The authors discuss the results of Gamma Knife (Elekta AB, Stockholm, Sweden) radiosurgery (GKS) for brain metastases based on their retrospective review of 2645 cases. All patients were treated according to the same protocol, with the tumors being irradiated with GKS without up-front whole-brain radiation therapy at the initial treatment. New distant lesions, detected by gadolinium-enhanced magnetic resonance imaging (MRI) performed every 2 to 3 months, were treated primarily with GKS. New distant lesions are generally well controlled with GKS salvage treatment. However, careful observation with enhanced MRI and appropriate salvage treatments are needed to prevent neurologic death and maintain activities of daily life.
Key points
- •
Good indications for Gamma Knife (Elekta AB, Stockholm, Sweden) radiosurgery (GKS) are (1) volume of the largest tumor less than 10 cm 3 , (2) a Karnofsky performance status score of 70 or more, (3) no magnetic resonance imaging evidence of cerebrospinal fluid dissemination, (4) total tumor volume of 15 cm 3 or less, and (5) tumor number of 10 or less.
- •
The local tumor control rates at 1 year were 84.8% for less than 1 cm 3 , 86.0% for 1 to 4 cm 3 , 76.2% for 4 to 10 cm 3 , and 55.3% for more than 10 cm 3 lesions. Two-staged or 3-staged GKS may be useful for large tumors.
- •
A total skull absorbed energy dose of 10J is the limitation, regardless of tumor number and size, in GKS. Within these limits, 25 tiny, 10 small, or 3 to 4 medium-sized lesions can be safely treated.
- •
A prospective, multi-institutional trial (UMIN ID 0000001812) is ongoing to assess the noninferiority, in terms of survival period, of GKS alone for treating patients with 5 to 10 brain metastases as compared with those with 2 to 4.
Introduction
Whole-brain radiation therapy (WBRT), with or without surgery, has been the gold standard of treatment of patients with brain metastases. Stereotactic radiosurgery (SRS) offers many benefits as compared with surgery and/or WBRT because the procedures are minimally invasive and can also be performed as one-day treatment. In the same session, SRS may be used to treat multiple lesions. Furthermore, SRS can be used for disparate or eloquent locations not conducive to open surgical approaches by delivering higher radiation doses. SRS also avoids leukoencephalopathy, which develops in some patients after WBRT.
Surgical resection of a single brain metastasis has been shown to improve tumor control and prolong survival, particularly when combined with WBRT. However, surgical resection may be contraindicated in most patients because of poor general condition or inaccessible locations. For more than 2 decades, SRS has provided patients who have metastatic brain tumors with a local treatment alternative to surgery. Studies have shown that SRS is very effective in controlling brain metastases, preventing neurologic death, and maintaining good activities of daily living. Moreover, SRS is minimally invasive and can be performed with a short hospitalization, which are important considerations for quality of life and health care economics as compared with surgery. Another treatment option for brain metastases, chemotherapy, has been considered ineffective because of poor penetration across the blood-brain barrier. However, cytotoxic chemotherapy is potentially effective, particularly for chemosensitive tumor types, such as small cell lung cancer and breast cancer. Recently, molecular targeting agents, such as tyrosine kinase inhibitors, which target epidermal growth receptor (EGFR) and human epidermal growth factor 2 (HER2), have been shown to be very effective for brain metastases from lung cancer with the EGFR mutation or breast cancer overexpressing HER2. Under such circumstances, these molecular targeting agents might be effective even in cases with cerebral and/or cerebrospinal small fluid (CSF) dissemination not receiving WBRT.
In this article, the authors present the results of Gamma Knife (Elekta AB, Stockholm, Sweden) radiosurgery (GKS) for brain metastases based on their retrospective review of 2645 brain metastasis cases treated during a 15-year period, focusing on 5 prognostic factors.
Introduction
Whole-brain radiation therapy (WBRT), with or without surgery, has been the gold standard of treatment of patients with brain metastases. Stereotactic radiosurgery (SRS) offers many benefits as compared with surgery and/or WBRT because the procedures are minimally invasive and can also be performed as one-day treatment. In the same session, SRS may be used to treat multiple lesions. Furthermore, SRS can be used for disparate or eloquent locations not conducive to open surgical approaches by delivering higher radiation doses. SRS also avoids leukoencephalopathy, which develops in some patients after WBRT.
