Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases (PREOP-2)

A Multicenter Prospective, Interventional, Randomized Trial of Preoperative Radiosurgery Compared With Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases

The research question is whether a single fraction of preoperative radiosurgery can reduce the incidence of leptomeningeal disease 12 months following resection of a brain metastasis (BM) as compared with 5 fractions of postoperative stereotactic radiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases, Adult
• Intervention / Treatment: Radiation: preoperative radiosurgery; Radiation: postoperative hypofractionated stereotactic radiotherapy

Detailed Description

Neurosurgical resection of a brain metastasis in patients with a diagnosis of cancer may be indicated however the recurrence rate approximates 50% and adjuvant radiotherapy is standard. Single fraction postoperative stereotactic radiosurgery (SRS) has been widely adopted as a standard therapy as it achieves equivalent survival and prevents loss of neurocognitive function as compared with whole brain radiotherapy and improves cavity local control rates as compared with observation. Hypofractionated stereotactic radiotherapy in 3 to 5 fractions (hfSRT) is also used in the postoperative setting.

Nodular leptomeningeal disease (nLMD) is a recognised pattern of failure after postoperative SRS and hfSRT. A 16.9% incidence of nodular LMD was seen after surgery and a similar incidence of 11%-28%is reported following postoperative SRS in retrospective series. These data suggest that postoperative SRS/hfSRT have no significant effect on the development of LMD following surgery.

The incidence of LMD following single fraction preoperative SRS is only 6.1% according to the largest retrospective series. Preoperative SRS takes advantage of the easier delineation of an intact BM and sterilizes tumor cells disseminated at surgery. Side effects are minimized by a smaller planning margin, a dose reduction and resection of the irradiated volume. In addition, there is no delay to systemic therapy due to wound healing/complications. Furthermore, a single fraction offers patient convenience.

This trial will randomise and compare intracranial outcomes between single fraction preoperative SRS and 5 fraction postoperative hFSRT.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Oliver Riesterer, Prof.; Phone Number: +41 62 838 4249; Email: oliver.riesterer@ksa.ch
• Study Contact Backup: Name: Susanne Rogers, MD PhD; Phone Number: +41 62 838 57 26; Email: Susanne.rogers@ksa.ch

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Active, not recruiting
    • Tirol Kliniken Innsbruck
• Germany
  • Bochum, Germany
    • Recruiting
    • Knappschaft Kliniken, Universitätsklinikum Bochum GmbH
    • Contact: Dorothea Miller, Dr. med.; Email: Dorothea.Miller@Knappschaft-Kliniken.de
  • Giessen, Germany
    • Recruiting
    • UKGM-Giessen
    • Contact: Daniel Hebermehl; Email: Daniel.Habermehl@uk-gm.de
  • Kiel, Germany, 24103
    • Recruiting
    • Universitätsklinikum Schleswig Holstein
    • Contact: Michael Synowitz, Prof. Dr. med.; Phone Number: 0049 431-50023601; Email: Michael.Synowitz@uksh.de
    • Contact: Oliver Blanck, Priv.-Doz. Dr.; Phone Number: +49 431 50026666; Email: oliver.blanck@uksh.de
• Switzerland
  • Chur, Switzerland, 7000
    • Recruiting
    • Kantonsspital Graubünden
    • Contact: Thomas Mader, Dr. med.; Phone Number: +41 81 256 64 90; Email: thomas.mader@ksgr.ch
  • Lucerne, Switzerland, 6000
    • Recruiting
    • Luzerner Kantonsspital
    • Contact: Gabriela Studer, Prof. Dr. med.; Phone Number: +41 205 58 01; Email: gabriela.studer@luks.ch
  • Sankt Gallen, Switzerland, 9000
    • Recruiting
    • Kantonsspital St. Gallen
    • Contact: Detlef Brugge, Dr. med.; Phone Number: +41 71 494 2192; Email: detlef.brugge@kssg.ch
  • Winterthur, Switzerland, 8400
    • Recruiting
    • Kantonsspital Winterthur
    • Contact: Christoph Oehler, PD Dr. med.; Phone Number: +41 52 266 26 58; Email: christoph.oehler@ksw.ch
  • Canton of Aargau
    • Aarau, Canton of Aargau, Switzerland, 5001
      • Recruiting
      • Kantonsspital Aarau
      • Contact: Susanne J Rogers, MD PhD; Phone Number: 0041628385726; Email: susanne.rogers@ksa.ch
      • Contact: Sonja Schwenne; Phone Number: 0041628386259; Email: sonja.schwenne@ksa.ch
  • Freiburgstrasse
    • Bern, Freiburgstrasse, Switzerland, 3010
      • Recruiting
      • Inselspital, Universitätsklinik für Radio-Onkologie
      • Contact: Ekin Ermis, Dr. med.; Phone Number: +41 31 632 26 32; Email: erkin.ermis@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Age ≥18
4. Karnofsky performance status ≥60
5. Histological diagnosis of a malignant primary or metastatic tumour
6. Ability to take steroids
7. No contraindication to magnetic resonance imaging (MRI)
8. MRI-diagnosis of a clearly demarcated contrast-enhancing brain metastasis up to 4.0 cm diameter indicated for neurosurgical resection (tumorboard decision). Up to 3 other brain metastases suitable for primary radiosurgery/ stereotactic radiotherapy
9. Survival estimated by primary clinician > 12 months
10. Platelet count > 100/ml, INR < 1.3, Hb > 7.5 g/dL

