title: Brain damage following prophylactic cranial irradiation in lung cancer survivors.
abstract: Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population.
authors.affiliation: Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, 08097, Spain.|Neuro-oncology Unit, Hospital Universitari de Bellvitge - ICO Hospital Duran i Reynals, L'Hospitalet del Llobregat, Barcelona, 08907, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Simó
authors.affiliation: Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, 08097, Spain.|Department of Basic Psychology, Campus Bellvitge, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, 08097, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Vaquero
authors.affiliation: Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, 08097, Spain.|Department of Basic Psychology, Campus Bellvitge, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, 08097, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ripollés
authors.affiliation: Radiation Oncology Department, ICO Hospital Germans Trias i Pujol, Badalona, Barcelona, 08916, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Jové
authors.affiliation: Radiation Oncology Department, ICO Hospital Doctor Josep Trueta, Girona, 17007, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fuentes
authors.affiliation: Lung Cancer Unit, Medical Oncology Department, ICO Hospital Duran i Reynals, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Cardenal
authors.affiliation: Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, 08097, Spain.|Department of Basic Psychology, Campus Bellvitge, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, 08097, Spain.|Catalan Institution for Research and Advanced Studies, ICREA, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Rodríguez-Fornells
authors.affiliation: Neuro-oncology Unit, Hospital Universitari de Bellvitge - ICO Hospital Duran i Reynals, L'Hospitalet del Llobregat, Barcelona, 08907, Spain. 35078jbe@comb.cat.|Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain. 35078jbe@comb.cat.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain. 35078jbe@comb.cat.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruna
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000528:radiation effects*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D015331:Cohort Studies; D016371:Cranial Irradiation / Q000009:adverse effects* / Q000379:methods; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000528:radiation effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D055752:Small Cell Lung Carcinoma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D066127:White Matter / Q000000981:diagnostic imaging / Q000528:radiation effects
keywords: Cognitive deterioration; Diffusion tensor imaging; Prophylactic cranial irradiation; Small cell lung cancer; Voxel-based morphometry