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Title: Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation

Purpose: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β–related processes could characterize the neurochemical response to cranial radiation. Methods and Materials: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. Results: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. Conclusion: In conclusion, we were able to detect radiation therapy–induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and alteredmore » amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.« less
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [4] ; ;  [5] ;  [1] ;  [6] ;  [2] ;  [6] ;  [7]
  1. Department of Clinical Neuroscience and Rehabilitation, Insitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden)
  2. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden)
  3. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden)
  4. Department of Neurology, Karolinska University Hospital, Stockholm (Sweden)
  5. Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg (Sweden)
  6. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal (Sweden)
  7. (United Kingdom)
Publication Date:
OSTI Identifier:
22420347
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 89; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOLOGICAL MARKERS; BRAIN; CEREBROSPINAL FLUID; HYPOTHESIS; INFLAMMATION; LUNGS; METABOLISM; NEOPLASMS; NMR IMAGING; PATIENTS; PROTEINS; RADIATION DOSES; RADIOTHERAPY