title: Brain metabolomic profiles of lung cancer patients prior to treatment characterized by proton magnetic resonance spectroscopy.
abstract: Cancer patients without evidence of brain metastases often exhibit constitutional symptoms, cognitive dysfunction and mood changes at the time of clinical diagnosis, i.e. prior to surgical and/or chemotherapy treatment. At present however, there is limited information on brain metabolic and functional status in patients with systemic cancers such as lung cancer prior to initiation of treatment. Therefore, a prospective, observational study was conducted on patients with a clinical diagnosis of lung cancer to assess the cerebral metabolic status before treatment using proton magnetic resonance spectroscopy ((1)HMRS). Together with neurocognitive testing, (1)HMRS was performed in the parietal and occipital cortices of patients diagnosed with a lung mass (N=17) and an age-matched control group (N=15). Glutamate concentrations in the occipital cortex were found to be lower in the patients compared to controls and the concentrations of creatine and phosphocreatine were significantly lower in the parietal cortex of the patients. The lung cancer patients were also characterized by greater fatigue scores (but not depression) prior to treatment when compared to controls. In addition, the serum concentration of interleukin-6 (proinflammatory cytokine) was higher in patients compared to controls; and the concentration of tumor-necrosis factor alpha ([TNF-α]) was positively correlated to the metabolic activity of the lung tumor as defined by the 2-deoxy-2-((18)F)fluoro-D-glucose ((18)FDG) positron emission tomography (PET) derived maximal standardized uptake values (SUV(max)). Finally, multivariate statistical modeling revealed that the concentration of N-acetyl-aspartate [NAA] in the occipital cortex was negatively associated with [TNF-α]. In conclusion, our data demonstrate that the cerebral metabolic status of patients with lung cancer is changed even prior to treatment. In addition, the association between inflammatory cytokines, SUV(max) and [NAA] points towards interactions between the cancer's inherent metabolic activity, systemic subclinical inflammation and brain function.
authors.forename: Helene
authors.initials: H
authors.lastname: Benveniste
authors.forename: Shaonan
authors.initials: S
authors.lastname: Zhang
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Reinsel
authors.forename: Haifang
authors.initials: H
authors.lastname: Li
authors.forename: Hedok
authors.initials: H
authors.lastname: Lee
authors.forename: Mario
authors.initials: M
authors.lastname: Rebecchi
authors.forename: William
authors.initials: W
authors.lastname: Moore
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Bilfinger