Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases

Kondziolka, Douglas; Patel, Atul; Lunsford, L.Dade; Kassam, Amin; Flickinger, John C

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Volume 45, Issue 2 , Pages 427-434, 1 September 1999

Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases☆

Douglas Kondziolka, M.D. (M.Sc., FRCS(C))
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA
- Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Image-Guided Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA
- Douglas Kondziolka, M.D., UPMC-Presbyterian, Department of Neurological Surgery, Suite B-400, 200 Lothrop St., Pittsburgh, PA, 15213
Atul Patel, M.D.
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA
L.Dade Lunsford, M.D.
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA
- Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Image-Guided Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA
Amin Kassam, M.D. (FRCS(C))
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA
John C Flickinger, M.D.
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA
- Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Image-Guided Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA

Accepted 25 February 1999.

Abstract

Purpose: Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases.

Methods: Patients with two to four brain metastases (all ≤25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care.

Results: The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was 6 months after WBRT alone (95% confidence interval [CI], 3.5–8.5) in comparison to 36 months (95% CI, 15.6–57) after WBRT plus radiosurgery (p = 0.0005). The median time to any brain failure was improved in the radiosurgery group (p = 0.002). Tumor control did not depend on histology (p = 0.85), number of initial brain metastases (p = 0.25), or extent of extracranial disease (p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months (p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease (p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery.

Conclusions: Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.

Keywords: Brain metastases, Cancer, Radiation therapy, Radiosurgery, Survival