Turkiye Klinikleri Journal of Medical Sciences

.: REVIEW
The Efficacy and Safety of Denosumab for Treating Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis
Kemiğin Dev Hücreli Tümörünün Tedavisinde Denosumabın Etkililiği ve Güvenliliği: Sistematik Bir Derleme ve Meta-Analiz
Chairul Arby DESIYANTOa, Rady DWIPAYANAb, Rieva ERMAWANc, Iwan SUTANTOd, Astri SOETANTOe, Jonny Karunia FAJARf
aGeneral Practitioner, Sofifi General Hospital, Sofifi, North Maluku, INDONESIA
bConsultant of Orthopaedic Spine, Department of Orthopaedic and Traumatology, Dr. Ramelan Navy Hospital, Surabaya, East Java, INDONESIA
cConsultant of Orthopaedic Spine, Department of Orthopaedic and Traumatology, Sebelas Maret University, Surakarta, Central Java, INDONESIA
dConsultant of Orthopaedic Hand and Microsurgery, Department of Orthopaedic and Traumatology, Dr. Ramelan Navy Hospital, Surabaya, East Java, INDONESIA
eGeneral Practitioner, Ba'a General Hospital, Rote Ndao, East Nusa Tenggara, INDONESIA
fBrawijaya Internal Medicine Research Center, Department of Internal Medicine, Faculty of Medicine, Brawijaya University, Malang, East Java, INDONESIA
Turkiye Klinikleri J Med Sci. 2022;42(1):53-61
doi: 10.5336/medsci.2021-85869
Article Language: EN
Full Text
ABSTRACT
 The adjuvant treatment of denosumab for the management of giant cell tumor of bone (GCTB) has been widely investigated. However, the inconclusive findings were observed. Therefore, our study aimed to assess the efficacy of denosumab for the adjuvant therapy in the management of GCTB. We conducted a meta-analysis study during the period of FebruaryAugust. Article search was conducted in PubMed, ScienceDirect, and Cochrane library. The predictor was denosumab administration, and the outcomes measures were local recurrence, blood loss, Musculoskeletal Tumor Society (MSTS) score, lung metastase, and malignant transformation. Data were analyzed using Z test to evaluate the association. We included 11 papers, consisting of 253 cases and 1,145 controls. The quality of the included article was evaluated using the Newcastle-Ottawa scale (NOS). Our results identified that denosumab administration was associated with lower blood loss and improved MSTS score compared to those without denosumab administration in patients with GCTB. However, GCTB patients with and without denosumab administration shared similar findings in the context of local recurrence, lung metastase, and malignant transformation. Our study has verified that denosumab administration as an adjuvant treatment for the management of GCTB is associated with lower blood loss during surgical procedure and improved MSTS score.

Keywords: Giant cell tumor of bone; denosumab; blood loss; local recurrence; Musculoskeletal Tumor Society score
ÖZET
 Kemiğin dev hücreli tümörünün (KDHT) yönetiminde denosumab ile adjuvan tedavi geniş olarak araştırılmıştır. Fakat birbiriyle uyuşmayan sonuçlar gözlenmiştir. Bu nedenle çalışmamızda KDHT'nin yönetiminde adjuvan tedavi için denosumabın etkinliğinin değerlendirilmesi amaçlanmıştır. Şubat-Ağustos döneminde bir meta-analiz çalışması gerçekleştirdik. PubMed, ScienceDirect ve Cochrane kütüphanesinde makale araştırması yapıldı. Ön gördürücü denosumab uygulaması idi ve sonuç ölçümleri lokal nüks, kan kaybı, Kas-iskelet Tümörleri Derneği (Musculoskeletal Tumor Society -MSTS) skoru, akciğer metastazı ve malign transformasyon idi. Veriler ilişkiyi değerlendirmek için Z testi ile incelendi. Toplam 253 olgu ve 1.145 kontrol içeren 11 yazıyı aldık. Dahil edilen makalenin kalitesi Newcastle-Ottawa ölçeği (NOS) kullanılarak değerlendirildi. Bulgularımız denosumab uygulamasının KDHT olan ve denosumab uygulanmayan hastalar göre daha az kan kaybı ve daha iyi MSTS skoru ile ilişkili olduğunu göstermiştir. Fakat denosumab uygulanan ve uygulanmayan hastalar lokal nüks, akciğer metastazı ve malign transformasyon bakımından benzer sonuçlara sahipti. Çalışmamız KDHT yönetiminde adjuvan tedavi olarak denosumab uygulamasının cerrahi işlem sırasında daha az kan kaybı ile ve daha iyi MSTS skoru ile ilişkili olduğunu doğrulamıştır.

