Jurgen Peerlings1, Lien Van De Voorde2, Cristina Mitea3, Ruben Larue2, Ala Yaromina2, Sebastian Sandeleanu2, Linda Spiegelberg2, Ludwig Dubois2, Philippe Lambin2, Felix M Mottaghy4. 1. MAASTRO Clinic, Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands. Electronic address: Jurgen.peerlings@maastro.nl. 2. MAASTRO Clinic, Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands. 3. Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands. 4. Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Nuclear Medicine, University Hospital RWTH Aachen University, Aachen, Germany.
Abstract
PURPOSE: In this systematic review, the existing evidence of available hypoxia-associated molecular response biomarkers in esophageal cancer (EC) patients is summarized and set into the context of the role of hypoxia in the prediction of esophageal cancer, treatment response and treatment outcome. METHODS: A systematic literature search was performed in Web of Science, MEDLINE, and PubMed databases using the keywords: hypoxia, esophagus, cancer, treatment outcome and treatment response. Eligible publications were independently evaluated by two reviewers. In total, 22 out of 419 records were included for systematic review. The described search strategy was applied weekly, with the last update being performed on April 3rd, 2017. RESULTS: In esophageal cancer, several (non-)invasive biomarkers for hypoxia could be identified. Independent prognostic factors for treatment response include HIF-1α, CA IX, GLUT-1 overexpression and elevated uptake of the PET-tracer 18F-fluoroerythronitroimidazole (18F-FETNIM). Hypoxia-associated molecular responses represents a clinically relevant phenomenon in esophageal cancer and detection of elevated levels of hypoxia-associated biomarkers and tends to be associated with poor treatment outcome (i.e., overall survival, disease-free survival, complete response and local control). CONCLUSION: Evaluation of tumor micro-environmental conditions, such as intratumoral hypoxia, is important to predict treatment outcome and efficacy. Promising non-invasive imaging-techniques have been suggested to assess tumor hypoxia and hypoxia-associated molecular responses. However, extensive validation in EC is lacking. Hypoxia-associated markers that are independent prognostic factors could potentially provide targets for novel treatment strategies to improve treatment outcome. For personalized hypoxia-guided treatment, safe and reliable makers for tumor hypoxia are needed to select suitable patients.
PURPOSE: In this systematic review, the existing evidence of available hypoxia-associated molecular response biomarkers in esophageal cancer (EC) patients is summarized and set into the context of the role of hypoxia in the prediction of esophageal cancer, treatment response and treatment outcome. METHODS: A systematic literature search was performed in Web of Science, MEDLINE, and PubMed databases using the keywords: hypoxia, esophagus, cancer, treatment outcome and treatment response. Eligible publications were independently evaluated by two reviewers. In total, 22 out of 419 records were included for systematic review. The described search strategy was applied weekly, with the last update being performed on April 3rd, 2017. RESULTS: In esophageal cancer, several (non-)invasive biomarkers for hypoxia could be identified. Independent prognostic factors for treatment response include HIF-1α, CA IX, GLUT-1 overexpression and elevated uptake of the PET-tracer 18F-fluoroerythronitroimidazole (18F-FETNIM). Hypoxia-associated molecular responses represents a clinically relevant phenomenon in esophageal cancer and detection of elevated levels of hypoxia-associated biomarkers and tends to be associated with poor treatment outcome (i.e., overall survival, disease-free survival, complete response and local control). CONCLUSION: Evaluation of tumor micro-environmental conditions, such as intratumoral hypoxia, is important to predict treatment outcome and efficacy. Promising non-invasive imaging-techniques have been suggested to assess tumor hypoxia and hypoxia-associated molecular responses. However, extensive validation in EC is lacking. Hypoxia-associated markers that are independent prognostic factors could potentially provide targets for novel treatment strategies to improve treatment outcome. For personalized hypoxia-guided treatment, safe and reliable makers for tumor hypoxia are needed to select suitable patients.
Authors: Maria Davern; Noel E Donlon; Margaret R Dunne; Robert Power; Conall Hayes; Ross King; John V Reynolds Journal: Br J Cancer Date: 2021-04-26 Impact factor: 7.640
Authors: Sebastian Sanduleanu; Alexander M A van der Wiel; Relinde I Y Lieverse; Damiënne Marcus; Abdalla Ibrahim; Sergey Primakov; Guangyao Wu; Jan Theys; Ala Yaromina; Ludwig J Dubois; Philippe Lambin Journal: Cancers (Basel) Date: 2020-05-22 Impact factor: 6.639
Authors: Linda Spiegelberg; Ruud Houben; Raymon Niemans; Dirk de Ruysscher; Ala Yaromina; Jan Theys; Christopher P Guise; Jeffrey B Smaill; Adam V Patterson; Philippe Lambin; Ludwig J Dubois Journal: Clin Transl Radiat Oncol Date: 2019-01-18