Cancer Cachexia
Conditions
Keywords
anorexia, cancer, hypothalamus, inflammation
Brief 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.
Interventions
None listed
Sponsors
University of Roma La Sapienza
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Lung cancer patients at diagnosis
Exclusion criteria
* Patients treated with immunosuppressors, with concomitant wasting diseases (e.g. AIDS, trauma, end-stage renal disease)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE | TIME 0 (BASELINE) | We observed different BOLD signal in the region of the hypothalamus between the 3 groups. The BOLD signal and the activation/no activation areas were statistically analyzed by a specific statistical method (i.e., parametric mapping). |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ANOREXIC CANCER PATIENTS Based on the anorexia instruments that we used, we considered these patients as anorexic. | 9 |
| NON-ANOREXIC CANCER PATIENTS Based on the anorexia instruments that we used, we considered these patients as non-anorexic | 4 |
| CONTROL GROUP These were healthy subjects. 1 MD working at the Oncology Dept. , 1 family member of one of the patients enrolled. | 2 |
| Total | 15 |
Baseline characteristics
| Characteristic | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP | ANOREXIC CANCER PATIENTS | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 7 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Age, Continuous | 76.25 years STANDARD_DEVIATION 6.95 | 65 years STANDARD_DEVIATION 7.1 | 71.1 years STANDARD_DEVIATION 9.4 | 71.66 years STANDARD_DEVIATION 8.76 |
| Region of Enrollment Italy | 4 participants | 2 participants | 9 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 4 | 0 / 2 |
| serious Total, serious adverse events | 0 / 9 | 0 / 4 | 0 / 2 |
Outcome results
Primary
ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE
We observed different BOLD signal in the region of the hypothalamus between the 3 groups. The BOLD signal and the activation/no activation areas were statistically analyzed by a specific statistical method (i.e., parametric mapping).
Time frame: TIME 0 (BASELINE)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ANOREXIC CANCER PATIENTS | ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE | 585.57 BOLD | Standard Deviation 55.69 |
| NON-ANOREXIC CANCER PATIENTS | ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE | 667.92 BOLD | Standard Deviation 33.18 |
| CONTROL GROUP | ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE | 511.22 BOLD | Standard Deviation 79.43 |