Anahtar Kelimeler: Kemiğin dev hücreli tümörü; denosumab; kan kaybı; lokal nüks; Kas-iskelet Tümörleri Derneği skoru
REFERENCES:
  1. van der Heijden L, Dijkstra PD, van de Sande MA, Kroep JR, Nout RA, van Rijswijk CS, et al. The clinical approach toward giant cell tumor of bone. Oncologist. 2014;19(5):550-61. [Crossref]  [PubMed]  [PMC] 
  2. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69(1):106-14. [Crossref]  [PubMed] 
  3. Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14(9):901-8. [Crossref]  [PubMed] 
  4. Chen Z, Yang Y, Guo W, Yang R, Tang X, Yan T, et al. Therapeutic benefits of neoadjuvant and post-operative denosumab on sacral giant cell tumor: a retrospective cohort study of 30 cases. J BUON. 2018;23(2):453-9. [PubMed] 
  5. Lipplaa A, Dijkstra S, Gelderblom H. Challenges of denosumab in giant cell tumor of bone, and other giant cell-rich tumors of bone. Curr Opin Oncol. 2019;31(4):329-35. [Crossref]  [PubMed]  [PMC] 
  6. Malek F, Krueger P, Hatmi ZN, Malayeri AA, Faezipour H, O'Donnell RJ. Local control of long bone giant cell tumour using curettage, burring and bone grafting without adjuvant therapy. Int Orthop. 2006;30(6):495-8. [Crossref]  [PubMed]  [PMC] 
  7. Hakozaki M, Tajino T, Yamada H, Hasegawa O, Tasaki K, Watanabe K, et al. Radiological and pathological characteristics of giant cell tumor of bone treated with denosumab. Diagn Pathol. 2014;9:111. [Crossref]  [PubMed]  [PMC] 
  8. Verschoor AJ, Bovée JVMG, Mastboom MJL, Sander Dijkstra PD, Van De Sande MAJ, Gelderblom H. Incidence and demographics of giant cell tumor of bone in The Netherlands: First nationwide Pathology Registry Study. Acta Orthop. 2018;89(5):570-4. [Crossref]  [PubMed]  [PMC] 
  9. Tubbs WS, Brown LR, Beabout JW, Rock MG, Unni KK. Benign giant-cell tumor of bone with pulmonary metastases: clinical findings and radiologic appearance of metastases in 13 cases. AJR Am J Roentgenol. 1992;158(2):331-4. [Crossref]  [PubMed] 
  10. Errani C, Tsukamoto S, Leone G, Righi A, Akahane M, Tanaka Y, et al. Denosumab may increase the risk of local recurrence in patients with giant-cell tumor of bone treated with curettage. J Bone Joint Surg Am. 2018;100(6):496-504. [Crossref]  [PubMed] 
  11. Wijsbek AE, Vazquez-Garcia BL, Grimer RJ, Carter SR, Abudu AA, Tillman RM, et al. Giant cell tumour of the proximal femur: Is joint-sparing management ever successful? Bone Joint J. 2014;96-B(1):127-31. [Crossref]  [PubMed] 
  12. Girolami I, Mancini I, Simoni A, Baldi GG, Simi L, Campanacci D, et al. Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. J Clin Pathol. 2016;69(3):240-7. [Crossref]  [PubMed] 
  13. Ueda T, Morioka H, Nishida Y, Kakunaga S, Tsuchiya H, Matsumoto Y, et al. Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial. Ann Oncol. 2015;26(10):2149-54. [Crossref]  [PubMed]  [PMC] 
  14. Arbeitsgemeinschaft Knochentumoren, Becker WT, Dohle J, Bernd L, Braun A, Cserhati M, et al. Local recurrence of giant cell tumor of bone after intralesional treatment with and without adjuvant therapy. J Bone Joint Surg Am. 2008;90(5):1060-7. [Crossref]  [PubMed] 
  15. Vult von Steyern F, Bauer HC, Trovik C, Kivioja A, Bergh P, Holmberg Jörgensen P, et al; Scandinavian Sarcoma Group. Treatment of local recurrences of giant cell tumour in long bones after curettage and cementing. A Scandinavian Sarcoma Group study. J Bone Joint Surg Br. 2006;88(4):531-5. [Crossref]  [PubMed] 
  16. Yang Y, Li Y, Liu W, Xu H, Niu X. A nonrandomized controlled study of sacral giant cell tumors with preoperative treatment of denosumab. Medicine (Baltimore). 2018;97(46):e13139. [Crossref]  [PubMed]  [PMC] 
  17. Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol. 2008;134(9):969-78. [Crossref]  [PubMed] 
  18. Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, et al. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015;22(9):2860-8. [Crossref]  [PubMed]  [PMC] 
  19. Chinder PS, Hindiskere S, Doddarangappa S, Pal U. Evaluation of local recurrence in giant-cell tumor of bone treated by neoadjuvant denosumab. Clin Orthop Surg. 2019;11(3):352-60. [Crossref]  [PubMed]  [PMC] 
  20. Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res. 2011;469(2):591-9. [Crossref]  [PubMed]  [PMC] 
  21. Mak IW, Evaniew N, Popovic S, Tozer R, Ghert M. A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am. 2014;96(15):e127. [Crossref]  [PubMed] 
