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Risk factors for neurocognitive decline in lung cancer patients treated with prophylactic cranial irradiation: A systematic review
Affiliation:1. Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands;2. Department of Pulmonary Diseases, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands;3. Department of Respiratory Medicine, Medical Centre Leeuwarden, Leeuwarden, the Netherlands;4. Department of Clinical Epidemiology and Medical Technology Assessment, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands;1. Neuro Oncology Group, Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India;2. Department of Endocrinology, King Edward Memorial Hospital, Mumbai, India;3. Department of Medical Physics, Tata Memorial Centre, Mumbai, India;4. Department of Biostatistics, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai, India;1. Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland;2. Department of Radiation Oncology, University of Bern, Switzerland;3. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands;4. Institut Gustave Roussy, Villejuif, France;5. Université Paris Sud, Le Kremlin Bicetre, France;6. Division of Cancer Sciences, University of Manchester, UK;7. Department of Medical Oncology, The Christie National Health Service Foundation Trust, Manchester, UK;8. Cancer Research UK Lung Cancer Centre of Excellence at University College London, London, UK;9. University of Manchester, UK;10. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom;11. Department of Medical Oncology, Manchester University NHS Foundation Trust, Manchester, United Kingdom;12. Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom;13. Director Oncology and Hematology Department, AUSL Romagna, Ravenna, Italy;14. Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy;15. Vall d''Hebron University Hospital and Vall d''Hebron Institute of Oncology, Barcelona, Spain;p. Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland;q. Division of Molecular and Clinical Cancer Sciences, University of Manchester & the Christie NHS Foundation Trust, UK;r. Department of Medical Oncology/Hematology, Cantonal Hospital of St. Gallen, St. Gallen, University of Bern, Switzerland;s. Hospital Universitario Ramón y Cajal, Madrid, Spain;t. Department of Radiation Oncology, Gustave Roussy, France;u. Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, London, UK;v. Department of Radiation Oncology, Kliniken Maria Hilf, Moenchengladbach, Germany;w. Department of Radiation Oncology, University Hospital Freiburg, Germany;x. Oncology Department, AOU San Luigi, University of Turin, Italy;y. Department of Medicine, The Royal Marsden NHS Foundation Trust, Sutton, UK;z. Hospital Universitario, Madrid, Spain;11. Maastricht University Medical Center, Department of Radiation Oncology (Maastro Clinic), School for Oncology and Developmental Biology (GROW), the Netherlands;12. Department of Radiation Oncology, West German Tumor Centre, University of Duisburg-Essen Medical School, Germany;13. Department of Radiation Oncology, Campus Bio-Medico University, Rome, Italy;14. LungenClinic Airway Research Center North (ARCN), German Center for Lung Research, Grosshansdorf, Germany;15. Department of Radiation Oncology, VU University Medical Center, Amsterdam, the Netherlands;16. OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Germany;17. Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany;18. Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiooncology – OncoRay, Dresden, Germany;19. German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany;110. Department Radiation Oncology, Institut Bordet, Université Libre Bruxelles, Belgium;111. CHU de Besançon, INSERM UMR 1098, Université de Bourgogne, Franche-Comté, Besançon, France;112. Department of Radiotherapy, Comprehensive Cancer Center, Medical University of Vienna, Austria;113. Service de radiothérapie, CHU Lyon Sud, hospices civils de Lyon, 165, chemin du Grand-Revoyet, Pierre-Bénite, France;1. Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE;2. Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD;3. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX;1. Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 0431, Houston, TX 77030, USA;2. Section of Neuropsychology, Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 0431, Houston, TX 77030, USA;1. Medical University of Gdansk, Department of Clinical Oncology and Radiotherapy, ul. Dębinki 7, 80-952 Gdańsk, Poland;2. University of Gdansk, Institute of Psychology, ul. Jana Bażyńskiego 4, 80-309 Gdańsk, Poland;1. Department of Research, Comprehensive Cancer Organization, Utrecht, The Netherlands;2. Department of Radiation Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands;3. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Abstract:BackgroundProphylactic cranial irradiation (PCI) reduces brain metastasis incidence in lung cancer, however with risk of neurocognitive decline. Nevertheless, risk factors for neurocognitive decline after PCI remain unclear.MethodsWe systematically reviewed the PubMed database according to the PRISMA guideline. Inclusion criteria were: randomized clinical trials (RCTs) and observational/single arm trials evaluating PCI, including ≥20 patients, reporting neurocognitive test results for lung cancer. Primary aim: evaluate risk factors associated with neurocognitive decline after PCI.ResultsTwenty records were eligible (8 different RCTs, 8 observational studies), including 3553 patients in total (858 NSCLC, 2695 SCLC) of which 73.6% received PCI. Incidence of mild/moderate cognitive decline after PCI varied from 8 to 89% (grading not always provided); for those without PCI, this was 3.4–42%. Interestingly, 23–95% had baseline cognitive impairment. Risk factors were often not reported. In one trial, both age (>60 years) and higher PCI dose (36 Gy) including twice-daily PCI were associated with a higher risk of cognitive decline. In one trial, white matter abnormalities were more frequent in the concurrent or sandwiched PCI arm, but without significant neuropsychological differences. One trial identified hippocampal sparing PCI to limit the neurocognitive toxicities of PCI and another reported an association between hippocampal dose volume effects and memory decline. As neurocognition was a secondary endpoint in most RCTs, and was assessed by various instruments with often poor/moderate compliance, high-quality data is lacking.ConclusionsAge, PCI dose, regimen and timing might be associated with cognitive impairment after PCI in lung cancer patients, but high-quality data is lacking. Future PCI trials should collect and evaluate possible risk factors systematically.
Keywords:Lung cancer  Prophylactic cranial irradiation  Neurocognitive decline  Cognition impairment  Risk factor
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