Giant cell tumour of bone (GCTB) is one of the most common local aggressive tumourous lesions with a wide variety of biological behaviour. However, there are no clear indicative criteria when choosing the type of procedure and the complication rates remain high, especially in terms of local recurrence. The purpose of the study was to (1) identify the main risk factors for local recurrence, (2) evaluate the recurrence-free survival in dependence on neoadjuvant denosumab use and the type of procedure, and (3) compare the functional outcomes after curettage and en bloc resection. The group included 102 patients with GCTB treated between 2006 and 2020. The mean age of patients was 34.4 years (15-79). The follow-up period was 8.32 years (2-16) on average. Local recurrence occurred in 14 patients (29.8%) who underwent curettage and in 5 patients (10.6%) after en bloc resection. Curettage was shown to be a factor in increasing recurrence rates (OR = 3.64 [95% CI: 1.19-11.15]; p = 0.023). Tibial location was an independent risk factor for local recurrence regardless of the type of surgery (OR = 3.22 [95% CI: 1.09-9.48]; p = 0.026). The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments at five years postoperatively (p = 0.0307). Functional ability and pain as reported by patients at the latest follow-up were superior after curettage compared to resection for upper and lower extremity (mean difference: -4.00 [95% CI: -6.81 to -1.18]; p < 0.001 and mean difference: -5.36 [95% CI: -3.74 to -6.97]; p < 0.001, respectively). Proximal tibia tumour location and curettage were shown to be major risk factors for local recurrence in GCTB regardless of neoadjuvant denosumab treatment. The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments. The functional outcome of patients after curettage was better compared to en bloc resection.

1st Department of Orthopaedic Surgery St Anne's University Hospital 60200 Brno Czech Republic

1st Department of Pathology St Anne's University Hospital 60200 Brno Czech Republic

Clinic of Comprehensive Cancer Care Masaryk Memorial Cancer Institute 60200 Brno Czech Republic

Department of Pediatric Oncology University Hospital Brno 66263 Brno Czech Republic

Faculty of Medicine Masaryk University 62500 Brno Czech Republic

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Campanacci M., Baldini N., Boriani S., Sudanese A. Giant-Cell Tumor of Bone. J. Bone Jt. Surg. Am. 1987;69:106–114. doi: 10.2106/00004623-198769010-00018. PubMed DOI

Thomas D.M., Skubitz K.M. Giant Cell Tumour of Bone. Curr. Opin. Oncol. 2009;21:338–344. doi: 10.1097/CCO.0b013e32832c951d. PubMed DOI

Van der Heijden L., Dijkstra P.D.S., van de Sande M.A.J., Kroep J.R., Nout R.A., van Rijswijk C.S.P., Bovée J.V.M.G., Hogendoorn P.C.W., Gelderblom H. The Clinical Approach Toward Giant Cell Tumor of Bone. Oncologist. 2014;19:550–561. doi: 10.1634/theoncologist.2013-0432. PubMed DOI PMC

Balke M., Schremper L., Gebert C., Ahrens H., Streitbuerger A., Koehler G., Hardes J., Gosheger G. Giant Cell Tumor of Bone: Treatment and Outcome of 214 Cases. J. Cancer Res. Clin. Oncol. 2008;134:969–978. doi: 10.1007/s00432-008-0370-x. PubMed DOI

Errani C., Ruggieri P., Asenzio M.A.N., Toscano A., Colangeli S., Rimondi E., Rossi G., Longhi A., Mercuri M. Giant Cell Tumor of the Extremity: A Review of 349 Cases from a Single Institution. Cancer Treat. Rev. 2010;36:1–7. doi: 10.1016/j.ctrv.2009.09.002. PubMed DOI

Klenke F.M., Wenger D.E., Inwards C.Y., Rose P.S., Sim F.H. Giant Cell Tumor of Bone: Risk Factors for Recurrence. Clin. Orthop. Relat. Res. 2011;469:591–599. doi: 10.1007/s11999-010-1501-7. PubMed DOI PMC

