Intraoperative Radiotherapy in Patients With Brain Metastases

Sponsor

Parc de Salut Mar (Other)

Overall Status

Recruiting

CT.gov ID

NCT04847284

Collaborator

(none)

Enrollment

Location

Arm

37.9

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Intraoperative radiotherapy (IORT) is a new alternative for local radiotherapy with the advantages of dose escalation, reduced overall treatment time, and enhanced patient convenience, however the degree of efficacy is unknown, as well as and which is the most efficient dose.

The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy is at least as effective and safe as other forms of radiation therapy in patients with resection of brain metastases.

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases	Radiation: Intraoperative radiotherapy	N/A

Detailed Description

INTRODUCTION

Brain metastases occur in roughly 30% of all cancer patients during their course of disease. Their incidence is believed to rise due to the aging population that develops more cancer per se, an increase in overall survival due to more effective extracranial therapies but with only few (novel) substances crossing the blood-brain barrier and more broadly available and more advanced imaging techniques.

Neurosurgical treatment remains a cornerstone in the management of brain metastasis, especially for lesions causing mass effects or neurological deficits or in case tissue is necessary to establish a diagnosis. As local recurrence rates are as high as 50-60% after surgical resection alone, adjuvant therapies to prevent such are necessary.

Whole brain radiotherapy (WBRT) does not influence survival but rather impairs neurocognitive functions and, as histologic in-depth exams of cavity borders showed that most brain metastases infiltrate only 0.3-1.2 mm into the surrounding healthy brain tissue, therefore treatment is to date usually confined to the cavity margin. Thus, the currently recommended standard of care is post-operative stereotactic radiosurgery (SRS) to the resection cavity. One of the drawbacks of this modality is the incidence of radionecrosis, especially in large tumor volumes. As an alternative to radiosurgery, hypofractionated local radiotherapy is also used, reducing the risk of radionecrosis in large volumes. There are no prospective randomized studies comparing both techniques.

The need to find a modality of radiotherapy that achieves al least the efficacy of radiosurgery or hypofractionated local radiotherapy, without the disadvantages thereof, makes IORT as a possible treatment alternative.

OBJECTIVES

Primary Objective

Median local progression free survival (lPFS), defined as time span (in months) between surgery and recurrence within a 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
Radiation-related (acute / late) neurotoxicity, assessed by regular neurological examinations and serial MRI scans.

Secondary objectives

Median regional PFS (rPFS), resembling the time (in months) from surgery to any progression outside of the 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
Global PFS (gPFS), defined as the time (in months) from surgery to any intra- and extracranial tumor progress.
Median overall survival (OS), defined as the time (in months) from surgery of brain metastases to death from by any cause.

DESIGN

This trial is an open, single arm, single institution, prospective trial to determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases. A total of 25 patients will be included.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Intraoperative Radiotherapy in Patients With Brain Metastases

Actual Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arms To determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases	Radiation: Intraoperative radiotherapy Intraoperative radiotherapy application immediately following resection of brain metastases.

Arm

Intervention/Treatment

Experimental: Single arms

To determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases

Radiation: Intraoperative radiotherapy

Intraoperative radiotherapy application immediately following resection of brain metastases.

Outcome Measures

Primary Outcome Measures

Median local progression free survival (lPFS) [6 months from the date of surgery.]
Recurrence within a 0.5 cm margin around the resection cavity, assessed by serial MRI scans and response assessment criteria in neuro-oncology (RANO)
Radiation-related acute neurotoxicity [3 months from the date of surgery.]
Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity - Acute toxicity: cerebral edema
Radiation-related late neurotoxicity [6 months from the date of surgery.]
Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity - Late toxicity: radionecrosis.

Secondary Outcome Measures

Median regional PFS (rPFS) [6 months from the date of surgery]
To any progression outside of the 0.5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment in neuro-oncology .
Global PFS (gPFS) [6 months from the date of surgery]
The time (in months) from surgery to any intra- and extracranial tumor progress
Median overall survival (OS) [6 months from the date of surgery]
The time (in months) from surgery of brain metastases to death from by any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Karnofsky Performance Status ≥ 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

Exclusion Criteria:

Leptomeningeal spread and dural attachment (assessed pre- and intraoperatively)
Frozen section reveals primary CNS tumor, lymphoma, SCLC (Small-cell lung cancer) or germinoma
More than one brain metastasis
Psychiatric or social condition potentially interfering with compliance
Contraindication against anesthesia, surgery, MRI and/or contrast agents
Pregnant or breast-feeding women