Intraoperative Radiotherapy After the Resection of Brain Metastases

Not Applicable

• Conditions: Brain Metastases
• Interventions: Radiation: Intraoperative Radiotherapy

• Registration Number: NCT03226483
• Lead Sponsor: Universitätsmedizin Mannheim

Brief Summary

INTRAMET examines prospectively the effectiveness of an intraoperative radiotherapy immediate after the surgical resection of brain metastases. Patients won't receive further radiation therapy of the intraoperatively treated lesion.

Detailed Description

Brain metastases occur in up to 40% of all patients diagnosed with systemic cancer. Without adjuvant radiotherapy after resection of space occupying lesions local recurrence rates are high. That is why guidelines recommend a cavity boosting with x-rays. External beam radiotherapy can lower the risk of local recurrence but means longer hospitalization, prolongs the time to systemic salvage therapies and bears risks of radionecrosis and leucoencephalopathy with neurological and cognitive decline. A solution for this problem could be onetime intraoperative radiotherapy (IORT) with soft x-rays to sterilize the resection cavity, which may provide both: freedom from local recurrence fast track salvage therapy initiation.

INTRAMET is a single institution, open-label, prospective, phase 2 feasibility study for intraoperative radiotherapy immediately following resection of brain metastases. 50 adult patients with resectable not dural brain metastases should be treated in surgery after tumor resection with IORT with 20-30Gy prescribed to the margin of the resection cavity. The highest dose tolerable to surrounding risk structures (N. opticus, brainstem) should be used.

With this method, the investigators hope to show similar local control rates to postoperative external beam radiotherapy in line with guideline recommendations with less patient hospitalization and faster start of rescue therapies which could lead to a favorable overall outcome and less cognitive side effects.

Study Timeline

• Study Start: 2017-03-28
• Study First Submitted: 2017-07-18
• Study First Submitted QC: 2017-07-20
• Study First Posted: 2017-07-21
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-02
• Last Update Posted: 2022-06-03
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Karnofsky Performance index ≥ 50%
• MRI T1 Gadolinium enhancing non-dural resectable lesion
• Informed consent
• Adequate birth control
• Frozen section confirms metastasis
• Adequate distance to optic nerve and brainstem

Exclusion Criteria

• Dural lesions or meningeal carcinomatosis
• Frozen section reveals glioma, lymphoma,small cell lung cancer or germinoma
• Psychiatric or social condition interfering compliance
• Contraindication against anesthesia, surgery, MRI and/or Gadolinium
• Pregnant or breast-feeding women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intraoperative radiotherapy	Intraoperative Radiotherapy	After neurosurgical resection and proven metastasis (frozen section) a local intraoperative radiotherapy with soft energy x-rays is applied to the resection cavity. To perform this an applicator is inserted into the situs in the tightest fit rule. The highest possible dose between 30-20 Gy is chosen depending on nearby risk structures (Optic nerve, brainstem) is prescribed. After radiotherapy the applicator is removed and the surgery will be finished in standard way.

Primary Outcome Measures

Name	Time	Method
Median local progression-free-survival	2 years	Rate of recurrence of the treated lesion in the brain

Secondary Outcome Measures

Name	Time	Method
Time to further therapy	6 month	Time to further cancer therapy (e.g. salvage chemotherapy)
Patients cognitive performance	5 years	Neuropsychological battery
Overall-survival	5 years	Survival differentiated between death due to systemic cancer progress and death due to cerebral progress
Regional progression-free-survival	2 years	Progression-free survival concerning other brain metastases
Patients quality of life	5 years	Patient questionary
Intraoperative radiotherapy caused dose-limiting toxicities	6 month after intervention	Occurrence of wound healing disorders or infection requiring surgical revision, cerebral bleeding or ischemia, radionecrosis requiring surgical intervention
Global progression-free-survival	2 years	Systemic cancer progression-free-survival

Trial Locations

Locations (1)

Universitätsmedizin Mannheim; 🇩🇪 Mannheim, Germany