Brain Metastases, Adult
Conditions
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.
Interventions
RADIATIONpreoperative radiosurgery
single fraction radiosurgery
fractionated stereotactic radiotherapy /radiosurgery in 1 to 6 fractions according to local standard of care
Sponsors
Susanne Rogers
University of Basel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Leptomeningeal disease | 12 months after intervention | time to leptomeningeal disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local control of the surgical cavity | 12 months after intervention | No evidence of tumour recurrence on contrast-enhanced MRI |
| Distant brain failure | 12 months after intervention | New brain metastases |
| Radionecrosis | 12 months after intervention | Adverse radiation effects |
| Quality of life assessment | 3,6,12 months after intervention | EORTC questionnaire core questionnaire QLQ30, EORTC questionnaire brain module BN 20 (1-4, low scores reflect better QoL) |
Countries
Austria, Germany, Switzerland
Contacts
CONTACTSusanne Rogers, MD PhD
CONTACTOliver Riesterer, Prof.
PRINCIPAL_INVESTIGATORSusanne Rogers, MD PhD
Kantonsspital Aarau, Radio-Onkologie-Zentrum Mittelland
Outcome results
None listed