REVI E W Open Access

A concise review of the efficacy of stereotactic

radiosurgery in the management of melanoma

and renal cell carcinoma brain metastases

Peter W Hanson

1,2

, Ameer L Elaimy

1,2

, Wayne T Lamoreaux

1,2

, John J Demakas

1,3

, Robert K Fairbanks

1,2

Alexander R Mackay

1,4

, Blake Taylor

1,2

, Barton S Cooke

, Sudheer R Thumma

1,2

and Christopher M Lee

1,2,5*

Abstract

Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain.

Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood

brain barrier and whole brain radiation therapy (WBRT) is a relatively ineffective treatment against these

radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS) has emerged as an effective and

minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical

treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the

management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS

to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and

highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating

patients with radioresistant brain metastases.

Background

The United States faces roughly 170,000 new cases of brain

metastases each year, and this number is expected to in-

crease as diagnostic technologies, such as magnetic reson-

ance imaging (MRI), improve and as cancer patients acquire

longer survival times [1-3]. The average survival of patients

with brain metastases is one to two m onths with corticoster -

oid treatment alone, and four to seven months with whole

brain radiotherapy (WBRT) alone [4]. The Radiation Ther-

apy Oncology Group (RTOG) recursive partitioning analysis

(RPA), which categorizes patients into one of three classes

based on the patient’s Karnofsky Performance Score (KPS),

age, number of extracranial metastases, and status of pri-

mary cancer, with a higher class statistically indicating a

worse prognosis, is the most common method for stratifying

patients with brain metastases [4]. Out of all new brain me-

tastases cases, approximately 1,200 to 5,100 originate from

renal cell carcinoma annually, while roughly 10% originate

from melanoma annually [5,6].

Both melanoma and renal cell carcinoma have a well-

documented tendency to cause brain metastases. Melan-

oma represents the third most common primary origin of

brain metastases, following non-small-cell lung cancer and

breast cancer [7]. The reported clinical occurrence of brain

metastases is 8 to 46% in patients diagnosed with melan-

oma, and autopsy studies found brain metastases in 55 to

75% of these patients [7-10]. In a sizable autopsy series, the

occurrence of brain metastases resulting from renal cell

carcinoma was reported to be 11% [11,12]. Unfortunately,

the expected survival time for these patients is quite low

and maximizing these patients’ period of survival and com-

fort level is of great importance for clinicians. For untreated

patients with intracranial melanoma, the median survival

time is less than one month without treatment, and for

treated patients the median survival time ranges from two

to eight months [7,9,13-17]. Renal cell carcinoma patients

with brain metastases have a reported mean survival time

of three months if left untreated, and with treatment of

WBRT the median survival time ranges from two to nine

months [12,18-20]. Historically, brain metastases have been

treated with WBRT, surgery or both, but increasingly

* Correspondence: [email protected]

Gamma Knife of Spokane, 910 W 5th Ave, Suite 102, Spokane, WA 99204,

USA

Cancer Care Northwest, 910 W 5th Ave, Suite 102, Spokane, WA 99204, USA

Full list of author information is available at the end of the article

WORLD JOURNAL OF

SURGICAL ONCOLOGY

Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and

reproduction in any medium, provided the original work is properly cited.

Hanson et al. World Journal of Surgical Oncology 2012, 10:176

http://www.wjso.com/content/10/1/176

stereotactic radiosurgery (SRS) is emerging as an attractive

treatment modality.

SRSisaprocedurethatemploysahighdoseofextremely

conformal radiation to treat lesions of a small volume in a

single treatment session. Prior to treatment, a gadolinium

enhanced magnetic resonance imaging is taken of the

patient’s head, within a coordinate frame if necessary. A

neurosurgeon, radiation oncologist and medical physicist

jointly analyze the size, location and shape of the metastases

and develop appropriate treatment planning. There are

three machine types commonly used for SRS delivery: the

linear accelerator (LINAC), the CyberKnife and the Gamma

Knife (GK). Studies have shown that the machine type used

to apply SRS does not affect treatment outcome [21].

