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Tyerman et al. J Cancer Metastasis Treat 2022;8:29 https://dx.doi.org/10.20517/2394-4722.2022.20 Page 7 of 9

Table 2. Current trials exploring utility of ctDNA in pancreatic cancer
Estimated Recruitment
Trial number Trial name ctDNA focus and aims Study type
completion status
NCT04616131 Evaluating the response to neoadjuvant chemotherapy with Detection of ctDNA in patients with resectable pancreatic Prospective October 2021 Recruiting
circulating tumor DNA in pancreatic cancer cancer before, during and after treatment and comparison observational cohort
with Ca-19-9, histologic regression, and margin assessment
NCT02818907 Evaluation of survival prognostic factors for patients with Collection of clinical, biological, and quality of life data from Prospective May 2023 Recruiting
exocrine pancreatic cancer resectable or potentially resectable patients with a borderline or resectable pancreatic observational cohort
(Pancreas-CGE) cancer to identify new biomarkers evaluation of treatment
response and surveillance post-treatment
NCT04241367 Verification of predictive biomarkers for pancreatic cancer Quantification and monitoring of KRAS mutations in ctDNA Prospective December 2025 Recruiting
treatment using multicenter liquid biopsy in pancreatic cancer pretreatment and at multiple timepoints observational cohort
thereafter; Discovery of biomarkers through ctDNA panel using
genomic DNA and ctDNA
NCT03250078 A pancreatic cancer screening study in hereditary high risk Screening patients at high risk for pancreatic cancer with Prospective November 2026 Recruiting
individuals MRI/MRCP and collection of serum to correlate biomarkers observational cohort
(including ctDNA) with early pancreatic cancer
ctDNA: Circulating tumor DNA; Ca-19-9: cancer antigen 19-9; KRAS: Kirsten rat sarcoma viral oncogene; MRI: magnetic resonance imaging; MRCP: magnetic resonance cholangiopancreatography.

ctDNA may also enhance pancreatic cancer post-treatment surveillance. In the previously described prospective study, Pietrasz and colleagues collected
longitudinal plasma samples at various time points (every 10-30 days) in a subgroup of 8 patients. They noted that ctDNA levels correlated with radiologic
[33]
change, and progression of disease was detected at a median of 2.4 months using ctDNA compared to 4 months with CT scan surveillance . Similarly, in a
study containing nine patients with postoperative cancer recurrence, ctDNA levels were detectable at an average of 3.1 months, compared to 9.6 months for
detectable change on CT scan (n = 9, P = 0.0004, paired t-test) .
[40]

CONCLUSION
Despite advances in surgical management and chemotherapy, pancreatic cancer remains a difficult disease to treat. Given its often late presentation and high
rates of distant recurrence, biomarkers are needed to enhance surveillance and treatment decision making. ctDNA may be a key biomarker to better
understand the burden of disease and guide neoadjuvant and adjuvant therapies in pancreatic cancer. Utilizing ctDNA assessment to identify early-stage
disease, guide therapy based on risk profile, and monitor for early recurrence may also have an impact on survival. Refinement of ctDNA detection techniques
to make this biomarker more scalable and affordable to test, and more experience with its interpretation during the natural history of the disease, may affirm
ctDNA as a useful biomarker in pancreatic cancer.