Katiyar, Vatsala

Objective: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Summary Background Data: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. Methods: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. Results: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Conclusions: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.

Background Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (MF), have a significant risk of venous thromboembolism (VTE). We aim to determine the trends in annual rates of VTE-related admissions, associated cost, length of stay (LOS), and in-hospital mortality in patients with MPN. Methods We identified patients with PV, ET, and MF from the Nationwide Inpatient Sample (NIS) database from 2006 to 2014 using ICD-9CM coding. Hospitalizations where VTE was among the top-three diagnoses were considered VTE-related. We compared in-hospital outcomes between VTE and non-VTE hospitalizations using chi-square and Mann–Whitney U-test and used linear regression for trend analysis. Results We identified 1,046,666 admissions with a diagnosis of MPN. Patients were predominantly white (65.6%), females (52.7%), with a median age of 66 years (range: 18–108). The predominant MPN was ET (54%). There was no difference in in-hospital mortality between groups (VTE: 3.4% vs. non-VTE: 3.2%; p = 0.12); however, VTE admissions had a longer LOS (median: 6 vs. 5 days; p < 0.01) and higher cost (median: VTE US$32,239 vs. 28,403; p ≤ 0.01).The annual rate of VTE admissions decreased over time (2006: 3.94% vs. 2014: 2.43%; p ≤ 0.01), compared with non-VTE–related admissions. Conclusion In our study, VTE-related admissions had similar in-hospital mortality as compared with non-VTE–related admissions. The rates of hospitalizations due to VTE have decreased over time but are associated with a higher cost and LOS. Newer risk assessment tools may assist in preventing VTE in high-risk patients and optimizing resource utilization.