SRS is a desirable and effective treatment option for

many patients with newly diagnosed radioresistant brain

metastases due to its ability to improve local control,

minimally-invasive nature and capability of treating mul-

tiple metastases in one setting. SRS has widened the range

of treatable patients with radioresistant brain metastases by

offering a treatment modality that addresses unresectable

brain metastases and results in superior local control when

compared to WBRT. We present a concise review of litera-

ture analyzing the efficacy of SRS in the management of

patients with melanoma and renal cell carcinoma brain

metastases.

Review

Cumulative research shows that SRS is an effective and

safe treatment option for patients with radioresistant brain

metastases. A recent study by Clarke et al. [22] found that

GK SRS is a safe and effective treatment for patients with

single radioresistant brain metastases, reporting a median

survival of 8.1 months. A study by Jensen et al. [23] found

SRS to be a well-tolerated and well suited treatment mo-

dality for patients with radioresistant brain metastases,

reporting median survival rates of 7.4 months for patients

with intracranial metastatic melanoma and 6.1 months for

patients with intracranial metastatic renal cell carcinoma.

In a study by Yu et al. [14], the overall median survival for

patients with intracranial metastatic melanoma was

7 months from treatment of GK SRS, 9.1 months from the

occurrence of brain metastasis and 46.7 months from the

diagnosis of melanoma. A study by Mori et al. [7] found

that SRS is an effective and safe treatment modality for

patients with intracranial metastatic melanoma, and

reported a median survival of seven months following SRS.

AstudybyNoelet al. [12] found SRS to be an effective

and efficient treatment for brain metastases originating

from renal cell carcinoma, reporting an 11-month median

survival. A study by Samlowski et al. [5] found SRS-based

treatment for patients with intracranial metastatic renal

cell carcinoma to result in excellent central nervous system

(CNS) control, reporting a median survival of 10.1 months

after diagnosis of brain metastases. In our experience at

Gamma Knife of Spokane, patients with intracranial meta-

static melanoma and intracranial metastatic renal cell car-

cinoma have benefited from stereotactic radiosurgery. We

have published that patients with intracranial metastatic

melanoma treated with SRS at Gamma Knife of Spokane

have a median survival time of 9.7 months [24].

The SRS dose depends on the shape, position and size of

the image-guided target. Reported optimal dose ranges are

15 to 22 Gy, with a median of 20 Gy [22]. The RTOG

recommends that the maximum tolerated dose is 24 Gy for

tumors whose diameters are less than or equal to 20 mm,

18 Gy for tumors 21 to 30 mm in diameter and 15 Gy for

tumors 31 to 40 mm in diameter [4]. The surrounding nor-

mal brain and outside organs are protected by the con-

formality of the technique. For example, in GK treatment,

only 1/201th of the total radiation dose passes through the

bodyonthewaytothetargetsitebecausethereare201

converging beams. It is only where the 201 beams converge

on the metastatic brain tumor that the high dose is depos-

ited. Software programs are also used to help target the ra-

diation at optimal angles and doses to minimize radiation

exposure to the rest of the body. Special care is taken when

treating metastases around radiosensitive areas, such as the

optic nerves or the brainstem.

