Comparative Analysis of Inflammatory Indexes in Lung Cancer Patients With and Without Brain Metastases.

Introduction Lung cancer is the leading cause of oncological deaths worldwide. Various combined inflammatory indexes, such as the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) have shown associations with pretreatment survival prognosis in patients suffering of lung cancer with or without brain metastases. This study aimed to compare the average values of NLR, PLR, LMR, and SII in healthy patients, patients with lung cancer without any other metastases, and patients with lung cancer and brain metastases. Materials and methods In this prospective study, we have divided the patients into three groups: Group 1 included patients diagnosed with lung cancer and one or more brain metastases of lung cancer origin, Group 2 included patients diagnosed with lung cancer without known metastases, and Group 3 was the control group which included healthy subjects. Preoperative complete blood counts were extracted for all included patients and we calculated the values of SII, NLR, PLR, and LMR for each individual patient in each group. The next step was to calculate the average values of SII, NLR, PLR, and LMR for each group of patients and to identify the differences between groups. Results A total number of 228 patients were enrolled in the study. Group 1 included 67 patients with average values of SII = 2020.98, NLR = 7.25, PLR = 199.46, and LMR = 2.97. Group 2 included 88 patients with average values of SII = 1638.01, NLR = 4.58, PLR = 188.42, and LMR = 3.43. Group 3 included 73 subjects with the following average values of the inflammatory indexes: SII = 577.41, NLR = 2.34, PLR = 117.84, and LMR = 3.56. Conclusion We observed statistically significant differences in SII, NLR, and PLR among the three groups of patients, suggesting their potential role as prognostic markers. Furthermore, our analysis revealed significant correlations between inflammatory markers within lung cancer patients, highlighting their involvement in tumor microenvironment modulation. Our findings demonstrate an escalation in SII, NLR, and PLR values as the disease progresses. These parameters of inflammation and immune status are readily and cost-effectively, and repeatedly assessable in routine clinical practice.

Metabolic Contrasts: Fatty Acid Oxidation and Ketone Bodies in Healthy Brains vs. Glioblastoma Multiforme.

The metabolism of glucose and lipids plays a crucial role in the normal homeostasis of the body. Although glucose is the main energy substrate, in its absence, lipid metabolism becomes the primary source of energy. The main means of fatty acid oxidation (FAO) takes place in the mitochondrial matrix through ß-oxidation. Glioblastoma (GBM) is the most common form of primary malignant brain tumor (45.6%), with an incidence of 3.1 per 100,000. The metabolic changes found in GBM cells and in the surrounding microenvironment are associated with proliferation, migration, and resistance to treatment. Tumor cells show a remodeling of metabolism with the use of glycolysis at the expense of oxidative phosphorylation (OXPHOS), known as the Warburg effect. Specialized fatty acids (FAs) transporters such as FAT, FABP, or FATP from the tumor microenvironment are overexpressed in GBM and contribute to the absorption and storage of an increased amount of lipids that will provide sufficient energy used for tumor growth and invasion. This review provides an overview of the key enzymes, transporters, and main regulatory pathways of FAs and ketone bodies (KBs) in normal versus GBM cells, highlighting the need to develop new therapeutic strategies to improve treatment efficacy in patients with GBM.

Preoperative Immune-Inflammatory Status of the Patients With Newly-Diagnosed Glioblastoma - Could It Genuinely Predict Their Survival?

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive brain tumor affecting adult patients, with an extremely reduced overall survival despite rapid diagnosis and treatment. Therefore, it is crucial to establish accurate and affordable markers that allow an individualized approach to GBM patients. Serum biomarkers could be the most accessible, as complete blood counts should be performed on all GBM patients before undergoing any surgical and/or pharmacological treatment. However, their prognostic role is still unclear. Our study aims to assess the influence of various hematological markers of inflammation in predicting the outcome of GBM patients. MATERIAL AND METHODS: We retrospectively analyzed all adult patients diagnosed with primary glioblastoma in the Neurosurgery Department of the Emergency Clinical County Hospital of Târgu Mureș, Romania, from January 2017 until December 2019. We aimed to discover whether the immune/inflammatory status of the patients before receiving any kind of pharmacological or surgical treatment influenced their overall survival. RESULTS: Our study showed that pre-therapeutic elevated white blood count could predict reduced overall survival in not otherwise specified subtype (NOS) of GBMs (HR 0.4153, 95% CI 0.1825-0.9449, p 0.0362). Furthermore, patients with increased systemic immune response index (SIRI) had much larger tumors at the time of diagnosis (p 0.0359). In wild type, isocitrate dehydrogenase subpopulation (IDHwt), the higher values of neutrophil-to-lymphocyte ratio (NLR, p 0.0412), platelet-to-lymphocyte ratio (PLR, p 0.0376) and monocyte-to-lymphocyte ratio (MLR, p 0.0412) were related to more advanced age at the moment of diagnosis. Moreover, our results revealed a weakly positive association between tumor size and NLR values in the NOS group (Spearman r 0.3212, p 0.0493). CONCLUSIONS: Our study does not provide enough evidence for the immune/inflammatory status of GBM patients to be used as an efficient prognostic marker to guide the therapeutic approach.

The Role of Ketone Bodies in Treatment Individualization of Glioblastoma Patients.

Glioblastoma is the most common and aggressive primary brain tumor in adults. According to the 2021 WHO CNS, glioblastoma is assigned to the IDH wild-type classification, fulfilling the specific characteristic histopathology. We have conducted a prospective observational study to identify the glucose levels, ketone bodies, and the glucose-ketone index in three groups of subjects: two tumoral groups of patients with histopathological confirmation of glioblastoma (9 male patients, 7 female patients, mean age 55.6 years old) or grade 4 astrocytoma (4 male patients, 2 female patients, mean age 48.1 years old) and a control group (13 male patients, 9 female patients, mean age 53.9 years old) consisting of subjects with no personal pathological history. There were statistically significant differences between the mean values of glycemia (p value = 0.0003), ketones (p value = 0.0061), and glucose-ketone index (p value = 0.008) between the groups of patients. Mortality at 3 months in glioblastoma patients was 0% if the ketone levels were below 0.2 mM and 100% if ketones were over 0.5 mM. Patients with grade 4 astrocytoma and the control subjects all presented with ketone values of less than 0.2 mM and 0.0% mortality. In conclusion, highlighting new biomarkers which are more feasible to determine such as ketones or glucose-ketone index represents an essential step toward personalized medicine and survival prolongation in patients suffering from glioblastoma and grade 4 astrocytoma.