  22. Mendenhall WM, Zlotecki RA, Scarborough MT, Gibbs CP, Mendenhall NP. Giant cell tumor of bone. Am J Clin Oncol. 2006;29(1):96-9. [Crossref]  [PubMed] 
  23. Luengo-Alonso G, Mellado-Romero M, Shemesh S, Ramos-Pascua L, Pretell-Mazzini J. Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature. Arch Orthop Trauma Surg. 2019;139(10):1339-49. [Crossref]  [PubMed] 
  24. Müller DA, Beltrami G, Scoccianti G, Campanacci DA, Franchi A, Capanna R. Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series. World J Surg Oncol. 2016;14(1):281. [Crossref]  [PubMed]  [PMC] 
  25. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al; AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821-31. [Crossref]  [PubMed] 
  26. Jamshidi K, Gharehdaghi M, Hajialiloo SS, Mirkazemi M, Ghaffarzadehgan K, Izanloo A. Denosumab in patients with giant cell tumor and its recurrence: a systematic review. Arch Bone Jt Surg. 2018;6(4):260-8. [Crossref]  [PubMed]  [PMC] 
  27. Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11(3):275-80. [Crossref]  [PubMed] 
  28. McInnes MDF, Moher D, Thombs BD, McGrath TA, Bossuyt PM; and the PRISMA-DTA Group, Clifford T, Cohen JF, Deeks JJ, Gatsonis C, Hooft L, Hunt HA, et al. Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: The PRISMA-DTA Statement. JAMA. 2018;319(4):388-96. Erratum in: JAMA. 2019;322(20):2026. [Crossref]  [PubMed] 
  29. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-5. [Crossref]  [PubMed] 
  30. Lim CY, Liu X, He F, Liang H, Yang Y, Ji T, et al. Retrospective cohort study of 68 sacral giant cell tumours treated with nerve-sparing surgery and evaluation on therapeutic benefits of denosumab therapy. Bone Joint J. 2020;102-B(2):177-85. [Crossref]  [PubMed] 
  31. Murphy B, Vodanovich D, Spelman T, Gullifer J, Slavin J, Powell G, et al. Clinical, radiological and pathological outcomes following treatment of primary giant cell tumour of bone with Denosumab. ANZ J Surg. 2020;90(12):2553-8. [Crossref]  [PubMed] 
  32. Tsukamoto S, Mavrogenis AF, Leone G, Righi A, Akahane M, Tanzi P, et al. Denosumab does not decrease the risk of lung metastases from bone giant cell tumour. Int Orthop. 2019;43(2):483-9. [Crossref]  [PubMed] 
  33. Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res. 1993;(286):241-6. [Crossref]  [PubMed] 
  34. Sano K, Suehara Y, Okubo T, Sasa K, Kurihara T, Akaike K, et al. Preoperative denosumab treatment with curettage may be a risk factor for recurrence of giant cell tumor of bone. J Orthop Surg (Hong Kong). 2020;28(2):2309499020929786. [Crossref]  [PubMed] 
  35. Scoccianti G, Totti F, Scorianz M, Baldi G, Roselli G, Beltrami G, et al. Preoperative denosumab with curettage and cryotherapy in giant cell tumor of bone: is there an increased risk of local recurrence? Clin Orthop Relat Res. 2018;476(9):1783-90. [Crossref]  [PubMed]  [PMC] 
  36. Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, et al. Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. World J Surg Oncol. 2018;16(1):160. [Crossref]  [PubMed]  [PMC] 
  37. Zou C, Lin T, Wang B, Zhao Z, Li B, Xie X, et al. Managements of giant cell tumor within the distal radius: A retrospective study of 58 cases from a single center. J Bone Oncol. 2018;14:100211. [Crossref]  [PubMed]  [PMC] 
  38. Yayan J. Denosumab for effective tumor size reduction in patients with giant cell tumors of the bone: a systematic review and meta-analysis. Cancer Control. 2020;27(3):1073274820934822. [Crossref]  [PubMed]  [PMC] 
  39. Chen X, Li H, Zhu S, Wang Y, Qian W. Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2020;21(1):256. [Crossref]  [PubMed]  [PMC] 
  40. Gaston CL, Grimer RJ, Parry M, Stacchiotti S, Dei Tos AP, Gelderblom H, et al. Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone. Clin Sarcoma Res. 2016;6(1):15. [Crossref]  [PubMed]  [PMC] 
  41. Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18(16):4415-24. [Crossref]  [PubMed] 
  42. Goldschlager T, Dea N, Boyd M, Reynolds J, Patel S, Rhines LD, et al. Giant cell tumors of the spine: has denosumab changed the treatment paradigm? J Neurosurg Spine. 2015;22(5):526-33. [Crossref]  [PubMed] 

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www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com