Cancer Anorexia and the Central Nervous System
Condition: Cancer Cachexia
MeSH terms: Anorexia; Cachexia
Study type: Observational

Summary: 
      The pathogenesis of cancer anorexia is complex and multifactorial. However, a number of
      consistent and robust evidence point to a prominent role for the central nervous system. In
      particular, the hyperactivation of the immune system, due to tumour growth, causes a systemic
      inflammatory response primarily mediated by pro-inflammatory cytokines. At the central level,
      inflammatory response profoundly alters the activity of the hypothalamic nuclei, which are
      involved in the regulation of energy homeostasis. In particular, pro-inflammatory cytokines
      inhibit prophagic neurons activity, while enhance the activation of the anorexigenic neurons.
      Although supported by compelling experimental evidence, it should be acknowledged that this
      pathogenic hypothesis has not been confirmed yet by human studies.

      Aim of the present study is to determine the specific pattern(s) of the brain activation
      after assumption of a standard meal in both anorexic and non-anorexic cancer patients to
      reveal potential differences, which will be correlated with the levels of concurrently
      measured circulating pro-inflammatory cytokines. The results obtained would help in assessing
      the role of the central nervous system and, in particular of the hypothalamus, in the
      pathogenesis of cancer anorexia.
    

Detailed description: 
      After approval of the study protocol by the Ethical Committee of our Institution (Azienda
      Policlinico Umberto I, Sapienza University, Rome, Italy), 9 anorexic cancer patients, 4
      non-anorexic cancer patients and 2 healthy individuals will be studied. The sample size is
      based on studies of neuroimaging already published and available on international journals.

      Patients with confirmed cancer diagnosis will be enrolled before the initiation of any
      anti-cancer treatments. The presence/absence of anorexia will be investigated using a
      specific questionnaire (Cangiano et al., 1990) and a visual analogue scale (VAS). After an
      overnight fasting, blood samples will be collected from cancer patients and control subjects
      and interleukin(IL)-1, IL-6 and Tumor Necrosis Factor-α (TNF-α) levels will be measured by a
      commercially available ELISA kit.

      On the same day, hypothalamic activation pattern(s) will be evaluated in patients and in
      control subjects by fMRI. After basal evaluation, all the groups will receive a standard oral
      meal, i.e., a 200 mL hypercaloric oral nutritional supplement providing 300 Kcal, and then a
      second fMRI scan will be performed. Using a computerized software, the average value of the
      grey for the hypothalamus will be calculated, and normalized for the one obtained in the
      basal condition, to obtain the percentage (%) of activation (or inhibition) of the
      hypothalamus.

      Data obtained will be statistically analyzed using the t-Student and Bonferroni tests.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Lung cancer patients with confirmed cancer diagnosis before the initiation of any
        anti-cancer treatments will be enrolled. Nine anorexic cancer patients, 4 non-anorexic
        cancer patients and 2 healthy individuals will be studied.
      
Biospecimen description: 
      serum
    
Keywords: anorexia; cancer; hypothalamus; inflammation