Stereotactic Radiotherapy of the Resection Cavity of Brain Metastases vs. Post-operative Whole-brain Radiotherapy
NCT ID: NCT03285932
Last Updated: 2022-11-03
Study Results
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Basic Information
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COMPLETED
PHASE2
56 participants
INTERVENTIONAL
2018-02-01
2021-07-08
Brief Summary
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Concerning treatment, brain metastases remain a major clinical problem and a multidisciplinary approach to management should be adopted. Neurosurgical resection with postoperative whole brain radiotherapy (WBRT) is one major treatment option in solitary or symptomatic brain metastases. Furthermore, WBRT is recommended for multiple brain metastases. For a limited number of brain metastases stereotactic radiosurgery (SRS) has been established as a highly effective treatment alternative.
Recently, a new treatment approach combing neurosurgery with postoperative stereotactic radiotherapy (SRT) of the resection cavity is emerging. Based on available evidence, postoperative SRT of the resection cavity improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated (1).
This protocol is aimed at primarily evaluating the safety and toxicity profile of SRT to the resection cavity following neurosurgical resection combined with SRT of potentially further unresected brain metastases, compared to postoperative whole-brain radiotherapy (WBRT). Secondary, the local effect of SRT in patients with brain metastases will be assessed by measuring time to local recurrence (LR), local and loco-regional progression-free survival (PFS).
Additional systemic treatment will be carried out according to the standards of the National Center for Tumor Therapy (NCT).
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Detailed Description
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Trial Objectives: This protocol is primarily aimed at evaluating the safety and toxicity profile of SRS following neurosurgical resection and compares it to that of WBRT as the established standard of care. Secondary, the local effect of radiation therapy in patients with brain metastases will be assessed by measuring time to local and loco-regional recurrence, local and loco-regional PFS and overall survival at 12 months after treatment.
Patients´Selection: Patients with the diagnosis of brain metastases from solid tumors that have undergone neurosurgical resection of one brain metastasis will be evaluated and screened for the protocol. All patients fulfilling the inclusion and exclusion criteria will be informed about the study and included into the study if they declare informed consent. Registration for the study must be performed before the start of RT.
Trial Design: The trial will be performed as a single-center two-armed prospective randomized Phase II study. Patients will be randomized into an experimental arm and a control arm. All patients will receive post-operative contrast-enhanced cranial MRI imaging and imaging will be assessed by a radiologist. All available MRI sequences, including SPACE will be taken into consideration for the definition of treatment target lesions. Patients for whom the post-operative MRI reveals more than 10 suspect intracranial lesions (all sequences taken into account) will not be included in the trial.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Post-operative SRS of resection cavity
High-resolution contrast-enhanced post-operative MRI imaging in preparation for Cyberknife SRS. Cyberknife SRS of the resection cavity and all potential additional metastases diagnosed in the treatment planning MRI (up to 10 lesions)
Resection cavity:
7 x 5 Gy @ 95%-isodose
Potential additional brain metastases:
20 Gy @ 70%-isodose (lesions \< 2 cm max. diameter) 18 Gy @ 70%-isodose (lesions 2 - 3 cm max. diameter) 6 x 5 Gy @ 70%-isodose (lesions \> 3 cm max. diameter)
post-operative stereotactic radiosurgery (SRS)
For radiosurgery, patients will be immobilized. Treatment planning including the MRI and planning CT should be performed 1 -2 weeks before SRT and treatment finished at latest 3-4 weeks after surgery. Planning should be as close to SRT as possible.
Organs at risk such as the brain stem, optic nerves, chiasm and spinal cord will be contoured. The Clinical Target Volume 1 (CTV1) will be defined as the resection cavity based on MRI and CT including T1 contrast enhanced changes around the resection cavity. The Clinical Target Volume 2 (CTV2) will be defined as a 3mm margin added to CTV1 by isotropic expansion and slightly adjusted as deemed appropriated by the experienced contouring physician. The Planning Target Volume (PTV) will be an additional margin of 1mm added to CTV2 by isotropic expansion.
