Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors. Most patients are diagnosed at an advanced stage where curative surgery is not an option. The aim of this study was to identify a panel of circulating proteins that could distinguish patients with PDAC from non-PDAC individuals. Experimental Design: We investigated 92 proteins known to be involved in inflammation, development, and progression of PDAC using the Olink immuno-oncology panel in serum samples from 701 patients with PDAC (stage I–IV), 102 patients with nonmalignant pancreatic diseases, and 180 healthy blood donors. Patients were included prospectively between 2008 and 2018. Plasma carbohydrate antigen 19-9 (CA19-9) was measured in all samples. The protein panels with the best diagnostic performances were developed by two bioinformaticians working independently, using LASSO and Ridge regression models. Results: Two panels of proteins (index I, containing 9 proteins + CA19-9, and index II, containing 23 proteins + CA19-9) were identified. Index I was able to discriminate patients with PDAC from all patients with non-PDAC, with a ROC AUC value of 0.92 [95% confidence interval (CI), 0.89–0.96] in the discovery cohort and 0.92 (95% CI, 0.87–0.97) in the replication cohort. For index II, the AUC value was 0.96 (95% CI, 0.95–0.98) in the discovery cohort and 0.93 (95% CI, 0.90–0.96) in the replication cohort. All nine serum proteins of index I were found in index II. Conclusions: This study identified two circulating protein indices with the potential to discriminate between individuals with and without PDAC.

Background: Allogeneic haematopoietic stem cell transplantation (HSCT) is a procedure with inherent complications and intensive care may be necessary. We evaluated the short- and long-term outcomes of the HSCT recipients requiring admission to the intensive care unit (ICU). Methods: We retrospectively examined the outcome of 54 adult haematological HSCT recipients admitted to the ICU at the University Hospital Rigshospitalet between January 2007 and March 2012. Results: The overall in-ICU, in-hospital, 6-month and 1-year mortality rates were 46.3, 75.9, 79.6 and 86.5%, respectively. Mechanical ventilation had a statistically significant effect on in-ICU (p = 0.02), 6-month (p = 0.049) and 1-year (p = 0.014) mortality. Renal replacement therapy also had a statistically significant effect on in-hospital (p = 0.038) and 6-month (p = 0.026) mortality. Short ICU admissions, i.e. <10 days, had a statistically significant positive effect on in-hospital, 6-month and 1-year mortality (all p < 0.001). The SAPS II, APACHE II and SOFA scoring systems grossly underestimated the actual in-hospital mortality observed for these patients. Conclusion: The poor prognosis of critically ill HSCT recipients admitted to the ICU was confirmed in our study. Mechanical ventilation, renal replacement therapy and an ICU admission of ≥10 days were each risk factors for mortality in the first year after ICU admission.

Purpose: Changes in ctDNA levels during systemic treatment may predict treatment efficacy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC), but quantitative response criteria are not yet established. This study evaluates our recently proposed ctDNA-RECIST. Experimental Design: Blood samples were collected before treatment, before the second treatment cycle, and at the time of the first CT evaluation from 220 patients with metastatic PDAC receiving first-line palliative chemotherapy. Plasma ctDNA levels were measured using Droplet Digital PCR with HOXA9 methylation assays. ctDNA response was determined according to ctDNA-RECIST and correlated with overall survival (OS). Results: ctDNA was positive before treatment in 71% of the patients and was related to OS [HR = 1.61; 95% confidence interval (CI), 1.19–2.19; P = 0.002]. Among ctDNA-positive patients, ctDNA maximal response (MR; n = 41) and ctDNA disease control (DC; n = 107) before the second treatment cycle had longer OS compared with ctDNA progressive disease (PD; n = 5; median OS: MR 11.9 months, DC 7.2 months, PD 3.6 months; P = 0.002). In Cox regression, ctDNA DC (HR = 1.55; 95% CI, 1.07–2.26; P = 0.021) and ctDNA PD (HR = 4.50; 95% CI, 1.74–11.6; P = 0.002) showed shorter OS compared with ctDNA MR. The same applied to ctDNA response at the time of the first CT evaluation assessed from the second treatment cycle (P < 0.001) and from treatment start (P < 0.001). Conclusions: ctDNA-RECIST applied to liquid biopsies holds potential for early evaluation of treatment benefit in patients with metastatic PDAC, offering a novel, minimally invasive method to guide early clinical decision-making. Future studies should validate ctDNA-RECIST prospectively, preferably in randomized controlled trials.

Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. We aimed to find a prognostic protein signature for overall survival (OS) in patients with advanced PDAC, and to explore whether early changes in circulating-protein levels could predict survival. We investigated 92 proteins using the Olink Immuno-Oncology panel in serum samples from 363 patients with advanced PDAC. Protein panels for several survival cut-offs were developed independently by two bioinformaticians using LASSO and Ridge regression models. Two panels of proteins discriminated patients with OS < 90 days from those with OS > 2 years. Index I (CSF-1, IL-6, PDCD1, TNFRSF12A, TRAIL, TWEAK, and CA19-9) had AUCs of 0.99 (95% CI: 0.98–1) (discovery cohort) and 0.89 (0.74–1) (replication cohort). For Index II (CXCL13, IL-6, PDCD1, and TNFRSF12A), the corresponding AUCs were 0.97 (0.93–1) and 0.82 (0.68–0.96). Four proteins (ANGPT2, IL-6, IL-10, and TNFRSF12A) were associated with survival across all treatment groups. Longitudinal samples revealed several changes, including four proteins that were also part of the prognostic signatures (CSF-1, CXCL13, IL-6, TNFRSF12A). This study identified two circulating-protein indices with the potential to identify patients with advanced PDAC with very short OS and with long OS.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Less than 20% of patients are diagnosed with resectable disease. Identifying truly resectable disease is challenging because 20%–40% of the patients subjected to resection are found to have advanced disease during surgery. The aim of our study was to identify panels of circulating proteins that could be used to distinguish patients with unresectable PDAC from patients with resectable PDAC and to identify prognostic signatures for both groups.Methods: We measured 92 circulating immuno‐oncology‐related proteins using the proximity extension assay from Olink Proteomics in 273 patients eligible for surgery for PDAC. Two bioinformaticians worked independently of one another on the same data. LASSO and Ridge regression were used in the statistical analyses.Results: One protein index for determining resectability had an AUC value of 0.66. Several indices for prognosis had AUC values between 0.50 and 0.75 and were therefore not better than existing prognostic markers.Discussion: Our study did not reveal any new high‐performing protein panels that could be used to identify patients with inoperable PDAC before surgery. The panel of 92 proteins investigated has previously been found to be applicable for diagnostic use in patients with PDAC, but it does not seem to warrant further investigation regarding resectability in the subgroup of patients with PDAC referred to surgery.