This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.

Background/Objectives: Cardiovascular diseases (CVDs) frequently limit the feasibility and effectiveness of cancer treatment. However, CVD burden has not been comprehensively described in pancreatic cancer. In our systematic review and meta-analysis, we evaluated the prevalence and incidence of CVDs in pancreatic ductal adenocarcinoma (PDAC). Methods: We conducted the systematic search in PubMed, EMBASE, and CENTRAL on 5 February 2024. Studies reporting the prevalence or incidence of CVDs in PDAC were included. Subgroup analyses were performed based on cancer stage and treatment type. Pooled proportions with the 95% confidence interval (CI) were calculated using a random-effects model. (PROSPERO: CRD42023482295). Results: We included 197 articles. At PDAC diagnosis, non-thrombotic cardiovascular diseases (NT-CVDs) were as prevalent as in the general population: hypertension in 33% (CI: 27–40%), ischemic heart disease in 6% (CI: 3–12%), and heart failure, arrhythmia, and stroke each in 2–3%. Their incidence during treatment remained low (1–10%). Thrombotic events, excluding pulmonary embolism, were present in 11% (CI: 7–15%) at diagnosis, with an incidence of 8–10% regardless of stage or treatment. Pulmonary embolism affected 3% at diagnosis and occurred at a similar rate during treatment. Conclusions: Thromboembolic events are common in PDAC and occur both at diagnosis and during follow-up. Their incidence remains stable across treatment modalities and disease stages, suggesting that the tumor itself is the primary driver of thrombotic risk. The prevalence of NT-CVDs in PDAC is comparable to that in the general population and shows minimal variation across cancer stages or treatment modalities.