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Stereotactic body radiotherapy and tyrosine kinase inhibitors in patients with oligometastatic renal cell carcinoma: a multi-institutional study

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Abstract

Purpose

Few studies have determined the viability of stereotactic body radiotherapy (SBRT) and tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell carcinoma (mRCC). We examined the results of RCC patients who had five or fewer lesions and were treated with TKI and SBRT.

Methods

The clinical data of 42 patients with 96 metastases treated between 2011 and 2020 were retrospectively evaluated. The prognostic factors predicting overall survival (OS) and progression-free survival (PFS) were assessed in uni- and multivariable analyses.

Results

Median follow-up and time between TKI therapy and SBRT were 62.3 and 3.7 months, respectively. The 2‑year OS and PFS rates were 58.0% and 51.3%, respectively, and 2‑year local control rate was 94.1% per SBRT-treated lesion. In univariable analysis, the time between TKI therapy and SBRT and treatment response were significant prognostic factors for OS and PFS. In multivariable analysis, a time between TKI therapy and SBRT of less than 3 months and complete response were significant predictors of better OS and PFS. Only 12 patients (28.6%) had a systemic treatment change at a median of 18.2 months after SBRT, mostly in patients with a non-complete treatment response after this therapy. Two patients (4.8%) experienced grade III toxicity, and all side effects observed during metastasis-directed therapy subsided over time.

Conclusion

We demonstrated that SBRT in combination with TKIs is an effective and safe treatment option for RCC patients with ≤ 5 metastases. However, distant metastasis was observed in 60% of the patients, indicating that distant disease control still has room for improvement.

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References

  1. Motzer RJ, Jonasch E, Agarwal N et al (2014) Kidney cancer, version 2.2014. J Natl Compr Canc Netw 12(2):175–182. https://doi.org/10.6004/jnccn.2014.0018

    Article  CAS  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551

    Article  PubMed  Google Scholar 

  3. Wood SL, Brown JE (2012) Skeletal metastasis in renal cell carcinoma: current and future management options. Cancer Treat Rev 38(4):284–291. https://doi.org/10.1016/j.ctrv.2011.06.011

    Article  PubMed  Google Scholar 

  4. Motzer RJ, Rini BI, McDermott DF et al (2019) Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol 20(10):1370–1385. https://doi.org/10.1016/S1470-2045(19)30413-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Motzer RJ, Tannir NM, McDermott DF et al (2018) Nivolumab plus Ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378(14):1277–1290. https://doi.org/10.1056/NEJMoa1712126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rini BI, Plimack ER, Stus V et al (2019) Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380(12):1116–1127. https://doi.org/10.1056/NEJMoa1816714

    Article  CAS  PubMed  Google Scholar 

  7. Dabestani S, Marconi L, Hofmann F et al (2014) Local treatments for metastases of renal cell carcinoma: a systematic review. Lancet Oncol 15(12):e549–561. https://doi.org/10.1016/S1470-2045(14)70235-9

    Article  PubMed  Google Scholar 

  8. Meyer CP, Sun M, Karam JA et al (2017) Complications after metastasectomy for renal cell carcinoma—a population-based assessment. Eur Urol 72(2):171–174. https://doi.org/10.1016/j.eururo.2017.03.005

    Article  PubMed  Google Scholar 

  9. Griffioen AW, Mans LA, de Graaf AMA et al (2012) Rapid angiogenesis onset after discontinuation of sunitinib treatment of renal cell carcinoma patients. Clin Cancer Res 18(14):3961–3971. https://doi.org/10.1158/1078-0432.CCR-12-0002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Franzese C, Franceschini D, Di Brina L et al (2019) Role of stereotactic body radiation therapy for the management of oligometastatic renal cell carcinoma. J Urol 201(1):70–75. https://doi.org/10.1016/j.juro.2018.08.049

    Article  PubMed  Google Scholar 

  11. Stenman M, Sinclair G, Paavola P et al (2018) Overall survival after stereotactic radiotherapy or surgical metastasectomy in oligometastatic renal cell carcinoma patients treated at two Swedish centres 2005–2014. Radiother Oncol 127(3):501–506. https://doi.org/10.1016/j.radonc.2018.04.028

    Article  CAS  PubMed  Google Scholar 

  12. Onal C, Hurmuz P, Guler OC et al (2022) The role of stereotactic body radiotherapy in switching systemic therapy for patients with extracranial oligometastatic renal cell carcinoma. Clin Transl Oncol 24(8):1533–1541. https://doi.org/10.1007/s12094-022-02793-z

    Article  PubMed  Google Scholar 

  13. Walsh L, Stanfield JL, Cho LC et al (2006) Efficacy of ablative high-dose-per-fraction radiation for implanted human renal cell cancer in a nude mouse model. Eur Urol 50(4):795–800. https://doi.org/10.1016/j.eururo.2006.03.021 (discussion 800)

    Article  PubMed  Google Scholar 

  14. De Meerleer G, Khoo V, Escudier B et al (2014) Radiotherapy for renal-cell carcinoma. Lancet Oncol 15(4):e170–177. https://doi.org/10.1016/S1470-2045(13)70569-2

