• Differentiation of chronic mass-forming pancreatitis from pancreatic ductal adenocarcinoma using contrast-enhanced computed tomography

      Ren, S.; Chen, R.; Guo, K. (Dove Medical Press Ltd, 2019)
      Purpose: Both chronic mass-forming pancreatitis (CMFP) and pancreatic ductal adenocarcinoma (PDAC) are focal pancreatic lesions and share very similar clinical symptoms and imaging performance. There is great clinical value in preoperative differentiation of those two lesions. The purpose of this study was to investigate the value of computed tomography (CT) features in discriminating CMFP from PDAC. Patients and methods: Forty-seven patients with pathologically confirmed PDAC and 21 patients with CMFP were included in this study. Demographic and CT features, including tumor location, size, margin, pancreatic or bile duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, and tumor contrast enhancement, were retrospectively analyzed and compared. Multivariate logistic regression analyses were adopted to identify relevant CT imaging features to discriminate CMFP from PDAC. Results: There were significant differences between CMFP and PDAC with respect to main pancreatic duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, and tumor contrast enhancement. Delayed contrast enhancement (>70.5 Hounsfield units) showed high sensitivity and specificity of 84.2% and 84.7%. The areas under the curve (AUCs) of the predicting models based on qualitative and quantitative variables were 0.770 (95% CI: 0.660–0.880) and 0.943 (95% CI: 0.888–0.999), respectively. When all significant variables were used in combination to build a predicting model, the AUC was 0.969 (95% CI: 0.930–1.000) with 84.2% sensitivity and 94.7% specificity. Conclusion: Main pancreatic duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, tumor size, and tumor contrast enhancement were shown to be useful CT imaging features in discriminating CMFP from PDAC. Copyright 2019 Ren et al.
    • Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia

      Uy, G.L.; Aldoss, I.; Foster, M.C.; Sayre, P.H.; Wieduwilt, M.J.; Advani, A.S.; Godwin, J.E.; Arellano, M.L.; Sweet, K.L.; Emadi, A.; et al. (Elsevier B.V., 2020-09-14)
      Approximately 50% of acute myeloid leukemia (AML) patients do not respond to induction therapy (primary induction failure [PIF]) or relapse after <6 months (early relapse [ER]). We have recently shown an association between an immune-infiltrated tumor microenvironment (TME) and resistance to cytarabine-based chemotherapy but responsiveness to flotetuzumab, a bispecific DART antibody-based molecule to CD3? and CD123. This paper reports the results of a multicenter, open-label, phase 1/2 study of flotetuzumab in 88 adults with relapsed/refractory AML: 42 in a dose-finding segment and 46 at the recommended phase 2 dose (RP2D) of 500 ng/kg per day. The most frequent adverse events were infusion-related reactions (IRRs)/cytokine release syndrome (CRS), largely grade 1-2. Stepwise dosing during week 1, pretreatment dexamethasone, prompt use of tocilizumab, and temporary dose reductions/interruptions successfully prevented severe IRR/CRS. Clinical benefit accrued to PIF/ER patients showing an immune-infiltrated TME. Among 30 PIF/ER patients treated at the RP2D, the complete remission (CR)/CR with partial hematological recovery (CRh) rate was 26.7%, with an overall response rate (CR/CRh/CR with incomplete hematological recovery) of 30.0%. In PIF/ER patients who achieved CR/CRh, median overall survival was 10.2 months (range, 1.87-27.27), with 6- and 12-month survival rates of 75% (95% confidence interval [CI], 0.450-1.05) and 50% (95% CI, 0.154-0.846). Bone marrow transcriptomic analysis showed that a parsimonious 10-gene signature predicted CRs to flotetuzumab (area under the receiver operating characteristic curve = 0.904 vs 0.672 for the European LeukemiaNet classifier). Flotetuzumab represents an innovative experimental approach associated with acceptable safety and encouraging evidence of activity in PIF/ER patients. This trial was registered at www.clinicaltrials.gov as #NCT02152956. Key Points: - Flotetuzumab is associated with acceptable safety and evidence of activity in AML patients with PIF/ER. - A 10-gene immune signature predicts response to flotetuzumab with greater accuracy than the ELN risk classifier. Copyright 2021 American Society of Hematology