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Published in: Journal of Neuro-Oncology 1/2016

01-10-2016 | Clinical Study

Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma

Authors: YueJun Du, Sascha Pahernik, Boris Hadaschik, Dogu Teber, Stephan Duensing, Dirk Jäger, Markus Hohenfellner, Carsten Grüllich

Published in: Journal of Neuro-Oncology | Issue 1/2016

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Abstract

Patients with brain metastasis (BM) from renal cell carcinoma (RCC) are associated with poor prognosis. Between 1990 and 2015, data of consecutive RCC patients with BM were retrospectively analyzed from a urologic oncologic database. The treatment outcome was evaluated by overall survival (OS), which was defined as interval from initial diagnosis of BM to death or last follow-up. Statistical analyses of clinical and pathological variables were performed using Cox regression and the Kaplan–Meier method. A total of 116 RCC patients with BM were included. Median time from initial diagnosis of RCC to BM was 15.8 months (95 % CI 11.6–20.0). Median OS after diagnosis of brain metastases of the whole cohort was 5.8 months (95 % CI 4.3–7.2). On multivariate Cox regression analysis, age and histology of non-clear cell RCC were associated with poorer outcome, while targeted therapy (n = 26) (OS 9.9 months, 95 % CI 3.3–16.5) and BM resection (n = 33) (OS 24.7 months, 95 % CI 4–40) were associated with better survival. Furthermore, patients who underwent both targeted therapy and BM resection (n = 5) had the best outcome with median OS of 52.4 months. In conclusion, BM from RCC is associated with a poor oncological outcome. Furthermore, age and histology of non-clear cell RCC are risk factors for poor prognosis. Patients with resectable BM may comprise a better prognostic group. Here, a better OS for resected than unresected patients was observed, which warrants BM resection. A combined modality approach of resection and targeted therapy appears to further improve the outcome of these patients while additional radiation seems to add no benefit.
Literature
1.
go back to reference Athar U, Gentile TC (2008) Treatment options for metastatic renal cell carcinoma: a review. Can J Urol 15:3954–3966PubMed Athar U, Gentile TC (2008) Treatment options for metastatic renal cell carcinoma: a review. Can J Urol 15:3954–3966PubMed
2.
go back to reference Brookman-May S, May M, Shariat SF, Xylinas E, Stief C, Zigeuner R, Chromecki T, Burger M, Wieland WF, Cindolo L et al (2013) Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project). Eur Urol 64:472–477CrossRefPubMed Brookman-May S, May M, Shariat SF, Xylinas E, Stief C, Zigeuner R, Chromecki T, Burger M, Wieland WF, Cindolo L et al (2013) Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project). Eur Urol 64:472–477CrossRefPubMed
3.
go back to reference Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P et al (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23:973–980CrossRefPubMed Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P et al (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23:973–980CrossRefPubMed
4.
go back to reference Schouten LJ, Rutten J, Huveneers HA, Twijnstra A (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698–2705CrossRefPubMed Schouten LJ, Rutten J, Huveneers HA, Twijnstra A (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698–2705CrossRefPubMed
5.
go back to reference Decker DA, Decker VL, Herskovic A, Cummings GD (1984) Brain metastases in patients with renal cell carcinoma: prognosis and treatment. J Clin Oncol 2:169–173PubMed Decker DA, Decker VL, Herskovic A, Cummings GD (1984) Brain metastases in patients with renal cell carcinoma: prognosis and treatment. J Clin Oncol 2:169–173PubMed
6.
go back to reference Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, Pantuck AJ, Belldegrun AS (2008) Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival. Cancer 113:1641–1648CrossRefPubMed Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, Pantuck AJ, Belldegrun AS (2008) Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival. Cancer 113:1641–1648CrossRefPubMed
