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

Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD.  J Neurosurg. 2003 Feb;98(2):342-9.

Department of Neurological Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, Pennsylvania, USA. jps2f@virginia.edu

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.

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

Hoshi S, Jokura H, Nakamura H, Shintaku I, Ohyama C, Satoh M, Saito S, Fukuzaki A, Orikasa S, Yoshimoto T. Int J Urol. 2002 Nov;9(11):618-25

Department of Urology, Tohoku University School of Medicine, Aobaku, Sendai, Japan. hoshi@uro.med.tohoku.ac.jp

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.

Gamma knife radiosurgery for renal cell carcinoma brain metastases.

Hernandez L, Zamorano L, Sloan A, Fontanesi J, Lo S, Levin K, Li Q, Diaz F.  J Neurosurg. 2002 Dec;97(5 Suppl):489-93.

Department of Neurological Surgery, Wayne State University, Detroit, Michigan 48201, USA.

OBJECT: The purpose of this study was to clarify the effectiveness of gamma knife radiosurgery (GKS) in achieving a partial or complete remission of so-called radioresistant metastases from renal cell carcinoma (RCC) and to propose guidelines for optimal treatment METHODS: During a 5-year period, 29 patients (19 male and 10 female) with 92 brain metastases from RCC underwent GKS. The median tumor volume was 4.7 cm3 (range 0.5-14.5 cm3). Fourteen patients (48%) also underwent whole-brain radiotherapy (WBRT) before GKS, and two patients (6.8%) after GKS. The mean GKS dose delivered to the 50% isodose at the tumor margin was 16.8 Gy (range 13-30 Gy). All cases were categorized according to the Recursive Partitioning Analysis (RPA) classification for brain metastases. Univariate analysis was performed to determine significant prognostic factors and survival. The overall median survival was 7 months after GKS treatment. Age, sex, Karnofsky Performance Scale score, and controlled primary disease were not predictors of survival. Combined WBRT/GKS resulted in median survival of 18, 8.5, and 5.3 months for RPA Classes I, II, and III, respectively, compared with the median survival 7.1, 4.2, and 2.3 months for patients treated with WBRT alone. CONCLUSIONS: These results suggest that WBRT combined with GKS may improve survival in patients with brain metastases from RCC. Furthermore, this improvement in survival was seen in all RPA classes.

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

Wowra B, Siebels M, Muacevic A, Kreth FW, Mack A, Hofstetter A.   J Neurosurg. 2002 Oct;97(4):785-93

Gamma Knife Praxis, Department of Urology, Ludwig-Maximilians-Universily, Munich, Germany. wowra@gammaknife.de

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.

Brain metastases in renal cell carcinoma: management with gamma knife radiosurgery.
Amendola BE, Wolf AL, Coy SR, Amendola M, Bloch L.   Cancer J. 2000 Nov-Dec;6(6):372-6.

Miami Neuroscience Center, Coral Gables, Florida, USA.

PURPOSE: The purpose of this study was to evaluate survival and local control of brain metastases in patients with renal cell carcinoma. METHODS AND MATERIALS: From November 1993 through March 1999, 38 radiosurgical treatments using the Leksell gamma knife unit were performed on 22 patients with renal cell carcinoma. The indications for treatment were failure after whole-brain radiation therapy or de novo treatment. All radiosurgical treatments were given on an outpatient basis. The workup included computed tomography and magnetic resonance imaging. The age of the patients ranged from 38 to 80 years (median age, 60 years). The mean minimum tumor dose was 18 Gy, and the mean volume was 3.9 cc. Previous whole-brain radiation therapy was used in 11/22 (50%) patients. Four of 22 patients presented with single metastasis. Thirteen patients were treated once, one patient was treated four times and one patient seven times for new lesions. The number of lesions treated ranged from one to 21. RESULTS: One patient is al ive at 63 months of fol low-up. Twenty-one patients died, with a median survival of 8 months (range, 1-38 months). Eighteen of 21 patients died of nonneurologic causes. Overall local control was 98.5%. One patient developed radiation necrosis. CONCLUSIONS The long-term survival achieved in patients with renal cell carcinoma requires aggressive management, even in the presence of multiple brain metastases. Gamma knife radiosurgery for renal cell carcinoma is an effective noninvasive modality of treatment. It offers high local control rate and improved quality of life and survival.

Radiosurgery for the treatment of brain metastases in renal cell carcinoma.

Becker G, Duffner F, Kortmann R, Weinmann M, Grote EH, Bamberg M.  Anticancer Res. 1999 Mar-Apr;19(2C):1611-7

Department of Radiotherapy, University Hospital, Tubingen, Germany.

BACKGROUND: In the treatment of brain metastases using a stereotactically modified linear accelerator it could be shown that a single dose between 15 and 25 Gy leads to partial or complete remission of so-called radioresistant metastases from melanoma and hypernephroma. Radiosurgery of brain metastases then started in centers all over the world, however, experiences with brain metastases of renal cell carcinoma are yet limited. The aim of this analysis is therefore to present the treatment results of radiosurgery of brain metastases. Furthermore, in this paper prognostic subgroups shall be defined, in order to establish guidelines for an optimal therapy strategy. MATERIALS AND METHODS: Radiosurgery means stereotactically guided high-precision irradiation methods by extremely focussing ionizing radiation within the target volume as a single dose application. The characteristic steep dose decrease allows the selective destruction of small intracranial lesions, while the surrounding brain tissue is optimally protected. Two methods, Gamma Knife and stereotactic modified linear accelerator are clinically available. RESULTS: In larger studies from different groups all over the world, local tumor control rates from 85% to 95%, recurrence rates from 6% to 15% and side effects between 3% and 15% have been attained, independent of the system used. Prognostic factors, like volume of metastases < 10 ml, applied dose > 18 Gy, one or two metastases, absence of extracranial metastases, good patient performance with a Karnofsky score > 70%, primary treatment and more than one year between primary diagnosis and brain metastases showed a trend toward improved survival. Depending on the prognostic factors the median survival after radiosurgery ranged from 6 to 12 months. Retrospective comparison of radiosurgery and surgical series suggest that both modalities attain similar results. The dose can be applied with an accuracy of 0.3 mm. DISCUSSION: Based on these experiences, brain metastases can be treated by radiosurgery, primarily in patients with one or two metastases or in combination with whole brain irradiation as a boost in patients with more than two metastases. Furthermore with radiosurgery a new treatment modality exists to re-irradiate patients who have been failed after surgery or whole brain irradiation.

Gamma-knife radiosurgery for brain metastases of renal cell carcinoma: results in 23 patients.

Schoggl A, Kitz K, Ertl A, Dieckmann K, Saringer W, Koos WT.   Acta Neurochir (Wien). 1998;140(6):549-55

Department of Neurosurgery, University of Vienna, Austria.

From Jan. 1993 to Sept. 1995 23 patients suffering from brain metastases from renal cell carcinoma were treated with the Leksell Gamma Knife at the University of Vienna. At the time of diagnosis 13 patients had single and 10 patients presented with multiple metastatic lesions with a total of 44 metastases in MRI scans. Median tumour volume was 5500 cmm (range 100-24000 cmm). Predominant neurological symptoms and signs were different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness, ataxia and CN XII paresis. Fourteen patients received Gamma Knife Radiosurgery (GKRS) with a median dose of 22 Gy (range 8-30 Gy) at the tumour margin. Nine patients underwent a combined treatment of a radiosurgical boost with a median dose of 18 Gy (range 10-22 Gy) at the tumour margin followed by Whole Brain Radiotherapy (total dose 30 Gy/2 weeks). In 20 patients tumour volume reduction up to 30% of the primary tumour volume was found after 4 weeks, evaluated on CT or MRI. A total remission was seen in 4 cases 3 months after GKRS. We achieved a local tumour control of 96%. Rapid neurological improvement after GKRS was seen in 17 patients. The median survival time was 11 months; the one-year actual survival in this unselected group was 48%. Five long term survivors were still alive, 18 patients had subsequently died, 15 of them of general tumour progression. GKRS induces a significant tumour remission accompanied by rapid neurological improvement and therefore provides the opportunity for extended high quality survival. Neither local tumour control was improved nor CNS relapse free survival was prolonged significantly by additional WBRT.

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

Siebels M, Oberneder R, Buchner A, Zaak D, Mack A, Petrides PE, Hofstetter A, Wowra B.  Urologe A. 2002 Sep;41(5):482-8.

Urologische Klinik und Poliklinik, LMU Munchen, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munchen. Siebels@uro.med.uni-muenchen.de

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.