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Brain damage following prophylactic cranial irradiation in lung cancer survivors

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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.

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Conflict of interest

Marta Simó, Lucía Vaquero, Pablo Ripollés, Josep Jové, Rafael Fuentes, Felipe Cardenal, Antoni Rodríguez-Fornells, and Jordi Bruna reviewed and approved the manuscript content and there is no conflict of interest.

Ethical Statement

All procedures performed in this study, which involve human participants, were in accordance with the ethical standards of the local Ethical Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all participants included in the study (both patients and healthy controls).

Funding

This work was supported by Fundació Marató-TV3 [Acquired Spinal Cord and Brain Injuries Program (2012–2014) awarded to ARF] and the Catalan Government [Generalitat de Catalunya, 2009 SGR 93 to ARF]. Marta Simó was a recipient of a Rio Hortega research contract (code: CM11/00256) from the Carlos III National Health Institute (Spanish Government).

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Authors and Affiliations

  1. Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, 08097, Spain

    Marta Simó, Lucía Vaquero, Pablo Ripollés & Antoni Rodríguez-Fornells

  2. Neuro-oncology Unit, Hospital Universitari de Bellvitge - ICO Hospital Duran i Reynals, L’Hospitalet del Llobregat, Barcelona, 08907, Spain

    Marta Simó & Jordi Bruna

  3. Department of Basic Psychology, Campus Bellvitge, University of Barcelona, L’Hospitalet de Llobregat, Barcelona, 08097, Spain

    Lucía Vaquero, Pablo Ripollés & Antoni Rodríguez-Fornells

  4. Radiation Oncology Department, ICO Hospital Germans Trias i Pujol, Badalona, Barcelona, 08916, Spain

    Josep Jové

  5. Radiation Oncology Department, ICO Hospital Doctor Josep Trueta, Girona, 17007, Spain

    Rafael Fuentes

  6. Lung Cancer Unit, Medical Oncology Department, ICO Hospital Duran i Reynals, L’Hospitalet del Llobregat, Barcelona, Spain

    Felipe Cardenal

  7. Catalan Institution for Research and Advanced Studies, ICREA, Barcelona, Spain

    Antoni Rodríguez-Fornells

  8. Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain

    Jordi Bruna

  9. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain

    Jordi Bruna

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  1. Marta Simó
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  2. Lucía Vaquero
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Correspondence to Jordi Bruna.

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Simó, M., Vaquero, L., Ripollés, P. et al. Brain damage following prophylactic cranial irradiation in lung cancer survivors. Brain Imaging and Behavior 10, 283–295 (2016). https://doi.org/10.1007/s11682-015-9393-5

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