Preoperative Stereotactic Radiosurgery for Brain Metastases

Study Overview
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Brief Summary
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STEP is a French multicentre, prospective, non-randomized, phase II study designed to assess 6-months local control after pre-operative stereotactic radiosurgery (SRS) for patients with brain metastases

Official Title
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Phase II Study to Assess Preoperative Hypofractionated Stereotactic Radiotherapy of Brain Metastases

Conditions
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Brain Metastases

Intervention / Treatment
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* Procedure: Preoperative SRS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≤ 4 distinct brain metastases, one with surgical indication Diagnosis of primary histologically proven breast, digestive or non-small cells lung cancer ≤ 5 cm larger diameter Karnofsky performance status ≥ 70 No contraindication for MRI Possibility for the patient to be treat with both surgery and stereotactic radiotherapy ≥ 18 years old Estimated overall survival ≥ 6 months according to diagnosis specific - graded prognostic assessment (DS GPA) Written inform consent signed Affiliation to the French social security system For women of childbearing age including those on luteinizing hormone-releasing hormone (LH-RH) agonists for ovarian suppression: inclusion negative serum pregnancy test (≤ 7 days prior to the start of preoperative stereotactic radiosurgery (SRS). Exclusion Criteria: Lymphoma, leukaemia, multiple myeloma, germinal tumours or cerebral primary cancer Metastases from small-cells lung cancer, kidney cancer, melanoma or sarcoma Mass effect with deflection ≥ 5 mm from median line or hydrocephaly or compression 4th ventricle, patient neurologically unstable, need for emergency decompressive surgery > 4 brain metastases Contraindication to anaesthesia, MRI or gadolinium injection Proximity of the tumour with organs at risk which do not allow the prescribed dose to be reached in the envelope Pregnant or breastfeeding woman Anti vascular endothelial growth factor (VEGF) within 6 weeks before treatment Documented leptomeningeal injury History of irradiation of the encephalon in toto History of stereotactic radiotherapy on metastasis to be operated on Non-candidate patient for surgery Surgical delay > 3 days compared to stereotactic radiotherapy Estimated survival < 6 months by DS GPA Patient under guardianship or curators Psychological disorder (cognitive disorders, mental alertness, etc.) or social (deprivation of liberty by judicial or administrative decision) or geographical reasons that may compromise medical monitoring of the trial or compliance with treatment Woman of childbearing age without effective contraception Patient participating in another intervention study within 4 weeks prior to inclusion

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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm (all patients)<br>Patients will receive preoperative hypofractionated stereotactic radiosurgery (SRS). According to the association of french-speaking neuro-oncologists (ANOCEF) recommendations, total dose and fractionation will be 33 Gy in 3 fractions at the isocenter, 23.1 Gy in envelope (70% isodose), i.e. 30 Gy in growth tumor volume (GTV) envelope.) Surgery will take place within 3 days of the preoperative SRS. | Procedure: Preoperative SRS<br>* Patient will be treat with preoperative SRS and then surgery for brain metastases is realized within 3 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of 6-months local control rate after preoperative SRS | Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. | 6 months after preoperative SRS (M6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of 1-year local control rate after preoperative SRS | Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the RANO-BM criteria. | 12 months after preoperative SRS (M12) | 
| Evaluation of 1-year radionecrosis rate after preoperative SRS | Radionecrosis is defined either histologically post-operatively according to the anatomopathological report or in the absence of salvage surgery by the appearance or increase of gadolinium contrast on T1 MRI sequences associated with an increase in the cerebral brain volume (CBV) ratio (brain blood volume of the tumour / brain blood volume of the non-tumour white matter) of less than 2 on perfusion MRI sequences and/or a standard uptake volume (SUV max) of less than 1, 59 on positron emission tomography (PET) scanners at 6-fluoro-[18 fluoro]-L-dihydroxyphenylalanine (F-DOPA) | 12 months after preoperative SRS (M12) | 
| Evaluation of overall survival | defined as the time interval between the date of preoperative radiosurgery and the date of death from any cause. | At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12) | 
| Evaluation of acute (less than 3 months post preoperative SRS) and delayed toxicities (more than 3 months after preoperative SRS) | They will be collected and graded according to the NCI-CTCAE v5.0 scale. An adverse event of grade ≥ 3 will be considered severe. | At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12) | 
| Rate of leptomeningeal relapses | According to cerebral MRI | At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12) | 
| Evaluation of cerebral distant control | Follow by MRI | At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12) | 
| Determination of predictive factors for local brain control, complication and prognosis factors for survival |  | At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12) | 
| Evaluation of cognitive function | Mini-mental state examination (MMSE) | At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12) | 
| Evaluation of quality of life | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30) | At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain metastases, preoperative stereotactic radiosurgery, local control, radionecrosis, overall survival