Glutamate Excitotoxicity in Brain Metastases From Lung, Breast and Melanoma Treated With Stereotactic Radiosurgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Glutamate Excitotoxicity in Brain Metastases From Lung, Breast and Melanoma Treated With Stereotactic Radiosurgery

Conditions
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Brain Metastases, Adult

Intervention / Treatment
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* Radiation: Stereotactic radiosurgery
* Diagnostic Test: Blood samples


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BM patients<br>Adult patients carrying new diagnosed BM confirmed by MRI | Radiation: Stereotactic radiosurgery<br>* Gamma Knife stereotactic radiosurgery (SRS-GK)<br>Diagnostic Test: Blood samples<br>* Serum Glu levels and Glu-regulation markers assessed prior to and following SRS-GK in BM or benign lesions or at baseline in non-BM patients.<br>|
| No BM patients<br>Adult patients carrying extracranial tumor without BM as confirmed by MRI | Diagnostic Test: Blood samples<br>* Serum Glu levels and Glu-regulation markers assessed prior to and following SRS-GK in BM or benign lesions or at baseline in non-BM patients.<br>|
| Benign lesion patients<br>Adult patients carrying intracranial extra-axial tumor as as confirmed by MRI | Radiation: Stereotactic radiosurgery<br>* Gamma Knife stereotactic radiosurgery (SRS-GK)<br>Diagnostic Test: Blood samples<br>* Serum Glu levels and Glu-regulation markers assessed prior to and following SRS-GK in BM or benign lesions or at baseline in non-BM patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, before SRS treatment. | GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl. | Baseline (pre-SRS); | 
| Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, after SRS treatment. | GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl. | Baseline (pre-SRS) and at 3, 6 and 9 months | 
| Serum markers determination in melanoma, lung or breast cancer patients without BM. | Comparison of serum GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels between BM and non-BM patients. All measures in mg/dl. | Baseline | 
| Serum markers determination in patients carrying benign intracranial lesions before and after SRS treatment. | Comparison of serum GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels between BM and benign lesion patients. All measures in mg/dl. | Baseline (pre-SRS) and at 3, 6 and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Studying correlation of serum markers levels with MRI changes following SRS-GK | Correlation between trends of markers and incidence of MRI changes. | 3, 6 and 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain metastases, Glutamate, Stereotactic radiosurgery