Non Invasive Methods for Differential Diagnosis Radionecrosis/Recurrence After Radiosurgery of Brain Metastases (CV-METANEC)

Non Invasive Methods for Differential Diagnosis Radionecrosis/Recurrence After Radiosurgery of Brain Metastases. CV-METANEC

The purpose of this multicenter study is to assess a diagnostic strategy concerning differential diagnosis between radiation necrosis and relapse in brain metastases treated with radiosurgery. Two non-invasive tests - positron emission tomography (PET) with 1F-fluoro-ethyl-tyrosine (FET) and magnetic resonance spectroscopy (MRS) - will be compared to histology in a cohort of patients presenting growing lesions 6 months after radiosurgical treatment.

The results of this study should help to earlier diagnosis of recurrences after radiosurgery and to perform an appropriate treatment for patients.

Study Overview

• Status: Completed
• Conditions: Brain Metastases; Growing Lesions After Radiosurgical Treatment
• Intervention / Treatment: Other: imaging

Detailed Description

The purpose of the study is to assess a diagnostic strategy by monitoring brain metastases after radio surgical treatment . Data from two non-invasive techniques: PET-FET (positron emission tomography using 1-Fluoro-Ethyl-Tyrosine) and MSR (magnetic resonance spectroscopy) will be compared to histological examination (gold standard) in patients with active persistent and increased lesion 4 months after radiosurgery. The study should develop a decision-making algorithm based on non-invasive tests and allow improving the length and quality of life of these patients.

Early differential diagnosis between relapse and radio necrosis after radiosurgery would allow:

• To perform resection of tumor relapse
• To treat feasable/inoperable tumor relapse with a salvage radiosurgery
• To avoid irradiation for patients presenting radiation necrosis
• To reduce the corticosteroid prescription period. Validation of non-invasive diagnostic tools should in fine avoid biopsy. In addition, the results of this study should help to better estimate the true incidence of radiation necrosis and better specify the predictors of this complication.

CV-METANEC is a prospective, multicenter, open, multidisciplinary study involving the following departments: neurosurgery, neuroradiology, nuclear medicine and neuropathology.

4 centers participating in the study: Groupe Hospitalier Pitié-Salpêtrière University Hospital, Lariboisière Hospital, Lille University Hospital of Clermont Ferrand and Toulouse University Hospital.

Patients are included if they were treated by radiosurgery for one or more brain metastases. The interval between the radiosurgical treatment and the inclusion is at least 6 months. The lesion is clinically and / or MRI evolving.

The criterion used to measure the discriminating power of the algorithm to rank the differential between recurrences with or without radionecrosis or only radionecrosis is the area under the ROC (receiver operating characteristic) curve. The inclusion of 90 subjects will achieve a standard deviation of the area under the curve 0.04.

The duration of study participation will be five weeks, from inclusion until the end of hospitalization. Subsequently, the patient will be followed as usual.

Inclusion D0: whether the conditions of inclusion are applied, the patient signs the consent form and exams before surgery are planned: SRI-MRI, examination of scintigraphy and anesthesia consultation.

D15: MRI (neuroradiology) and anesthetic consultation (neurosurgery).

D30-D33 (+/- 7 days): 3 days of hospitalization:

D30: MRI / MRS always done before-FET PET D31: stereotactic biopsy for histological samples. D33: CT scan before the patient is discharged. Total study duration: 5 years

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • CHU Pitié-Salpêtrière - Service de Neurochirurgie du Pr Philippe Cornu - Babinsky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age between 18 and 75 years.
• Patient treated with radiosurgery for one or more brain metastases Free -Intervally between radiosurgical treatment and inclusion in the study at least four months.
• Lesion (S) treated (s) and followed (s) with the criteria for a clinically active lesion (progressive deficit, seizures, intracranial hypertension steroid-dependent) and / or MRI (increased volume of contrast enhancement with peri-lesional edema and mass effect on two successive examinations at 1 month interval).
• Karnofsky index> 50.
• Prognostic compatible for survival with a follow-up at least three months from the date of inclusion.
• Effective contraception for women of childbearing potential or negative pregnancy test within 72 hours.
• Signed informed consent obtain
• Affiliation to the social security system

Exclusion Criteria:

• Contraindication to MRI examination
• Clearance of the creatinine incompatible with the injection of gadolinium
• No potential follow-up in middle or long term
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: diagnostic imaging strategy; PET-FET (positron emission tomography using 1-Fluoro-Ethyl-Tyrosine) and MSR (magnetic resonance spectroscopy) before biopsy	Other: imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the choline /N-acetyl aspartate ratio at MR spectroscopy		Day 30
the lipid / lactate ratio at MR spectroscopy		Day 30
peak creatine at MR spectroscopy		Day 30
lesional tissue / normal tissue ratio at PET with FET		Day 30
Histological result at biopsy	histology as the gold standard for the diagnostic between radiation necrosis and relapse	Day 31

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Charles-Ambroise VALERY, MD, PhD, CHU Pitié-Salpêtrière - Service de Neurochirurgie du Pr Philippe Cornu - Babinsky

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: December 8, 2015
• First Submitted That Met QC Criteria: December 17, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Estimate): April 11, 2016
• Last Update Submitted That Met QC Criteria: April 8, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: relapse; radiosurgery; radiation necrosis; brain metastases; diagnostic strategy; PET-FET and MSR
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Recurrence; Brain Neoplasms
• Other Study ID Numbers: P071243; 2009-014458-14 (EudraCT Number)