Clinical Investigation
Three-Staged Stereotactic Radiotherapy Without Whole Brain Irradiation for Large Metastatic Brain Tumors

https://doi.org/10.1016/j.ijrobp.2008.10.035Get rights and content

Purpose

To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm3 in volume.

Patients and Methods

Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 ± 6.3 cm3 (mean ± SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method.

Results

At the time of the second and third fractions, mean tumor volumes were 14.3 ± 6.5 (18.8% reduction) and 10.6 ± 6.1 cm3 (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively.

Conclusions

The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases.

Introduction

With advances in cancer treatment, increasing attention has recently been paid to treating brain metastases. Stereotactic radiosurgery (SRS) has a critical role in the treatment of brain metastases; however, a large tumor volume is not suitable for SRS. Local tumor control is reportedly unsatisfactory for metastatic brain tumors exceeding 3 cm in diameter 1, 2, 3.

Tumor size strongly correlates with decreased responsiveness to radiation and an increased risk of neurotoxicity. The prescribed dose should be decreased for large tumors. However, low radiosurgical doses (< 18 Gy) have been shown to be associated with poorer outcomes (1). Although large metastatic brain tumors (> 3 cm in diameter) would presumably be treated with surgery, the selection of patients for operative intervention depends on the surgical accessibility of the tumor and the status of systemic diseases (4). In treating malignant tumors, therapeutic ratios between tumor control and late effects are anticipated to be improved by treatment delivery in a small number of fractions (5). Fractionated stereotactic radiotherapy (SRT) has been used as a treatment option for large brain metastases in patients with surgical contraindications (4); however, there is as yet no standard procedure for dose fractionation in stereotactic irradiation for brain metastases.

We therefore developed an alternative protocol for staged SRT with a dose of 30 Gy in three fractions. This is a unique protocol with a 2-week interval between fractions. Our aims were tumor volume shrinkage within 2 weeks and, when possible, a reduction in the irradiated volume. We report here the results of staged SRT for brain metastases.

Section snippets

Patient characteristics

Forty-three patients with large brain metastases were enrolled in this study between December 2002 and September 2006. The tumor volume was more than 10 cm3 in all 43 patients. Patient characteristics are shown in Table 1. Patient ages ranged from 41 to 84 years with a median of 64 years. The primary cancers were in the colon, lung, or breast. On recursive partitioning analysis (RPA) (6), 36 patients were Class 2 and 7 were Class 3. The graded prognosis assessment (GPA) (7) score was ≥ 2.5 in

Changes in tumor volume during treatment protocol

The mean tumor volume decreased 18.8% and 39.8% with the second and third fractions, respectively, compared with the initial tumor volume (Table 3), which are statistically significant reductions (Student t test, p < 0.001). Although the prescribed irradiation volumes were reduced for the second and third treatments, four lesions (9.3%) showed volume decreases of < 5% with the third treatment. The primary pathologies of these four low responders were non–small cell lung cancer, colon cancer,

Efficacy of staged stereotactic radiotherapy for large brain metastases

Staged SRT with a 2-week interval produced acceptable tumor control. The local control rate was 75.5% 1 year after treatment. As previously reported, local tumor control of large brain metastases is unsatisfactory using SRS 2, 3. Staged SRT is therefore a potential alternative strategy for large metastatic brain tumors, although there have been no studies examining staged SRT. Several authors have reported hypofractionated SRT alone for brain metastases to achieve good tumor control 10, 11, 12,

Conclusions

The management of brain metastases depends on the number of lesions and their volumes. A patient's systemic condition and the surgical accessibility of the tumor also affect the treatment strategy. Large brain metastases are suitable for surgical resection, whereas radiosurgery has not achieved sufficient local control for large lesions. Three-stage SRT is a unique treatment protocol. A 2-week interval between fractions allowed the treatment volume to be reduced, which might be of benefit in

Acknowledgments

The authors thank Bierta E. Barfod, M.D., for her assistance in the preparation of the manuscript.

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Conflict of interest: none.

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