Toxicity of Radiosurgery for Brainstem Metastases

doi:10.1016/j.wneu.2018.07.263

World Neurosurgery

Volume 119, November 2018, Pages e757-e764

https://doi.org/10.1016/j.wneu.2018.07.263 Get rights and content

Highlights

•
For BSM treated via SRS, the median prescription doses vary from 13–18 Gy.
•
For BSM treated via SRS, the local control rate is 86.7 ± 5.9%.
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For BSM treated via SRS, the rate of grade 3 or greater toxicity is 3.4 ± 2.9%.
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The median time to toxicity is 3 months for BSM treated by SRS.
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Volume and location do not predict for toxicity for BSM treated via SRS.

Background

Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed.

Methods

Twenty-nine retrospective studies investigating SRS for BSM were reviewed.

Results

The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811).

Conclusions

Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04–2.8 cc does not predict for toxicity.

Introduction

Stereotactic radiosurgery (SRS) for brainstem metastases (BSM) has been shown to be a safe and effective modality.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 Reported rates of local tumor control in patients who received SRS for BSM vary from 74% to 100%, and the median survival ranges from 4 to 12 months.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31 Despite the promising results of SRS with respect to local control and survival, toxicity due to radiation is always a concern, with severe to life-threatening toxicities being reported in 0%–9.5% of patients with BSM treated with SRS.2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31 The majority of papers have not analyzed the impact of location on toxicity or volume of lesions on toxicity.2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31 As the result of a relatively small sample size, the preferred dose to treat BSM remains controversial, with the literature varying on the dosing strategies.2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31 This review paper aims to synthesize the collective literature available on SRS to BSM.

Section snippets

Methods

To identify brainstem location specific toxicity after SRS, “brainstem metastases radiosurgery” was searched as a key word in PubMed and Ovid (Medline). Primary literature specific to treatment of BSM with SRS was reviewed. Only retrospective studies of patients treated with SRS for BSM were available; (shown in Figure 1). This literature review does not include BSM that are described in larger non-brainstem studies. Some authors were contacted for the details regarding the reported toxicities.2

Results

The searches identified 29 retrospective studies of BSM treated with SRS published from 1999 to 2017. The details of these reports are summarized in Table 2,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31 listed chronologically and by first author. SRS modalities reported include Gamma Knife, linear accelerator, and Cyber Knife. A total of 2037 SRS-treated metastases were reported in 1878 patients. The median age ranged from 50 to 69

Discussion

Radiosurgery has consistently been proven to be a safe and effective treatment for BSM, yet toxicity remains a concern for both the patient and physician.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31 The last review article that addressed clinical outcomes after SRS for BSM was published in 2013 and synthesized 12 reports.¹¹ Based on limited number of cases in previously published reports about BSM, it has been difficult to

Conclusions

In conclusion, for BSM treated via SRS, the median prescription doses vary from 13 to 18 Gy, with a local control rate of 86.7 ± 5.9% and a rate of toxicity of 3.4 ± 2.9%. The most common site of BSM is the pons. The median time to toxicity is 3 months for BSM treated by SRS. The current literature reports that some BSM may be safely treated with a prescription dose of up to 18 Gy or more and that volume and location do not predict for toxicity. More research is needed to further clarify these

Acknowledgments

We thank Patti Raley, MS, ELS, for help with editing the manuscript.

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: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Original ArticleToxicity of Radiosurgery for Brainstem Metastases

Highlights

Background

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Acknowledgments

Clin Neurol Neurosurg

Clin Neurol Neurosurg

Int J Radiat Oncol Biol Phys

J Clin Neurosci

Surg Neurol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

World Neurosurg

Int J Radiat Oncol Biol Phys

Lancet

Neuro-Chirurgie

Brainstem metastases: management using gamma knife radiosurgery

Neurosurgery

Outcomes and prognostic factors for patients with brainstem metastases undergoing stereotactic radiosurgery

Neurosurgery

Stereotactic radiosurgery for brainstem metastases

J Neurosurg

Gamma knife radiosurgery for brainstem metastases: the UCSF experience

J Neurooncol

Gamma Knife surgery for patients with brainstem metastases

J Neurosurg

Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women's Cancer Center experience

J Neurooncol

Local control and toxicity outcomes in brainstem metastases treated with single fraction radiosurgery: is there a volume threshold for toxicity?

J Neurooncol

A review of the clinical outcomes for patients diagnosed with brainstem metastasis and treated with stereotactic radiosurgery

ISRN Surg

Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

Radiat Oncol

Original Article
Toxicity of Radiosurgery for Brainstem Metastases