International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationA Phase 2 Trial of Stereotactic Radiosurgery Boost After Surgical Resection for Brain Metastases
Introduction
Brain metastases occur in 20% to 30% of all cancer patients with systemic disease 1, 2. Historically, brain metastases do not respond well to systemic agents, and the outcome for patients with brain metastases is generally poor, with median survivals after whole brain radiation therapy (WBRT) alone in the range of 3 to 6 months 3, 4, 5. The treatment approach of WBRT as the primary therapy for brain metastases has been gradually changing with use of surgery and stereotactic radiosurgery (SRS) to achieve intracranial disease control. Although WBRT remains as the main treatment modality for patient with multiple brain metastases, randomized trials support the use of surgery and, more recently, SRS in addition to WBRT in patients with limited brain metastases 3, 6, 7, 8 in reducing intracranial progression.
Although older series of patients with solitary brain metastasis treated with surgery followed by WBRT showed an overall survival (OS) of less than 1 year, with death due to systemic disease in the vast majority of patients (9), updated studies of patients with limited brain metastases have reported longer OS, reflecting in part the improved efficacy of modern systemic therapies 10, 11. As systemic control improves, durable control of CNS metastases becomes increasingly imperative. While adjuvant WBRT may be effective for improving local control (LC) significant neurocognitive deficit associated with WBRT has been reported (12). Furthermore, WBRT can delay systemic therapy during the weeks of administration of the radiation treatments and for several weeks afterward as patients continue to recover from its acute side effects.
Adjuvant SRS has been used as another method in the delivery of RT to the post-surgical cavity 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25. It is established as an effective alternative to WBRT as the primary treatment for limited brain metastases 6, 8 by offering excellent LC and minimal acute and long-term toxicity as a stand-alone modality 6, 12. In the postoperative setting for patients with single intracranial metastasis, adjuvant of SRS to the surgical bed may be favored over WBRT, as it is well tolerated with minimal impact on a patient's quality of life and does not significantly interfere with systemic therapy schedules.
This study was designed to test the hypothesis that adjuvant SRS to the surgical cavity for patients with 1 or 2 brain metastases would achieve favorable LC and allow avoidance of up-front WBRT. While several retrospective studies of postoperative SRS 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 have reported local control rates between 70% and 90% at 12 months, this is the first prospective study investigating its efficacy.
Section snippets
Patient selection
This phase 2 study received institutional review board approval and was opened on June 8, 2004, and closed to accrual on January 27, 2009, after 50 patients were enrolled. Inclusion and exclusion criteria are listed in Table 1. The primary objective of this study was to evaluate the local control of brain metastases with combination therapy of surgical resection followed by postoperative SRS.
Surgery
Study patients were accrued from a population eligible for surgery and for whom surgery rather than
Patient characteristics
From 2004 to 2008, a total of 50 patients enrolled in this prospective study of SRS boost after surgical resection for brain metastases. One patient expired before surgery 1 week after enrollment and was therefore excluded from all analyses. The median age of patients was 59 years. Ten patients did not receive SRS due to early CNS progression (n=4, 3 with local failure and 1 with regional failure), large cavity size (n=2), general medical decline due to systemic progression (n=3), and failure
Discussion
The importance of WBRT after surgery in patients with limited brain metastases has been demonstrated in prospective randomized studies, showing an improvement in LC. Patchell et al demonstrated a decrease in LF from 46% to 10% in patients treated with adjuvant WBRT compared to untreated patients (9), and Kocher et al demonstrated a decrease from 59% to 27% at 2 years (8). Nevertheless, WBRT is associated with an acute decline in quality of life in some patients 27, 28 as well as delayed
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Conflict of interest: none.
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Dr. C.B. and Dr. T.J. Y. contributed equality to this article and are considered as co-first authors.