Abstract
Patients newly diagnosed with metastatic pancreatic ductal adenocarcinoma generally have poor survival, with heterogeneous rates of progression. Biomarkers that could predict progression and/or survival would help inform patients and providers as they make care decisions. In a previous retrospective study, we discovered that circulating thrombospondin-2 (THBS2) could, in combination with CA19-9, better distinguish patients with PDAC versus healthy controls. Here we evaluated whether THBS2 levels, previously not known to be prognostic, were associated with outcome in 68 patients at time of diagnosis of metastatic PDAC. Specifically, we interrogated the association of THBS2 level, alone or in combination with CA19-9, with progression by 90 days and/or survival to 180 days. The results indicate that elevated THBS2 levels alone, at the time of a metastatic PDAC diagnosis, can identify patients with a shorter time to death and thus help patients and providers when planning treatment.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced stages of disease, with unresectable tumors that respond poorly to systemic therapy [1, 2]
The challenges of early detection have led to the suggestion that resources should be shifted towards better predictors of progression and survival for clinical management of individuals already diagnosed with PDAC [9]
The receiver operator characteristic (ROC) derived area under the curve (AUC) was 0.671 and the cut point for THBS2 was 72.9 (Figure 1C, dashed line; 1D, red line)
Summary
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced stages of disease, with unresectable tumors that respond poorly to systemic therapy [1, 2]. The low incidence of PDAC and the absence of a known genetic or familial predisposition in most cases make it challenging to develop biomarkers with necessary sensitivity and specificity for early detection [3,4,5]. The challenges of early detection have led to the suggestion that resources should be shifted towards better predictors of progression and survival for clinical management of individuals already diagnosed with PDAC [9]. In a retrospective study of controls and PDAC patients with various stages of disease at the time of diagnosis, plasma thrombospondin-2 (THBS2) levels, combined with serum CA19-9 [12, 13], could discriminate PDAC from controls with an overall specificity of 98% at a sensitivity of 87% [14]. In a subsequent analysis of prospectively collected samples, neither THBS2, CA19-9, nor the combination were able to sensitively predict PDAC up to one year prior to a clinical diagnosis [15]
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