Denosumab combined with radiotherapy as an alternative to surgery for advanced metastatic bone lesions and pathologic fractures: a retrospective case study of 38 patients
DOI:
https://doi.org/10.2340/1651-226X.2024.40977Keywords:
Denosumab, radiotherapy, pathologic fracture, impending fracture, metastatic bone lesion, bone metastases, non-surgical treatmentAbstract
Background and purpose: Pathologic and impending fractures occur in patients with advanced metastatic disease and necessitate surgical interventions with high risk of complications. The aim of this study was to analyze the efficacy of combined treatment with denosumab and radiotherapy as an alternative to surgery in treating bone metastases of the pelvis and extremities.
Methods: This retrospective cohort study included 38 patients with impending and pathologic fractures due to carcinoma metastases who received monthly injections of denosumab (120 mg/dose) and radiotherapy. Twenty-three patients received denosumab and single-dose radiotherapy of 8 Gy, and 15 patients received denosumab and fractionated radiotherapy. We assessed pain, radiographic signs of fracture healing, survival and complications.
Results: Of the 38 patients 36 experienced pain reduction. Callus formation was observed in 11/17 patients with pathologic fractures, and increased mineralization was found in 12/21 patients with impending fractures. In 23/38 patients, we found both pain reduction and callus formation or increased mineralization. There were no statistically significant differences in treatment outcomes between the patients who received denosumab and single-dose radiotherapy and those who received denosumab and fractionated radiotherapy. The survival rates at 30 days and 1 year were 95% and 56%, respectively.
Interpretation: Combined treatment with denosumab and radiotherapy may reduce pain and promote bone healing in patients with metastatic impending and pathologic fractures. In this combined treatment, the effect of single-dose radiotherapy appears to be comparable to that of fractionated regimens
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Van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007 Sep;18(9):1437–49.
https://doi.org/10.1093/annonc/mdm056 DOI: https://doi.org/10.1093/annonc/mdm056
Vieira C, Fragoso M, Pereira D, Medeiros R. Pain prevalence and treatment in patients with metastatic bone disease. Oncol Lett. 2019 Mar;17(3):3362–70.
https://doi.org/10.3892/ol.2019.10013 DOI: https://doi.org/10.3892/ol.2019.10013
Coleman R, Hadji P, Body JJ, Santini D, Chow E, Terpos E, et al. Bone health in cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2020 Dec;31(12):1650–63.
https://doi.org/10.1016/j.annonc.2020.07.019 DOI: https://doi.org/10.1016/j.annonc.2020.07.019
Willeumier JJ, van der Linden YM, van de Sande MAJ, Dijkstra PDS. Treatment of patholog-ical fractures of the long bones. EFORT Open Rev. 2017 Mar 13;1(5):136–45.
https://doi.org/10.1302/2058-5241.1.000008 DOI: https://doi.org/10.1302/2058-5241.1.000008
Raschka T, Weiss S, Reiter A, Barg A, Schlickewei C, Frosch KH, et al. Outcomes and prog-nostic factors after surgery for bone metastases in the extremities and pel-vis: a retrospective analysis of 140 patients. J Bone Oncol. 2022 Apr 6;34:100427.
https://doi.org/10.1016/j.jbo.2022.100427
Tsuda Y, Yasunaga H, Horiguchi H, Fushimi K, Kawano H, Tanaka S. Complications and postoperative mortality rate after surgery for pathological femur fracture re-lated to bone metastasis: analysis of a nationwide database. Ann Surg On-col. 2016 Mar;23(3):801–10.
https://doi.org/10.1245/s10434-015-4881-9 DOI: https://doi.org/10.1245/s10434-015-4881-9
Westendorf JJ, Kahler RA, Schroeder TM. Wnt signaling in osteoblasts and bone diseas-es. Gene. 2004;341:19–39.
https://doi.org/10.1016/j.gene.2004.06.044 DOI: https://doi.org/10.1016/j.gene.2004.06.044
Maurizi A, Rucci N. The osteoclast in bone metastasis: player and target. Cancers (Basel). 2018 Jun 27;10(7):218.
https://doi.org/10.3390/cancers10070218 DOI: https://doi.org/10.3390/cancers10070218
Miller PD. Denosumab: anti-RANKL antibody. Curr Osteoporos Rep. 2009 Mar;7(1):18–22.
https://doi.org/10.1007/s11914-009-0004-5 DOI: https://doi.org/10.1007/s11914-009-0004-5
Zheng GZ, Chang B, Lin FX, Xie D, Hu QX, Yu GY, et al. Meta-analysis comparing denosum-ab and zoledronic acid for treatment of bone metastases in patients with advanced solid tumours. Eur J Cancer Care (Engl). 2017;26(6).
https://doi.org/10.1111/ecc.12541 DOI: https://doi.org/10.1111/ecc.12541
Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomized, double-blind study. Lancet. 2011 Mar 5;377(9768):813–22.