Surgical resection of a single brain metastasis has been shown to improve tumor control and prolong survival, particularly when combined with WBRT. However, surgical resection may be contraindicated in most patients because of poor general condition or inaccessible locations. For more than 2 decades, SRS has provided patients who have metastatic brain tumors with a local treatment alternative to surgery. Studies have shown that SRS is very effective in controlling brain metastases, preventing neurologic death, and maintaining good activities of daily living. Moreover, SRS is minimally invasive and can be performed with a short hospitalization, which are important considerations for quality of life and health care economics as compared with surgery. Another treatment option for brain metastases, chemotherapy, has been considered ineffective because of poor penetration across the blood-brain barrier. However, cytotoxic chemotherapy is potentially effective, particularly for chemosensitive tumor types, such as small cell lung cancer and breast cancer. Recently, molecular targeting agents, such as tyrosine kinase inhibitors, which target epidermal growth receptor (EGFR) and human epidermal growth factor 2 (HER2), have been shown to be very effective for brain metastases from lung cancer with the EGFR mutation or breast cancer overexpressing HER2. Under such circumstances, these molecular targeting agents might be effective even in cases with cerebral and/or cerebrospinal small fluid (CSF) dissemination not receiving WBRT.
In this article, the authors present the results of Gamma Knife (Elekta AB, Stockholm, Sweden) radiosurgery (GKS) for brain metastases based on their retrospective review of 2645 brain metastasis cases treated during a 15-year period, focusing on 5 prognostic factors.
Radiosurgical technique
Patient characteristics are summarized in Table 1 . All aspects of patient selection, dose planning, dose selection, performing GKS, and collecting follow-up data, were undertaken by the first author (T.S.). All patients were treated according to the same protocol, as reported previously. At the initial treatment, all lesions were irradiated with GKS without up-front WBRT. In some cases with tumor volumes exceeding 10 cm 3 , staged GKS was chosen. In all patients with a total tumor volume exceeding 15 cm 3 and/or tumor numbers greater than 25, the GKS procedures were divided into 2 or 3 sessions to ensure a total skull absorbed energy (TSAE) of less than 10 J, thereby preventing acute brain swelling. New distant lesions, detected by gadolinium-enhanced magnetic resonance imaging (MRI) performed every 2 to 3 months, were treated mainly with GKS and sometimes with WBRT, only if cerebral and/or CSF dissemination was detected. The standard prescribed dose at the tumor periphery of 20 Gy was changed depending on the primary cancer, physical status, tumor location, and tumor volume (including in the staged GKS cases).
| Characteristics | Covariates | Total |
|---|---|---|
| Case number | Total | 2645 |
| Age (y) | Median (min-max) | 65 (27–96) |
| Gender | Male | 1583 (59.8%) |
| Female | 1062 (40.2%) | |
| Extracranial disease | Controlled | 326 (12.3%) |
| Active | 2319 (87.7%) | |
| Pretreatment KPS score | Median (min-max) | 100 (50–100) |
| Primary organ | Lung | 1729 (65.4%) |
| GI-tract | 332 (12.5%) | |
| Breast | 290 (11.0%) | |
| Urogenital | 167 (6.3%) | |
| Others | 127 (4.8%) | |
| Number of brain lesions | Median (min-max) | 3 (1–100) |
| Single | 728 (27.5%) | |
| 2–4 | 885 (33.5%) | |
| 5–10 | 581 (22.0%) | |
| >10 | 451 (17.1%) | |
| Maximum lesion volume (cm 3 ) | Median (min-max) | 2.8 (0.1–72.5) |
| Total tumor volume (cm 3 ) | Median (min-max) | 4.5 (0.1–100.0) |
| Neurologic symptoms | Yes | 1434 (54.2%) |
| No | 1211 (45.8%) | |
| RTOG-RPA classification | Class I | 142 (5.4%) |
| Class II | 2150 (81.3%) | |
| Class III | 353 (13.3%) |
Prognostic factors
Tumor Size
Fig. 1 demonstrates tumor progression-free survival curves according to the tumor volume treated with GKS in 2374 lesions, with the largest volume selected in each case (excluding 271 lesions treated using the staged GKS). Tumor volumes were divided into 4 groups: tiny (<1 cm 3 ), small (1–4 cm 3 ), medium (4–10 cm 3 ), and large (>10 cm 3 ). Control of GKS-treated lesions was defined as the lack of any significant increase in tumor diameter (<20%). The tumor control rates at 1 year were 84.8% for 794 tiny tumors (mean dose, 21.2 Gy), 86.0% for 854 small tumors (mean dose, 20.6 Gy), 76.2% for 588 medium-sized tumors (mean dose, 19.6 Gy), and 55.3% for 238 large tumors (mean dose, 17.2 Gy). The differences in tumor control were statistically significant between all pairs of adjacent tumor volume groups (tiny vs small, P <.0001; small vs medium, P = .0002; medium vs large, P = .0002). These results suggest that for large tumors, staged GKS should be considered, depending on life expectancy, as the authors previously proposed.
Related posts:
Stereotactic Radiosurgery of Intracranial Meningiomas
Stereotactic Radiosurgery of Pituitary Adenomas
Stereotactic Radiosurgery of Intracranial Cavernous Malformations
Stereotactic Radiosurgery of Intracranial Chordomas, Chondrosarcomas, and Glomus Tumors
Stereotactic Radiosurgery of Intracranial Dural Arteriovenous Fistulas
Stereotactic Radiosurgery for Intracranial Gliomas
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