SRS alone has established itself as an effective treatment

modality for the treatment of radioresistant brain metasta-

ses, and the addition of WBRT remains controversial. Spe-

cifically, WBRT may benefit patients who are younger, have

a higher KPS (equal to or greater than 70), or a lower Re-

cursive Partitioning Analysis (RP A) class (1 or 2). A multi-

institutional Japanese phase III trial comparing SRS alone

vs. SRS plus WBRT in treating patients with intracranial

metastases did not find statistically significant differences in

both survival and death as a result of neurologic causes be-

tween the two treatment arms; however, there was a signifi-

cantly higher rate of intracranial failures (approximately

50% of patients after six months) in the SRS alone arm

[3,25]. One of the arguments against WBRT is the possibil-

ity of neurocognitive decline as a side effect, but whether or

not WBRT is detrimental to neurocognitive performance is

inconclusive and more sensitive tests evaluating neurocog-

nitive performance levels need to be conducted to deter -

mine if this is a valid potential side effect [3,26]. However,

prospective data from a phase III randomized trial compar-

ing SRS and SRS plus WBRT in patients with one to three

brain metastases conducted at M.D. Anderson Cancer Cen-

ter suggest that post-treatment decline in neurocognitive

performance is more likely related to WBRT than to intra-

cranial tumor progression [22]. The addition of WBRT to

SRS has shown very limited effectiveness at treating radio-

resistant histologies, so the inclusion of WBRT should be

decided on a case by case basis, based on the patient’s

informed decision on whether or not any possible marginal

Hanson et al. World Journal of Surgical Oncology 2012, 10:176 Page 2 of 4

http://www.wjso.com/content/10/1/176

benefits gained from WBRT are worth the downsides of the

treatment.

Further randomized trials comparing WBRT alone vs.

WBRT plus SRS in treating patients with radioresistant

brain metastases are needed because the decision of in-

cluding WBRT with SRS in treating radioresistant brain

metastases is still controversial. These studies are needed

to help decisively determine the general standard of treat-

ment for patients with radioresistant brain metastases.

Conclusions

Melanoma and renal cell carcinoma, considered to be

radioresistant histologies, commonly cause brain metasta-

ses. SRS has proven to be an effective and safe treatment

option for many cases involving these metastases. A pro-

spective randomized trial that assesses the worth of adding

WBRT in patients with intracranial metastatic melanoma

or intracranial metastatic renal cell carcinoma treated with

SRS is necessary. Evidence in the form of data from rando-

mized trials comparing WBRT alone vs. SRS alone vs.

WBRT plus SRS in treating patients with radioresistant

brain metastases is needed in the future to further define

optimal treatment approaches for each patient.

Abbreviations

CNS: central nervous system; GK: Gamma Knife; KPS: Karnofsky Performance

Status; LINAC: linear accelerator; MRI: magnetic resonance imaging;

RPA: recursive partitioning analysis; RTOG: radiation therapy oncology group;

SRS: stereotactic radiosurgery; WBRT: whole-brain radiation therapy.

Competing interests

The authors declare no competing financial interests.

Authors’ contributions

PWH, ALE and CML reviewed relevant literature for this review and drafted

the manuscript. WTL, JJD, RFK, ARM, BSC and SRT provided expertise relevant

to this review and helped draft the manuscript. All authors read and

approved the final manuscript.

Acknowledgements

We would like to acknowledge Eric Reynolds, Rachel Garman and Jill Adams,

as well as the entire Gamma Knife of Spokane and Cancer Care Northwest

research staff, for their contributions to this manuscript.

Author details

Gamma Knife of Spokane, 910 W 5th Ave, Suite 102, Spokane, WA 99204,

USA.

Cancer Care Northwest, 910 W 5th Ave, Suite 102, Spokane, WA 99204,

USA.

Spokane Brain and Spine, 801 W 5th Ave, Suite 201, Spokane, WA

99204, USA.

MacKay Meyer, MDs, 711 S Cowley St, Suite 201, Spokane, WA

99024, USA.

Gamma Knife of Spokane and Cancer Care Northwest, 601 S.

Sherman, Spokane, WA 99202, USA.

Received: 5 June 2012 Accepted: 15 August 2012

Published: 29 August 2012

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doi:10.1186/1477-7819-10-176

Cite this article as: Hanson et al.: A concise review of the efficacy of

stereotactic radiosurgery in the management of melanoma and renal

cell carcinoma brain metastases. World Journal of Surgical Oncology 2012

10:176.

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