Treatment planning will be performed using Accuray's Multiplan or subsequent approved treatment planning systems for Cyberknife.
Post-operative WBRT
Post-operative WBRT will be performed according to the following dose regimen: 10 x 3 Gy
Whole brain radiotherapy (WBRT)
For WBRT, an individual head fixation mask is manufactured for each patient, and treatment planning is performed as virtual simulation or 3D-conformal RT planning based on CT-imaging. The portals include the whole brain with special focus as including the skull base areas and lamina cribrosa. For low infratentorial lesions, the treatment volume may include the whole brain down to the second cervical vertbra.
RT will be applied with two portals (e.g. 87°and 273°) using a 6 MeV linear accelerator.
For WBRT, a total dose of 30 Gy in 3 Gy fractions will be applied.
Interventions
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post-operative stereotactic radiosurgery (SRS)
For radiosurgery, patients will be immobilized. Treatment planning including the MRI and planning CT should be performed 1 -2 weeks before SRT and treatment finished at latest 3-4 weeks after surgery. Planning should be as close to SRT as possible.
Organs at risk such as the brain stem, optic nerves, chiasm and spinal cord will be contoured. The Clinical Target Volume 1 (CTV1) will be defined as the resection cavity based on MRI and CT including T1 contrast enhanced changes around the resection cavity. The Clinical Target Volume 2 (CTV2) will be defined as a 3mm margin added to CTV1 by isotropic expansion and slightly adjusted as deemed appropriated by the experienced contouring physician. The Planning Target Volume (PTV) will be an additional margin of 1mm added to CTV2 by isotropic expansion.
Treatment planning will be performed using Accuray's Multiplan or subsequent approved treatment planning systems for Cyberknife.
Whole brain radiotherapy (WBRT)
For WBRT, an individual head fixation mask is manufactured for each patient, and treatment planning is performed as virtual simulation or 3D-conformal RT planning based on CT-imaging. The portals include the whole brain with special focus as including the skull base areas and lamina cribrosa. For low infratentorial lesions, the treatment volume may include the whole brain down to the second cervical vertbra.
RT will be applied with two portals (e.g. 87°and 273°) using a 6 MeV linear accelerator.
For WBRT, a total dose of 30 Gy in 3 Gy fractions will be applied.
Eligibility Criteria
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Inclusion Criteria
* MRI confirmed cerebral metastases
* Neurosurgical resection of one cerebral metastasis
* age ≥ 18 years of age
* Karnofsky Performance Score \>60
* for women with childbearing potential, (and men) adequate contraception.
* ability to understand character and individual consequences of the clinical trial
* written informed consent (must be available before enrolment in the trial)
Exclusion Criteria
* previous radiotherapy to the brain
* \> 10 unresected brain metastases in postoperative MRI
* Patients who have not yet recovered from acute toxicities of prior therapies
* known carcinoma \< 2 years ago (excluding carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
* pregnant or lactating women
18 Years
ALL
No
Sponsors
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Heidelberg University
OTHER
Juergen Debus
OTHER
Responsible Party
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Juergen Debus
Prof. Dr. Dr. Jürgen Debus
Principal Investigators
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Juergen Debus, Prof. Dr. Dr.
Role: PRINCIPAL_INVESTIGATOR
Head of department Radiation Oncology
Locations
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Department of Radiotherapy, University of Heidelberg
Heidelberg, , Germany
Countries
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References
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Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, Xu W, Sahgal A. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012 Apr 18;2012(4):CD003869. doi: 10.1002/14651858.CD003869.pub3.
Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004 Jul 15;22(14):2865-72. doi: 10.1200/JCO.2004.12.149.
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Wang CC, Floyd SR, Chang CH, Warnke PC, Chio CC, Kasper EM, Mahadevan A, Wong ET, Chen CC. Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity after excision of large cerebral metastasis: efficacy and safety of an 800 cGy x 3 daily fractions regimen. J Neurooncol. 2012 Feb;106(3):601-10. doi: 10.1007/s11060-011-0697-z. Epub 2011 Aug 31.
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Other Identifiers
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ESTRON
Identifier Type: -
Identifier Source: org_study_id
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