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Outcome of re-operation for local recurrence following pre-operative denosumab administration and curettage for giant cell tumour of bone with difficult joint preservation

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Abstract 

Purpose

Denosumab enables joint-sparing surgery (curettage) and surgical downstaging in patients with giant cell tumour of bone (GCTB), where joint preservation is not possible. However, denosumab treatment causes osteosclerosis of the lesion, making it difficult to curet the lesion, leaving the tumour behind, and increasing the local recurrence rate. We performed a three-centre retrospective study to investigate the postoperative local re-recurrence rate, joint preservation status, and functional outcomes of locally recurrent lesions after preoperative denosumab treatment and curettage in patients with difficult joint preservation.

Methods

We included 38 of 142 patients with primary GCTB of the extremities who underwent preoperative denosumab and curettage between 2009 and 2021 with local recurrence. Preoperative denosumab was indicated in patients with minimal residual periarticular and subchondral bones, large extraosseous lesions (Campanacci stage 3), and pathological fractures that made joint preservation difficult.

Results

Local re-recurrence occurred in 6 (15.8%) of the 38 patients. In 29 patients who underwent re-curettage, local re-recurrence occurred in six patients (20.7%); however, in nine patients who underwent en bloc resection, no local re-recurrence was observed. The joint preservation rate was 63.2% (24 of 38 patients), with a median Musculoskeletal Tumor Society score of 28 (interquartile range: 26.8–29.0). The median follow-up period after surgery for local recurrence was 63.5 months (interquartile range: 42.5–82.4).

Conclusion

Since the local re-recurrence rate after re-curettage for local recurrence was low, and the joint preservation rate and affected limb function were good, preoperative denosumab administration may be considered in patients who require downstaging to maintain good limb function (joint preservation).

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Data availability

The datasets generated, analysed, or both during the present study are not publicly available because of privacy issues but are available from the corresponding author upon reasonable request.

References

  1. Flanagan AM, Larousserie F, O’Donnell PG, Yoshida A (2020) Giant cell tumour of bone. In: The WHO classification of tumours editorial board. WHO classification of tumours, 5th ed.: Soft tissue and bone tumours. Lyon, IARC, pp440–446

  2. Tsukamoto S, Mavrogenis AF, Kido A, Errani C (2021) Current concepts in the treatment of giant cell tumors of bone. Cancers (Basel) 13:3647. https://doi.org/10.3390/cancers13153647

    Article  CAS  Google Scholar 

  3. Errani C, Tsukamoto S, Ciani G, Donati DM (2019) Present day controversies and consensus in curettage for giant cell tumor of bone. J Clin Orthop Trauma 10:1015–1020. https://doi.org/10.1016/j.jcot.2019.09.017

    Article  Google Scholar 

  4. Balke M, Ahrens H, Streitbuerger A et al (2009) Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol 135:149–158. https://doi.org/10.1007/s00432-008-0427-x

    Article  Google Scholar 

  5. Vult von Steyern F, Bauer HCF, Trovik C et al (2006) 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 88:531–535. https://doi.org/10.1302/0301-620X.88B4.17407

    Article  CAS  Google Scholar 

  6. O’Donnell RJ, Springfield DS, Motwani HK et al (1994) Recurrence of giant-cell tumors of the long bones after curettage and packing with cement. J Bone Joint Surg Am 76:1827–1833

    Article  Google Scholar 

  7. Prosser GH, Baloch KG, Tillman RM, et al (2005) Does curettage without adjuvant therapy provide low recurrence rates in giant-cell tumors of bone? Clin Orthop Relat Res 211–218

  8. Wan R, Zhang W, Xu J et al (2012) The outcome of surgical treatment for recurrent giant cell tumor in the appendicular skeleton. J Orthop Sci 17:464–469. https://doi.org/10.1007/s00776-012-0228-6

    Article  Google Scholar 

  9. Klenke FM, Wenger DE, Inwards CY et al (2011) Recurrent giant cell tumor of long bones: analysis of surgical management. Clin Orthop Relat Res 469:1181–1187. https://doi.org/10.1007/s11999-010-1560-9

    Article  Google Scholar 

  10. Chawla S, Henshaw R, Seeger L et al (2013) 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 14:901–908. https://doi.org/10.1016/S1470-2045(13)70277-8

    Article  CAS  Google Scholar 

  11. Rutkowski P, Ferrari S, Grimer RJ et al (2015) Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol 22:2860–2868. https://doi.org/10.1245/s10434-015-4634-9

    Article  Google Scholar 

  12. Errani C, Tsukamoto S, Leone G et al (2018) Denosumab may increase the risk of local recurrence in patients with giant-cell tumor of bone treated with curettage. J Bone Joint Surg Am 100:496–504. https://doi.org/10.2106/JBJS.17.00057

    Article  Google Scholar 

  13. Tsukamoto S, Tanaka Y, Mavrogenis AF et al (2020) Is treatment with denosumab associated with local recurrence in patients with giant cell tumor of bone treated with curettage? a systematic review. Clin Orthop Relat Res 478:1076–1085. https://doi.org/10.1097/CORR.0000000000001074

