Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases

Brain Metastases, Adult Clinical Trial

— PREOP-2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05124236
• Other study ID #: 410.000.146
• Status: Recruiting
• Phase: N/A
• Start date: July 29, 2022
• Est. completion date: December 30, 2025

Study information

• Verified date: September 2022
• Source: Kantonsspital Aarau
• Contact: Susanne Rogers, MD PhD
• Phone: +41 62 838 5726
• Email: Susanne.rogers[@]ksa.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases, Adult
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Radiation:
• preoperative radiosurgery
single fraction radiosurgery
• postoperative hypofractionated stereotactic radiotherapy
5 fraction stereotactic radiotherapy /fractionated radiosurgery

Locations

Country	Name	City	State
Switzerland	Kantonsspital Aarau	Aarau	Aargau
Switzerland	Inselspital, Universitätsklinik für Radio-Onkologie	Bern	Freiburgstrasse
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Luzerner Kantonsspital	Luzern
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Kantonsspital Winterthur	Winterthur

Sponsors (3)

Lead Sponsor	Collaborator
Susanne Rogers	Technische Universität München, University of Basel

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Leptomeningeal disease	Incidence (%)	12 months after intervention
Secondary	Local control of the surgical cavity	No evidence of tumour recurrence on contrsat-enhanced MRI	12 months after intervention
Secondary	Distant brain failure	New brain metastases	12 months after intervention
Secondary	Radionecrosis	Adverse radiation effects	12 months after intervention
Secondary	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