    Article  PubMed  Google Scholar 

  15. Kao J, Chen CT, Tong CC et al (2014) Concurrent sunitinib and stereotactic body radiotherapy for patients with oligometastases: final report of a prospective clinical trial. Target Oncol 9(2):145–153. https://doi.org/10.1007/s11523-013-0280-y

    Article  PubMed  Google Scholar 

  16. Cheung P, Patel S, North SA et al (2021) Stereotactic radiotherapy for oligoprogression in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor therapy: a phase 2 prospective multicenter study. Eur Urol 80(6):693–700. https://doi.org/10.1016/j.eururo.2021.07.026

    Article  CAS  PubMed  Google Scholar 

  17. Staehler M, Haseke N, Stadler T et al (2012) Feasibility and effects of high-dose hypofractionated radiation therapy and simultaneous multi-kinase inhibition with sunitinib in progressive metastatic renal cell cancer. Urol Oncol 30(3):290–293. https://doi.org/10.1016/j.urolonc.2010.02.006

    Article  CAS  PubMed  Google Scholar 

  18. He L, Liu Y, Han H et al (2020) Survival outcomes after adding stereotactic body radiotherapy to metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors. Am J Clin Oncol 43(1):58–63. https://doi.org/10.1097/coc.0000000000000622

    Article  PubMed  Google Scholar 

  19. Gebbia V, Girlando A et al (2020) Stereotactic radiotherapy for the treatment of patients with oligo-progressive metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitor: data from the real world. Anticancer Res 40(12):7037–7043. https://doi.org/10.21873/anticanres.14730

    Article  CAS  PubMed  Google Scholar 

  20. Liu Y, Zhang Z, Han H et al (2021) Survival after combining stereotactic body radiation therapy and tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma. Front Oncol 11:607595. https://doi.org/10.3389/fonc.2021.607595

    Article  PubMed  PubMed Central  Google Scholar 

  21. Khan M, Zhao Z, Arooj S et al (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 

  22. Ning S, Trisler K, Wessels BW et al (1997) Radiobiologic studies of radioimmunotherapy and external beam radiotherapy in vitro and in vivo in human renal cell carcinoma xenografts. Cancer 80(12):2519–2528. https://doi.org/10.1002/(sici)1097-0142(19971215)80:12+〈2519::aid-cncr26〉3.3.co;2‑t

    Article  CAS  PubMed  Google Scholar 

  23. Timmerman RD (2008) An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol 18(4):215–222. https://doi.org/10.1016/j.semradonc.2008.04.001

    Article  PubMed  Google Scholar 

  24. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  25. Yu X, Wang B, Li X et al (2015) The significance of metastasectomy in patients with metastatic renal cell carcinoma in the era of targeted therapy. Biomed Res Int 2015:176373. https://doi.org/10.1155/2015/176373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zaorsky NG, Lehrer EJ, Kothari G et al (2019) Stereotactic ablative radiation therapy for oligometastatic renal cell carcinoma (SABR ORCA): a meta-analysis of 28 studies. Eur Urol 2(5):515–523. https://doi.org/10.1016/j.euo.2019.05.007

    Article  Google Scholar 

  27. Rini BI, Battle D, Figlin RA et al (2019) The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC). J Immunother Cancer 7(1):354. https://doi.org/10.1186/s40425-019-0813-8

    Article  PubMed  PubMed Central  Google Scholar 

  28. Onal C, Guler OC, Hurmuz P et al (2022) Bone-only oligometastatic renal cell carcinoma patients treated with stereotactic body radiotherapy: a multi-institutional study. Strahlenther Onkol. https://doi.org/10.1007/s00066-022-01962-x

    Article  PubMed  Google Scholar 

  29. Kroeze SG, Fritz C, Hoyer M et al (2017) Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev 53:25–37. https://doi.org/10.1016/j.ctrv.2016.11.013

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Adana Dr. Turgut Noyan Research and Treatment Center, Baskent University Faculty of Medicine, 01120, Adana, Turkey

    Cem Onal & Ozan Cem Guler

  2. Division of Radiation Oncology, Iskenderun Gelisim Hospital, Hatay, Turkey

    Cem Onal & Ezgi Oymak

  3. Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Burak Tilki, Pervin Hurmuz & Gokhan Ozyigit

  4. Department of Radiation Oncology, Baskent University Faculty of Medicine, Ankara, Turkey

    Cem Onal, Guler Yavas & Cagdas Yavas

Authors
  1. Cem Onal
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  2. Ezgi Oymak
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Correspondence to Cem Onal.

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Conflict of interest

C. Onal, E. Oymak, O.C. Guler, B. Tilki, G. Yavas, P. Hurmuz, C. Yavas, and G. Ozyigit declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Baskent University Institutional Review Board (project no: KA22/313) and supported by the Baskent University Research Fund.

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Onal, C., Oymak, E., Guler, O.C. et al. Stereotactic body radiotherapy and tyrosine kinase inhibitors in patients with oligometastatic renal cell carcinoma: a multi-institutional study. Strahlenther Onkol 199, 456–464 (2023). https://doi.org/10.1007/s00066-022-02026-w

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