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

Overview

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.

Interventions

• Radiation preoperative radiosurgery
  single fraction radiosurgery
• Radiation postoperative hypofractionated stereotactic radiotherapy
  fractionated stereotactic radiotherapy /radiosurgery in 1 to 6 fractions according to local standard of care

Primary outcome measures

• Leptomeningeal disease [Time frame: 12 months after intervention]

Secondary outcome measures (4)

• Local control of the surgical cavity [Time frame: 12 months after intervention]
• Distant brain failure [Time frame: 12 months after intervention]
• Radionecrosis [Time frame: 12 months after intervention]
• Quality of life assessment [Time frame: 3,6,12 months after intervention]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Age ≥18
• Karnofsky performance status ≥60
• Histological diagnosis of a malignant primary or metastatic tumour
• Ability to take steroids
• No contraindication to magnetic resonance imaging (MRI)
• 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
• Survival estimated by primary clinician > 12 months
• Platelet count > 100/ml, INR < 1.3, Hb > 7.5 g/dL

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Switzerland · 6 centers

• Kantonsspital Aarau — Aarau
• Inselspital, Universitätsklinik für Radio-Onkologie — Bern
• Kantonsspital Graubünden — Chur
• Luzerner Kantonsspital — Lucerne
• Kantonsspital St. Gallen — Sankt Gallen
• Kantonsspital Winterthur — Winterthur

Germany · 3 centers

• Knappschaft Kliniken, Universitätsklinikum Bochum GmbH — Bochum
• UKGM-Giessen — Giessen
• Universitätsklinikum Schleswig Holstein — Kiel

Austria · 1 center

• Tirol Kliniken Innsbruck — Innsbruck

Identifiers

NCT: NCT05124236 · 410.000.146

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