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Purpose To develop and validate neural network (NN) vs logistic regression (LR) diagnostic prediction models in patients with suspected giant cell arteritis (GCA). Design: Multicenter retrospective chart review. Methods An audit of consecutive patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at 14 international medical centers. The outcome variable was biopsy-proven GCA. The predictor variables were age, gender, headache, clinical temporal artery abnormality, jaw claudication, vision loss, diplopia, erythrocyte sedimentation rate, C-reactive protein, and platelet level. The data were divided into three groups to train, validate, and test the models. The NN model with the lowest false-negative rate was chosen. Internal and external validations were performed. Results Of 1,833 patients who underwent TABx, there was complete information on 1,201 patients, 300 (25%) of whom had a positive TABx. On multivariable LR age, platelets, jaw claudication, vision loss, log C-reactive protein, log erythrocyte sedimentation rate, headache, and clinical temporal artery abnormality were statistically significant predictors of a positive TABx ( P ≤0.05). The area under the receiver operating characteristic curve/Hosmer–Lemeshow P for LR was 0.867 (95% CI, 0.794, 0.917)/0.119 vs NN 0.860 (95% CI, 0.786, 0.911)/0.805, with no statistically significant difference of the area under the curves ( P =0.316). The misclassification rate/false-negative rate of LR was 20.6%/47.5% vs 18.1%/30.5% for NN. Missing data analysis did not change the results. Conclusion Statistical models can aid in the triage of patients with suspected GCA. Misclassification remains a concern, but cutoff values for 95% and 99% sensitivities are provided ( https://goo.gl/THCnuU ).

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RESEARCH • RECHERCHE Feasibility analysis for the development of a video-assisted thoracoscopic (VATS) lobectomy 23-hour recovery pathway Background: Video-assisted thoracoscopic (VATS) lobectomy has been demonstrated to offer several benefits over open surgery. The purpose of this study was to assess the feasibility and safety of an ultra-fast-track 23-hour recovery pathway for VATS lobectomy.

Targeting the dynamic tumor immune microenvironment can provide effective therapeutic strategies for cancer. Neutrophils (polymorphonuclear neutrophils, PMNs) are the predominant circulating leukocyte population in humans and are vital to fight infection. Despite mounting evidence that PMNs can promote tumor progression, depleting PMNs is not a viable therapeutic option. Neutrophil extracellular traps (NETs) are networks of extracellular neutrophil DNA fibers that are capable of trapping tumor cells and promoting their growth and their metastasis. Targeting NETs can therefore be a potentially successful therapeutic option to block the tumor promoting functions of PMNs. Here we demonstrate that circulating NET levels are elevated in esophageal, gastric and lung cancer patients compared to healthy controls. This increase correlates with disease stage and NET levels are independent predictors of advanced stage. Using pre-clinical murine models of lung and colon cancer, we observe elevated NET levels in tumor bearing mice compared to non-tumor bearing mice; these levels correlated with tumor size. NET levels significantly decrease following tumor resection or treatment with DNase1, a NET degrader, or neutrophil elastase inhibitor (NEi), a NET inhibitor. NET levels do not rise following tumor inoculation in peptidyl arginine deiminase-IV knock out (PAD4-/-) mice; PAD4 being an enzyme essential for citrullination of histones, a crucial step in NET release. Moreover, PMNs from tumor bearing mice are more primed for NETosis than PMNs from non-tumor bearing mice or NEi-treated or PAD4-/- tumor bearing mice. Finally, elevated in vivo hepatic adhesion and spontaneous liver and lung metastases are observed in tumor bearing mice compared to DNase1- or NEi-treated or PAD4-/- tumor bearing mice. Therefore, inhibiting NETs represents a promising strategy to impede metastatic dissemination in several types of cancer patients. Citation Format: Roni F. Rayes, Jack G. Mouhanna, Ioana Nicolau, Phil Vourtzoumis, Carson Wong, Jules Eustache, France Bourdeau, Betty Giannias, Aya Siblini, Emma Lee, Veena Sangwan, Simon Rousseau, Daniela Quail, Logan Walsh, Nicholas Bertos, Jonathan Cools-Lartigue, Lorenzo E. Ferri, Jonathan D. Spicer. Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1508.

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180 Background: Esophago-gastric cancers are aggressive malignancies requiring numerous investigations to plan complex multi-modal therapy. The path from initial diagnosis to treatment can be associated with a long delay. This delay and complex patient trajectory may impact quality of life. Given the poor prognosis and highly symptomatic nature of upper GI cancer, a clear and timely access to treatment of crucial importance. We sought to determine the impact of a newly implemented streamlined and structure interdisciplinary pathway for newly diagnosed esophageal and gastric cancer on access times to treatment and quality of life (QoL). Methods: A streamlined pathway for patients referred to a high volume Upper GI Cancer clinic was generated with input from physicians, nutritionists, specialized nurses, and social workers. New diagnosis of esophageal or gastric cancer from 2014-16 were enrolled in this program and consenting patients completed serial QoL questionnaires (ESAS) at baseline, pre-treatment, 1 month post treatment. Dysphagia (DS) was quantified on a 5 point scale. Time intervals (days) were evaluated at various points between diagnosis and start of treatment (diagnosis, CT imaging, first visit with upper GI program, start of treatment). Data presented as median(IQR), * p < 0.05. Results: Of the 251 patients with Upper GI cancer, 153 (61%) consented to participate including 140 esophageal/EGJ and 13 gastric cancer patients. Clinical stage distribution was 17.9% I, 30.7% II, 42.6% III, 8.7% IV. Of the 82 Esoph/EGJ patients with completed QoL questionnaires, 15 (18.3%) patients had severe dysphagia (DS = 3-4) and were prioritized for treatment. Patients with severe dysphagia had reduced time from index endoscopy to treatment (29 (16.3-39.3) vs 43 (32.8-68.0)days)* and first Upper GI clinic to treatment (15 (8.0-23.0) vs 25 (21.0-36.0)*. ESAS surveys showed increased QoL for both patients with and without dysphagia from baseline to pre-treatment indicating that simply entry into the streamlined program improved QoL. Conclusions: Structured interdisciplinary investigative and treatment programs for upper GI cancers can expedite time to treatment and improve QoL.