7.
go back to reference Grüllich C, Vallet S, Hecht C, Duensing S, Hadaschik B, Jager D, Hohenfellner M, Pahernik S (2015) Local salvage therapy for late (≥2 years) metastatic and local relapse of renal cell cancer is a potentially curative treatment irrespective of the site of recurrence. Urol Oncol. doi: 10.1016/j.urolonc.2015.11.022 Grüllich C, Vallet S, Hecht C, Duensing S, Hadaschik B, Jager D, Hohenfellner M, Pahernik S (2015) Local salvage therapy for late (≥2 years) metastatic and local relapse of renal cell cancer is a potentially curative treatment irrespective of the site of recurrence. Urol Oncol. doi: 10.​1016/​j.​urolonc.​2015.​11.​022
8.
go back to reference Remon J, Lianes P, Martinez S (2012) Brain metastases from renal cell carcinoma. Should we change the current standard? Cancer Treat Rev 38:249–257CrossRefPubMed Remon J, Lianes P, Martinez S (2012) Brain metastases from renal cell carcinoma. Should we change the current standard? Cancer Treat Rev 38:249–257CrossRefPubMed
10.
go back to reference Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134CrossRefPubMed Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134CrossRefPubMed
11.
go back to reference Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111CrossRefPubMed Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111CrossRefPubMed
12.
go back to reference Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281CrossRefPubMed Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281CrossRefPubMed
13.
go back to reference Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456CrossRefPubMed Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456CrossRefPubMed
14.
go back to reference Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124CrossRefPubMed Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124CrossRefPubMed
15.
go back to reference Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG et al (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378:1931–1939CrossRefPubMed Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG et al (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378:1931–1939CrossRefPubMed
16.
go back to reference Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068CrossRefPubMed Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068CrossRefPubMed
17.
go back to reference Vallet S, Pahernik S, Hofner T, Tosev G, Hadaschik B, Duensing S, Sedlaczek O, Hohenfellner M, Jager D, Grüllich C, Renal Cancer Center at the National Center for Tumor Diseases (2015) Efficacy of targeted treatment beyond third-line therapy in metastatic kidney cancer: retrospective analysis from a large-volume cancer center. Clin Genitourin Cancer 13:e145–e152CrossRefPubMed Vallet S, Pahernik S, Hofner T, Tosev G, Hadaschik B, Duensing S, Sedlaczek O, Hohenfellner M, Jager D, Grüllich C, Renal Cancer Center at the National Center for Tumor Diseases (2015) Efficacy of targeted treatment beyond third-line therapy in metastatic kidney cancer: retrospective analysis from a large-volume cancer center. Clin Genitourin Cancer 13:e145–e152CrossRefPubMed
18.
go back to reference Gore ME, Hariharan S, Porta C, Bracarda S, Hawkins R, Bjarnason GA, Oudard S, Lee SH, Carteni G, Nieto A et al (2011) Sunitinib in metastatic renal cell carcinoma patients with brain metastases. Cancer 117:501–509CrossRefPubMed Gore ME, Hariharan S, Porta C, Bracarda S, Hawkins R, Bjarnason GA, Oudard S, Lee SH, Carteni G, Nieto A et al (2011) Sunitinib in metastatic renal cell carcinoma patients with brain metastases. Cancer 117:501–509CrossRefPubMed
19.
go back to reference Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J et al (2010) Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 116:1272–1280CrossRefPubMed Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr, Hainsworth JD, Henderson CA, George JR, Hajdenberg J et al (2010) Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 116:1272–1280CrossRefPubMed
20.
go back to reference Kusuda Y, Miyake H, Terakawa T, Furukawa J, Muramaki M, Fujisawa M (2011) Treatment of brain metastases from renal cell carcinoma with sunitinib and radiotherapy: our experience and review of the literature. Int J Urol 18:326–329CrossRefPubMed Kusuda Y, Miyake H, Terakawa T, Furukawa J, Muramaki M, Fujisawa M (2011) Treatment of brain metastases from renal cell carcinoma with sunitinib and radiotherapy: our experience and review of the literature. Int J Urol 18:326–329CrossRefPubMed
21.
go back to reference Lim ZD, Mahajan A, Weinberg J, Tannir NM (2013) Outcome of patients with renal cell carcinoma metastatic to the brain treated with sunitinib without local therapy. Am J Clin Oncol Cancer Clin Trials 36:258–260CrossRef Lim ZD, Mahajan A, Weinberg J, Tannir NM (2013) Outcome of patients with renal cell carcinoma metastatic to the brain treated with sunitinib without local therapy. Am J Clin Oncol Cancer Clin Trials 36:258–260CrossRef
22.
go back to reference Verma J, Jonasch E, Allen P, Tannir N, Mahajan A (2011) Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. Cancer 117:4958–4965CrossRefPubMedPubMedCentral Verma J, Jonasch E, Allen P, Tannir N, Mahajan A (2011) Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. Cancer 117:4958–4965CrossRefPubMedPubMedCentral
23.
go back to reference Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37: 745–751CrossRefPubMed Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37: 745–751CrossRefPubMed
24.
go back to reference Bastos DA, Molina AM, Hatzoglou V, Jia X, Velasco S, Patil S, Voss MH, Feldman DR, Motzer RJ (2015) Safety and efficacy of targeted therapy for renal cell carcinoma with brain metastasis. Clin Genitourin Cancer 13:59–66CrossRefPubMed Bastos DA, Molina AM, Hatzoglou V, Jia X, Velasco S, Patil S, Voss MH, Feldman DR, Motzer RJ (2015) Safety and efficacy of targeted therapy for renal cell carcinoma with brain metastasis. Clin Genitourin Cancer 13:59–66CrossRefPubMed
25.
go back to reference Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590CrossRefPubMedPubMedCentral Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590CrossRefPubMedPubMedCentral
26.
go back to reference Verma J, Jonasch E, Allen PK, Weinberg JS, Tannir N, Chang EL, Mahajan A (2013) The impact of tyrosine kinase inhibitors on the multimodality treatment of brain metastases from renal cell carcinoma. Am J Clin Oncol 36:620–624CrossRefPubMedPubMedCentral Verma J, Jonasch E, Allen PK, Weinberg JS, Tannir N, Chang EL, Mahajan A (2013) The impact of tyrosine kinase inhibitors on the multimodality treatment of brain metastases from renal cell carcinoma. Am J Clin Oncol 36:620–624CrossRefPubMedPubMedCentral
27.
go back to reference Patil S, Figlin RA, Hutson TE, Michaelson MD, Negrier S, Kim ST, Huang X, Motzer RJ (2011) Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol 22:295–300CrossRefPubMed Patil S, Figlin RA, Hutson TE, Michaelson MD, Negrier S, Kim ST, Huang X, Motzer RJ (2011) Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol 22:295–300CrossRefPubMed
28.
go back to reference Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799CrossRefPubMed Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799CrossRefPubMed
29.
go back to reference Lin J, Jandial R, Nesbit A, Badie B, Chen MK (2015) Current and emerging treatments for brain metastases. Oncol New York 29:250–257 Lin J, Jandial R, Nesbit A, Badie B, Chen MK (2015) Current and emerging treatments for brain metastases. Oncol New York 29:250–257
30.
go back to reference Cannady SB, Cavanaugh KA, Lee SY, Bukowski RM, Olencki TE, Stevens GH, Barnett GH, Suh JH (2004) Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study. Int J Radiat Oncol Biol Phys 58:253–258CrossRefPubMed Cannady SB, Cavanaugh KA, Lee SY, Bukowski RM, Olencki TE, Stevens GH, Barnett GH, Suh JH (2004) Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study. Int J Radiat Oncol Biol Phys 58:253–258CrossRefPubMed
Metadata
Title
Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma
Authors
YueJun Du
Sascha Pahernik
Boris Hadaschik
Dogu Teber
Stephan Duensing
Dirk Jäger
Markus Hohenfellner
Carsten Grüllich
Publication date
01-10-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-016-2238-2

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