Outcome Predictors of Gamma Knife Radiosurgery for Renal Cell Carcinoma Metastases

Neurosurgery ◽  
2011 ◽  
Vol 69 (6) ◽  
pp. 1232-1239 ◽  
Author(s):  
Hideyuki Kano ◽  
Aditya Iyer ◽  
Douglas Kondziolka ◽  
Ajay Niranjan ◽  
John C. Flickinger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
Renal Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gamma Knife Radiosurgery ◽  
Tumor Control

Abstract BACKGROUND Although whole-brain radiation therapy (WBRT) has been a standard palliative management for brain metastases from renal cell carcinoma, its benefit has been elusive because of radiobiological resistance. OBJECTIVE To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from renal cell carcinoma. METHODS We reviewed records from 158 consecutive patients (men = 111, women = 47) who underwent SRS for 531 brain metastases from renal cell carcinoma. The median patient age was 61 years (range, 38-83 years), and the median number of tumors per patient was 1 (range, 1–10). Seventy-nine patients (50%) had solitary brain metastasis. Fifty-seven patients (36%) underwent prior WBRT. The median total tumor volume for each patient was 3.0 cm3 (range, 0.09-47 cm3). RESULTS The overall survival after SRS was 60%, 38%, and 19% at 6, 12, and 24 months, respectively, with a median survival of 8.2 months. Factors associated with longer survival included younger age, longer interval between primary diagnosis and brain metastases, lower recursive partitioning analysis class, higher Karnofsky performance status, smaller number of brain metastases, and no prior WBRT. Median survival for patients with > 2 brain metastases, higher Karnofsky performance status (> 90), and no prior WBRT was 12 months after SRS. Sustained local tumor control was achieved in 92% of patients. Symptomatic adverse radiation effects occurred in 7%. Overall, 70% of patients improved or remained neurologically stable. CONCLUSION Stereotactic radiosurgery is an especially valuable option for patients with higher Karnofsky performance status and smaller number of brain metastases from renal cell carcinoma.

Gamma knife radiosurgery for melanoma/renal cell carcinoma brain metastases 1 -10 lesions with optimized margin dose: Improved tumor control and survival

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8581-8581
Author(s):  
A. O. Fregene ◽  
P. Mobit ◽  
L. Zamorano ◽  
F. Diaz ◽  
M. Guthikonda ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Renal Cell ◽  
Karnofsky Performance Status ◽  
Gamma Knife Radiosurgery ◽  
Brain Lesions ◽  
Tumor Control ◽  
The Impact

8581 Background: Radioresistant brain metastases melanoma/renal cell carcinoma cause significant morbidity and mortality: response to whole brain external beam radiotherapy (WBXRT) is minimal, chemotherapy role is investigative, and surgery has its indications and limitations. Reports of survival with Gamma Knife Radiosurgery (GK) is mixed. Reports indicate that 80 to 90% of tumor failure following GK is in the margin: recent multivariate analyses indicate tumor control dependence on margin dose. This study evaluates the impact of better control of brain lesions and consequent reduction of CNS death on overall survival. Methods: Between 10/2002 and 12/2005, 24 consecutive patients with melanoma and renal cell carcinoma male/female radio 14/10, 20 melanoma and 4 renal cell were treated by WBXRT followed by GK radiosurgery utilizing optimized margin dose. Dose was (16 - 20 Gy) to the 50% line with adequate margin to reduce systematic and other associated errors. This was achieved by combining the separate errors associated with the procedure; extent of tumor infiltration beyond gross tumor margin; GK/procedure mechanical precision limitations; MRI image transfer spatial limitations and beam profile margin dose sensitivity. Karnofsky Performance status was 70 - 90%. Follow-up period was 52 months. Results: The mean survival period for the 24 patients with 1 - 10 lesions was 14.11 months: median survival by Kaplan-Meier was 12.0 months. This result is a significant improvement on the 5.5 months reported earlier from this institution for 1 - 5 lesions treated with non-optimized GK dosage; and data by Lavin, et al, at 8 months for predominantly solitary lesions. Conclusions: Melanoma and renal cell carcinoma brain metastases respond very well to GK radiosurgery with optimized margin dose: mean survival for these patients with 1 -3 and 4 - 10 lesions is 14.11 months and comparable to the survival of patients with brain metastases from lung and breast patients: More studies along this line are called for. Patients with multiple metastatic brain lesions from melanoma and renal cell cancers stand to benefit. No significant financial relationships to disclose.

Gamma knife radiosurgery for renal cell carcinoma brain metastases

2002 ◽  
Vol 97 ◽  
pp. 489-493 ◽  
Author(s):  
Laura Hernandez ◽  
Lucia Zamorano ◽  
Andrew Sloan ◽  
James Fontanesi ◽  
Simon Lo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Median Survival ◽  
Renal Cell ◽  
Univariate Analysis ◽  
Gamma Knife Radiosurgery ◽  
Content Type ◽  
Fine Print

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.

Stereotactic Radiosurgery for Patients with “Radioresistant” Brain Metastases

Neurosurgery ◽  
2002 ◽  
Vol 51 (3) ◽  
pp. 656-667 ◽  
Author(s):  
Paul D. Brown ◽  
Cerise A. Brown ◽  
Bruce E. Pollock ◽  
Deborah A. Gorman ◽  
Robert L. Foote
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
Local Control ◽  
Renal Cell ◽  
Class I

Abstract 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.

Pathologic Complete Response in Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery

2007 ◽  
Vol 5 (5) ◽  
pp. 334-337 ◽  
Author(s):  
Bin S. Teh ◽  
Charles Bloch ◽  
Arnold C. Paulino ◽  
Steven Shen ◽  
Lisa Hinckley ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Stereotactic Radiosurgery ◽  
Renal Cell ◽  
Pathologic Complete Response ◽  
Complete Response

Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up.

1993 ◽  
Vol 11 (7) ◽  
pp. 1368-1375 ◽  
Author(s):  
L M Minasian ◽  
R J Motzer ◽  
L Gluck ◽  
M Mazumdar ◽  
V Vlamis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Interferon Alfa ◽  
Advanced Renal Cell Carcinoma ◽  
Survival Duration

PURPOSE Three trials were conducted to define the efficacy and toxicity of interferon alfa-2a in the treatment of metastatic renal cell cancer. Univariate and multivariate analyses were performed to identify prognostic factors for survival. PATIENTS AND METHODS Prospectively, 159 patients were treated with interferon alfa-2a. In the first trial, 42 patients received 50 x 10(6) U/m2 intramuscularly three times per week. In the second trial, 64 patients received gradually escalating doses of interferon alfa-2a from 3 to 36 x 10(6) U subcutaneously administered daily. The third trial was randomized; 25 patients received daily interferon alfa-2a alone and 28 were treated with daily interferon alfa-2a and 0.15 mg/kg vinblastine every 3 weeks. RESULTS The overall response proportion was 10% (two complete and 14 partial responses). The median response duration was 12.2 months. The median survival duration was 11.4 months, with 3% of patients alive at 5 or more years. A univariate statistical analysis showed that a Karnofsky performance status > or = 80, prior nephrectomy, and interval from diagnosis to treatment of longer than 365 days were significant prognostic factors for survival. In a multivariate analysis, only prior nephrectomy and Karnofsky performance status > or = 80 were shown to be independent predictors of survival. CONCLUSION Interferon alfa-2a had minimal antitumor activity in patients with advanced renal cell carcinoma and long-term survival was achieved in a small proportion of patients. The need for continued investigation and the identification of more effective therapy for advanced renal cell carcinoma is evident from the poor overall survival rate observed in these 159 patients. The investigation of new agents and of interferon alfa-2a in combination with other agents remains a priority.

Efficacy of cabozantinib (XL184) in patients (pts) with metastatic, refractory renal cell carcinoma (RCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
Toni K. Choueiri ◽  
Sumanta Kumar Pal ◽  
David F. McDermott ◽  
David A. Ramies ◽  
Stephanie Morrissey ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Primary Objective ◽  
Heavily Pretreated ◽  
Cell Components ◽  
Anti Tumor Activity

4504 Background: Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2 that is currently undergoing evaluation in several oncology indications. Renal cell carcinoma (RCC) was chosen as an indication in this drug-drug interaction (DDI) study based on involvement of the MET and VEGFR signaling pathways in this disease. The primary objective of this study is to determine the effect of cabo on single dose PK of the CYP2C8 substrate rosiglitazone (rosi). Anti-tumor activity was also evaluated. Methods: Eligible pts were required to have RCC with clear cell components with metastases, Karnofsky performance status of ≥70 and measurable disease by RECIST. Pts needed to have experienced PD following standard therapies. Cabo was given daily at a dose of 140 mg free base (equivalent to 175 mg salt form) starting at Day 2. Rosi (4 mg) was given Day 1 and Day 22 to complete PK assessment for DDI. Cabo was continued until PD. On Day 57 and every 8 weeks thereafter subjects underwent tumor assessments by mRECIST. Results: Enrollment is complete at 25 RCC pts; 17/25 (64%) RCC pts had received ≥ 2 prior agents; 13/25 (52%) with at least 1 VEGF pathway inhibitor and 1 mTOR inhibitor. The majority of pts were in an intermediate (21/25) or poor (3/25) prognostic category (1/25 in favorable category) per Heng et al (JCO, 2009, v27, p5794). ORR by mRECIST: 7/25 (28%). Disease control rate (PR + SD): 72% at 16 weeks; 19/21 (90%) pts with ≥1 post-baseline scan experienced tumor regression (range: 4 - 63% reduction in measurements). 10/25 (36%) pts remain on cabo. Median PFS is 14.7 months (95% CI: 7.3, upper limit not reached) with a median follow-up of 7.7 months. AEs ≥ Grade 3 severity: hypophosphatemia (36%), hyponatremia (20%), and fatigue (16%). PK data suggest that clinically relevant doses of cabo do not alter the Cmax or AUC0-24h of rosi, consistent with no inhibition of CYP2C8. Conclusions: Cabo demonstrates encouraging anti-tumor activity in heavily pretreated RCC pts with a toxicity profile similar to that of other VEGFR TKIs. PK data suggest no DDI between cabo and rosi (CYP2C8 substrate).

Activity of cabozantinib (XL184) in patients (pts) with metastatic, refractory renal cell carcinoma (RCC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
Toni K. Choueiri ◽  
Sumanta Kumar Pal ◽  
David F. McDermott ◽  
David A. Ramies ◽  
Stephanie Morrissey ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Primary Objective ◽  
Risk Category ◽  
Efficacy Evaluation ◽  
Prior Therapy

364 Background: Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2 that is currently undergoing clinical efficacy evaluation in several oncology indications. Renal cell carcinoma (RCC) was chosen as an indication in this drug-drug interaction (DDI) study based on involvement of the MET and VEGFR signaling pathways in this disease. The primary objective of this study is to determine the effect of cabo on single dose PK of the CYP2C8 substrate rosiglitazone (rosi). The exploratory objective of this study is to evaluate the preliminary antitumor activity of cabo in pts with RCC. Methods: Eligible pts were required to have RCC with clear cell components with metastases, Karnofsky performance status of ≥70 and measurable disease by RECIST. Pts needed to have experienced PD following standard therapies. Method for DDI study: Day 1, 4 mg rosi; Days 2 - 22, cabo given daily at a dose of 175 mg; Day 22, 4 mg rosi to complete PK assessment for DDI. Cabo continued until PD. On Day 57 and every 8 weeks thereafter subjects underwent tumor assessments by mRECIST. Results: Enrollment is complete at 25 RCC pts with a median of 2 prior regimens; 17/25 (68%) RCC pts had received ≥ 2 lines of prior therapy and 13/25 (52%) with at least 1 VEGF pathway inhibitor and 1 mTOR inhibitor. All pts were intermediate (24/25) or poor (1/25) risk category per Heng et al prognostic strata (JCO 2009). Related AEs ≥ Grade 3 severity: hypophosphatemia 8 (32%), PE 3 (12%; all were incidental / resolved) and diarrhea 3 (12%). Preliminary PK data suggest that clinically relevant doses of cabo do not markedly alter the Cmax or AUC0-24h of rosi consistent with lack of inhibition of CYP2C8. RCC pts with confirmed PR by mRECIST: 6/25 (24%). Additionally, 1 pt had an unconfirmed PR. Disease control rate (PR + SD): 68% at 16 weeks; 18/21 (86%) pts with ≥1 post-baseline scan experienced tumor regression (range: 4 – 63% reduction in measurements). 14/25 (56%) remain on cabo with a median follow-up of 4 months. Median PFS and OS have not been reached. Conclusions: Cabo demonstrates encouraging anti-tumor activity in heavily pretreated pts with RCC with a toxicity profile similar to that of other TKIs. Preliminary data suggest no DDI between cabo and rosi (CYP2C8 substrate).

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