Clinical Investigation
Multidose Stereotactic Radiosurgery (9 Gy × 3) of the Postoperative Resection Cavity for Treatment of Large Brain Metastases

https://doi.org/10.1016/j.ijrobp.2013.03.037Get rights and content

Purpose

To evaluate the clinical outcomes with linear accelerator-based multidose stereotactic radiosurgery (SRS) to large postoperative resection cavities in patients with large brain metastases.

Methods and Materials

Between March 2005 to May 2012, 101 patients with a single brain metastasis were treated with surgery and multidose SRS (9 Gy × 3) for large resection cavities (>3 cm). The target volume was the resection cavity with the inclusion of a 2-mm margin. The median cavity volume was 17.5 cm3 (range, 12.6-35.7 cm3). The primary endpoint was local control. Secondary endpoints were survival and distant failure rates, cause of death, performance measurements, and toxicity of treatment.

Results

With a median follow-up of 16 months (range, 6-44 months), the 1-year and 2-year actuarial survival rates were 69% and 34%, respectively. The 1-year and 2-year local control rates were 93% and 84%, with respective incidences of new distant brain metastases of 50% and 66%. Local control was similar for radiosensitive (non-small cell lung cancer and breast cancer) and radioresistant (melanoma and renal cell cancer) brain metastases. On multivariate Cox analysis stable extracranial disease, breast cancer histology, and Karnofsky performance status >70 were associated with significant survival benefit. Brain radionecrosis occurred in 9 patients (9%), being symptomatic in 5 patients (5%).

Conclusions

Adjuvant multidose SRS to resection cavity represents an effective treatment option that achieves excellent local control and defers the use of whole-brain radiation therapy in selected patients with large brain metastases.

Introduction

The addition of whole-brain radiation therapy (WBRT) to surgery for a single brain metastasis has been considered the standard of care in cancer patients. Few randomized and retrospective studies have shown that adjuvant WBRT after surgical resection is able to reduce the risk of local recurrence from 46%-59% to 10%-28% and the incidence of new brain metastases from 37%-42% to 14%-23%, although without improving survival 1, 2, 3. For this reason, in clinical practice many physicians prefer to withhold WBRT because it may result in a decline of neurocognitive function and quality of life (QOL) 4, 5. Moreover, WBRT doses for “radioresistant” brain metastases such as melanoma and renal cell carcinoma are considered suboptimal, and its role has been questioned (6).

More recently, surgery in combination with stereotactic radiosurgery (SRS), which includes both traditional single-dose SRS and multidose SRS up to a maximum of 5 doses, has been used in several centers on the basis of the belief that this approach may offer excellent local control without compromising survival, and potentially avoiding the risk of the detrimental neurocognitive effects of WBRT. Several retrospective studies have shown actuarial 12-month local control in the range of 70% to 85% and a median survival of 12 to 17 months 7, 8, 9, 10. Multidose SRS is usually used as an alternative to single-dose SRS for target volumes larger than 3 cm or in proximity to highly sensitive areas of the brain 9, 11; however, there is limited information on the efficacy and safety of this multimodality approach in patients with large brain metastases, especially from radioresistant tumors. We report our initial experience with linear accelerator (LINAC)-based multidose SRS (9 Gy × 3) to large postoperative resection cavities. The primary objective of the study was to analyze local control. Secondary endpoints were survival and distant failure rates, cause of death, performance measurements, and toxicity of treatment.

Section snippets

Patients

Patients’ data were obtained from a prospectively maintained database of patients with brain tumors treated with stereotactic irradiation at our institution. We identified 101 patients with a single brain metastasis, derived from different histologically confirmed systemic cancers, who underwent complete resection followed by adjuvant multidose SRS (9 Gy × 3) from March 2005 to May 2012. The postoperative resection cavities were required to have a diameter >3 cm with no evidence of residual

Patient and treatment characteristics

Between March 2005 and May 2012, a total of 101 patients who met the inclusion criteria were evaluated. Patients and tumor characteristics are summarized in Table 1. According to surgical reports, an “en bloc” resection was achieved in 73 cases. All the patients received the planned dose (9 Gy × 3) to the resection cavity. The median minimum PTV coverage was 98% (range, 95%-100%). Median prescription isodose was 83%, and median conformity index was 1.54 ± 0.22. Median time from surgery to

Discussion

Multimodality therapy of surgery followed by adjuvant SRS of the resection cavity has been used in many centers to treat patients with brain metastases. Recent studies have reported 1-year local control and median survival of 70% to 85% and 12 to 18 months after single-dose SRS, respectively, with a 1-year incidence of new metastases of 45% to 60% 7, 8, 9, 10, 11. Multidose SRS is usually used as an alternative to single-dose SRS for cavities >3 cm. Using 2-5 sessions and doses of 22-35 Gy, few

Acknowledgment

The authors thank the nursing staff at the Radiation and Medical Oncology Departments of Sant’Andrea, Neuromed, and Umberto I hospitals for their help, and all the patients who participated in this study.

References (23)

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This study was supported in part by a grant (00SA19162) from University of Rome “Sapienza.”

Conflict of interest: none.

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