PREOPERATIVE DENOSUMAB AND FEASIBILITY OF LESS MORBID SURGERY IN CAMPANACCI STAGE 3 GIANT CELL TUMOUR OF BONE

Authors

  • Muhammad Asif Rasheed Combined Military Hospital, Rawalpindi-Pakistan
  • Muhammad Suhail Amin Combined Military Hospital, Rawalpindi-Pakistan
  • Muhammad Sohaib Nadeem Combined Military Hospital, Rawalpindi-Pakistan
  • Muhammad Nadeem Chaudhry Combined Military Hospital, Rawalpindi-Pakistan
  • Areej Fatima Combined Military Hospital, Rawalpindi-Pakistan

DOI:

https://doi.org/10.55519/JAMC-03-13367

Abstract

Background: Giant cell tumour of bone (GCTB) is a rare, locally aggressive benign bone tumour with slight female sex predilection and affecting young adults 20–40 years of age. World health organization (WHO) has recently categorized GCTB as an intermediate malignant tumour. GCTB is known to be driven pathologically via expression of pro-osteoclastic signals by stromal cells. This is mediated precisely via the expression of RANKL by stromal cells acting in an autocrine fashion on RANK receptor-positive osteoclast-like giant cells and their precursors. While the treatment is primarily surgical, we hypothesized that preoperative denosumab therapy facilitates conversion to a less morbid procedure in an aggressive campanacci grade 3 GCTB, otherwise amenable to joint resection and reconstruction/arthrodesis. Methods: A prospective, single arm, interventional study was conducted in Orthopaedics and radiation oncology department of combined military hospital (CMH) Rawalpindi. The duration of study was 36 months. Patients were recruited by purposive sampling technique as per inclusion/exclusion criteria. Denosumab was administered as preoperative adjuvant therapy for 3 months. Pain was assessed utilizing Brief Pain Inventory –Short Form (BPI-SF) and functional status was assessed as per Musculoskeletal tumour society score at baseline and 12 weeks after commencement of denosumab therapy. The intent of surgery pre and post denosumab therapy was ascertained. Results: Total of 23 patients were a part of this study. Mean pain scores and MSTS scores prior to and after denosumab were statistically significant with p-value <0.01. Pre-denusomab, there was inclination towards resection arthroplasty as the treatment procedure (56.5%). After denusomab therapy, intralesional curettage was choice of procedure with intent executed for 78.3% of cases.  Conclusion: Denosumab has potential role for giant cell tumour of bone, it makes a less morbid surgery technically feasible. However, recurrence needs to be probed in long term follow up studies.  

References

Patel S, Chiu RG, Rosinski CL, Ansari D, Chaker AN, Nunna RS, et al. Incidence, Management, and Outcomes of Spinal Giant Cell Tumour of Bone in Adult Patients: A National Cancer Database Analysis. World Neurosurg 2020;144:e296–305.

Turcotte RE, Wunder JS, Isler MH, Bell RS, Schachar N, Masri BA, et al. Giant cell tumour of long bone: a Canadian Sarcoma Group study. Clin Orthop Relat Res 2002;397:248–58.

Choi JH, Ro JY. The 2020 WHO Classification of Tumours of Soft Tissue: Selected Changes and New Entities. Adv Anat Pathol 2021;28(1):44–58.

Thomas DM, Skubitz KM. Giant cell tumour of bone. Curr Opin Oncol 2009;21(4):338–44.

Forsyth RG, Krenács T, Athanasou N, Hogendoorn PCW. Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis. Cancers (Basel) 2021;13(20):5119.

Peters S, Clézardin P, Márquez-Rodas I, Niepel D, Gedye C. The RANK-RANKL axis: An opportunity for drug repurposing in cancer? Clin Transl Oncol 2019;21(8):977–91.

Balke M, Hardes J. Denosumab: a breakthrough in treatment of giant-cell tumour of bone? Lancet Oncol 2010;11(3):218–9.

Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, et al. Denosumab in patients with giant-cell tumour of bone: an openlabel, phase 2 study. Lancet Oncol 2010;11(3):275–80.

Atrayee BM, Chawla SP. Giant Cell Tumour of Bone: An Update. Curr Oncol Rep 2021;23(5):51.

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.

Martin-Broto J, Cleeland CS, Glare PA, Engellau J, Skubitz KM, Blum RH, et al. Effects of denosumab on pain and analgesic use in giant cell tumour of bone: interim results from a phase II study. Acta Oncol 2014;53(9):1173–9.

Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SPD, Pienkowski A, et al. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumour of bone. Ann Surg Oncol 2015;22(9):2860–8.

Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain 1995;61(2):277–84.

Guyatt GH, Osoba D, Wu AW, Wyrwich KW, Norman GR, Clinical Signifi cance Consensus Meeting Group. Methods to explain the clinical signifi cance of health status measures. Mayo Clin Proc 2002;77(4):371–83.

Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumours of the musculoskeletal system. Clin Orthop Relat Res 1993;(286):241–6.

Traub F, Singh J, Dickson BC, Leung S, Mohankumar R, Blackstein ME, et al. Efficacy of denosumab in joint preservation for patients with giant cell tumour of the bone. Eur J Cancer 2016;59:1–12.

Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumour of bone. J Bone Joint Surg Am 1987;69(1):106–14.

Amin MS, Chaudhary AA, Shah F. Management of Campanacci type III giant cell tumour. Int J Orthop Sci 2017;3(1):836–41.

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 Joint J 2019;101-B(2):170–7.

Yue J, Sun W, Li S. Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumour of bone: A randomized clinical trial. J Bone Oncol 2022;35:100441.

Palmerini E, Pazzaglia L, Cevolani L, Pratelli L, Pierini M, Quattrini I, et al. Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumours of Bone (GCTB): A Phase II Trial Correlative Study. Cancers (Basel) 2022;14(12):2863.

Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas D, et al. Denosumab Induces Tumour Reduction and Bone Formation in Patients with Giant-Cell Tumour of Bone. Clin Cancer Res 2012;18:4415–24.

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.

Niu X, Yang Y, Wong KC, Huang Z, Ding Y, Zhang W. Giant cell tumour of the bone treated with denosumab: How has the blood supply and oncological prognosis of the tumour changed? J Orthop Transl 2019;18:100–8.

Deventer N, Budny T, Gosheger G, Rachbauer A, Puetzler J, Theil JC, et al. Giant cell tumour of bone: A single center study of 115 cases. J Bone Oncol 2022;33:100417.

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 Tumour of Bone Treated with Curettage. J Bone Joint Surg Am 2018;100(6):496–504.

Chinder PS, Hindiskere S, Doddarangappa S, Pal U. Evaluation of Local Recurrence in Giant-Cell Tumour of Bone Treated by Neoadjuvant Denosumab. Clin Orthop Surg 2019;11(3):352–60.

Downloads

Published

2024-09-08