Cyberknife for brain metastases of malignant melanoma and renal cell carcinoma.

Hara W, Tran P, Li G, Su Z, Puataweepong P, Adler JR Jr, Soltys SG, Chang SD, Gibbs IC. Neurosurgery. 2009 Feb;64(2 Suppl):A26-32

Department of Radiation Oncology, Stanford University, Stanford Cancer Center

OBJECTIVE: To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma. METHODS: We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified. RESULTS: The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%). CONCLUSION: CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.

Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma.

Powell JW, Chung CT, Shah HR, Canute GW, Hodge CJ, Bassano DA, Liu L, Mitchell L, Hahn SS.J Neurosurg. 2008 Dec;109 Suppl:122-8.

Department of Radiation Oncology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.

OBJECT: The purpose of this study was to examine the results of using Gamma Knife surgery (GKS) for brain metastases from classically radioresistant malignancies. METHODS: The authors retrospectively reviewed the records of 76 patients with melanoma (50 patients), renal cell carcinoma (RCC; 23 patients), or sarcoma (3 patients) who underwent GKS between August 1998 and July 2007. Overall patient survival, intracranial progression, and local progression of individual lesions were analyzed. RESULTS: The median age of the patients was 57 years (range 18-85 years) and median Karnofsky Performance Scale (KPS) score was 80 (range 20-100). Sixty-two patients (81.6%) had uncontrolled extracranial disease. A total of 303 intracranial lesions (average 3.97 per patient, range 1-27 lesions) were treated using GKS. More than 3 lesions were treated in 30 patients (39.5%). Median GKS tumor margin dose was 18 Gy (range 8-30 Gy). Thirty-seven patients (48.7%) underwent whole brain radiation therapy. The actuarial 12-month rate for freedom from local progression for individual lesions was 77.7% and was significantly higher for RCC compared with melanoma (93.6 vs 63.0%; p = 0.001). The percentage of coverage of the prescribed dose to target volume was the only treatment-related variable associated with local control: 12-month actuarial rate of freedom from local progression was 71.4% for lesions receiving >or= 90% coverage versus 0.0% for lesions receiving < 90% (p = 0.00048). Median overall survival was 5.1 months after GKS and 8.4 months after the discovery of brain metastases. Univariate analysis revealed that KPS score (p = 0.000004), recursive partitioning analysis class (p = 0.00043), and single metastases (p = 0.028), but not more than 3 metastases, to be prognostic factors of overall survival. The KPS score remained significant after multivariate analysis. Overall survival for patients with a KPS score >or= 70 was 7.1 months compared with 1.3 months for a KPS score <or= 60 (p = 0.013). CONCLUSIONS: Gamma Knife surgery is an effective treatment option for patients with radioresistant brain metastases. In this setting, KPS score appeared to be a more important factor in predicting survival than having > 3 metastases. Higher rates of local tumor control were achieved for RCC in comparison with melanoma, and this may have an effect on survival in some patients. Although outcomes generally remained poor in this study population, these results suggest that GKS can be considered as a treatment option for many patients with radioresistant brain metastases, even if these patients have multiple lesions.

Gamma Knife surgery for the treatment of melanoma metastases: the effect of intratumoral hemorrhage on survival.

Redmond AJ, Diluna ML, Hebert R, Moliterno JA, Desai R, Knisely JP, Chiang VL.J Neurosurg. 2008 Dec;109 Suppl:99-105.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.

OBJECT: Gamma Knife surgery (GKS) improves overall survival in patients with malignant melanoma metastatic to the brain. In this study the authors investigated which patient- or treatment-specific factors influence survival of patients with melanoma brain metastases; they pay particular interest to pre- and post-GKS hemorrhage. METHODS: Demographic, treatment, and survival data on 59 patients with a total of 208 intracranial metastases who underwent GKS between 1998 and 2007 were abstracted from treatment records and from the Connecticut Tumor Registry. Multivariate analysis was used to identify factors that independently affected survival. RESULTS: Survival was significantly better in patients with solitary metastasis (p = 0.04), lesions without evidence of pre-GKS hemorrhage (p = 0.004), and in patients with total tumor volume treated < 4 cm(3) (p = 0.02). Intratumoral bleeding occurred in 23.7% of patients pre-GKS. Intratumoral bleeding occurred at a mean of 1.8 months post-GKS at a rate of 15.2%. Unlike the marked effect of pretreatment bleeding, posttreatment bleeding did not independently affect survival. Sex, systemic control, race, metastases location, whole-brain radiation therapy, chemotherapy, history of antithrombotic medications, and cranial surgery had no independent association with survival. CONCLUSIONS: These data corroborate previous findings that tumor burden (either as increased number or total volume of lesions) at the time of GKS is associated with diminished patient survival in those with intracerebral melanoma metastases. Patients who were noted to have hemorrhagic melanoma metastases prior to GKS appear to have a worse prognosis following GKS compared with patients with nonhemorrhagic metastases, despite similar rates of bleeding pre- and post-GKS treatment. Gamma Knife surgery itself does not appear to increase the rate of hemorrhage.

Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site.

Golden DW, Lamborn KR, McDermott MW, Kunwar S, Wara WM, Nakamura JL, Sneed PK.J Neurosurg. 2008 Dec;109 Suppl:77-86

Department of Internal Medicine, Kaiser Permanente Medical Center, Oakland, USA.

OBJECT: The authors conducted a study to determine whether prognostic factors and the applicability of prognostic systems vary by primary tumor site in patients treated with radiosurgery for brain metastases. METHODS: The authors evaluated data obtained in patients who underwent radiosurgery with or without whole-brain radiotherapy (WBRT) from 1991 to 2005 for newly diagnosed brain metastases. Four groups were analyzed: 1) all primary sites combined, 2) breast, 3) lung, and 4) melanoma primary sites. Kaplan-Meier, log-rank, Cox proportional hazard uni- and multivariate analysis, and recursive partitioning analysis (RPA) were used to assess prognostic factors and 4 prognostic systems: Radiation Therapy Oncology Group (RTOG) RPA, Graded Prognostic Assessment (GPA), basic score for brain metastases (BSBM), and the newly proposed Golden grading system (GGS). The GGS divides patients into 4 prognostic groups by age >or= 65 years, Karnofsky Performance Scale (KPS) score < 70, and known presence of extracranial metastases. RESULTS: Data acquired in 479 newly diagnosed patients with 1664 lesions were analyzed. The median survival time from diagnosis of brain metastases was 12.1 months; the median follow-up was 25.4 months in 73 patients who were censored. Survival and prognostic factors were equivalent for 369 patients treated with radiosurgery compared with 110 patients treated with radiosurgery and WBRT, so these subsets were combined. Multivariate analysis of all primary sites combined demonstrated age < 65 years, KPS score >or= 70, no known extracranial metastases, and <or= 3 brain metastases were associated with longer survival, and primary tumor control was not. In subgroup multivariate analysis of patients with breast, lung, or melanoma primaries, favorable factors included only primary tumor control in 87 patients with breast primary; age < 65 years, no known extracranial metastases, and <or= 3 brain metastases in 169 patients with lung primary; and KPS >or= 70 years, primary tumor control, and <or= 3 brain metastases in 137 patients with melanoma primary. The median survival for <or= 3 versus > 3 metastases was 15.6 and 16.9 months, respectively, for breast, 16.5 and 11.3 months for lung, and 9.0 and 5.7 months for melanoma. Analysis of the 4 prognostic systems (RTOG RPA, BSBM, GPA, and GGS) showed that each prognostic system's clinical applicability varied depending on primary tumor site. The RPA confirmed that GGS and primary tumor site are significant variables for prognosis. CONCLUSIONS: Favorable prognostic factors for patients with newly diagnosed brain metastases treated with radiosurgery vary by primary site. The 4 prognostic grading systems analyzed were applicable to different primary sites depending on which prognostic factors each individual system incorporated. Therefore, the authors recommend further development and use of primary-specific prognostic systems.

Stereotactic radiosurgery for patients with "radioresistant" brain metastases.

Brown PD, Brown CA, Pollock BE, Gorman DA, Foote RL.Neurosurgery. 2008 Feb;62 Suppl 2:790-801

Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.

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.

 

Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features.

Raizer JJ, Hwu WJ, Panageas KS, Wilton A, Baldwin DE, Bailey E, von Althann C, Lamb LA, Alvarado G, Bilsky MH, Gutin PH.Neuro Oncol. 2008 Apr;10(2):199-207. Epub 2008 Feb 20.

Feinberg School of Medicine, Department of Neurology, Northwestern University, 710 North Lake Shore Drive, Chicago, IL 60611, USA. jraizer@nmff.org

Brain metastases (BM) are among the most devastating and debilitating complications of melanoma. This retrospective study was conducted to gain a better understanding of patient and disease characteristics that have the greatest impact on overall survival in melanoma patients with BM; therapeutic interventions were also assessed. The records of all patients diagnosed with cutaneous melanoma and BM who were seen at Memorial Sloan-Kettering Cancer Center between 1991 and 2001 were retrospectively reviewed. A variety of factors, including age at diagnosis of stage IV disease, gender, race, disease stage at diagnosis, presence of BM at diagnosis of stage IV disease, neurologic symptoms, radiographic findings, number of BM, status and site(s) of extracranial metastasis, and treatment modalities, were analyzed for correlation with overall survival using univariate and multivariate Cox regression models. The records of 355 patients with BM were included in the analysis. On univariate analysis, seven patient and disease characteristics were significantly associated with poorer survival: age > 65 years, extracranial metastases, BM at stage IV diagnosis, neurologic symptoms, four or more BM, hydrocephalus, and leptomeningeal metastases. Of these, age, extracranial metastasis, neurologic symptoms, and number of BM were significantly associated with poorer survival in a multivariate analysis. Multivariate analysis of treatment modalities suggested that patients who had surgery, radiosurgery, or chemotherapy with temozolomide had improved survival outcomes, although this analysis has limitations. The prognostic factors identified in this retrospective study should be considered when making treatment decisions for patients with BM and used as stratification factors in future clinical trials.