Hypofractionated stereotactic radiotherapy for the treatment of brain metastases

BACKGROUND:

This retrospective review evaluated the efficacy and toxicity profiles of various dose fractionations using hypofractionated stereotactic radiotherapy (HSRT) in the treatment of brain metastases.

METHODS:

Between 2004 and 2007, 36 patients with 66 brain metastases were treated with HSRT. Nine of these subjects were excluded because of the absence of post‐treatment magnetic resonance imaging scans, resulting in 27 patients with a total of 52 lesions. Of these 52 lesions, 45 lesions were treated with whole‐brain radiotherapy plus a HSRT boost and 7 lesions were treated with HSRT as the primary treatment. The median prescribed dose was 25 grays (Gy) (range, 20 Gy‐36 Gy) with a median of 5 fractions (range, 4 fractions‐6 fractions) to a median 85% isodose line (range, 50%‐100%). The median follow‐up interval was 6.6 months (range, 0.9 months‐26.8 months).

RESULTS:

The median overall survival time was 10.8 months, and 66.7% of patients died of disease progression. After HSRT treatment of 52 brain lesions, 13 lesions demonstrated complete responses, 12 lesions demonstrated partial responses, 22 lesions demonstrated stable disease, and 5 lesions demonstrated progressive disease. Actuarial local tumor control rates at 6 months and 1 year were 93.9% and 68.2%, respectively. Maximum tumor dimension, concurrent chemotherapy, and a tumor volume <1 cc were found to be statistically significant factors for local tumor control. One patient had a grade 3 toxicity (according to National Cancer Institute Common Terminology Criteria for Adverse Events).

CONCLUSIONS:

HSRT provides a high level of tumor control with minimal toxicity comparable to single‐fraction stereotactic radiosurgery (SRS). The results of the current study warrant a prospective randomized study comparing single‐fraction SRS with HSRT in this patient population. Cancer 2009. © 2009 American Cancer Society.     

Contemporary practice patterns of stereotactic radiosurgery for brain metastasis: A review of published Australian literature

There has been a shift in the management of brain metastasis (BM), with increasing use of stereotactic radiosurgery (SRS) and delaying/avoiding whole‐brain radiotherapy (WBRT), given the concern regarding the long‐term neurocognitive effect and quality of life impact of WBRT. It is, however, unclear as to the contemporary practice pattern and outcomes of SRS in Australia. We conducted a literature search in PubMed and MEDLINE using a series of keywords: ‘stereotactic’, ‘radiosurgery’ and ‘brain metastases’, limiting to Australian studies, which report on clinical outcomes following SRS. Eight studies – one randomized trial and seven retrospective cohort studies – were identified and included in this review. A total of 856 patients were included, with the most common primary tumour types being melanoma, lung cancer and breast cancer. Approximately half of the patients had solitary BM, while 7% had 10 or more BM lesions. SRS is not routinely given in combination with WBRT. The 6‐month intracranial control and 1‐year intracranial control following SRS were reported in the range of 67–87% and 48–82%, respectively, whereas the 1‐year overall survival and 2‐year overall survival were reported in the range of 37–60% and 20–36%, respectively. There are limited data reported on SRS‐related toxicities in all included studies. Overall, despite increasing use of SRS for BM, there is a low number of published Australian series in the literature. There is a potential role for establishing an Australian clinical quality registry or collaborative consortium for SRS in BM, to allow for systematic prospective data collection, and benchmarking of quality and outcomes of SRS.     

Extent of perilesional edema differentiates radionecrosis from tumor recurrence following stereotactic radiosurgery for brain metastases

Background

Differentiation of tumor recurrence from radionecrosis is a critical step in the follow-up management of patients treated with stereotactic radiosurgery (SRS) for brain metastases. A method that can reliably differentiate tumor recurrence from radiation necrosis using standard MR sequences would be of significant value.

Methods

We analyzed the records of 49 patients with 52 brain metastases treated with SRS who subsequently underwent surgical resection of the same lesion. Forty-seven of the lesions had preoperative MRI available for review (90%), including T1 postcontrast, T2, and fluid attenuated inversion recovery sequences. Pre-SRS and preoperative lesion and edema volumes were manually contoured and measured in a blinded fashion using radiation treatment planning software. A neuropathologist analyzed samples for the presence of tumor and/or radiation necrosis.