https://doi.org/10.1016/S0140-6736(10)62344-6 DOI: https://doi.org/10.1016/S0140-6736(10)62344-6
Groenen KHJ, Pouw MH, Hannink G, Hosman AJF, Yvette MVDL, Verdonschot N, et al. The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. A systemat-ic review. Radiother Oncol, 2016 May;119(2):194–201.
https://doi.org/10.1016/j.radonc.2016.03.001 DOI: https://doi.org/10.1016/j.radonc.2016.03.001
Tanaka H, Makita C, Manabe Y, Kajima M, Matsuyama K, Matsuo M. Radiation therapy combined with bone-modifying agents ameliorates local control of osteo-lytic bone metastases in breast cancer. J Radiat Res. 2020 May 22;61(3):494–8.
https://doi.org/10.1093/jrr/rraa020 DOI: https://doi.org/10.1093/jrr/rraa020
Harrington KD. Impending pathologic fractures from metastatic malignancy: evaluation and management. Instr Course Lect. 1986;35:357–81.
Ross JR, Saunders Y, Edmonds PM, Patel S, Wonderling D, Normand C, et al. A systematic review of the role of bisphosphonates in metastatic disease. Health Tech-nol Assess. 2004;8(4):1–176.
https://doi.org/10.3310/hta8040 DOI: https://doi.org/10.3310/hta8040
Puljula E, Turhanen P, Vepsäläinen J, Monteil M, Lecouvey M, Weisell J. Structural require-ments for bisphosphonate binding on hydroxyapatite: NMR study of bisphosphonate partial esters. ACS Med Chem Lett. 2015 Feb 21;6(4):397–401.
https://doi.org/10.1021/ml5004603 DOI: https://doi.org/10.1021/ml5004603
Hanley DA, Adachi JD, Bell A, Brown V. Denosumab: mechanism of action and clinical outcomes. Int J Clin Pract. 2012 Dec;66(12):1139–46.
https://doi.org/10.1111/ijcp.12022 DOI: https://doi.org/10.1111/ijcp.12022
Berenson JR, Rajdev L, Broder M. Pathophysiology of bone metastases. Cancer Biol Ther. 2006 Sep;5(9):1078–81.
https://doi.org/10.4161/cbt.5.9.3306 DOI: https://doi.org/10.4161/cbt.5.9.3306
Sarahrudi K, Hora K, Heinz T, Millington S, Vécsei V. Treatment results of pathological frac-tures of the long bones: a retrospective analysis of 88 patients. Int Orthop. 2006 Dec;30(6):519–24.
https://doi.org/10.1007/s00264-006-0205-9 DOI: https://doi.org/10.1007/s00264-006-0205-9
Hill T, D’Alessandro P, Murray K, Yates P. Prognostic factors following pathological 337 fractures. ANZ J Surg. 2015 Mar;85(3):159–63.
https://doi.org/10.1111/ans.12830 DOI: https://doi.org/10.1111/ans.12830
Raschka T, Weiss S, Reiter A, Barg A, Schlickewei C, Frosch KH, et al. Outcomes and prog-nostic factors after surgery for bone metastases in the extremities and pel-vis: a retrospective analysis of 140 patients. J Bone Oncol. 2022 Apr 6;34:100427.
https://doi.org/10.1016/j.jbo.2022.100427 DOI: https://doi.org/10.1016/j.jbo.2022.100427
Weiss RJ, Forsberg JA, Wedin R. Surgery of skeletal metastases in 306 patients with pros-tate cancer. Acta Orthop. 2012 Feb;83(1):74–9.
https://doi.org/10.3109/17453674.2011.645197 DOI: https://doi.org/10.3109/17453674.2011.645197
Ehrenstein V, Heide-Jørgensen U, Schiødt M, Akre O, Herlofson BB, Hansen S, et al. Oste-onecrosis of the jaw among patients with cancer treated with denosumab or zoledronic acid: results of a regulator-mandated cohort postauthoriza-tion safety study in Denmark, Norway, and Sweden. Cancer. 2021 Nov 1;127(21):4050–8.
https://doi.org/10.1002/cncr.33802 DOI: https://doi.org/10.1002/cncr.33802
Groot OQ, Ogink PT, Janssen SJ, Paulino Pereira NR, Lozano-Calderon S, Raskin K, et al. High risk of venous thromboembolism after surgery for long bone metas-tases: a retrospective study of 682 patients. Clin Orthop Relat Res. 2018 Oct;476(10):2052–61.
https://doi.org/10.1097/CORR.0000000000000463 DOI: https://doi.org/10.1097/CORR.0000000000000463
van der Linden YM, Lok JJ, Steenland E, Martijn H, van Houwelingen H, Marijnen CA, et al. Dutch Bone Metastasis Study Group. Single fraction radiotherapy is effica-cious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):528–37.
https://doi.org/10.1016/j.ijrobp.2003.10.006 DOI: https://doi.org/10.1016/j.ijrobp.2003.10.006
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