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

Susanne Rogers200 enrolled

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

200

Conditions

Brain Metastases, Adult

Interventions

preoperative radiosurgeryRADIATION

single fraction radiosurgery

postoperative hypofractionated stereotactic radiotherapyRADIATION

5 fraction stereotactic radiotherapy /fractionated radiosurgery

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

Tirol Kliniken Innsbruck

Innsbruck, Austria

RECRUITING

Universitätsklinikum Schleswig Holstein

Kiel, Germany

RECRUITING

Kantonsspital Aarau

Aarau, Canton of Aargau, Switzerland

Outcomes

Primary Outcomes

Leptomeningeal disease

time to Leptomeningeal disease

Time frame: 12 months after intervention

Secondary Outcomes

Local control of the surgical cavity

No evidence of tumour recurrence on contrsat-enhanced MRI

Time frame: 12 months after intervention

Distant brain failure

New brain metastases

Time frame: 12 months after intervention

Radionecrosis

Adverse radiation effects

Time frame: 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)

Time frame: 3,6,12 months after intervention

Central Contacts

Susanne Rogers, MD PhD

CONTACT

+41 62 838 57 26 Susanne.rogers@ksa.ch

Oliver Riesterer, Prof.

CONTACT

+41 62 838 4249 oliver.riesterer@ksa.ch

Data from ClinicalTrials.gov

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