Evaluation by neurological FDG-PET/MRI and serum biomarkers of neuronal and glial injury in patients submitted to chemotherapy for Breast Cancer treatment: a cross-modal study for chemotherapy-related cognitive decline (chemobrain)

• Grant number: 22/15776-3
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2023
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ricardo Nitrini
• Grantee: Ricardo Nitrini
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Artur Martins Novaes Coutinho ; Caio Augusto Colombo ; Carlos Alberto Buchpiguel ; Laura Testa ; Marcelo Houat de Brito ; Marcos Castello Barbosa de Oliveira ; Maria Concepción García Otaduy ; Raquel Andrade Moreno ; Sonia Maria Dozzi Brucki ; Soniza Vieira Alves Leon

Abstract

The prospect of the continuous increase in the number of individuals undergoing chemotherapy in the coming years, due to the increase in the incidence and prevalence of oncological diseases, makes it necessary to assess better the side effects of this treatment that have a considerable impact on functionality. Among these, cognitive decline is of great importance and still needs more research to understand better its pathophysiology, clinical aspects, and diagnostic methods. There are studies evaluating some potential biomarkers of chemotherapy-related cognitive decline, mainly through advanced neuroimaging techniques and, to a lesser extent, serum biomarker analysis. However, there is a lack of research that evaluates several potential biomarkers simultaneously and that follows the main recommendations of the International Cancer and Cognition Task Force (ICCTF) for this type of study. Objectives: To analyze, simultaneously, potential serum biomarkers and structural and functional neuroimaging associated with cognitive decline in patients undergoing adjuvant chemotherapy for breast cancer, aiming to correlate these findings with the objective and subjective cognitive assessment of patients, in addition to comparing them directly to each other. Methodology: Volunteers with breast cancer with an indication of adjuvant chemotherapy and healthy volunteers matched by age and education will be recruited to compose the treatment and the control group, respectively. Before and after the chemotherapy regimen in the volunteers of the treatment group and once in the volunteers of the control group, a multimodal evaluation will be carried out. This will include objective cognitive evaluation through neuropsychological tests recommended by the ICCTF, subjective cognitive evaluation through the FACT-Cog scale, measurement of serum levels of NfL, tau, GFAP, and UCH-L1 by the SIMOA technique, brain FDG-PET/MRI examination (including analysis of brain metabolism, volumes, DTI, rs-fMRI, and multivoxel spectroscopy) and application of anxiety, depression, fatigue, insomnia and quality of life scales. The data obtained will be subjected to statistical analysis to assess the correlations and comparisons intended for the study. (AU)