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

NCT04785521 | Active Not Recruiting

• 1 other identifier: NCH04-2020
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastases, Adult

Keywords

Brain metastases; Glutamate; Stereotactic radiosurgery

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Studying correlation of serum markers levels with MRI changes following SRS-GK

  3, 6 and 9 months

Study Arms (3)

BM patients

Adult patients carrying new diagnosed BM confirmed by MRI

Radiation: Stereotactic radiosurgery; Diagnostic Test: Blood samples

No BM patients

Adult patients carrying extracranial tumor without BM as confirmed by MRI

Diagnostic Test: Blood samples

Benign lesion patients

Adult patients carrying intracranial extra-axial tumor as as confirmed by MRI

Radiation: Stereotactic radiosurgery; Diagnostic Test: Blood samples

Interventions

Stereotactic radiosurgery RADIATION

Gamma Knife stereotactic radiosurgery (SRS-GK)

BM patients; Benign lesion patients

Blood samples DIAGNOSTIC_TEST

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.

BM patients; Benign lesion patients; No BM patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Adult patients carrying melanoma, breast or lung cancer BM of new diagnosis
• Patients eligible to SRS-GK treatment
• \- Adult patients carrying melanoma, breast or lung cancer without BM
• Adult patients carrying intracranial extra-axial benign tumor
• Patients eligible to SRS-GK treatment

You may not qualify if:

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

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele Scientific Institute

Milan, Milan, 20132, Italy

Location

Related Publications (7)

• Lowery FJ, Yu D. Brain metastasis: Unique challenges and open opportunities. Biochim Biophys Acta Rev Cancer. 2017 Jan;1867(1):49-57. doi: 10.1016/j.bbcan.2016.12.001. Epub 2016 Dec 6.

  PMID: 27939792 BACKGROUND

• Franzin A, Snider S, Picozzi P, Bolognesi A, Serra C, Vimercati A, Passarin O, Mortini P. Evaluation of different score index for predicting prognosis in gamma knife radiosurgical treatment for brain metastasis. Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):707-13. doi: 10.1016/j.ijrobp.2008.08.062. Epub 2008 Dec 25.

  PMID: 19095375 BACKGROUND

• Robert SM, Sontheimer H. Glutamate transporters in the biology of malignant gliomas. Cell Mol Life Sci. 2014 May;71(10):1839-54. doi: 10.1007/s00018-013-1521-z. Epub 2013 Nov 27.

  PMID: 24281762 BACKGROUND

• Miladinovic T, Nashed MG, Singh G. Overview of Glutamatergic Dysregulation in Central Pathologies. Biomolecules. 2015 Nov 11;5(4):3112-41. doi: 10.3390/biom5043112.

  PMID: 26569330 BACKGROUND

• Sharma MK, Seidlitz EP, Singh G. Cancer cells release glutamate via the cystine/glutamate antiporter. Biochem Biophys Res Commun. 2010 Jan 1;391(1):91-5. doi: 10.1016/j.bbrc.2009.10.168. Epub 2009 Nov 5.

  PMID: 19896463 BACKGROUND

• Zeng Q, Michael IP, Zhang P, Saghafinia S, Knott G, Jiao W, McCabe BD, Galvan JA, Robinson HPC, Zlobec I, Ciriello G, Hanahan D. Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature. 2019 Sep;573(7775):526-531. doi: 10.1038/s41586-019-1576-6. Epub 2019 Sep 18.

  PMID: 31534217 BACKGROUND

• Willard SS, Koochekpour S. Glutamate signaling in benign and malignant disorders: current status, future perspectives, and therapeutic implications. Int J Biol Sci. 2013 Aug 9;9(7):728-42. doi: 10.7150/ijbs.6475. eCollection 2013.

  PMID: 23983606 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Radiosurgery; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures

Study Officials

• Pietro Mortini, MD, Prof.

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of department

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 8, 2021
• Study Start: July 1, 2020
• Primary Completion: July 31, 2025
• Study Completion: December 31, 2025
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)