Results

Longer time between SRS and resection (P < .001) and a larger edema/lesion volume ratio (high T2/T1c, P = .002) were found to be predictive of radionecrosis as opposed to tumor recurrence. Using a cutoff value of 10 for the edema/lesion volume ratio, we were able to predict the presence of tumor with a positive predictive value of 92%, which increased to 100% when looking only at patients who underwent resection <18 months following SRS.

Conclusions

On follow-up imaging, lesions with a high edema/lesion volume ratio and lesions that progress later after SRS are more likely to contain radionecrosis. These indices may help guide clinical decision making in the context of evolving lesions after SRS for brain metastases and thereby avoid unnecessary interventions.     

Predictors of distant brain recurrence for patients with newly diagnosed brain metastases treated with stereotactic radiosurgery alone

PURPOSE: To ascertain predictors of distant brain failure (DBF) in patients treated initially with stereotactic radiosurgery alone for newly diagnosed brain metastases. We hypothesize that these factors may be used to group patients according to risk of DBF. METHODS AND MATERIALS: We retrospectively analyzed 100 patients with newly diagnosed brain metastases treated from 2003 to 2005 at our Gamma Knife radiosurgery facility. The primary endpoint was DBF. Potential predictors included number of metastases, tumor volume, histologic characteristics, extracranial disease, and use of temozolomide. RESULTS: One-year actuarial risk of DBF was 61% for all patients. Significant predictors of DBF included more than three metastases (hazard ratio, 3.30; p = 0.004), stable or poorly controlled extracranial disease (hazard ratio, 2.16; p = 0.04), and melanoma histologic characteristics (hazard ratio, 2.14; p = 0.02). These were confirmed in multivariate analysis. Those with three or fewer metastases, no extracranial disease, and nonmelanoma histologic characteristics (N = 18) had a median time to DBF of 89 weeks vs. 33 weeks for all others. One-year actuarial freedom from DBF for this group was 83% vs. 26% for all others. CONCLUSIONS: Independent significant predictors of DBF in our series included number of metastases (more than three), present or uncontrolled extracranial disease, and melanoma histologic characteristics. These factors were combined to identify a lower risk subgroup with significantly longer time to DBF. These patients may be candidates for initial localized treatment, reserving whole-brain radiation therapy for salvage. Patients in the higher risk group may be candidates for initial whole-brain radiation therapy or should be considered for clinical trials.     

Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: an update

Brain metastases are unfortunately a common occurrence in patients with cancer. Whole-brain radiation therapy (WBRT) is still considered the standard of care in the treatment of brain metastases. Stereotactic radiosurgery (SRS) offers the additional ability to treat tumors with relative sparing of normal brain tissue in a single fraction. While the addition of SRS to WBRT has been shown to improve survival and local tumor control in selected patients, the idea of deferring WBRT in order to avoid its effects on normal tissues and using SRS alone continues to generate significant discussion and interest. Three recent randomized trials from Japan, Europe and the MD Anderson Cancer Center (TX, USA) have attempted to address this issue. In this article, we update a previous review by discussing these trials to compare the outcomes for SRS alone versus SRS plus WBRT for limited metastases. We also discuss recent nonrandomized evidence for the use of SRS alone for oligometastatic disease.     

X线立体定向放射治疗脑转移瘤的疗效分析

目的观察立体定向放射手术治疗脑转移瘤的疗效。方法X线立体定向放射治疗脑转移瘤患者47例,采用10MV的直线加速器多个非共面弧旋转照射,肿瘤剂量为18～25Gy(平均22.1Gy)。40例患者在术后接受了肿瘤剂量30～40Gy的全脑放疗。结果中位生存期为11个月,1年生存率37.5%,疗后3个月的肿瘤控制率为90.7%,KPS≥70、原发肿瘤已控和无颅外转移患者的预后较好(P<0.05)。结论立体定向放射治疗脑转移瘤是安全和有效的。     

Prospective study of stereotactic radiosurgery without whole brain radiotherapy in patients with four or less brain metastases: incidence of intracranial progression and salvage radiotherapy

This prospective study was conducted to evaluate the treatment outcome after stereotactic radiosurgery (SRS) alone with special attention to its influence on intracranial freedom from progression (FFP), local control, time to whole brain radiotherapy (WBRT), and survival. Forty-one patients with brain metastases who met the inclusion criteria were enrolled in this prospective cohort and treated by SRS alone between January 1998 and September 2001. The overall local control rate was 76%. The one year actuarial intracranial FFP was 33%. Ten patients (24%) had relapse at treated site. Twenty-three patients (56%) had intracranial progression with a median time of 4.25 months (1–24.6). Salvage radiotherapy was given in 21 patients (51%). Only 12 (29%) patients required WBRT with the median time to WBRT after SRS of 4.85 months. Nine patients (22%) underwent additional SRS at the median time of 5 months after the first procedure. The median survival was 10 months. At the time of follow up, 16 patients (39%) were still alive with a range of 6–31 months. This prospective study suggests that the omission of WBRT in the initial treatment of patients with SRS for four or less brain metastases may allow up to 70% of patients to avoid WBRT.     

Focal radiation therapy of brain metastases after complete surgical resection

Brain metastases are a frequent occurrence in cancer patients and result in significant morbidity and mortality. The three main treatments for brain metastases include surgery, radiation, and/or chemotherapy, alone or in combination. After resection alone, local recurrence rates are high. Whole brain radiation therapy can decrease the probability of recurrence; however, this has some disadvantages. Focal radiation therapy (FRT) may provide many of the same benefits without some of these disadvantages. In this study, we retrospectively analyzed patients with single brain metastases treated with FRT after surgery. Doses ranged from 14 Gy as single dose stereotactic radiosurgery (SRS) to 54 Gy in 27 2-Gy fractions as conformal fractionated radiotherapy. Four of the seven patients had a same-site recurrence, with an average time to recurrence of 115.5 d. Median dose in the patients that had same-site recurrence was 42 Gy. One of these patients is currently living. Two patients did not have recurrence, and one patient had a recurrence at a different site within the brain. The low rate of out-of-field recurrences during the patients life indicates focal radiation may be a reasonable therapeutic alternative. Given the number of patients with same-site recurrences, wide field margins around the tumor volume or higher radiation doses than those typically used in palliative regimens may be useful in post-excisional FRT. Additionally, we found that a longer delay in the initiation of FRT after initial diagnosis may result in a decreased time to same-site recurrence. However, further studies are warranted given the small number of patients in this study.     

Stereotactic radiosurgery for brain metastases: Comparison of lung carcinoma vs. non-lung tumors

In the medical literature, stereotactic radiosurgery (SRS) for brain metastases results in rates of local control of 65 to 85%. To define patient selection criteria, we measured the survival in a population with a high proportion of non-small cell lung carcinoma (NCS lung) metastases that occurred soon after primary diagnosis. Between 9/89 and 10/93 30 adults (21 M, 9 F) had SRS for metastatic NSC lung carcinoma (14 patients) vs. non-lung carcinomas (16 patients having breast (3), renal (3), melanoma (3), GI (2, thyroid (1) or carcinoma of unknown origin (4)). The metastases were solitary for 22 patients and multiple for 8 patients. Average ages (y) (± SD) were 58.6 ± 10.4 for NSC lung patients and 53.4 ± 12.5 (p=0.32) for non-lung patients. The average interval (months) from diagnosis of the primary to metastasis was 23.8 ± 41.4 for all patients. This interval was shorter for NSC lung patients: 3.1 ± 6.0 vs. 48.0 ± 51.7 (p < 0.001) for non-lung patients. Twenty seven patients had conventional radiotherapy (XRT) before (24 patients) or after (3 patients) SRS. Doses (cGy) were 3303 ± 841 for 13 NSC lung patients and 4256 ± 992 for 14 non-lung patients (p = 0.034). The median time from primary diagnosis to SRS was shorter for the NSC lung patients (11 mo) compared to the non-lung patients (35 mo). SRS was given for recurrence of metastases after XRT for 11/14 NSC lung patients and 13/16 non-lung patients. The doses (cGy) of SRS were 1579 ± 484 vs. 1682 ± 476 (p=0.45) for the NSC lung and non-lung groups, respectively. After SRS a decrease in metastasis diameter was observed in 10 of 14 NSC lung patients vs. 12 of 16 non-lung patients (p=0.85 Chi-square). Twenty-seven of the 30 patients have died. For all patients, the median survival after diagnosis of the primary and after radiosurgery was 31.3 and 8.4 months, respectively. The median survival (95% CI) from primary diagnosis was 24.3 months (13.2–27.3) for NSC lung patients and 46.5 months (39.2–65.5) for non-lung patients (p=0.005 logrank test). The median survival (95% CI) after SRS was 7.9 months (3.0–14.3) for the NSC lung patients and 8.4 (2.9–11.9) months for the non-lung patients (p=0.98 logrank test). Within the two groups, no difference in survival was observed for patients who had SRS sooner (< 1 yr for NSC lung; < 3 yr for non-lung) after primary diagnosis: 9.3 vs. 6.5 mo for NSC lung (p = 0.21) and 10.5 vs. 7.2 mo for non-lung (p=0.87). In this series, the shortened intervals from primary diagnosis to SRS for NSC lung metastases was associated with post-SRS survivorship that was equivalent to the more favorable non-lung group.     

Biochemotherapy of metastatic melanoma in patients with or without recently diagnosed brain metastases

BACKGROUND: Brain metastases are an alarming complication of advanced melanoma, frequently contributing to patient demise. The authors performed a retrospective analysis to determine whether the treatment of metastatic melanoma with biochemotherapy would result in similar outcomes if brain metastases were first controlled with aggressive, central nervous system (CNS)-directed treatment. METHODS: Seventy melanoma patients were treated with biochemotherapy for metastatic melanoma between 1999 and 2005. Of these, 20 patients had recently diagnosed brain metastases, whereas 50 did not. Brain metastases (if present) were treated with stereotactic radiosurgery >or=28 days prior to systemic therapy. All patients were treated with biochemotherapy consisting of either dacarbazine or temozolomide in combination with a 96-hour continuous intravenous infusion of interleukin-2 and subcutaneous interferon-alpha-2B. The primary endpoint was survival from the time of the initial diagnosis of metastatic disease. RESULTS: Median survival from the time of the diagnosis of metastatic melanoma was 15.8 months for patients with brain metastases and 11.1 months for those without CNS involvement (P = .26 by the log-rank test; P = .075 by the Gehan Wilcoxon test). Dacarbazine-based and temozolomide-based regimens appeared similar with regard to their effect on overall survival and CNS disease progression. A plateau in further brain recurrences was observed in patients who survived for > 20 months. CONCLUSIONS: Data from the current study suggest that the outcome of biochemotherapy is comparable in patients with and those without brain metastases, if brain metastases are controlled with multidisciplinary treatment. Prolonged survival can be achieved in approximately 15% of patients, regardless of whether or not brain metastases are present.     

Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases

Background

To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases.

Methods

Between 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups.

Results

Patients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001).

Conclusions

Targeted agent use with SRS appears to improve survival and intracranial outcomes.     

Brain metastases of breast cancer

Brain metastases of breast cancer remain a difficult problem for clinical management. Their incidence appears to be increasing, which is likely due to longer survival times for advanced breast cancer patients as well as additional and improved tools for detection. Molecular features of tumors associated with this syndrome are not yet understood. In general, survival may be improving for brain metastases due to better local control in the CNS, as well as improvements in systemic disease management. Selected patients with brain metastases are able to undergo surgical resection, which has been associated with extended disease control in some patients. However, whole-brain radiation has been the mainstay for treatment for most patients. Stereotactic radiosurgery is playing an increasing role in the primary treatment of brain metastases, as well as for salvage after whole-brain radiation. Recent series have reported median survivals of 13 months or longer with stereotactic radiosurgery. Further improvements in radiation-based approaches may come from ongoing studies of radiosensitizing agents. The ability of systemic treatments to impact brain metastases has been debated, and specific treatment regimens have yet to be defined. New approaches include chemotherapy combinations, biologic therapies and novel drug-delivery strategies.     

Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma

BACKGROUND:

This multicenter study aimed to identify prognostic factors in patients with brain metastases from malignant melanoma (BM‐MM).

METHODS:

In a retrospective survey in 9 cancer centers of the German Cancer Society, 692 patients were identified with BM‐MM during the period 1986 through 2007. Overall survival was analyzed using a Kaplan‐Meier estimator and compared with log‐rank analysis. Cox proportional hazards models were used to identify prognostic factors significant for survival.

RESULTS:

The median overall survival of the entire cohort was 5.0 months (95% confidence interval [95% CI], 4 months‐5 months). Significant prognostic factors in the univariate Kaplan‐Meier analysis were Karnofsky performance status (≥70% vs <70%; P < .001), number of BM‐MM (single vs multiple; P < .001), pretreatment levels of lactate dehydrogenase (LDH) (normal vs elevated; P < .001) and S‐100 (normal vs elevated; P < .001), prognostic groups according to Radiation Therapy Oncology Group (class I vs class II vs class III; P = .0485), and treatment choice (for the cohort with single BM‐MM only) (stereotactic radiotherapy or neurosurgical metastasectomy vs others; P = .036). Cox proportional hazards models revealed pretreatment elevated level of serum LDH (hazard ratio [HR], 1.6; 95% CI, 1.3‐2.0 [P = .00013]) and number of BM‐MM (HR, 1.6; 95% CI, 1.3‐2.0 [P = .00011]) to be independent prognostic variables in the entire cohort, whereas in patients with a single BM‐MM, treatment choice (HR, 1.5; 95% CI, 1.1‐1.9 [P = .0061]) was identified as a unique prognostic factor.

CONCLUSIONS:

The overall survival of patients with BM‐MM primarily depends on the number of metastases and pretreatment level of LDH. In the case of a single brain metastasis, stereotactic radiotherapy or neurosurgical metastasectomy is by far the most important factor for improving survival. Cancer 2011. © 2010 American Cancer Society.     

Isolated brain metastases as first site of recurrence in prostate cancer: case report and review of the literature

Fewer than 2% of patients with metastatic prostate cancer (pca) develop brain metastases. Autopsy series have confirmed the rarity of brain metastases. When present, brain metastases occur in end stage, once the pca is castrate-resistant and spread to other sites is extensive. Here, we present a rare case of a patient with pca who developed a solitary parenchymal brain metastasis as first site of relapse 9 years after radical therapy. The patient underwent craniotomy and excision of the tumour. A second recurrence was also isolated to the brain. In the literature, pca patients with brain metastases have a poor mean survival of 1–7.6 months. The patient in our case report experienced a relatively favourable outcome, surviving 19 months after his initial brain relapse.     

Multidisciplinary management of colorectal brain metastases: a retrospective study

BACKGROUND: The incidence of brain metastases (BM) from colorectal cancer (CRC) is increasing, and the management of this previously rare complication at a single institution is reported. METHODS: The records of all patients with BM from 1994 to 2005 were reviewed, and 49 patients (33 men, 16 women) with 102 BM from CRC were identified. Associations between patient and tumor characteristics, treatment modality, and survival were assessed. RESULTS: The median age at diagnosis of BM from CRC was 66 years. Forty patients (82%) had other systemic disease. The median survival after a diagnosis of BM from CRC was 5.1 months. Fifteen patients (31%) underwent surgery at some point, 14 patients (29%) underwent stereotactic radiosurgery (SRS), and 42 patients (86%) received whole-brain radiotherapy during their management. Seven patients (14%) underwent upfront SRS. On multivariate analysis, a longer interval from diagnosis of CRC to diagnosis of BM was associated significantly with shorter survival (p = .01). Sex, Karnofsky performance status, tumor location, recursive partitioning analysis class, and initial treatment modality did not have an impact on survival. CONCLUSIONS: Because BM from CRC are a late-stage phenomenon, the majority of patients in the current study had other systemic involvement, and survival after CNS involvement was poor. The results indicated that a high prevalence of systemic disease limits the proportion of patients who are strong candidates for upfront SRS, thereby limiting the impact that this modality has on outcomes in this population as a whole. Late development (>1 year after the primary tumor diagnosis) of CNS involvement may predict for poorer survival after therapy for patients with BM from CRC.     

Multimodality treatment of melanoma brain metastases incorporating stereotactic radiosurgery (SRS)

BACKGROUND: Brain metastases are a frequent complication in advanced melanoma. A 3.6 to 4.1-month median survival has been reported after treatment with whole brain radiotherapy. We performed a retrospective analysis of our institutional experience of multimodality treatment utilizing linear accelerator (Linac)-based stereotactic radiosurgery (SRS). METHODS: Forty-four melanoma patients with brain metastases underwent 66 SRS treatments for 156 metastatic foci between 1999 and 2004. Patients were treated with initial SRS if or=70, but 37 patients had active systemic metastases (Recursive Partition Analysis Class 2). Survival was calculated from the time of diagnosis of brain metastases. Minimum follow-up was 1 year after SRS. The potential role of prognostic factors on survival was evaluated including age, sex, interval from initial diagnosis to brain metastases, surgical resection, addition of whole brain radiotherapy (WBRT), number of initial metastases treated, and number of SRS treatments using Cox univariate analysis. RESULTS: The median survival of melanoma patients with brain metastases was 11.1 months (95% confidence interval [CI]: 8.2-14.9 months) from diagnosis. One-year and 2-year survivals were 47.7% and 17.7%, respectively. There was no apparent effect of age or sex. Surgery or multiple stereotactic radiotherapy treatments were associated with prolonged survival. Addition of WBRT to maintain control of brain metastases in a subset of patients did not improve survival. CONCLUSIONS: Our results suggest that aggressive treatment of patients with up to 5 melanoma brain metastases including SRS appears to prolong survival. Subsequent chemotherapy or immunotherapy after SRS may have contributed to the observed outcome.     

Management of brain metastases from ovarian and endometrial carcinoma with stereotactic radiosurgery

BACKGROUND

Metastases to the brain from ovarian and endometrial carcinoma are uncommon and to the authors' knowledge consensus regarding optimal management is lacking. Stereotactic radiosurgery (SRS) has proven useful for the treatment of many benign and malignant brain tumors. In the current study, the authors evaluated outcomes after SRS in patients with ovarian and endometrial carcinoma.

METHODS

Twenty‐seven patients with brain metastases underwent gamma–knife SRS. Six patients had endometrial carcinoma, whereas 21 patients had ovarian carcinoma. Eighteen patients also received whole–brain radiotherapy. A total of 68 tumors were treated with gamma–knife SRS.

RESULTS

At the time of last follow–up, 1 patient was still alive and 26 had died. The median survival was 7 months after the initial diagnosis of brain metastasis and 5 months after SRS. The 1‐year survival rate after radiosurgery was 15% and that from the diagnosis of brain metastases was 22%. On final imaging, all tumors were controlled without further growth. Two patients (7.4%) developed new or progressive neurologic deficits after SRS.

CONCLUSIONS

SRS is an acceptable choice for the treatment of brain metastases resulting from ovarian and endometrial carcinoma, and provides local tumor control with limited morbidity. Careful patient selection is warranted in the setting of patients with uncontrolled systemic disease in whom a limited survival benefit is expected. Cancer 2008. © 2008 American Cancer Society.     

Stereotactic radiosurgery for multiple brain metastases

Stereotactic radiosurgery (SRS) alone has become one of the treatment options for patients with 1–4 metastases as the detrimental effects of whole brain radiation therapy on neurocognition and quality of life are becoming well known. Multiple randomized control trials also failed to show overall survival benefit of adding whole brain radiation therapy to SRS. However, the role of SRS in multiple brain metastases, especially those with ≥4 tumors, remains controversial. The literature is emerging, and the limited evidence suggests that the local control benefit is independent of the number of metastases, and that patients with more than four brain metastases have similar overall survival compared to those with 2–4 tumors. This review aims at summarizing the current evidence of SRS for multiple brain metastases, divided into limited (2–3) and multiple (≥4) lesions. It also reviews the technical aspects and cost–effectiveness of SRS.     

Factors associated with tumor response and survival in radiosurgery for brain metastasis

Background We reviewed our experience with radiosurgery for brain metastasis and focused on factors associated with tumor response and survival. Methods Our study consists of 19 patients with 25 brain metastases who underwent linear accelerator radiosurgery. There was evidence of extra-central nervous system (CNS) tumors in 15 patients. The maximum diameter of the tumors ranged from 3 to 40 mm with a mean of 20 mm. Tumor doses at the isocenter varied from 16 to 25 Gy with a mean of 21 Gy. Eighteen lesions were treated by radiosurgery alone and 7 lesions received combined radiosurgery with fractionated radiotherapy. Of the 11 patients who experienced CNS failure either in or out of the radiosurgery field, 6 patients had salvage radiotherapy. Results Median survival was 7 months, and the 1-year actuarial survival rate was 40%. Death was due to extra-CNS tumor manifestations in 11 patients. In 3 patients, CNS failure was the cause of death. One died of local progression, and the other 2 died of newly developed metastases. Poor Karnofsky performance scores and the presence of extra-CNS tumors significantly affected 1-year survival in univariate analysis (P<0.05). Local tumor control was achieved in 80% of the lesions. The 1-year actuarial tumor control rate was 51%. Newly developed brain metastases were observed in 7 patients. The tumor diameter was mostly associated with tumor response in multiple regression analysis (P=0.0031). Conclusion We concluded that radiosurgery is effective in controlling small brain metastasis. Survival benefit is expected for those with good performance status and adequately controlled extra-CNS disease. Part of this work was presented at the 7th Asian and Oceanian Congress of Radiology, Kuala Lumpur, Malaysia, May 28-June 1, 1995.