Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Medical University Innsbruck
Sponsor:
Collaborators:
Marcel Seiz-Rosenhagen MD, PD
Meinhard Nevinny-Stickel MD, Prof.
Christian F Freyschlag MD
Günther Stockhammer MD, Prof.
Bernhard Holzner MD, Doz
Johannes Giesinger Mag
Margarete Delazer MD, Prof.
Thomas Bodner MD, MSc
Claudius Thomé MD, Prof.
Information provided by (Responsible Party):
Kerschbaumer Johannes, Medical University Innsbruck
ClinicalTrials.gov Identifier:
NCT01667640
First received: August 7, 2012
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients.

To minimize the risk of intracranial recurrence whole brain irradiation has been established as standard adjuvant treatment in those patients. Sector irradiation resembles a brain - tissue - sparing method by focusing the irradiation in the area of the tumor bed and a surrounding 1mm security margin.

The aim of this study is to investigate whether adjuvant "sector""-irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.


Condition Intervention
Metastatic Malignant Neoplasm to the Adult Brain
Radiation: sector irradiation
Radiation: whole brain irradiation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sector Irradiation Versus Whole Brain Irradiation After Resection of Singular or Solitary Brain Metastasis - a Prospective Randomized Monocentric Trial

Resource links provided by NLM:


Further study details as provided by Medical University Innsbruck:

Primary Outcome Measures:
  • local tumor control [ Time Frame: time from date of randomization until the date of first documented progression, assessed up to 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • distant brain metastasis [ Time Frame: Time from date of randomization until the date of first documented progression elsewhere than the resection cavity, assessed at 3, 6, 12 and 36 months ] [ Designated as safety issue: No ]
  • time to clinical deterioration [ Time Frame: Time from randomization to clinical deterioration, assessed by neurosurgeon in regular follow up visits at 3, 6, 12 and 36 months ] [ Designated as safety issue: No ]
  • local progression free survival [ Time Frame: Time from randomization to the first documented tumor progressions in the resection cavity borders, assessed up to 36 months ] [ Designated as safety issue: No ]
  • quality of life [ Time Frame: 3, 6, 12 and 36 months ] [ Designated as safety issue: No ]
    standardized assessment via "EORTC QLQ-C30/BN20" and the "FACT-Br" - questionary at 3, 6, 12 and 36 months after date of randomization

  • neurocognitive functions [ Time Frame: 3, 6, 12 and 36 months postoperative ] [ Designated as safety issue: No ]
    Neurocognitive testing by independent neuropsychologist at 3, 6, 12 and 36 months after date of randomization

  • steroid dosage [ Time Frame: 3, 6, 12 and 36 months postoperative ] [ Designated as safety issue: No ]
    Need of adjuvant steroid, assessed at 3, 6, 12 and 36 months after date of randomization

  • overall survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: April 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: whole brain irradiation
whole brain irradiation with 40 Gy, with fixation mask, radiation of the entire brain, skull base and meninges
Radiation: whole brain irradiation

For whole brain radiation the entire brain, the base of the skull and the meninges are included.

Radiation is performed fractionated with 40 Gy. The caudal boundary of the radiation-target volume is between the 2. and the 3. cervical vertebra. The radiation is performed via two lateral, opposing and isocentric contra fields. The face/ventral skull is shielded with individual blocs or MLC.

The used energy for the radiation fields should be between 6 and 16 MV. The specification point of the dose or the standardization point has to be chosen in that way that the point is in the middle of the target volume. The target volume is radiated within the tolerance range of 95% - 107 %. The maximum/minimum doses in the target volume and possible doses peaks are documented.

Experimental: sector irradiation
irradiation of the resection margin plus 5 mm safety margin with 30 Gy in 5 fractions
Radiation: sector irradiation

Gross Tumor Volume (GTV) is defined as the visible margin of the resection on post- operative MRI and planning- CT-scan. The Clinical Treatment Volume (CTV) is the same as the GTV plus a 5 mm margin The Planning Treatment Volume (PTV) includes the CTV plus a 1mm margin.

A non-invasive immobilization is used for the planning CT and treatment delivery with an accuracy of ≤ 1mm.

Treatment planning will conform to ICRU 50/62 rules for coverage of GTV, CTV and PTV. Additionally, organs at risk are delineated according to the ICRU 62 rules.