Hu P., Zhao L., Zhang H., Yu X., Wang Z., Ye Z., Wu S., Guo S., Zhang G., Wang J., et al. Recurrence Rates and Risk Factors for Primary Giant Cell Tumors around the Knee: A Multicentre Retrospective Study in China. Sci. Rep. 2016;6:36332. doi: 10.1038/srep36332. PubMed DOI PMC

Siddiqui M.A., Seng C., Tan M.H. Risk Factors for Recurrence of Giant Cell Tumours of Bone. J. Orthop. Surg. 2014;22:108–110. doi: 10.1177/230949901402200127. PubMed DOI

Lin X., Liu J., Xu M. The Prognosis of Giant Cell Tumor of Bone and the Vital Risk Factors That Affect Its Postoperative Recurrence: A Meta-Analysis. Transl. Cancer Res. TCR. 2021;10:1712–1722. doi: 10.21037/tcr-20-3100. PubMed DOI PMC

Li Z., Müller R., Ruffoni D. Bone Remodeling and Mechanobiology around Implants: Insights from Small Animal Imaging: Bone remodeling and mechanobiology around implants. J. Orthop. Res. 2017;36:584–593. doi: 10.1002/jor.23758. PubMed DOI

Errani C., Tsukamoto S., Mavrogenis A.F. How Safe and Effective Is Denosumab for Bone Giant Cell Tumour? Int. Orthop. (SICOT) 2017;41:2397–2400. doi: 10.1007/s00264-017-3536-9. PubMed DOI

Kivioja A.H., Blomqvist C., Hietaniemi K., Trovik C., Walloe A., Bauer H.C.F., Jorgensen P.H., Bergh P., Follerås G. Cement Is Recommended in Intralesional Surgery of Giant Cell Tumors: A Scandinavian Sarcoma Group Study of 294 Patients Followed for a Median Time of 5 Years. Acta Orthop. 2008;79:86–93. doi: 10.1080/17453670710014815. PubMed DOI

Su Y.-P., Chen W.-M., Chen T.-H. Giant-Cell Tumors of Bone: An Analysis of 87 Cases. Int. Orthop. (SICOT) 2004;28:239–243. doi: 10.1007/s00264-004-0564-z. PubMed DOI PMC

Asano N., Saito M., Kobayashi E., Morii T., Kikuta K., Watanabe I., Anazawa U., Takeuchi K., Suzuki Y., Susa M., et al. Preoperative Denosumab Therapy Against Giant Cell Tumor of Bone Is Associated with an Increased Risk of Local Recurrence After Curettage Surgery. Ann. Surg. Oncol. 2022;29:3992–4000. doi: 10.1245/s10434-022-11411-9. PubMed DOI

Sano K., Suehara Y., Okubo T., Sasa K., Kurihara T., Akaike K., Kubota D., Torigoe T., Hasegawa N., Ishii M., et al. Preoperative Denosumab Treatment with Curettage May Be a Risk Factor for Recurrence of Giant Cell Tumor of Bone. J. Orthop. Surg. 2020;28:230949902092978. doi: 10.1177/2309499020929786. PubMed DOI

Cheng D., Hu T., Zhang H., Huang J., Yang Q. Factors Affecting the Recurrence of Giant Cell Tumor of Bone After Surgery: A Clinicopathological Study of 80 Cases from a Single Center. Cell Physiol. Biochem. 2015;36:1961–1970. doi: 10.1159/000430164. PubMed DOI

Van der Heijden L., Sander Dijkstra P.D., Campanacci D.A., Gibbons C.L.M.H., van de Sande M.A.J. Giant Cell Tumor with Pathologic Fracture: Should We Curette or Resect? Clin. Orthop. Relat. Res. 2013;471:820–829. doi: 10.1007/s11999-012-2546-6. Erratum in Clin. Orthop. Relat. Res. 2012, 470, 3626. PubMed DOI PMC

