Clinical Investigation
Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases

https://doi.org/10.1016/j.ijrobp.2010.05.033Get rights and content

Purpose

To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT).

Methods and Materials

Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group.

Results

With a median follow-up period of 7 months, the median survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group (p = 0.89). Local progression–free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05).

Conclusions

Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.

Introduction

Brain metastases (BMs) are the most common intracranial malignant neoplasm in adults and occur in up to 25% to 35% of cancer patients (1). Therapeutic options include whole-brain radiotherapy (WBRT), surgery, and stereotactic radiosurgery. Prognosis remains poor, and prognostic indicators include the number, size, and location of BMs; the patient's Karnofsky performance status (KPS), age, extent of systemic disease, and primary disease status; the recursive partitioning analysis (RPA) class; and the graded prognostic assessment (GPA) score 2, 3, 4. Evidence indicates that survival and quality of life improve with more aggressive treatment in a subgroup of patients with favorable prognostic features including a good KPS, a lower number of BMs, and limited systemic disease, among other factors. For example, surgical resection of a single BM followed by WBRT in patients with a good KPS resulted in a median survival (MS) of 40 weeks, which is significantly longer than the 15-week survival time reported after WBRT alone (5). In addition, recurrence at the site of the original metastasis occurred less frequently in the group who underwent surgery than the group who did not (20% and 52%, respectively; p = 0.02). In a subsequent randomized study that compared surgical resection followed by WBRT with surgical resection alone (6), combination treatment with WBRT had a greater effect on prevention of recurrence at the site of the original metastases, with recurrence rates of 10% and 46%, respectively (p < 0.001). Recurrence at other sites in the brain also occurred less frequently when patients were treated with both surgery and WBRT compared with surgery alone, with recurrence rates of 14% and 37%, respectively (p < 0.01). Local progression–free survival (LPFS) rates have been estimated to range from 54% to 80% after surgical resection without WBRT. Radiosurgery combined with WBRT also improved survival for patients with a single BM compared with treatment with WBRT alone (MS, 6.5 and 4.9 months, respectively; p = 0.04) (7). Patients treated with radiosurgery and WBRT were more likely than patients treated with WBRT alone to have a stable or improved KPS at the 6-month follow-up (43% and 27%, respectively; p = 0.03). Local progression–free survival rates after radiosurgery have been estimated to range from 70% to 80% without WBRT 7, 8. Although no randomized trial has compared radiosurgery with surgery, radiosurgery does not appear to be inferior to surgery with respect to LPFS. Currently, radiosurgery is frequently used to treat BM and is sometimes preferred over surgery as a less invasive alternative.

Although single-dose radiosurgery (SRS) is much less invasive than surgery, concerns regarding the risks of toxicity have been raised for cases in which the target is large or is located near or within critical brain structures such as the brainstem, optic pathway, or motor cortex. In these cases a fractionated radiotherapy regimen could be beneficial for avoiding serious toxicity (9). In recent years several relocatable head frame systems have become available for fractionated delivery of stereotactic radiotherapy with acceptable levels of accuracy 10, 11, 12.

To assess the comparative efficacy of these therapeutic regimens, we retrospectively examined the records of patients with BMs that were either large or located near critical structures who had received fractionated stereotactic radiotherapy (FSRT). We then analyzed the efficacy and toxicity of FSRT and compared these results with those for patients who had received SRS.

Section snippets

Patient characteristics and treatment

We retrospectively analyzed 98 records of patients with BMs who were treated with stereotactic radiotherapy between November 2003 and December 2008. Consent for the treatment was obtained from each patient after the potential risks of treatment were disclosed and potential alternative treatments, including surgery or WBRT, were disclosed. Institutional review board approval was not required for the retrospective study at our institution. Of the patients, 58 (59%) were treated with SRS and 40

Objective tumor response and patterns of failure

The maximum volumetric tumor response was evaluated for 109 lesions after exclusion of 21 lesions for which no follow-up images were available. The complete response, PR, SD, and PD rates were 16%, 51%, 26%, and 7%, respectively, in the SRS group and 15%, 68%, 17%, and 0%, respectively, in the FSRT group. Among 85 patients with follow-up images, 11 showed LP, 28 showed RP, and 7 showed both. Local progression rates were 14% for the SRS group and 12% for the FSRT group (p > 0.99). Regional

Discussion

Although the reliability of the linear–quadratic (LQ) model has been questioned for hypofractionated radiotherapy (13), we elected to calculate the biological equivalent dose (BED) based on the LQ model to compare the effects of various fractionated schedules among studies, because this method has been most widely used in the clinic. By use of the LQ model, the BED of 20 Gy in 1 fraction was 60 Gy10 (BED in gray when a/b is 10) for early effects and 153 Gy3 (BED in gray when a/b is 3) for late

References (19)

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Supported in part by NCC Grant 0210140 from the National Cancer Center, Korea.

Conflict of interest: none.

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