    Article  Google Scholar 

  14. Agarwal MG, Gundavda MK, Gupta R, Reddy R (2018) Does denosumab change the giant cell tumor treatment strategy? Lessons learned from early experience. Clin Orthop Relat Res 476:1773–1782. https://doi.org/10.1007/s11999.0000000000000243

    Article  Google Scholar 

  15. Scoccianti G, Totti F, Scorianz M et al (2018) Preoperative denosumab with curettage and cryotherapy in giant cell tumor of bone: is there an increased risk of local recurrence? Clin Orthop Relat Res 476:1783–1790. https://doi.org/10.1007/s11999.0000000000000104

    Article  Google Scholar 

  16. Yang Y, Li Y, Liu W et al (2018) A nonrandomized controlled study of sacral giant cell tumors with preoperative treatment of denosumab. Medicine (Baltimore) 97:e13139. https://doi.org/10.1097/MD.0000000000013139

    Article  CAS  Google Scholar 

  17. Medellin MR, Fujiwara T, Tillman RM et al (2018) Prognostic factors for local recurrence in extremity-located giant cell tumours of bone with pathological fracture. Bone Joint J 100-B:1626–1632. https://doi.org/10.1302/0301-620X.100B12.BJJ-2018-0189.R2

    Article  CAS  Google Scholar 

  18. Mak IWY, Evaniew N, Popovic S et al (2014) A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am 96:e127. https://doi.org/10.2106/JBJS.M.01332

    Article  Google Scholar 

  19. Traub F, Singh J, Dickson BC et al (2016) Efficacy of denosumab in joint preservation for patients with giant cell tumour of the bone. Eur J Cancer 59:1–12. https://doi.org/10.1016/j.ejca.2016.01.006

    Article  CAS  Google Scholar 

  20. Righi A, Mancini I, Gambarotti M et al (2017) Histone 3.3 mutations in giant cell tumor and giant cell-rich sarcomas of bone. Hum Pathol 68:128–135. https://doi.org/10.1016/j.humpath.2017.08.033

    Article  CAS  Google Scholar 

  21. Mancini I, Righi A, Gambarotti M et al (2017) Phenotypic and molecular differences between giant-cell tumour of soft tissue and its bone counterpart. Histopathology 71:453–460. https://doi.org/10.1111/his.13249

    Article  Google Scholar 

  22. Gamberi G, Morandi L, Benini S et al (2018) Detection of H3F3A p. G35W and p.G35R in giant cell tumor of bone by allele specific locked nucleic acid quantitative PCR (ASLNAqPCR). Pathol Res Pract 214:89–94. https://doi.org/10.1016/j.prp.2017.10.023

    Article  CAS  Google Scholar 

  23. Campanacci M, Baldini N, Boriani S, Sudanese A (1987) Giant-cell tumor of bone. J Bone Joint Surg Am 69:106–114

    Article  CAS  Google Scholar 

  24. Choi H, Charnsangavej C, Faria SC et al (2007) Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 25:1753–1759. https://doi.org/10.1200/JCO.2006.07.3049

    Article  Google Scholar 

  25. Enneking WF, Dunham W, Gebhardt MC et al (1993) A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res 286:241–246

    Article  Google Scholar 

  26. Basch E, Reeve BB, Mitchell SA et al (2014) Development of the national cancer institute’s patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst 106:dju244. https://doi.org/10.1093/jnci/dju244

    Article  Google Scholar 

  27. Tsukamoto S, Mavrogenis AF, Tanzi P et al (2020) Curettage as first surgery for bone giant cell tumor: adequate surgery is more important than oncology training or surgical management by high volume specialized teams. Eur J Orthop Surg Traumatol 30:3–9. https://doi.org/10.1007/s00590-019-02535-y

    Article  Google Scholar 

  28. Tsukamoto S, Mavrogenis AF, Tanzi P et al (2020) Denosumab for bone giant cell tumor of the distal radius. Orthopedics 43:284–291. https://doi.org/10.3928/01477447-20200721-03

    Article  Google Scholar 

  29. Errani C, Tsukamoto S, Leone G et al (2017) Higher local recurrence rates after intralesional surgery for giant cell tumor of the proximal femur compared to other sites. Eur J Orthop Surg Traumatol 27:813–819. https://doi.org/10.1007/s00590-017-1983-z

    Article  Google Scholar 

  30. Errani C, Ruggieri P, Asenzio MAN et al (2010) Giant cell tumor of the extremity: a review of 349 cases from a single institution. Cancer Treat Rev 36:1–7. https://doi.org/10.1016/j.ctrv.2009.09.002

    Article  Google Scholar 

  31. Puri A, Gulia A, Agarwal MG, Reddy K (2010) Ulnar translocation after excision of a Campanacci grade-3 giant-cell tumour of the distal radius: an effective method of reconstruction. J Bone Joint Surg Br 92:875–879. https://doi.org/10.1302/0301-620X.92B6.23194

