• Physical fitness and response to treatment [ Time Frame: 1 year ]
  Response Evaluation in solid tumors (RECIST 1.1) will be used to evaluate the relationship between physical fitness and response to chemotherapy.
• Physical fitness and toxicity [ Time Frame: 1 year ]
  Common terminology criteria for adverse events (CTCAE 5.0) will be used to evaluate the relationship between physical fitness and toxicities related to chemotherapy.
• Cancer cachexia skeletal muscle pathways [ Time Frame: 1 year ]
  Determination of down and up-regulated skeletal muscle pathways cachectic and non-cachectic patient using RNA-sec.
• Cluster of Differentiation 4+ (CD4+) population in cachectic and non-cachectic patient. [ Time Frame: 1 year ]
  Determination of CD4+ profile in cachectic and non-cachectic patients using flow cytometry.
• Cluster of Differentiation 25+ (CD25+) population. [ Time Frame: 1 year ]
  Determination of CD25+ profile in cachectic and non-cachectic patients using flow cytometry.
• Forkhead box P3 regulatory T (Fox-p3+) population. [ Time Frame: 1 year ]
  Determination of Fox-p3+ profile in cachectic and non-cachectic patients using flow cytometry.

Non-small-cell lung cancer (NSCLC) is currently the neoplasm leading in deaths worldwide and in Brazil, it figures as the second most common cancer in terms of the number of deaths. Patients are usually diagnosed in advanced stages and, consequently, more than 45% of all patients are diagnosed with cachexia. This syndrome is characterized by a loss of muscle mass with or without fat loss and it cannot be reversed by nutritional support. In the physiopathology of cachexia, generally are present exacerbated inflammation, severe loss of muscle contractile proteins, leading to fatigue and increased mortality. Furthermore, patients with cachexia usually do present lower response rates to anticancer treatments and it is also associated with a worse overall prognosis.

Treatments directed to mitigate muscle loss in these patients are awaited. Cohort studies do suggest a significant positive impact of physical fitness and prognosis in different chronic diseases; however, its impact in advanced NSCLC patients is not clear. Here our aim is to better understand the relationship between cachexia and physical fitness variables (muscle and cardiorespiratory function, body composition, and daily physical activity level) with prognosis and mortality in a group of NSCLC patients, as well as to study the effect of chemotherapy on these variables. Besides that, will be evaluated the skeletal muscle, Treg lymphocytes, and inflammatory biomarkers and compare cachectic and non-cachectic patients.

Sixty NSCLC patients will be accrued. Will be assessed the maximum oxygen consumption, daily physical activity, muscle function, muscle morphology, anxiety, depression, performance status, and fatigue pre-treatment. Blood and muscle biopsy samples will be collected. The prognostic impact of these physical fitness variables will be defined, as well as their predictive value in terms of response to anticancer treatments in advanced NSCLC patients.

Inclusion Criteria:

• Advanced stage IVa or IVb NSCLC patients histologically diagnosis.
• Eastern Cooperative Oncology Group Performance status 0 - 2
• Treatment-naive
• Current smokers or ex-smokers
• Normal renal, hepatic and hematological functions
• Able to perform the physical functional tests
• Able to read and sign the consent form

Exclusion Criteria:

• Initiate treatment before initiate
• Diagnostic of tumor mutation ( epidermal growth factor receptor, Anaplastic lymphoma kinase)

Obs: A smoker population with no known cancer will be used as controls (n=10)