Treatment with radiotherapy will start 2 to 3 weeks after surgery. The prescribed dose for the PTV is 30 Gy in 5 fractions.

Isodose distributions will be calculated through the target in three planes. Dose volume histograms will be reported.


Detailed Description:

Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients. Traditionally whole-brain irradiation is the treatment of choice following surgical resection. Whole brain irradiation has been the standard approach to minimize the risk of intracranial recurrence following resection of brain metastases. Almost 2 decades ago, Patchell et al. established the superiority of resection of solitary metastases followed by whole brain irradiation compared with whole brain irradiation alone with regard to survival, local control, and length of functional independence. A following study by the same group failed to show a survival advantage for the addition of whole brain irradiation compared to surgical resection alone in patients with a solitary intracranial metastasis, although the likelihood of local and distant recurrence and death from neurological causes were significantly reduced by whole brain irradiation. Due to potential delayed neurocognitive effects associated with whole brain irradiation, investigators have evaluated the use of partial brain irradiation in the form of stereotactic radiosurgery instead of whole brain irradiation after resection of brain metastases. They showed that despite whole brain irradiation means superior control of brain recurrence in sites other than the resection bed, stereotactic radiosurgery after resection resulted in equivalent survival times and neurological preservation. In a retrospective series of 52 patients Karlovits et al. could show that stereotactic radiosurgery following surgical resection leads to equal local control compared to standard whole brain irradiation.

Study objective

The aim of this study is to investigate whether adjuvant "sector" -irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.

Hypothesis

  1. Sector irradiation is equal to whole-brain irradiation in local tumor control after 3, 6, 12 and 36 months and
  2. Sector irradiation" is superior to whole-brain irradiation in terms of quality of life and neurocognitive function

Patients and Methods

Patients with a single brain metastasis amenable to surgical resection fulfilling the inclusion criteria will be consecutively enrolled in this study. After microsurgical complete resection documented by early postoperative MRI within 72 hours and histological proven brain metastasis patients will be randomized in arm A or B. Radiotherapy will start after 14th postoperative day within 3 weeks postoperatively. Study arm A means postoperative sector irradiation (30Gy), study arm B includes standard whole brain radiotherapy (40Gy). Follow up MRI will be every 3 months. Neurocognitive evaluation will be performed before radiotherapy and 6 and 12 months postoperatively. In case of local recurrence or developing further metastases a cross over to whole brain radiotherapy or focal irradiation is possible.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Solitary/singular brain metastasis
  • Karnofsky Performance Index > 60%
  • Stable extracranial disease /CUP
  • Informed consent

Exclusion Criteria:

  • Small cell lung cancer
  • Squamous cell lung cancer
  • HER2-negative breast cancer
  • Deep-seated location (e.g. basal ganglia)
  • Expected surgery related neurological deficit
  • Tumor diameter < 3cm
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01667640

Contacts
Contact: Johannes Kerschbaumer, MD +43-512-504-82848 johannes.kerschbaumer@uki.at
Contact: Christian F Freyschlag, MD +43-512-504-82595 christian.freyschlag@uki.at

Locations
Austria
Department of neurosurgery - Innsbruck Recruiting
Innsbruck, Tyrol, Austria, 6020
Contact: Sabine Strauss, Mag    +43-512-504-27286      
Sponsors and Collaborators
Medical University Innsbruck
Marcel Seiz-Rosenhagen MD, PD
Meinhard Nevinny-Stickel MD, Prof.
Christian F Freyschlag MD
Günther Stockhammer MD, Prof.
Bernhard Holzner MD, Doz
Johannes Giesinger Mag
Margarete Delazer MD, Prof.
Thomas Bodner MD, MSc
Claudius Thomé MD, Prof.
Investigators
Principal Investigator: Marcel Seiz-Rosenhagen, MD, PD Department of Neurosurgery, Medical University Innsbruck
  More Information

Additional Information:
No publications provided

Responsible Party: Kerschbaumer Johannes, MD, Medical University Innsbruck
ClinicalTrials.gov Identifier: NCT01667640     History of Changes
Other Study ID Numbers: Sektorradv_4.0_04-2012
Study First Received: August 7, 2012
Last Updated: October 22, 2012
Health Authority: Austria: Ethikkommission

Keywords provided by Medical University Innsbruck:
Brain metastases
radiation
sector
singular
solitary
neurocognition

Additional relevant MeSH terms:
Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on August 28, 2014