Brain metastases (BM) represents a devastating clinical reality, carrying an estimated survival time of less than one year. Number of reasons, including complicated tumor biology and difficulties in modeling metastatic cancer in brain microenvironment, do hinder research on this topic. BM are indeed the most frequent neoplasm in the central nervous system (CNS) and is estimated that up to 14% of all newly diagnosed cancers will metastasize to the brain. A number of reasons, including complicated tumor biology and difficulties in modeling metastatic cancer in brain microenvironment, do hinder research on this topic. Present knowledge regarding alterations in Glutamate (Glu) homeostasis and BM is poor. This study aims at investigating Glu balance in BM patients and providing supporting evidence to the identification of new putative biomarkers to be used as potential therapeutic targets.

Experimental procedure:

Serum levels of glutamic oxaloacetic transaminase (GOT1), glutamate Pyruvate Transaminase (GPT) and lactate dehydrogenase (LDH) levels and serum glutamate, aspartate and lactate levels of a total of 100 patients will be collected and divided in three different groups:

• A: BM group (n=50), patients affected by BM from lung, breast and melanoma, candidates to SRS
• B: Control group 1 (n=25), patients with the same primary controlled tumors without nor brain nor extracranial metastases
• C: Control group 2 (n=25), patients with benign intracranial lesions candidates to SRS treatment.

In A) and C) serum GOT1, GPT and LDH levels and serum glutamate, aspartate, lactate levels will be evaluated before and after SRS treatment (at 3, 6 and 9 months follow-up).

In B) serum biomarkers levels will be only collected at baseline.

• Oncological and imaging data will be collected during follow-up in patients enrolled in the present studies. MRI imaging will be performed at definite timepoints (baseline and 3, 6 and 9 months follow-up).

Serum levels of markers will be analyzed in each group and results will be compared between them. Moreover, MRI changes and oncological relevant outcomes will be investigated.

Inclusion Criteria (Target group)

• Adult patients carrying melanoma, breast or lung cancer BM of new diagnosis
• Patients eligible to SRS-GK treatment

Inclusion Criteria (Control group 1)

- Adult patients carrying melanoma, breast or lung cancer without BM

Inclusion Criteria (Control group 2)

• Adult patients carrying intracranial extra-axial benign tumor
• Patients eligible to SRS-GK treatment

Exclusion Criteria:

• Acute or chronic liver disease
• Severe anemia (Hb <8g/dl)
• Pregnant or breastfeeding patient
• Pediatric patients
• Patients not able to express informed consent

Target group:

Adult patients affected by melanoma, breast or lung cancer BM of new diagnosis as confirmed by MRI ongoing SRS-GK treatment.

Control group 1:

Adult patients affected by melanoma, breast or lung cancer without BM.

Control group 2:

Adult patients affected by intracranial extra-axial benign tumor as confirmed by MRI ongoing SRS-GK treatment.