Circulating tumor DNA as a predictive marker for occult metastases in pancreatic cancer patients with radiographically non‐metastatic disease

Abstract

Purpose To elucidate the effectiveness of circulating tumor DNA (ctDNA) for predicting occult metastases in patients with pancreatic cancer without apparent metastases. Methods Circulating tumor DNA was obtained from plasma samples of 165 patients with pancreatic cancer and analyzed using droplet digital PCR. The prevalence and allele frequencies of ctDNA were compared across different patterns and degrees of metastatic spread. Results Of the 142 patients without apparent metastases who underwent abdominal exploration, 39 (27.5%) harbored occult metastases including positive peritoneal lavage cytology. The prevalence of ctDNA was significantly higher in patients with occult metastases than in those without (41.0% vs 14.6%, P = .001). A markedly high prevalence of ctDNA was observed in patients with radiographically visible metastases (78.3%). ctDNA was found to be an independent predictor of the presence of occult metastases (odds ratio: 3.113, P = .039), and its diagnostic performance in combination with tumor markers had a sensitivity of 66.7% and a specificity of 81.6%. In 62 treatment‐naïve patients without metastases, multivariate analysis identified the presence of ctDNA as an independent prognostic factor (hazard ratio: 6.311, P = .001). Conclusion Circulating tumor DNA can help predict the presence of occult metastases in pancreatic cancer patients with radiographically non‐metastatic disease.

Importance of triple tumor markers as biomarkers in patients with pancreatic ductal adenocarcinoma

“…Novel biomarkers such as circulating tumor cells (CTCs) and cell‐free DNA (cfDNA) have been developed recently. 28 , 29 However, research on CTCs and cfDNA remains in the experimental stage, warranting future large trials. The levels of CTCs in peripheral blood are low; therefore, their detection is extremely challenging.…”

“…In clinical practice, the only noninvasive blood‐based biomarker routinely used is CA19‐9. Novel biomarkers such as circulating tumor cells (CTCs) and cell‐free DNA (cfDNA) have been developed recently 28,29 . However, research on CTCs and cfDNA remains in the experimental stage, warranting future large trials.…”

Defining the Optimal Duration of Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma

“…In 2021, Hata et al 121 studied circulating tumor DNA to observe its correlation with patterns of metastatic spread. They found not only a remarkably high prevalence of circulating tumor DNA in patients with evident radiographic metastases but also a significantly higher prevalence in patients with occult disease not initially seen on imaging 121 . In 2020, Nicolle et al 122 presented GemPred , a RNA-based whole transcriptome signature that was shown to act as a predictor of tumor sensitivity for patients receiving gemcitabine.…”

“…120 This study concluded that the preoperative number of CTCs was the only predictor for recurrence of malignancy within 12 months of resection. In 2021, Hata et al 121 studied circulating tumor DNA to observe its correlation with patterns of metastatic spread. They found not only a remarkably high prevalence of circulating tumor DNA in patients with evident radiographic metastases but also a significantly higher prevalence in patients with occult disease not initially seen on imaging.…”

“…They found not only a remarkably high prevalence of circulating tumor DNA in patients with evident radiographic metastases but also a significantly higher prevalence in patients with occult disease not initially seen on imaging. 121 In 2020, Nicolle et al 122 presented GemPred, a RNA-based whole transcriptome signature that was shown to act as a predictor of tumor sensitivity for patients receiving gemcitabine. They studied it in an adjuvant setting; however, there is potential for the discovered data to be assessed with a neoadjuvant setting in mind.…”