Clinical trial NCT05124236: Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases
Official title: A Multicenter Prospective, Interventional, Randomized Trial of Preoperative Radiosurgery Compared with Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Brain Metastases, Adult
Lead sponsor: Kantonsspital Aarau
Sponsor class: OTHER
Collaborators: name: University of Basel
First posted: 2021-11-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Leptomeningeal disease
timeFrame: 12 months after intervention
Secondary outcomes:
measure: Local control of the surgical cavity
timeFrame: 12 months after intervention
measure: Distant brain failure
timeFrame: 12 months after intervention
measure: Radionecrosis
timeFrame: 12 months after intervention
measure: Quality of life assessment
timeFrame: 3,6,12 months after intervention
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Tirol Kliniken Innsbruck
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig Holstein
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: Aargau
city: Bern
country: Switzerland
facility: Inselspital, Universitätsklinik für Radio-Onkologie
state: Freiburgstrasse
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
Study officials:
affiliation: Kantonsspital Aarau, Radio-Onkologie-Zentrum Mittelland
name: Susanne Rogers, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: