Stereotactic radiosurgery for patients with "radioresistant" brain metastases

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.     

Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control

OBJECT: Renal cell carcinoma is a leading cause of death from cancer and its incidence is increasing. In many patients with renal cell cancer, metastasis to the brain develops at some time during the course of the disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival in patients with renal cell carcinoma metastasis is approximately 3 to 6 months. In this study the authors examined the efficacy of gamma knife surgery in treating renal cell carcinoma metastases to the brain and evaluated factors affecting long-term survival. METHODS: The authors conducted a retrospective review of 69 patients undergoing stereotactic radiosurgery for a total of 146 renal cell cancer metastases. Clinical and radiographic data encompassing a 14-year treatment interval were collected. Multivariate analyses were used to determine significant prognostic factors influencing survival. The overall median length of survival was 15 months (range 1-65 months) from the diagnosis of brain metastasis. After radiosurgery, the median survival was 13 months in patients without and 5 months in those with active extracranial disease. In a multivariate analysis, factors significantly affecting the rate of survival included the following: 1) younger patient age (p = 0.0076); 2) preoperative Karnofsky Performance Scale score (p = 0.0012); 3) time from initial cancer diagnosis to brain metastasis diagnosis (p = 0.0017); 4) treatment dose to the tumor margin (p = 0.0252); 5) maximal treatment dose (p = 0.0127); and 6) treatment isodose (p = 0.0354). Prior tumor resection, chemotherapy, immunotherapy, or whole-brain radiation therapy did not correlate with extended survival. Postradiosurgical imaging of the brain demonstrated that 63% of the metastases had decreased, 33% remained stable, and 4% eventually increased in size. Two patients (2.9%) later underwent a craniotomy and resection for a tumor refractory to radiosurgery or a new symptomatic metastasis. Eighty-three percent of patients died of progression of extracranial disease. CONCLUSIONS: Stereotactic radiosurgery for treatment of renal cell carcinoma metastases to the brain provides effective local tumor control in approximately 96% of patients and a median length of survival of 15 months. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can offer patients an extended survival.     

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin

OBJECT: The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. METHODS: Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3-83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134-0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78-92%) in tumors treated with 24 Gy, compared with 49% (CI 30-68%) in tumors treated with 18 Gy and 45% (CI 23-67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. CONCLUSIONS: Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.     

Ambulatory radiosurgery in cerebral metastatic renal cell carcinoma. 5-year outcome in 58 patients

Brain metastases (BM) indicate an advanced stage of renal cell cancer (RCC). They pose an increasing challenge to urologists as a result of improved survival due to modern therapy. Median survival of untreated patients with BM who often suffer from neurological deficits is 3 months. Radiosurgery with the Gamma Knife (GK) has increased in use as an alternative to whole brain radiation therapy (WBRT) and/or surgery. This study reports the results of a consecutive series of RCC patients treated for BM by GK radiosurgery during a 5-year period. Between 1994 and 1999, 58 patients with a total of 277 BM and 3.0 (1-19) BM/patient were treated. Because of recurrent BM, 23 (40%) patients received repeated (multiple) GK sessions. The median tumor volume was 3.4 cm3 (0.1-19.1). The median interval between diagnosis of RCC and GK treatment was 2.2 years (0.1-17.2). Symptomatic side effects were detected in 9 (16%) of 58 patients. The median actuarial survival time was 9.9 months. Local tumor control could be achieved in 95% of patients. The GK therapy induced a significant tumor remission accompanied by rapid neurological improvement in 70% of patients. Compared to standard radiotherapy, GK radiosurgery is more effective, less time consuming, and can be repeated. Compared to surgery, radiosurgery is less invasive and better suited to treat multiple metastases in one single session. Surgery and radiosurgery, however, are supplementary methods that are highly effective to control intracerebral metastasizing RCC.     

Repeated gamma knife surgery for multiple brain metastases from renal cell carcinoma

OBJECT: The aim of this study was to evaluate the therapeutic profile of repeated gamma knife surgery (GKS) for renal cell carcinoma that has metastasized to the brain on multiple occasions. METHODS: Data from this study were culled from a single institution and cover a 6-year period of outpatient radiosurgery. A standard protocol for indication, dose planning, and follow up was established. In cases of distant or local recurrences, radiosurgery was undertaken repeatedly (up to six times in one individual). Seventy-five patients harboring 350 cerebral metastases were treated. Relief from pretreatment neurological symptoms occurred in 72% of patients within a few days or a few weeks after the procedure. The actuarial local tumor control rate after the initial GKS was 95%. In patients free from relapse of intracranial metastases after repeated radiosurgery, long-term survival was 91% after 4 years; median survival was 11.1+/-3.2 months after radiosurgery and 4.5+/-1.1 years after diagnosis of the primary kidney cancer. Survival following radiosurgery was independent of patient age and sex, side of the renal cell carcinoma, pretreatment of the cerebrum by using radiotherapy or surgery, number of brain metastases and their synchronization with the primary renal cell carcinoma, and the frequency of radiosurgical procedures. In contrast, survival was dependent on the patient's clinical performance score and the extracranial tumor status. Tumor bleeding was observed in seven patients (9%) and late radiation toxicity (LRT) in 15 patients (20%). Treatment-related morbidity was moderate and mostly transient. Late radiation toxicity was encountered predominantly in long-term survivors. CONCLUSIONS: Outpatient repeated radiosurgery is an effective and only minimally invasive treatment for multiple brain metastases from renal cell cancer and is recommended as being the method of choice to control intracranial disease, especially in selected patients with limited extracranial disease. Physicians dealing with such patients should be aware of the characteristic aspects of LRT.     

Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: Results in 42 patients

BACKGROUND: The present study provides data from clinical experience with gamma-knife radiosurgery (GK) in patients with brain metastasis from renal cell carcinoma (RCC) and shows the value of this less invasive treatment modality. METHODS: Forty-two patients received GK. Twenty of the 42 cases had multiple brain metastases. Extracranial metastases were observed in the lung (38 cases), bone (12 cases), liver (9 cases), lymph node (5 cases) and skin (6 cases). RESULTS: Neurological symptoms seen in 40 patients were rapidly improved after GK in 32 patients (80%). Magnetic resonance imaging (MRI) evaluation after GK in 32 patients showed the disappearance of brain tumor in 9 patients (28%). Complete response was obtained by GK in tumors up to 30 mm in diameter. Repeated GK for newly developed lesions was conducted in 11 patients. Extracranial tumor resection was conducted in 7 cases (lung: 3, skin: 2, liver: 1, adrenal: 1). Chemo-radiotherapy or immunotherapy was effective in 8 cases (lung: 5, liver: 2, bone: 1). The actual one-, two- and three-year survival rates were 44.9%, 16.8%, and 11.2%, respectively. The median survival time was 12.5 months. In univariate analysis, the patients with successfully treated extracranial metastases had significantly better prognosis. In multivariate analysis, the patients with Karnofsky performance scale (KPS) > or = 80%, who were treated by GK more than once and obtained complete response (CR) or partial response (PR) by GK, had significantly better prognosis. CONCLUSION: Gamma-knife radiosurgery for RCC is an effective non-invasive modality of treatment. It offers a high local control rate and an improved quality of life and survival rate.     

Safety and feasibility of image-guided robotic radiosurgery for patients with limited bone metastases of prostate cancer

ObjectiveTo determine the safety and feasibility after image-guided single fraction robotic stereotactic radiosurgery (SRS) in patients with bone metastases of prostate cancer.Materials and methodsForty patients with 64 bone metastases of prostate cancer were prospectively enrolled in a single center study and underwent 54 consecutive outpatient single session SRS procedures during a 4-year period. F-18 choline PET/CT in addition to standard CT imaging was done prior to SRS in all patients. Nineteen patients were under anti-androgen therapy, 8 patients had undergone chemotherapy before SRS. Overall survival and freedom from local tumor recurrence was analyzed with the Kaplan-Meier method.ResultsMean follow-up was 14 months (3–48 months). Seventy-five percent of patients had a single bone metastasis. The median tumor volume was 13 cc. The mean prescribed tumor dose was 20.2 Gy (16.5–22 Gy). Eight patients had died at the time point of the data analysis. The actuarial 6-months, 12-months, and 24-months local tumor control rate was 95.5% (95% CI: 83.0–98.8) as measured by MRI and PET CT imaging. The median initial PSA before SRS was 5.4 ng/dl (CI: 1.4–8.2) and dropped to 2.7 ng/dl (CI: 0.14–10) after 3 months. One case of progressive neurological deficits was documented.ConclusionsThis first report on single session, image-guided robotic SRS documents a safe, feasible, and patient-friendly treatment option in selected patients with bone metastases of prostate cancer.     

LINAC radiosurgery for brain metastasis of renal cell carcinoma

The purpose of the study was to evaluate the efficacy and toxicity of stereotactic radiotherapy in the treatment of the brain metastasis of renal cell carcinoma. From 1994 to 2001, 28 patients presenting with 65 metastases of renal cell cancer were treated by radiosurgery. Median age was 55 years (35-75), and median Karnofski performance status ranges between 50 and 100. Seven patients had received whole brain radiotherapy (WBRT) before radiosurgery. Twelve patients were treated by radiosurgery for 1 metastasis, 5 patients for two metastases and 6 for three, and 5 for more than three metastases. One procedure was performed in 22 patients and, 2 or 3 procedures for 6 patients. Median metastasis diameter was 19 mm (5-55 mm). Median metastasis volume was 1.28 cc (0.02-28 cc). Irradiation was delivered by linear accelerator. Median minimal dose (on the 70% isodose) was 14.7 Gy (10.8 Gy, 19.5 Gy), median maximal dose (at the isocenter) 20.5 Gy (14.3 Gy, 39.6 Gy). Median follow-up was 14 months (1-33). Two metastases progressed (3%), 2 and 12 months after radiosurgery. Overall, crude local control rate was 97% and 3-, 6- and 12-month local control rates were 98% +/- 2%, 98% +/- 2%, and 93% +/- 5%, respectively. In univariate analysis, no prognostic factor of local control was retrieved. Median brain disease-free survival was 25 months after RS. the 3-, 6- and 12-month distant brain control rates were 91% +/- 4%, 91% +/- 4%, and 70% +/- 12%, respectively. Median survival duration was 11 months. The 3-, 6-, 12- and 24-month overall survival rates were 82% +/- 7%, 67% +/- 9%, 48% +/- 10%, and 33% +/- 10%, respectively. According to univariate analysis, only site of metastasis was overall survival prognostic factor. Radiosurgery for brain metastasis of renal cell carcinoma is an effective and accurate treatment. The use of radiosurgery alone is an appropriate management strategy for many patients with brain metastasis of renal cell carcinoma. Radiosurgery is efficient even after development of new metastasis appearing after WBRT.     

Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome.

OBJECT: To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients. METHODS: Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%. CONCLUSIONS: The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.     

Factors affecting the outcome after treatment for metastatic melanoma to the brain

Background

Because of the difficulties inherent to the treatment of metastatic melanoma to the brain including high rates of disease progression and local treatment failure, we attempted to determine the prognostic factors that impacted the outcome of these patients, and reviewed patient outcome based on primary treatment with either surgical resection or SRS.

Methods

A retrospective review identified 37 patients treated for metastatic melanoma between July 2002 and April 2007. Information was obtained documenting systemic disease, preoperative symptoms, tumor size and location, disease recurrence, primary and secondary treatments, and survival time.

Results

Two patients were alive as of March 2008. The median survival time for patients primarily treated with surgical resection was 9.7 months compared to 7.9 months for patients initially treated with SRS. Solitary brain metastases and the absence of both preoperative hemorrhage and lung metastases served as prognostic factors increasing survival in both groups. Four patients undergoing primary treatment with SRS required subsequent surgical intervention secondary to radiation necrosis (3 patients) or local recurrence (1 patient). All 4 had lesions greater than 1.5 cm. For surgical patients, planned postoperative treatment with either radiosurgery or radiation therapy increased survival time to 12.3 months vs 7.3 months.

Conclusions

Patients with positive prognostic factors including solitary brain lesions, absence of hemorrhage preoperatively, and absence of lung disease are viable candidates for aggressive, surgical intervention followed by adjuvant therapy with radiosurgery or conventional radiation therapy. Other patients should be considered for more conservative treatment with radiosurgery or other palliative treatments.     

Stereotactic radiosurgical treatment of parenchymal brain metastases from prostate adenocarcinoma

BACKGROUND: Prostate cancer metastatic to the brain is uncommon and has been associated historically with a poor prognosis. It has been suggested that SRS may be an effective treatment. METHODS: We analyzed a prospective, institutional review board-approved database of patients treated with SRS and identified 5 patients with prostate cancer metastasis. Clinical, pathologic, radiographic, treatment, and outcome information regarding the primary/systemic disease status, and brain metastases were collected. RESULTS: Mean age at the time of treatment for CNS parenchymal metastasis was 72.0 +/- 8.3 years and lesions developed 82.0 +/- 65.1 months after the initial tumor was identified. Four patients had a single lesion and 1 had 4; 3 patients were treated with SRS alone, 1 with WBRT and SRS, and 1 with surgery, then WBRT and SRS. All were symptomatic. Stereotactic radiosurgery controlled the brain metastases in all 5 patients, with functional improvement and with a typical increase of 1 grade in the Karnofsky performance score. Mean survival was at least 10.0 +/- 6.7 months (range, 6-22+ months). Two patients died of conditions unrelated to prostate cancer and 2 of systemic disease progression; 1is alive and asymptomatic. There were no local SRS failures and no new CNS lesions. CONCLUSIONS: Stereotactic radiosurgery for prostate cancer metastatic to the brain, alone or in combination with brain radiation therapy and surgery, is a safe, effective treatment that improves neurologic symptoms and function and may prolong survival.     

Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? To date radiation therapy has had no oncological implication in renal cell carcinoma. Its use was limited to palliation in painful bone lesions. Radiation therapy was considered ineffective as renal cell cancer is resistant to the commonly used doses of radiotherapy. Side effects in combination with systemic therapy were not known, but heavy skin toxicities were expected. Only a few cases of combined radiation with systemic therapy were published. This is the only series where consecutive patients have been treated simultaneously with sunitnib and hypo‐fractionated high‐dose radiotherapy. Side effects were similar to those expected with systemic therapy or radiation therapy alone. Oncological results are extremely encouraging.

OBJECTIVE

? To analyse the safety and efficacy of simultaneous standard anti‐angiogenic therapy and stereotactic radiosurgery (SRS) in patients with spinal and cerebral metastases from renal cell carcinoma.

PATIENTS AND METHODS

? In all, 106 patients with spinal (n= 55) or cerebral (n= 51) metastatic lesions and an Eastern Cooperative Oncology Group status of 0 or 1 were treated with sorafenib or sunitinib and simultaneous SRS. ? The primary endpoint was local control. ? Secondary endpoints were toxicity and overall survival.

RESULTS

? Median follow up was 14.7 months (range 1–42 months). Forty‐five patients were treated with sunitinb and 61 patients with sorafenib. Two patients had asymptomatic tumour haemorrhage after SRS. ? No skin toxicity, neurotoxicity or myelopathy occurred after SRS, and SRS did not alter the adverse effects of anti‐angiogenic therapy. ? Local tumour control 15 months after SRS was 98% (95% confidence interval 89–99%). The median pain score before SRS was 5 (range 1–8) and was lowered to 0 (range 0–2, P < 0.01) after SRS. There were no treatment‐related deaths or late complications after SRS. ? Overall survival was 17.4 months in patients with spinal lesions and 11.1 month in patients with cerebral lesions (P= 0.038).

