Stereotactic radiosurgery (SRS) should be considered in the comprehensive treatment paradigm for all patients with brain metastases. This technique has proven benefits for local tumor control in individuals with as many as 4 lesions, and when combined with structured radiographic follow-up, will likely preserve a better quality of life for appropriately selected patients. Institutions and physicians treating patients with brain metastases should have the capability of safely performing SRS and individual cases should be prospectively reviewed by multidisciplinary teams to provide the best comprehensive care.
Stereotactic radiosurgery (SRS) has been established as an excellent treatment option for a large subset of patients with metastatic brain disease. Evidence-based practice guidelines have recently been published attempting to consolidate the wide variety of data available regarding when and how to implement SRS in the comprehensive treatment of this heterogeneous patient population. Although class I evidence is sparse in the current literature, many effective treatment paradigms have evolved centered around SRS.
Stereotactic radiosurgery—overview
SRS is a technique for treating lesions with a high dose of ionizing radiation, usually in a single session, using a stereotactic apparatus for accurate localization and patient immobilization. Unlike whole-brain radiation therapy (WBRT), SRS is designed to deliver a high amount of radiation to a focal target while minimizing the dose to surrounding brain tissue. The radiation dose within the target (ie, tumor) is much higher than that of surrounding tissue because of the sharp dose gradient achieved by multiple intersecting beams of radiation. Pathophysiological mechanisms behind the tumor-killing effects of SRS are not well established but likely involve endothelial cell damage, microvascular dysfunction, and the immune response.
SRS is currently performed with 3 modalities: protons and heavier charged particles, linear accelerator–produced bremsstrahlung x-ray beams, and the 60 Co Leksell Gamma Unit (LGU) ( Fig. 1 ). Proton-beam SRS uses a cyclotron-based device capable of precisely controlling the depth of proton penetration at the target, thereby depositing most of its energy within the tumor. Few institutions use this technology because of expense and space constraints. Linear accelerators (LINAC) are used to generate a high-energy x-ray beam by accelerating an electron at a metal target. These beams are sequentially directed at the tumor from multiple static beams or arcs through multileaf collimators. LINAC technology is versatile in that it can be modified to perform a variety of radiation procedures in multiple anatomic locations and its utility is not limited to cranial applications. Gamma knife radiosurgery (GKRS) is a technology dedicated to cranial and upper head and neck disease processes. The GKRS unit is composed of 192 individual 60 Co-based sources arranged in a conical tungsten shell designed to focus convergent gamma-ray beams at the target under control of a treatment computer. As a dedicated cranial unit, newer versions of this technology are designed to rapidly and efficiently treat multiple intracranial targets in a single planning session. Randomized trials comparing the efficacy of one SRS technology to another have not been performed. As a result, the decision to use one technology over another is subjective and based on physician preference and machine availability.
Clinical evidence
Many questions remain unanswered in terms of the best and most appropriate treatment strategy for any one particular patient with metastatic brain disease. The overarching goals of any treatment strategy must be to maximize patient survival and quality of life while controlling central nervous system disease burden. Recently published evidenced-based practice guidelines provide an excellent review and quality assessment of the current literature regarding the role of SRS in the management of patients with metastatic brain tumors. As with all complex disease processes, patients must always be treated on a case-by-case basis. In the current section, several SRS treatment combination strategies are discussed.
Stereotactic Radiosurgery and Whole-Brain Radiotherapy
Historically, WBRT has played a significant role in the treatment of patients with brain metastases. Conceptually, radiating the entire brain once a systemic cancer has demonstrated an ability to colonize and grow within the central nervous system makes sense and data have clearly supported the beneficial effects of WBRT on disease control and survival. More focused radiation administration techniques, as provided by single- or multiple-fraction SRS, represent another powerful tool in the fight against brain metastases.
The literature clearly supports the finding that a combination of single-fraction SRS in addition to WBRT has superior local tumor control rates when compared with WBRT alone for patients harboring as many as 4 intracranial metastases. In addition, there is strong evidence that combining SRS and WBRT provides a significant survival benefit for functionally independent patients with only one brain metastasis. Evidence also suggests that a similar survival advantage exists for patients with multiple brain metastases; however, prospective studies designed to specifically address this question are lacking.
Stereotactic Radiosurgery Alone
Single-fraction SRS alone has been compared with the combined technique of SRS plus WBRT as well. The best available data demonstrate equivalent survival results between patients treated with SRS alone versus SRS plus WBRT, with a higher frequency of intracranial relapse in patients when up-front WBRT is withheld. As a result, regular radiographic surveillance is strongly recommended at 2- to 3-month intervals if single-fraction SRS is used in isolation.
The comparison has also been made between SRS alone versus WBRT alone. Relevant studies included patients with 1 to 3 metastases and analyzed outcomes based on validated parameters such as age, performance status, and systemic tumor burden. Interestingly, in all of these reports, an overall survival benefit was reported in patients receiving SRS alone. The validity of this finding remains unclear and has yet to be studied in a randomized, prospective manner. It is possible that variables including, but not limited to, timing of systemic chemotherapy initiation or implementation of salvage surgical or radiation techniques may have influenced these results.
