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

Recruiting
Conditions
Brain Metastases, Adult
Interventions
Diagnostic Test: Blood samples
Radiation: Stereotactic radiosurgery
Registration Number
NCT04785521
Lead Sponsor
IRCCS San Raffaele
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
Inclusion Criteria

Not provided

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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
No BM patientsBlood samplesAdult patients carrying extracranial tumor without BM as confirmed by MRI
Benign lesion patientsBlood samplesAdult patients carrying intracranial extra-axial tumor as as confirmed by MRI
BM patientsBlood samplesAdult patients carrying new diagnosed BM confirmed by MRI
Benign lesion patientsStereotactic radiosurgeryAdult patients carrying intracranial extra-axial tumor as as confirmed by MRI
BM patientsStereotactic radiosurgeryAdult patients carrying new diagnosed BM confirmed by MRI
Primary Outcome Measures
NameTimeMethod
Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, before SRS treatment.Baseline (pre-SRS);

GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl.

Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, after SRS treatment.Baseline (pre-SRS) and at 3, 6 and 9 months

GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl.

Serum markers determination in melanoma, lung or breast cancer patients without BM.Baseline

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.

Serum markers determination in patients carrying benign intracranial lesions before and after SRS treatment.Baseline (pre-SRS) and at 3, 6 and 9 months

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.

Secondary Outcome Measures
NameTimeMethod
Studying correlation of serum markers levels with MRI changes following SRS-GK3, 6 and 9 months

Correlation between trends of markers and incidence of MRI changes.

Trial Locations

Locations (1)

IRCCS San Raffaele Scientific Institute

🇮🇹

Milan, Italy

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