CONCLUSIONS

? Simultaneous systemic anti‐angiogenic therapy and SRS for selected patients with renal cell carcinoma who have spinal and cerebral metastases is safe and effective. ? Single‐fraction delivery allows for efficacious integration of focal radiation treatment into oncological treatment concepts without additional toxicity. ? Further studies are needed to determine the limits of SRS for renal cell carcinoma metastases outside the brain and spine.     

Stereotactic radiosurgery for brainstem metastases.

OBJECT: Brainstem metastases portend a dismal prognosis. Surgical resection is not part of routine management and radiation therapy has offered little clinical benefit. Radiosurgery provides a safe and effective treatment for many patients with brain metastasis, but its role in the brainstem has not been evaluated. In this study the authors examine the role of radiosurgery in the treatment of brainstem metastases. METHODS: The authors reviewed the outcomes after stereotactic radiosurgery in 26 patients with 27 brainstem metastases. Tumor locations included the pons (21 tumors) and midbrain (six tumors): 14 patients had additional tumors in other locations. Twenty patients presented with brainstem signs. The median dose to the tumor margin was 16 Gy (range 12-20 Gy). Twenty-four patients received fractionated whole-brain radiation therapy (WBRT) and 12 underwent additional chemotherapy or immunotherapy. The median follow-up time in these patients was 9.5 months (range 1-43 months). After radiosurgery, the local control rate in brainstem tumors was 95%. In one patient in whom the tumor initially decreased in size, tumor enlargement was seen 7 months later. The median survival time was 11 months after diagnosis and 9 months after radiosurgery. Thirteen patients improved, 10 were stable, and three deteriorated. Eventually, 22 patients died, 18 of progression of their extracranial disease, three of new tumor growth (including one hemorrhage into a new brain metastasis), and one of extracranial disease plus new brain tumor growth. CONCLUSIONS: Although they have slightly lower than the expected survival rates of patients with nonbrainstem tumors, patients with brainstem metastases may achieve effective palliation after stereotactic radiosurgery and WBRT.     

Treatment of nasopharyngeal carcinoma: stereotactic radiosurgical boost following fractionated radiotherapy

Treatment of patients with nasopharyngeal carcinoma (NPC) using external beam radiation therapy (XRT) alone results in significant local recurrence. To improve local control, stereotactic radiosurgery (SRS) was used to boost radiation to the primary tumor site following XRT in 23 patients with NPC. SRS was delivered utilizing a frame-based linear accelerator as a boost (range 7-15 Gy, median 12 Gy) following XRT (range 64.8- 70 Gy, median 66 Gy). In all 23 patients (100%) receiving SRS following XRT local control was achieved at a mean follow-up of 21 months (range 2-64 months). There have been no complications of treatment caused by SRS. However, 8 patients (35%) have subsequently developed regional or distant metastases. SRS boost following XRT provides excellent local control in NPC and should be considered for patients with skull base involvement.     

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy?

OBJECTIVE: Whole brain radiotherapy (WBRT) provides benefit for patients with brain metastases but may result in neurological toxicity for patients with extended survival times. Stereotactic radiosurgery in combination with WBRT has become an important approach, but the value of WBRT has been questioned. As an alternative to WBRT, we managed patients with stereotactic radiosurgery alone, evaluated patients' outcomes, and assessed prognostic factors for survival and tumor control. METHODS: One hundred seventy-two patients with brain metastases were managed with radiosurgery alone. One hundred twenty-one patients were evaluable with follow-up imaging after radiosurgery. The median patient age was 60.5 years (age range, 16-86 yr). The mean marginal tumor dose and volume were 18.5 Gy (range, 11-22 Gy) and 4.4 ml (range, 0.1-24.9 ml). Eighty percent of patients had solitary tumors. RESULTS: The overall median survival time was 8 months. The median survival time in patients with no evidence of primary tumor disease or stable disease was 13 and 11 months. The local tumor control rate was 87%. At 2 years, the rate of local control, remote brain control, and total intracranial control were 75, 41, and 27%, respectively. In multivariate analysis, advanced primary tumor status (P = 0.0003), older age (P = 0.008), lower Karnofsky Performance Scale score (P = 0.01), and malignant melanoma (P = 0.005) were significant for poorer survival. The median survival time was 28 months for patients younger than 60 years of age, with Karnofsky Performance Scale score of at least 90, and whose primary tumor status showed either no evidence of disease or stable disease. Tumor volume (P = 0.02) alone was significant for local tumor control, whereas no factor affected remote or intracranial tumor control. Eleven patients developed complications, six of which were persistent. Nineteen (16.5%) of 116 patients in whom the cause of death was obtained died as a result of causes related to brain metastasis. CONCLUSION: Brain metastases were controlled well with radiosurgery alone as initial therapy. We advocate that WBRT should not be part of the initial treatment protocol for selected patients with one or two tumors with good control of their primary cancer, better Karnofsky Performance Scale score, and younger age, all of which are predictors of longer survival.     

Linac radiosurgery for brain metastasis of melanoma

PURPOSE: To evaluate the efficacy and toxicity of stereotactic radiotherapy in the treatment of brain metastases of melanoma. PATIENTS AND METHODS: From 1994 to 2001, 25 patients presenting with 61 metastases of cutaneous melanoma were treated with radiosurgery. Median age was 47 years (range: 25-73 years) and median Karnofski performance status 80 (range: 50-100). Twenty patients had one radiosurgery, 5 had two or three. Median metastasis diameter was 21 mm (range: 6-54.4 mm), and median metastasis volume was 1.7 cm(3) (range: 0.4-25.6 cm(3)). Irradiation was delivered by a linear accelerator. Median minimal dose was 14.1 Gy (range: 10-19.4 Gy), and median maximal dose was 20.5 Gy (range: 16-48 Gy). RESULTS: Mean follow-up was 12.6 months (range: 1-85 months). Five metastases progressed (9.8%), 2-12 months after radiosurgery. Three-, 6- and 12-month local control rates were 95 +/- 3, 90 +/- 5 and 84 +/- 7%, respectively. By univariate analysis, only absence of extracranial tumor was a prognostic factor of local control. Three-, 6- and 12-month brain-disease-free survival rates were 75 +/- 9, 68 +/- 11 and 38 +/- 13%, respectively. According to univariate analysis, only the Score Index for Radiosurgery in brain metastases (SIR) was a prognostic factor of brain-event-free survival (p = 0.03). Median survival was 8 months. Three-, 6- and 12-month overall survival rates were 75 +/- 9, 53 +/- 10, and 29 +/- 10%, respectively. According to univariate analysis, extracranial controlled disease status (p = 0.03), and SIR (p = 0.04) were prognostic factors for overall survival. According to multivariate analysis, none was an independent prognosticator for overall survival. Complications were minimal. CONCLUSION: Radiosurgical treatment of brain metastases of melanoma is effective and accurate. The use of radiosurgery alone is an appropriate management strategy for many patients with brain metastases of melanoma.     

Radiosurgery for non-small cell lung carcinoma metastatic to the brain: long-term outcomes and prognostic factors influencing patient survival time and local tumor control

OBJECT: Lung carcinoma is the leading cause of death from cancer. More than 25% of those patients with lung cancer develop a brain metastasis at some time during the course of their disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival for patients with lung carcinoma metastasis is approximately 3 to 6 months. The authors examine the efficacy of gamma knife radiosurgery (GKS) for treating non-small cell lung carcinoma (NSCLC) metastases to the brain and evaluate factors affecting long-term patient survival. METHODS: A retrospective review of 273 patients who had undergone GKS to treat a total of 627 NSCLC metastases was performed. Clinical and neuroimaging data encompassing a 14-year treatment interval were collected. Univariate and multivariate analyses were performed to determine significant prognostic factors influencing patient survival. The overall median patient survival time was 15 months (range 1-116 months) from the diagnosis of brain metastases. The median survival was 10 months from GKS treatment in those patients with adenocarcinoma and 7 months for those with other histological tumor types. In patients with no active extracranial disease at the time of GKS, the median survival time was 16 months. In multivariate analyses, factors significantly affecting survival included: 1) female sex (p = 0.014); 2) preoperative Karnofsky Performance Scale score (p < 0.0001); 3) adenocarcinoma histological subtype (p = 0.0028); 4) active systemic disease (p = 0.0001); and 5) time from lung cancer diagnosis to the development of brain metastasis (p = 0.0074). Prior tumor resection or whole-brain radiation therapy did not correlate with extended patient survival time. Postradiosurgical imaging of brain metastases revealed that 60% decreased, 24% remained stable, and 16% eventually increased in size. Factors affecting local tumor control included tumor volume (p = 0.042) and treatment isodose (p = 0.015). Fourteen patients (5.1%) later underwent craniotomy and tumor resection for tumor refractory to GKS or a new symptomatic metastasis. CONCLUSIONS: Gamma knife surgery for NSCLC metastases affords effective local tumor control in approximately 84% of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including GKS can afford patients an extended survival time.     

Stereotactic radiosurgery plus intracavitary irradiation in the salvage of nasopharyngeal carcinoma

BACKGROUND: We sought to assess the efficacy and complications of linear accelerator-based stereotactic radiosurgery (SRS) plus intracavitary irradiation (ICI) as salvage treatment for local persistent and recurrent nasopharyngeal carcinoma (NPC) after primary external beam radiotherapy (EBRT). METHODS: Between July 1995 and June 2003, 36 patients (25 men and 11 women; median age, 48 years; range, 22-66 years) with local recurrent NPC confined to the nasopharynx (rT1) or limited extension to the parapharynx and nasal cavity (rT2) were treated with SRS plus ICI. Nineteen patients had rT1 and 17 had rT2 disease. Five patients (13.8%) had persistent disease, and 31 patients (86.1%) had recurrent disease using the definition of >4 months after the primary treatment as recurrent relapse. The median target volume was 36.3 cm(3) (range, 10.3-56.2 cm(3)) for the SRS treatment. All patients received 18 Gy to the 90% isodose line followed by two separate ICI 6 Gy each to 0.5 cm from the surface of the endotracheal balloon. Patients were assessed with serial nasoendoscopy and repeat scans (CT or MRI) at 3 months, and suspicious lesions were rebiopsied. RESULTS: The median follow-up for surviving patients was 4.24 years (range, 0.73-8.81 years). Twenty-two of 36 (61%) patients were alive at the time of reporting. Twenty patients were free of disease, and two patients were alive with disease. Fourteen of 36 (39%) patients had died (five of distant metastases, six of local recurrences, two of both local disease and distant metastases, and one of unrelated cause). Patients with rT1 disease (median survival not reached) fared better that patients with rT2 disease (median survival, 4.6 years). The actuarial 5-year disease-free survival and overall survival (OS) were 57% (rT1 78%, rT2 39%) and 62% (rT1 80%, rT2 48%), respectively. The actuarial 5-year local control was 65% (rT1 82%, rT2 49%). The treatment was well tolerated with no significant acute complications. Sixteen patients (44%) had late complications, including palatal fibrosis in six patients (17%), trismus in seven patients (20%), cranial nerve palsies in seven patients (20%), temporal lobe necrosis in two patients (8%), and osteoradionecrosis of the skull base in six patients (17%). The complication-free survival rates at 2 and 5 years were 70% (95% confidence interval [CI], 56% to 87%) and 31% (95% CI, 17% to 56%), respectively. No patient died as a direct result of the late complication. CONCLUSION: Although our series is small, the combination of SRS and ICI seems to be an effective salvage treatment for early-stage recurrent NPC. The OS of 62% at 5 years is very encouraging and favorable compared with reported reirradiation or surgical series. The late complications are considerable but expected because of the high doses of radiation previously delivered. The ideal dose fractionation for SRS and ICI is unknown and remains to be defined.