Predictive Factors and the Role of Conventionally Fractionated Radiation Therapy for Bone Metastasis from Renal Cell Carcinoma in the Era of Targeted Therapy

Overview

Journal Medicina (Kaunas)

Publisher MDPI

Specialty General Medicine

Date 2024 Jul 27

PMID 39064478

Authors

Hye Jin Kang

Myungsoo Kim

Yoo-Kang Kwak

So Jung Lee

Affiliations

Soon will be listed here.

Abstract

: Despite rapid advances in targeted therapies for renal cell carcinoma (RCC), bone metastases remain a major problem that significantly increases morbidity and reduces patients' quality of life. Conventional fractionated radiotherapy (CF-RT) is known to be an important local treatment option for bone metastases; however, bone metastases from RCC have traditionally been considered resistant to CF-RT. We aimed to investigate the effectiveness of CF-RT for symptomatic bone metastasis from RCC and identify the predictive factors associated with treatment outcomes in the targeted therapy era. : Between January 2011 and December 2023, a total of 73 lesions in 50 patients treated with a palliative course of CF-RT for symptomatic bone metastasis from RCC were evaluated, and 62 lesions in 41 patients were included in this study. Forty-five lesions (72.6%) were treated using targeted therapy during CF-RT. The most common radiation dose fractionations were 30 gray (Gy) in 10 fractions (50%) and 39 Gy in 13 fractions (16.1%). : Pain relief was experienced in 51 of 62 lesions (82.3%), and the 12-month local control (LC) rate was 61.2%. Notably, 72.6% of the treatment course in this study was combined with targeted therapy. The 12-month LC rate was 74.8% in patients who received targeted therapy and only 10.9% in patients without targeted therapy ( < 0.001). Favorable Eastern Cooperative Oncology Group performance status ( = 0.026) and pain response ( < 0.001) were independent predictors of improved LC. Radiation dose escalation improved the LC in radiosensitive patients. A consistent treatment response was confirmed in patients with multiple treatment courses. : CF-RT enhances pain relief and LC when combined with targeted therapy. Patients who responded well to initial treatment generally showed consistent responses to subsequent CF-RT for additional painful bone lesions. CF-RT could therefore be an excellent complementary local treatment modality for targeted therapy.

References

Motzer R, Escudier B, Mcdermott D, George S, Hammers H, Srinivas S . Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1803-13. PMC: 5719487. DOI: 10.1056/NEJMoa1510665. View

Chow E, van der Linden Y, Roos D, Hartsell W, Hoskin P, Wu J . Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol. 2013; 15(2):164-71. DOI: 10.1016/S1470-2045(13)70556-4. View

Ryu S, Deshmukh S, Timmerman R, Movsas B, Gerszten P, Yin F . Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial. JAMA Oncol. 2023; 9(6):800-807. PMC: 10119775. DOI: 10.1001/jamaoncol.2023.0356. View

Guo Q, Zhang C, Guo X, Tao F, Xu Y, Feng G . Incidence of bone metastasis and factors contributing to its development and prognosis in newly diagnosed renal cell carcinoma: a population-based study. Cancer Manag Res. 2018; 10:2935-2944. PMC: 6118275. DOI: 10.2147/CMAR.S170083. View

McKay R, Kroeger N, Xie W, Lee J, Knox J, Bjarnason G . Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. Eur Urol. 2013; 65(3):577-84. PMC: 4123121. DOI: 10.1016/j.eururo.2013.08.012. View

M Van der Velden J, Peters M, Verlaan J, Versteeg A, Zhang L, Tsao M . Development and Internal Validation of a Clinical Risk Score to Predict Pain Response After Palliative Radiation Therapy in Patients With Bone Metastases. Int J Radiat Oncol Biol Phys. 2017; 99(4):859-866. DOI: 10.1016/j.ijrobp.2017.07.029. View

Zolnierek J, Nurzynski P, Langiewicz P, Oborska S, Wasko-Grabowska A, Kuszatal E . Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases. J Cancer Res Clin Oncol. 2009; 136(3):371-8. DOI: 10.1007/s00432-009-0664-7. View

Wilson D, Hiller L, Gray L, Grainger M, Stirling A, James N . The effect of biological effective dose on time to symptom progression in metastatic renal cell carcinoma. Clin Oncol (R Coll Radiol). 2003; 15(7):400-7. DOI: 10.1016/s0936-6555(03)00164-x. View

Ansari J, Farrag A, Ali A, Abdelgelil M, Murshid E, ALHamad A . Concurrent use of nivolumab and radiotherapy for patients with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab. Mol Clin Oncol. 2021; 15(4):214. PMC: 8408674. DOI: 10.3892/mco.2021.2376. View

10.

Tsukamoto S, Kido A, Tanaka Y, Facchini G, Peta G, Rossi G . Current Overview of Treatment for Metastatic Bone Disease. Curr Oncol. 2021; 28(5):3347-3372. PMC: 8482272. DOI: 10.3390/curroncol28050290. View

11.

Wei Q, He H, Lv L, Xu X, Sun W . The promising role of radiotherapy in the treatment of advanced or metastatic renal cell carcinoma: a narrative review. Transl Androl Urol. 2021; 9(6):2821-2830. PMC: 7807309. DOI: 10.21037/tau-20-1466. View

12.

Motzer R, Escudier B, Bukowski R, Rini B, Hutson T, Barrios C . Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma. Br J Cancer. 2013; 108(12):2470-7. PMC: 3694236. DOI: 10.1038/bjc.2013.236. View

13.

Makita K, Hamamoto Y, Kanzaki H, Nagasaki K, Takata N, Tsuruoka S . Factors affecting local control of bone metastases from radioresistant tumors treated with palliative external beam radiotherapy. Discov Oncol. 2023; 14(1):74. PMC: 10203063. DOI: 10.1007/s12672-023-00651-0. View

14.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

15.

Kalra S, Verma J, Atkinson B, Matin S, Wood C, Karam J . Outcomes of Patients With Metastatic Renal Cell Carcinoma and Bone Metastases in the Targeted Therapy Era. Clin Genitourin Cancer. 2017; 15(3):363-370. DOI: 10.1016/j.clgc.2017.01.010. View

16.

Zekri J, Ahmed N, Coleman R, Hancock B . The skeletal metastatic complications of renal cell carcinoma. Int J Oncol. 2001; 19(2):379-82. DOI: 10.3892/ijo.19.2.379. View

17.

Ganju R, TenNapel M, Mahan N, Zahra A, Shen X . The Efficacy of Conventionally Fractionated Radiation in the Management of Osseous Metastases from Metastatic Renal Cell Carcinoma. J Oncol. 2018; 2018:6384253. PMC: 5818960. DOI: 10.1155/2018/6384253. View

18.

Lee C, Tey J, Cheo T, Lee C, Wong A, Kumar N . Outcomes of patients with spinal metastases from renal cell carcinoma treated with conventionally-fractionated external beam radiation therapy. Medicine (Baltimore). 2020; 99(16):e19838. PMC: 7220059. DOI: 10.1097/MD.0000000000019838. View

19.

Santini D, Procopio G, Porta C, Ibrahim T, Barni S, Mazzara C . Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey. PLoS One. 2014; 8(12):e83026. PMC: 3875424. DOI: 10.1371/journal.pone.0083026. View

20.

Beuselinck B, Oudard S, Rixe O, Wolter P, Blesius A, Ayllon J . Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2010; 22(4):794-800. DOI: 10.1093/annonc/mdq554. View