Chawla S., Blay J.-Y., Rutkowski P., Le Cesne A., Reichardt P., Gelderblom H., Grimer R.J., Choy E., Skubitz K., Seeger L., et al. Denosumab in Patients with Giant-Cell Tumour of Bone: A Multicentre, Open-Label, Phase 2 Study. Lancet Oncol. 2019;20:1719–1729. doi: 10.1016/S1470-2045(19)30663-1. PubMed DOI

Van der Heijden L., Dijkstra P.D.S., Blay J.-Y., Gelderblom H. Giant Cell Tumour of Bone in the Denosumab Era. Eur. J. Cancer. 2017;77:75–83. doi: 10.1016/j.ejca.2017.02.021. PubMed DOI

Unni K.K., Inwards C.Y. Dahlin’s Bone Tumors: General Aspects and Data on 10,165 Cases. 6th ed. Lippincott Williams and Wilkins; Philadelphia, PA, USA: 2010.

Chinder P.S., Hindiskere S., Doddarangappa S., Pal U. Evaluation of Local Recurrence in Giant-Cell Tumor of Bone Treated by Neoadjuvant Denosumab. Clin. Orthop. Surg. 2019;11:352. doi: 10.4055/cios.2019.11.3.352. PubMed DOI PMC

Palmerini E., Staals E.L., Jones L.B., Donati D.M., Longhi A., Randall R.L. Role of (Neo)Adjuvant Denosumab for Giant Cell Tumor of Bone. Curr. Treat. Options Oncol. 2020;21:68. doi: 10.1007/s11864-020-00766-4. PubMed DOI

Mahdal M., Neradil J., Mudry P., Paukovcekova S., Staniczkova Zambo I., Urban J., Macsek P., Pazourek L., Tomas T., Veselska R. New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling. Cancers. 2021;13:3543. doi: 10.3390/cancers13143543. PubMed DOI PMC

Streitbürger A., Hardes J., Nottrott M., Guder W.K. Reconstruction Survival of Segmental Megaendoprostheses: A Retrospective Analysis of 28 Patients Treated for Intercalary Bone Defects after Musculoskeletal Tumor Resections. Arch. Orthop. Trauma Surg. 2022;142:41–56. doi: 10.1007/s00402-020-03583-4. PubMed DOI PMC

Enneking W.F., Dunham W., Gebhardt M.C., Malawar M., Pritchard D.J. A System for the Functional Evaluation of Reconstructive Procedures after Surgical Treatment of Tumors of the Musculoskeletal System. Clin. Orthop. Relat. Res. 1993;286:241–246. doi: 10.1097/00003086-199301000-00035. PubMed DOI

Thomas D.M. RANKL, Denosumab, and Giant Cell Tumor of Bone. Curr. Opin. Oncol. 2012;24:397–403. doi: 10.1097/CCO.0b013e328354c129. PubMed DOI

Turcotte R.E. Giant Cell Tumor of Bone. Orthop. Clin. N. Am. 2006;37:35–51. doi: 10.1016/j.ocl.2005.08.005. PubMed DOI

Errani C., Tsukamoto S., Ciani G., Donati D.M. Present Day Controversies and Consensus in Curettage for Giant Cell Tumor of Bone. J. Clin. Orthop. Trauma. 2019;10:1015–1020. doi: 10.1016/j.jcot.2019.09.017. PubMed DOI PMC

Machak G.N., Snetkov A.I. The Impact of Curettage Technique on Local Control in Giant Cell Tumour of Bone. Int. Orthop. 2021;45:779–789. doi: 10.1007/s00264-020-04860-y. PubMed DOI

Errani C., Tsukamoto S., Leone G., Akahane M., Cevolani L., Tanzi P., Kido A., Honoki K., Tanaka Y., Donati D.M. Higher Local Recurrence Rates after Intralesional Surgery for Giant Cell Tumor of the Proximal Femur Compared to Other Sites. Eur. J. Orthop. Surg. Traumatol. 2017;27:813–819. doi: 10.1007/s00590-017-1983-z. PubMed DOI

