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| Author(s): |
Willian das Neves Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2022-02-17 |
| Examining board members: |
Gilberto de Castro Junior;
Christina May Moran de Brito;
Dawit Albieiro Pinheiro Gonçalves
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| Advisor: | Gilberto de Castro Junior; Patricia Chakur Brum |
| Abstract | |
INTRODUCTION: Patients with non-small cell lung carcinoma (NSCLC) are often diagnosed at an advanced stage. Cancer-related cachexia can occur with high frequency in patients and is associated with functional impairment and poor prognosis. Chemotherapy is a treatment option for these patients and, although it offers an overall survival gain compared to better supportive care, it has considerable adverse effects (toxicity), which can compromise the quality of life. Therefore, proper identification of the best chemotherapy candidates is a critical aspect in the selection of treatment for patients diagnosed with advanced NSCLC, especially those diagnosed with cachexia. Treatments that increase the body composition do not improve the prognosis of the patients, in a manner, functional variables become prognostically important in this scenario and become useful for treatment selection. Therefore, this study aimed to assess the prognostic value of the physical fitness in patients with NSCLC, as well as the effects of chemotherapy on these variables. METHODS: 55 patients diagnosed with advanced NSCLC were included in a prospective cohort study. Aerobic fitness, muscular endurance, strength, and mobility were measured. In addition, body composition, the presence of cachexia, hematological markers, and quality of life variables were evaluated. The results were plotted on a survival curve to assess the prognosis. The correlation between all the variables was tested, as well as the association between the best mortality predictor and treatment response. The patients\' plasma was placed in muscle cell culture to assess its impact on cell metabolism. Metabolomic assay of these plasmas was performed to identify possible markers of prognosis and muscle function. A second study was conducted comparing these variables before and after treatment and evaluating the impact of chemotherapy on muscle cells. RESULTS: Of the 55 patients in the cohort, 87% were men, 75% heavy smokers. The mean age was 65 years, the most frequent histology was adenocarcinoma (58%), one-year overall survival was 29%, and mean follow-up in months was 8 months. Mobility, muscular endurance, and aerobic fitness were able to predict the prognosis. However, strength, muscle, and fat mass were not mortality predictors. Muscle cell metabolism was impaired when incubated with plasma from patients with lower muscle endurance. And plasmas from these patients present changes in inflammation-related metabolites. After chemotherapy, the patients showed loss of muscle mass and function, impairment of hematological variables without change in weight and body fat. Chemotherapy drugs caused metabolic dysfunction and morphological changes in cell cultures. CONCLUSION: Muscle function has a greater prognostic value when compared to body composition. After chemotherapy, patients present impairment in both, muscle function and body composition, and there is a deleterious effect of chemotherapy that directly affects skeletal muscle (AU) | |
| FAPESP's process: | 16/20187-6 - Caquexia in non-small cell lung cancer patient: physical fitness influence on prognosis |
| Grantee: | Willian das Neves Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |