Synchronous brain metastases as a poor prognosis factor in clear cell renal carcinoma: a strong argument for systematic brain screening

Abstract

Purpose

Brain metastases (BM) usually represent a poor prognostic factor in solid tumors. About 10% of patients with renal cancer (RCC) will present BM. Local therapies such as stereotactic radiotherapy (SRT), whole brain radiotherapy (WBRT), and surgery are used to achieve brain control. We compared survival between patients with synchronous BM (SynBM group) and metachronous BM (MetaBM group).

Methods

It is a retrospective study of patients with clear cell renal cell carcinoma (ccRCC) and BM treated with TKI between 2005 and 2019 at the Centre Léon Bérard in Lyon. We collected prognostic factors: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the TNM stage, the histological subtypes and the Fuhrman grade. Overall survival (OS) was defined from diagnosis of metastatic ccRCC to death. Brain progression-free survival (B-PFS) was defined from focal brain therapy to brain progression or death.

Results

99 patients were analyzed, 44 in the SynBM group and 55 in the MetaBM group. OS in the MetaBM group was 49.4 months versus 19.6 months in the SynBM group, p = 0.0002. The median time from diagnosis of metastasic disease to apparition of BM in the MetaBM group was 22.9 months (4.3; 125.7). SRT was used for 101 lesions (66.4%), WBRT for 25 patients (16.4%), surgery for 21 lesions (13.8%), surgery followed by radiation for 5 lesions (3.3%). B-PFS for all patients was 7 months (IC95% [5.0–10.5]).

Conclusions

Survival of patients with synchronous BM is inferior to that of patients with metachronous BM. Outcome is poor in both cases after diagnosis of BM. Brain screening should be encouraged at time of diagnosis of metastatis in ccRCC.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. 1.

    Cagney DN et al (2017) Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro-Oncol 19(11):1511–1521. https://doi.org/10.1093/neuonc/nox077

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Soffietti R et al (2013) A european organisation for research and treatment of cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 31(1):65–72. https://doi.org/10.1200/JCO.2011.41.0639

    Article  PubMed  Google Scholar 

  3. 3.

    Muldoon LL et al (2007) Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol 25(16):2295–2305. https://doi.org/10.1200/JCO.2006.09.9861

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Lesueur P et al (2018) Radiosurgery or hypofractionated stereotactic radiotherapy for brain metastases from radioresistant primaries (melanoma and renal cancer). Radiat Oncol 13(1):138. https://doi.org/10.1186/s13014-018-1083-1

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Soffietti R et al (2017) Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO). Neuro-Oncol 19(2):162–174. https://doi.org/10.1093/neuonc/now241

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Kumar AMS et al (2018) Postoperative hypofractionated stereotactic brain radiation (HSRT) for resected brain metastases: improved local control with higher BED10. J Neurooncol 139(2):449–454. https://doi.org/10.1007/s11060-018-2885-6

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Mahajan A et al (2017) Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 18(8):1040–1048. https://doi.org/10.1016/S1470-2045(17)30414-X

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Brown PD et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316(4):401. https://doi.org/10.1001/jama.2016.9839

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Niranjan A, Monaco E, Flickinger J, Lunsford LD (2019) Guidelines for multiple brain metastases radiosurgery. In: A. Niranjan, L. D. Lunsford, and H. Kano, Eds. S. Karger AG, Progress in Neurological Surgery, vol. 34, pp. 100–109

  10. 10.

    Bianchi M et al (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23(4):973–980. https://doi.org/10.1093/annonc/mdr362

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Chandrasekar T, Klaassen Z, Goldberg H, Kulkarni GS, Hamilton RJ, Fleshner NE (2017) Metastatic renal cell carcinoma: Patterns and predictors of metastases—A contemporary population-based series. Urol Oncol Semin Orig Investig 35(11):661.e7-661.e14. https://doi.org/10.1016/j.urolonc.2017.06.060

    Article  Google Scholar 

  12. 12.

    Decker DA, Decker VL, Herskovic A, Cummings GD (1984) Brain metastases in patients with renal cell carcinoma: prognosis and treatment. J Clin Oncol 2(3):169–173. https://doi.org/10.1200/JCO.1984.2.3.169

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Bennani O et al (2014) Brain metastasis from renal cell carcinoma. Neurochirurgie 60(1–2):12–16. https://doi.org/10.1016/j.neuchi.2013.12.001

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Dudek AZ et al (2013) Brain metastases from renal cell carcinoma in the era of tyrosine kinase inhibitors. Clin Genitourin Cancer 11(2):155–160. https://doi.org/10.1016/j.clgc.2012.11.001

    Article  PubMed  Google Scholar 

  15. 15.

    Choi SY et al (2017) Prognostic factors for survival of patients with synchronous or metachronous brain metastasis of renal cell carcinoma. Clin Genitourin Cancer 15(6):717–723. https://doi.org/10.1016/j.clgc.2017.05.010

    Article  PubMed  Google Scholar 

  16. 16.

    Khan M, Zhao Z, Arooj S, Liao G (2020) Impact of Tyrosine Kinase Inhibitors (TKIs) combined with radiation therapy for the management of brain metastases from renal cell carcinoma. Front Oncol 10:1246. https://doi.org/10.3389/fonc.2020.01246

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Sperduto PW et al (2020) Survival in patients with brain metastases: summary report on the updated diagnosis-specific graded prognostic assessment and definition of the eligibility quotient. J Clin Oncol. https://doi.org/10.1200/JCO.20.01255

    Article  PubMed  Google Scholar 

  18. 18.

    Yamamoto M et al (2014) Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15(4):387–395. https://doi.org/10.1016/S1470-2045(14)70061-0

    Article  PubMed  Google Scholar 

  19. 19.

    Wolf A et al (2018) Toward the complete control of brain metastases using surveillance screening and stereotactic radiosurgery. J Neurosurg 128(1):23–31. https://doi.org/10.3171/2016.10.JNS161036

    Article  PubMed  Google Scholar 

  20. 20.

    Massard C, Zonierek J, Gross-Goupil M, Fizazi K, Szczylik C, Escudier B (2010) Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann Oncol 21(5):1027–1031. https://doi.org/10.1093/annonc/mdp411

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    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: TKIs and Brain Metastasis in mRCC. Cancer 117(21):4958–4965. https://doi.org/10.1002/cncr.26138

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Gore ME et al (2011) Sunitinib in metastatic renal cell carcinoma patients with brain metastases. Cancer 117(3):501–509. https://doi.org/10.1002/cncr.25452

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    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 36(3):258–260. https://doi.org/10.1097/COC.0b013e3182467b9a

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Négrier S et al (2018) Activity of cabozantinib in radioresistant brain metastases from renal cell carcinoma: two case reports. J Med Case Reports 12(1):351. https://doi.org/10.1186/s13256-018-1875-9

    Article  Google Scholar 

  25. 25.

    Peverelli G et al (2019) Cabozantinib in renal cell carcinoma with brain metastases: safety and efficacy in a real-world population. Clin Genitourin Cancer 17(4):291–298. https://doi.org/10.1016/j.clgc.2019.05.002

    Article  PubMed  Google Scholar 

  26. 26.

    Chevreau C et al (2014) A phase II trial of sunitinib in patients with renal cell cancer and untreated brain metastases. Clin Genitourin Cancer 12(1):50–54. https://doi.org/10.1016/j.clgc.2013.09.008

    Article  PubMed  Google Scholar 

  27. 27.

    Derosa L et al (2017) Inter and intra-tumor heterogeneity of PD-L1 and MET expression in metastatic renal cell carcinoma (mRCC). J Clin Oncol 35(Suppl_15):4569–4569. https://doi.org/10.1200/JCO.2017.35.15_suppl.4569

    Article  Google Scholar 

  28. 28.

    Flippot R et al (2019) Safety and efficacy of nivolumab in brain metastases from renal cell carcinoma: results of the GETUG-AFU 26 NIVOREN multicenter phase II study. J Clin Oncol 37(23):2008–2016. https://doi.org/10.1200/JCO.18.02218

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Tawbi HA et al (2018) Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med 379(8):722–730. https://doi.org/10.1056/NEJMoa1805453

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Emamekhoo H et al (2019) Safety and efficacy of nivolumab plus ipilimumab (NIVO+IPI) in patients with advanced renal cell carcinoma (aRCC) with brain metastases: Interim analysis of CheckMate 920. J Clin Oncol 37(15_suppl):4517–4517. https://doi.org/10.1200/JCO.2019.37.15_suppl.4517

    Article  Google Scholar 

Download references

Funding

Aude Fléchon:- Honoraria and personal fees from BMS, IPSEN, ROCHE, PFIZER, MSD. Sylvie Négrier:—research grant, personal fees and non-financial support from PFIZER,—personal fees and non-financial support from BMS,—research grant, personal fees and non-financial support from IPSEN,—personal fees from NOVARTIS,—personal fees and non-financial support from MSD. Helen Boyle:—Travel expenses from BMS, Pfizer, Janssen, Astellas, Sanofi, Ipsen—Honoraria from Sanofi, Novartis, Janssen, Ipsen, Pfizer. Eve-Marie Neidhart:—Honoraria and personal fees from NOVARTIS, BMS, MSD. Other authors have no financial disclosure.

Author information

Affiliations

Authors

Contributions

Conception and design: VR, AF. Acquisition of data: VR, MC, GM, MPS, RT, HB, EMN, EJ, AF, SN. Analysis and interpretation of data: VR, AF. Drafting of the manuscript: VR, AF, SN, SR. Stastistical analysis: CS, VR. Supervision: AF, SN.

Corresponding author

Correspondence to Valentine Ruste.

Ethics declarations

Ethical approval

The authors did not receive support from any organization for the submitted work.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ruste, V., Sunyach, M.P., Tanguy, R. et al. Synchronous brain metastases as a poor prognosis factor in clear cell renal carcinoma: a strong argument for systematic brain screening. J Neurooncol 153, 133–141 (2021). https://doi.org/10.1007/s11060-021-03751-5

Download citation

Keywords

  • Clear cell renal cell carcinoma
  • Metastatic
  • Synchronous brain metastases
  • Stereotactic radiation
  • Cabozantinib
  • Immunotherapy