology. The study evaluated 100 ctDNA assays performed on 38 patients who underwent liver transplantation for primary liver cancer.
Evaluating ctDNA Test Performance in Post-Transplant Surveillance
Investigators tracked 38 patients undergoing liver transplantation between April 2018 and February 2023. Among this cohort, 33 patients had hepatocellular carcinoma, four had cholangiocarcinoma, and one had a mixed tumor. Researchers developed a personalized circulating tumor DNA assay, known commercially as Signatera, for each patient using whole exome sequencing of explanted tumor tissue. This process selected up to 16 somatic, clonal single nucleotide variants for tracking in peripheral blood samples.
Testing schedule protocols called for blood draws every 3 months for the first 2 years, followed by every 6 months for up to 5 years after transplant. Patients simultaneously underwent standard-of-care cross-sectional imaging and serum biomarker testing on the same timeline. Out of 100 total assays performed, researchers recorded 6 positive results, 85 negative results, and 9 results deemed insufficient to process due to lack of adequate tumor tissue.
Sensitivity, Specificity, and Predictive Values
Recurrence was diagnosed in 6 of the 38 patients, representing 15.8% of the study population. Among these recurring cases, the ctDNA assay returned positive results for three patients, a negative result for one patient, and insufficient results for two patients. When excluding the 9 insufficient-to-process samples, leaving 31 evaluable assays, the personalized test achieved a sensitivity of 75% and a specificity of 100%.
The assay yielded a negative predictive value of 96.4% and a positive predictive value of 100%. By comparison, standard-of-care serum biomarkers—alpha-fetoprotein for hepatocellular carcinoma and carbohydrate antigen 19-9 for cholangiocarcinoma—demonstrated a sensitivity of 75% and a specificity of 93% in the same patient population. Statistical analysis showed no significant difference in sensitivity or specificity between the personalized ctDNA test and standard biomarkers.
When researchers evaluated ctDNA, alpha-fetoprotein, and carbohydrate antigen 19-9 results jointly, combined sensitivity rose to 100% while specificity remained high at 94%. However, imaging maintained an advantage in early detection. Only one patient showed ctDNA positivity that preceded an imaging-based recurrence diagnosis, whereas standard cross-sectional imaging detected recurrence ahead of ctDNA in five of the six patients who experienced a recurrence.
Sample Processing Limitations and Clinical Implications
The overall rate of assays deemed insufficient to process reached approximately 10%, driven primarily by insufficient tumor tissue from explant pathology in eight of the nine affected samples. Researchers found that this processing failure rate associated significantly with the receipt of pre-transplant locoregional therapy, lower tumor stage, and poorer cellular differentiation on explant pathology.
Median recurrence-free survival for the cohort stood at 583 days, while median overall survival reached 728 days. In evaluating the clinical utility of the assay, study authors noted that ctDNA’s high specificity and positive predictive value exceed its sensitivity. Consequently, the authors concluded that the test functions best as a confirmatory tool for diagnostic uncertainty during standard surveillance rather than as a standalone screening mechanism, potentially reducing the need for invasive tissue biopsies when conventional imaging and biomarkers yield inconclusive results.
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