IORT After Surgical Resection of Brain Metastases

Study Overview
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Brief Summary
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To evaluate the feasibility and efficacy of the Intraoperative Radiation Therapy (IORT) after the resection of a brain metastases to reduce the incidence of local relapse

Official Title
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IORT After Surgical Resection of Brain Metastases: Feasibility and Efficacy Phase II Trial

Conditions
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Brain Neoplasms

Intervention / Treatment
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* Radiation: Intraoperative Radiotherapy (IORT)
* Procedure: Brain surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years, Karnofsky Performance Index ≥ 70. Newly diagnosed cerebral or cerebellar lesion (contrast enhancing on a T1- weighted MRI scan) amenable to total resection with no dural attachment. Frozen section confirming a metastasis of an extracranial (i.e. non-CNS) tumor. Adequate distance to optic nerve(s), chiasm and brainstem (organs at risk for radiotherapy). Adequate birth control. Informed consent. Exclusion Criteria: Leptomeningeal spread and dural attachment (assessed pre- and intraoperative). Frozen section reveals primary CNS tumor, lymphoma, SCLC or germinoma. Psychiatric or social condition potentially interfering with compliance. Contraindication against anesthesia, surgery, MRI and/or contrast agents. Pregnant or breast-feeding women.

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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Accepts Healthy Volunteers

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
Interventional Model Description: Intraoperative Radiation Therapy (IORT)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraoperative Radiotherapy (IORT)<br>Intraoperative Radiotherapy (IORT) administered during surgery | Radiation: Intraoperative Radiotherapy (IORT)<br>* If biopsy is positive, local treatment with IORT will be performed. After IORT (15,40 Gray at 2 mm dept), the applicator will be removed and surgery will be continued in a standard fashion.<br>Procedure: Brain surgery<br>* Surgery should be performed according to the local standard of care, preferentially as image-(neuronavigation) guided surgery. To establish the diagnosis of a metastasis and to exclude primary CNS tumors, lymphomas, SCLCs or germinomas it will be performed a peroperative biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median local progression free survival (PFS) | Time span (in months) between surgery and recurrence within a 0,5 cm margin around the resection cavity, evaluated through Response Assessment in Neuro-Oncology (RANO) criteria for brain metastasis obtained from serial Magnetic resonance imaging (MRI) scans. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median regional PFS (rPFS) | The time (in months) from surgery to any progression outside of the 0,5 cm margin around the resection cavity, evaluated through Response Assessment in Neuro-Oncology (RANO) criteria for brain metastasis obtained from serial Magnetic resonance imaging (MRI) scans. | 12 months | 
| Global PFS (gPFS) | Time (in months) from surgery to any intra- and extracranial tumor progression evaluated through Response Assessment in Neuro-Oncology (RANO) criteria for brain metastasis obtained from serial Magnetic resonance imaging (MRI) scans. | 12 months | 
| Median time to the initiation of systemic therapies | Time (in days) from surgery to the day of initiation of any systemic anti-tumor therapy (e.g., chemotherapy) | 12 months | 
| Median overall survival (OS) | Time (in months) from surgery of brain metastases to death by any cause | 12 months | 
| Change in neurocognitive performance (compared to baseline): Minimental | Assessed by minimal mental scale examination | 6, and 12 months | 
| Change in neurocognitive performance (compared to baseline): Trail making | Assessed by trail making test | 6, and 12 months | 
| Change in neurocognitive performance (compared to baseline): Repetition | Assessed by number repetition test (forward and backward) | 6, and 12 months | 
| Change in neurocognitive performance (compared to baseline): Oral | Assessed by controlled oral word association test | 6, and 12 months | 
| Change in neurocognitive performance (compared to baseline): Semantic | Assessed by semantic word association | 6, and 12 months | 
| Quality of life (QoL) | Assessed by European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaires (QLQ C30/BN20) | 6, and 12 months | 
| Radiation-related (acute / early delayed / late) neurotoxicity | Assessed by regular neurological examinations combined by serial MRI scans | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain metastases, neurosurgery, intraoperative radiotherapy, local therapy