    Article  CAS  Google Scholar 

  32. Müller DA, Beltrami G, Scoccianti G et al (2016) Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series. World J Surg Oncol 14:281. https://doi.org/10.1186/s12957-016-1034-y

    Article  Google Scholar 

  33. Rekhi B, Verma V, Gulia A et al (2017) Clinicopathological features of a series of 27 cases of post-denosumab treated giant cell tumors of bones: a single institutional experience at a tertiary cancer referral centre, India. Pathol Oncol Res 23:157–164. https://doi.org/10.1007/s12253-016-0123-0

    Article  CAS  Google Scholar 

  34. Niu X, Yang Y, Wong KC et al (2019) Giant cell tumour of the bone treated with denosumab: how has the blood supply and oncological prognosis of the tumour changed? J Orthop Translat 18:100–108. https://doi.org/10.1016/j.jot.2018.10.003

    Article  Google Scholar 

  35. McGough RL, Rutledge J, Lewis VO et al (2005) Impact severity of local recurrence in giant cell tumor of bone. Clin Orthop Relat Res 438:116–122. https://doi.org/10.1097/01.blo.0000180055.76969.08

    Article  Google Scholar 

  36. Perrin DL, Visgauss JD, Wilson DA et al (2021) The role of denosumab in joint preservation for patients with giant cell tumour of bone. Bone Joint J 103-B:184–191. https://doi.org/10.1302/0301-620X.103B1.BJJ-2020-0274.R1

    Article  Google Scholar 

  37. Engellau J, Seeger L, Grimer R et al (2018) Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol 16:191. https://doi.org/10.1186/s12957-018-1478-3

    Article  Google Scholar 

  38. Lau CPY, Huang L, Wong KC, Kumta SM (2013) Comparison of the anti-tumor effects of denosumab and zoledronic acid on the neoplastic stromal cells of giant cell tumor of bone. Connect Tissue Res 54:439–449. https://doi.org/10.3109/03008207.2013.848202

    Article  CAS  Google Scholar 

  39. Shibuya I, Takami M, Miyamoto A et al (2019) In vitro study of the effects of denosumab on giant cell tumor of bone: comparison with zoledronic acid. Pathol Oncol Res 25:409–419. https://doi.org/10.1007/s12253-017-0362-8

    Article  CAS  Google Scholar 

  40. Machak GN, Snetkov AI (2021) The impact of curettage technique on local control in giant cell tumour of bone. Int Orthop 45:779–789. https://doi.org/10.1007/s00264-020-04860-y

    Article  Google Scholar 

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Acknowledgements

The authors thank all the patients and their families.

Funding

This work was supported by the Grant of Japan Orthopaedics and Traumatology Research Foundation (Grant number (No. 495)).

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Nara Medical University, 840, Shijo-cho, Kashihara-City, Nara, 634-8521, Japan

    Shinji Tsukamoto, Kanya Honoki & Yasuhito Tanaka

  2. Department of Musculoskeletal Oncology, HCG Hospital, No. 8, P. Kalingarao Road, Sampangiramnagar, Bangalore, Karnataka, 560027, India

    Suraj Hindiskere & Pramod S. Chinder

  3. The Yellow Ribbon, #805, 2nd floor, 9th Main, 4th Block, Jayanagar, Bangalore, 560011, India

    Suraj Hindiskere & Pramod S. Chinder

  4. First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 41 Ventouri Street, 15562, Holargos, Athens, Greece

    Andreas F. Mavrogenis

  5. Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136, Bologna, Italy

    Davide Maria Donati & Costantino Errani

Authors
  1. Shinji Tsukamoto
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Contributions

S. Tsukamoto: collected and analysed the data and wrote the manuscript.

S. Hindiskere: collected the data and wrote the manuscript.

K. Honoki: conceptualised the study, developed the methodology, and revised manuscript.

A. F. Mavrogenis: conceptualised the study, developed the methodology and revised the manuscript.

Y. Tanaka: conceptualised the study, developed the methodology, and revised the manuscript.

P. S. Chinder: conceptualised the study, developed the methodology, and revised the manuscript.

D. M. Donati: conceptualised the study, developed the methodology, and revised the manuscript.

C. Errani: chief supervisor, collected the data and wrote the manuscript.

Corresponding author

Correspondence to Shinji Tsukamoto.

Ethics declarations

Ethics approval

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the individual Institutional Review Board (or Ethics Committee) of IRCCS Istituto Ortopedico Rizzoli, Nara Medical University, and HCG hospital.

Consent to participate

Informed consent was obtained from all individual participants in IRCCS Istituto Ortopedico Rizzoli and HCG hospital, and the requirement for written consent from participants in Nara Medical University was waived, because an “opt-out” process was used and the study has the retrospective nature.

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The authors declare no competing interests.

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Tsukamoto, S., Hindiskere, S., Honoki, K. et al. Outcome of re-operation for local recurrence following pre-operative denosumab administration and curettage for giant cell tumour of bone with difficult joint preservation. International Orthopaedics (SICOT) 47, 265–273 (2023). https://doi.org/10.1007/s00264-022-05613-9

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