O’Donnell R.J., Springfield D.S., Motwani H.K., Ready J.E., Gebhardt M.C., Mankin H.J. Recurrence of Giant-Cell Tumors of the Long Bones after Curettage and Packing with Cement. J. Bone Jt. Surg. Am. 1994;76:1827–1833. doi: 10.2106/00004623-199412000-00009. PubMed DOI

Sheth D.S., Healey J.H., Sobel M., Lane J.M., Marcove R.C. Giant Cell Tumor of the Distal Radius. J. Hand Surg. 1995;20:432–440. doi: 10.1016/S0363-5023(05)80102-9. PubMed DOI

Puchner S.E., Kutscha-Lissberg P., Kaider A., Panotopoulos J., Puchner R., Böhler C., Hobusch G., Windhager R., Funovics P.T. Outcome after Reconstruction of the Proximal Tibia--Complications and Competing Risk Analysis. PLoS ONE. 2015;10:e0135736. doi: 10.1371/journal.pone.0135736. PubMed DOI PMC

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;21:256. doi: 10.1186/s12891-020-03294-2. PubMed DOI PMC

Branstetter D.G., Nelson S.D., Manivel J.C., Blay J.-Y., Chawla S., Thomas D.M., Jun S., Jacobs I. Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone. Clin. Cancer Res. 2012;18:4415–4424. doi: 10.1158/1078-0432.CCR-12-0578. PubMed DOI

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. 2018;97:e13139. doi: 10.1097/MD.0000000000013139. PubMed DOI PMC

Savvidou O.D., Bolia I.K., Chloros G.D., Papanastasiou J., Koutsouradis P., Papagelopoulos P.J. Denosumab: Current Use in the Treatment of Primary Bone Tumors. Orthopedics. 2017;40:204–210. doi: 10.3928/01477447-20170627-04. PubMed DOI

Puri A., Gulia A., Hegde P., Verma V., Rekhi B. Neoadjuvant Denosumab: Its Role and Results in Operable Cases of Giant Cell Tumour of Bone. Bone Jt. J. 2019;101:170–177. doi: 10.1302/0301-620X.101B2.BJJ-2018-0907.R2. PubMed DOI

Rutkowski P., Gaston L., Borkowska A., Stacchiotti S., Gelderblom H., Baldi G.G., Palmerini E., Casali P., Gronchi A., Parry M., et al. Denosumab Treatment of Inoperable or Locally Advanced Giant Cell Tumor of Bone—Multicenter Analysis Outside Clinical Trial. Eur. J. Surg. Oncol. 2018;44:1384–1390. doi: 10.1016/j.ejso.2018.03.020. PubMed DOI

Zhang R.-Z., Ma T.-X., Qi D.-W., Zhao M., Hu T., Zhang G.-C. Short-Term Preoperative Denosumab with Surgery in Unresectable or Recurrent Giant Cell Tumor of Bone. Orthop. Surg. 2019;11:1101–1108. doi: 10.1111/os.12561. PubMed DOI PMC

Tsukamoto S., Mavrogenis A.F., Tanzi P., Leone G., Righi A., Akahane M., Kido A., Honoki K., Tanaka Y., Donati D.M., et al. Similar Local Recurrence but Better Function with Curettage versus Resection for Bone Giant Cell Tumor and Pathological Fracture at Presentation. J. Surg. Oncol. 2019;119:864–872. doi: 10.1002/jso.25391. PubMed DOI

Chen T.H., Chen W.M., Huang C.K. Reconstruction after Intercalary Resection of Malignant Bone Tumours: Comparison between segmental allograft and extracorporeally-irradiated autograft. J. Bone Jt. Surgery. Br. Vol. 2005;87:704–709. doi: 10.1302/0301-620X.87B5.15491. PubMed DOI

ASO Author Reflections: The Effect of Local Adjuvants on Cortical Bone Following Intralesional Curettage of Bone Tumors