Stereotactic Radiosurgery and Surgical Resection
Only a few reports directly address the issue comparing the efficacy of SRS plus WBRT versus surgery plus WBRT for brain metastases. For lesions amenable to either treatment paradigm, survival data would suggest that these strategies are comparable. Specific variables such as tumor size (>3 cm), tumor location (deep or eloquent cortex), and mass effect (midline shift >1 cm) should always be taken into account before initiating any treatment protocol, as these variables have not been studied extensively.
Only a few reports have attempted to compare SRS alone versus surgery plus WBRT in the setting of brain metastases. When analyzed together, these studies remain relatively inconclusive regarding a significant difference in overall survival between treatment strategies. SRS in lieu of resection plus WBRT is certainly a treatment option, and future trials designed to further investigate this question are eagerly awaited.
A strategy combining the strengths of surgical resection and SRS to treat all intracranial metastases up front while withholding WBRT can also be considered. A combination of focal treatment (SRS and/or resection) to all lesions with adjuvant fractionated SRS (2–5 doses) or local radiation therapy (RT) is yet another treatment paradigm currently being implemented at some cancer centers. As previously discussed, reserving WBRT for salvage therapy requires patient compliance with close radiographic surveillance and is implemented in an attempt to avoid potential cognitive impairment for young, functional patients with longer life expectancies.
Clinical evidence
Many questions remain unanswered in terms of the best and most appropriate treatment strategy for any one particular patient with metastatic brain disease. The overarching goals of any treatment strategy must be to maximize patient survival and quality of life while controlling central nervous system disease burden. Recently published evidenced-based practice guidelines provide an excellent review and quality assessment of the current literature regarding the role of SRS in the management of patients with metastatic brain tumors. As with all complex disease processes, patients must always be treated on a case-by-case basis. In the current section, several SRS treatment combination strategies are discussed.
Stereotactic Radiosurgery and Whole-Brain Radiotherapy
Historically, WBRT has played a significant role in the treatment of patients with brain metastases. Conceptually, radiating the entire brain once a systemic cancer has demonstrated an ability to colonize and grow within the central nervous system makes sense and data have clearly supported the beneficial effects of WBRT on disease control and survival. More focused radiation administration techniques, as provided by single- or multiple-fraction SRS, represent another powerful tool in the fight against brain metastases.
The literature clearly supports the finding that a combination of single-fraction SRS in addition to WBRT has superior local tumor control rates when compared with WBRT alone for patients harboring as many as 4 intracranial metastases. In addition, there is strong evidence that combining SRS and WBRT provides a significant survival benefit for functionally independent patients with only one brain metastasis. Evidence also suggests that a similar survival advantage exists for patients with multiple brain metastases; however, prospective studies designed to specifically address this question are lacking.
Stereotactic Radiosurgery Alone
Single-fraction SRS alone has been compared with the combined technique of SRS plus WBRT as well. The best available data demonstrate equivalent survival results between patients treated with SRS alone versus SRS plus WBRT, with a higher frequency of intracranial relapse in patients when up-front WBRT is withheld. As a result, regular radiographic surveillance is strongly recommended at 2- to 3-month intervals if single-fraction SRS is used in isolation.
The comparison has also been made between SRS alone versus WBRT alone. Relevant studies included patients with 1 to 3 metastases and analyzed outcomes based on validated parameters such as age, performance status, and systemic tumor burden. Interestingly, in all of these reports, an overall survival benefit was reported in patients receiving SRS alone. The validity of this finding remains unclear and has yet to be studied in a randomized, prospective manner. It is possible that variables including, but not limited to, timing of systemic chemotherapy initiation or implementation of salvage surgical or radiation techniques may have influenced these results.
Stereotactic Radiosurgery and Surgical Resection
Only a few reports directly address the issue comparing the efficacy of SRS plus WBRT versus surgery plus WBRT for brain metastases. For lesions amenable to either treatment paradigm, survival data would suggest that these strategies are comparable. Specific variables such as tumor size (>3 cm), tumor location (deep or eloquent cortex), and mass effect (midline shift >1 cm) should always be taken into account before initiating any treatment protocol, as these variables have not been studied extensively.
Only a few reports have attempted to compare SRS alone versus surgery plus WBRT in the setting of brain metastases. When analyzed together, these studies remain relatively inconclusive regarding a significant difference in overall survival between treatment strategies. SRS in lieu of resection plus WBRT is certainly a treatment option, and future trials designed to further investigate this question are eagerly awaited.
A strategy combining the strengths of surgical resection and SRS to treat all intracranial metastases up front while withholding WBRT can also be considered. A combination of focal treatment (SRS and/or resection) to all lesions with adjuvant fractionated SRS (2–5 doses) or local radiation therapy (RT) is yet another treatment paradigm currently being implemented at some cancer centers. As previously discussed, reserving WBRT for salvage therapy requires patient compliance with close radiographic surveillance and is implemented in an attempt to avoid potential cognitive impairment for young, functional patients with longer life expectancies.
Related posts:
Review of Imaging Techniques in the Diagnosis and Management of Brain Metastases
Radiotherapy for Brain Metastases
Management of Skull Base Metastases
Surgical Management of Brain Metastases
Investigational Therapies for Brain Metastases
Evidence-Based Guidelines for the Management of Brain Metastases
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