Exclusion Criteria:

1. Radiosensitive histology: germ cell tumour, lymphoma, multiple myeloma
2. >10 mm midline shift, effacement of the 4th ventricle or other sign of raised intracranial pressure requiring urgent decompressive surgery
3. More than 4 brain metastases or the diameter of the metastasis for resection >4.0 cm.
4. More than 1 metastasis requiring resection
5. Leptomeningeal disease in the CSF or on MRI (unless localized and can be irradiated then resected with the metastasis)
6. Prior radiation to the brain (SRS/SRT to lesion to be resected and /or WBRT)
7. Prior resection of a primary or secondary brain tumor
8. Prior diagnosis of a non-meningioma brain tumor
9. Prior radionuclide therapy within 30 days
10. Prior anti-VEGF therapy within 6 weeks
11. Unable to tolerate radiosurgery immobilization and treatment
12. Inability to give informed consent
13. Pregnancy or lactation
14. Females of reproductive potential not willing to use effective contraception for at least 6 months after radiotherapy
15. Males of reproductive potential not effective contraception for 3 months after radiotherapy
16. Lack of likely compliance with protocol and follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative radiosurgery; The interventional arm is single fraction preoperative radiosurgery to a brain metastasis identified for neurosurgical resection.	Radiation: preoperative radiosurgery; single fraction radiosurgery
Active Comparator: Postoperative hypofractionated stereotactic radiotherapy; The active comparator arm is the standard of care of postoperative hypofractionated stereotactic radiotherapy to the surgical cavity in 5 fractions following resection of the brain metastasis.	Radiation: postoperative hypofractionated stereotactic radiotherapy; fractionated stereotactic radiotherapy /radiosurgery in 1 to 6 fractions according to local standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leptomeningeal disease	time to leptomeningeal disease	12 months after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant brain failure	New brain metastases	12 months after intervention
Radionecrosis	Adverse radiation effects	12 months after intervention
Quality of life assessment	EORTC questionnaire core questionnaire QLQ30, EORTC questionnaire brain module BN 20 (1-4, low scores reflect better QoL)	3,6,12 months after intervention
Local control of the surgical cavity	No evidence of tumour recurrence on contrast-enhanced MRI	12 months after intervention

Collaborators and Investigators

• Sponsor: Susanne Rogers
• Collaborators: University of Basel
• Investigators: Principal Investigator: Susanne Rogers, MD PhD, Kantonsspital Aarau, Radio-Onkologie-Zentrum Mittelland

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2022
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: November 13, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: 410.000.146

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No