Prognostic host phenotypes based on body composition and systemic inflammation predict survival in patients with resected pancreatic and periampullary cancer
European Journal of Cancer, vol. 245, pp. 116933
Abstract
INTRODUCTION: Most present-day survival-models of patients with cancer do not account for tumor-host interactions. We hypothesized that host phenotypes based on systemic inflammation and body composition are prognostic of overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We performed a post-hoc analysis of the nationwide PORSCH-trial, including all patients undergoing pancreatoduodenectomy for PDAC. Primary outcome was OS. Body composition analysis was performed using automatic segmentation (Mosamatic™) of preoperative abdominal computed tomography scans. Low muscle mass and myosteatosis were defined using log-rank stratification of sex-standardized Z-values of skeletal muscle index and radiation attenuation, respectively. Patients were clustered in eight host phenotypes based on combinations of adverse host factors: [1] low muscle mass, [2] myosteatosis, [3] systemic inflammation (C-reactive protein >6mg/L). Their association with OS was tested using multivariable-adjusted Cox-proportional hazard-analysis. Distinct combinations of adverse host factors were stratified into low-, intermediate-, and high-risk phenotypes according to k-means clustering based on log hazard-ratio's. RESULTS: 549 patients were included. The high-risk phenotype, characterized by the presence of all adverse host factors, showed lower median OS than intermediate ([1], [2], [1 +2], [1 +3], [2 +3]) and low-risk ([3]; none) phenotypes (13.0 months [95%CI 11.4-19.3] vs. 21.9 months [95%CI 19.3-24.7] vs. 35.2 months [95%CI 29.2-45.3], respectively; p < 0.001). In multivariable analysis, host phenotypes were associated with OS (adjusted [a]HR 1.39 [95%CI 1.08-1.80, p = 0.01; aHR 2.10 [95%CI 1.53-2.88], p < 0.01, for intermediate- and high-risk respectively), independent of tumor stage. DISCUSSION: Host phenotypes based on body composition and systemic inflammation predict OS independent of tumor stage in patients with resected PDAC, underscoring the importance of tumor-host interactions for clinical survival prediction.
Authors 34
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Surgery, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Department of General Visceral, Vascular and Transplantation Surgery, University Medicine Essen, Essen, Germany
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Maastricht University Medical Centre · Maastricht University · Zuyderland Medisch Centrum
Affiliation as printed
Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Surgery, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Department of Surgery, Zuyderland Medisch Centrum, Sittard-Geleen, the Netherlands
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Cancer Center Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Surgery, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, the Netherlands; Laboratory of Medical Oncology, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
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University Medical Center Utrecht · St. Antonius Ziekenhuis
Affiliation as printed
Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein, University Medical Center Utrecht, Utrecht, the Netherlands
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University Medical Center Utrecht · St. Antonius Ziekenhuis
Affiliation as printed
Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein, University Medical Center Utrecht, Utrecht, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Center, Maastricht, the Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Center, Maastricht, the Netherlands
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Affiliation as printed
Department of Surgery, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
Department of Radiotherapy (MAASTRO), Maastricht University, Maastricht, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
Department of Surgery, OLVG, Amsterdam, the Netherlands
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Affiliation as printed
Department of Surgery, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands
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Affiliation as printed
Department of Surgery, Amphia Hospital, Breda, the Netherlands
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Affiliation as printed
Department of Surgery, Frisius Medical Center, Heerenveen, the Netherlands
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Radboud University Medical Center
Affiliation as printed
Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
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Affiliation as printed
Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
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Affiliation as printed
Department of Surgery, Medical Spectrum Twente, Enschede, the Netherlands
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Affiliation as printed
Department of Surgery, Isala, Zwolle, the Netherlands
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Affiliation as printed
Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands; Department of Epidemiology, GROW-Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Division of Medical Oncology, Department of Internal Medicine, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands
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German Cancer Research Center · Essen University Hospital · Deutsches Konsortium für Translationale Krebsforschung · University of Duisburg-Essen
Affiliation as printed
Bridge Institute of Experimental Tumor Therapy (BIT), Division of Solid Tumor Translational Oncology (DKTK) and Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), partner site Essen, a partnership between German Cancer Research Center (DKFZ) and University Hospital Essen, Essen, Germany
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Radiology, Medical Imaging Center Groningen, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
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Affiliation as printed
Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
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Cancer Center Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Surgery, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
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Cancer Center Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Surgery, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
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Amsterdam UMC Location University of Amsterdam · Cancer Center Amsterdam
Affiliation as printed
Cancer Center Amsterdam, Amsterdam, the Netherlands; Amsterdam UMC, location University of Amsterdam, Department of Surgery, the Netherlands
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University Medical Center Utrecht · St. Antonius Ziekenhuis
Affiliation as printed
Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein, University Medical Center Utrecht, Utrecht, the Netherlands
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University Medical Center Utrecht · St. Antonius Ziekenhuis
Affiliation as printed
Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein, University Medical Center Utrecht, Utrecht, the Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Surgery, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
Department of Surgery, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
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University Medical Center Utrecht · St. Antonius Ziekenhuis
Affiliation as printed
Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein, University Medical Center Utrecht, Utrecht, the Netherlands
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Steven W.M. Olde Damink corresponding
Maastricht University Medical Centre · Maastricht University · Essen University Hospital · University of Duisburg-Essen
Affiliation as printed
Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Surgery, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Bridge Institute of Experimental Tumor Therapy (BIT), Division of Solid Tumor Translational Oncology (DKTK) and Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), partner site Essen, a partnership between German Cancer Research Center (DKFZ) and University Hospital Essen, Essen, Germany; Department of General Visceral, Vascular and Transplantation Surgery, University Medicine Essen, Essen, Germany. Electronic address: steven.oldedamink@maastrichtuniversity.nl
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