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Adjuvant denosumab treatment in patients with resectable high-risk giant cell tumor of bone

Year 2024, , 225 - 228, 28.05.2024
https://doi.org/10.38053/acmj.1466741

Abstract

Aims: Giant cell tumor of bone (GCTB) is an uncommon, benign, but aggressive osteolytic skeletal neoplasm of young adults. Although denosumab is frequently used in neoadjuvant treatment and metastatic unresectable disease in these patients, its role in adjuvant therapy is unclear. In this study, we evaluated the efficacy and safety of denosumab as an adjuvant therapy in patients with resectable high-risk GCTB.
Methods: Patients with resectable high-risk GCTB over the age of 16 who received postoperative denosumab between January 2013 and September 2022 were included. Demographic and clinical characteristics of the patients, tumor localization, prior treatments, response to denosumab treatment, and adverse effects of the drug were analyzed retrospectively.
Results: A total of 18 patients (10 women) with a median age of 23 (16-45) years were recruited. The median follow-up time was 7.1 (4.2-8.7) years and the median denosumab treatment duration was 12 (12-90) months. One (6%) patient experienced a partial response, and 17 (94%) patients had stable disease. Grade 1 or 2 hypophosphatemia was the most frequent adverse effect (16.7%, n=3). No patients stopped therapy due to side effects, and no grade 3 or 4 incident were observed.
Conclusion: Postoperative denosumab may also be useful in the adjuvant treatment of patients with high-risk resectable GCTB.

References

  • Mendenhall WM, Zlotecki RA, Scarborough MT, Gibbs CP,Mendenhall NP. Giant cell tumor of bone. Am J Clin Oncol. 2006;29(1):96-99.
  • Verschoor AJ, Bovée J, 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):570-574.
  • Larsson SE, Lorentzon R, Boquist L. Giant-cell tumor of bone. A demographic, clinical, and histopathological study of all cases recorded in the Swedish Cancer Registry for the years 1958 through 1968. J Bone Joint Surg Am. 1975;57(2):167-173.
  • del Carmen Baena-Ocampo L, Ramirez-Perez E, Linares-Gonzalez LM, Delgado-Chavez R. Epidemiology of bone tumors in Mexico City: retrospective clinicopathologic study of 566 patients at a referral institution. Ann Diagn Pathol. 2009;13(1):16-21.
  • Szendröi M. Giant-cell tumour of bone. J Bone Joint Surg Br. 2004;86(1):5-12.
  • Balke M, Schremper L, Gebert C, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol. 2008;134(9):969-978.
  • Chrcanovic BR, Gomes CC, Gomez RS. Central giant cell lesion of the jaws: an updated analysis of 2270 cases reported in the literature. J Oral Pathol Med. 2018;47(8):731-739.
  • Cowan RW, Singh G. Giant cell tumor of bone: a basic science perspective. Bone. 2013;52(1):238-246.
  • Dougall WC, Glaccum M, Charrier K, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999;13(18):2412-2424.
  • Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309-319.
  • Xiong J, Piemontese M, Thostenson JD, Weinstein RS, Manolagas SC, O’Brien CA. Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone. 2014;66:146-154.
  • Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18(16):4415-4424.
  • Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11(3):275-280.
  • Chawla S, Henshaw R, Seeger L, 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):901-908.
  • Palmerini E, Chawla NS, Ferrari S, et al. Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): for how long? Eur J Cancer. 2017;76:118-124.
  • Ueda T, Morioka H, Nishida 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):2149-2154.
  • Errani C, Tsukamoto S, Mavrogenis AF. How safe and effective is denosumab for bone giant cell tumour? Int Orthop. 2017;41(11):2397-2400.
  • Prosser GH, Baloch KG, Tillman RM, Carter SR, Grimer RJ. Does curettage without adjuvant therapy provide low recurrence rates in giant-cell tumors of bone? Clin Orthop Relat Res. 2005;435:211-218.
  • Errani C, Tsukamoto S, Leone G, 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.
  • Borkowska A, Goryń T, Pieńkowski A, et al. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone. Oncol Lett. 2016;12(6):4312-4318.
  • Deventer N, Budny T, Gosheger G, et al. Giant cell tumor of bone: a single center study of 115 cases. J Bone Oncol. 2022;33:100417.
  • Rutkowski P, Gaston L, Borkowska A, 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(9):1384-1390.
  • Chawla S, Blay JY, Rutkowski P, et al. Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(12):1719-1729.
  • Basu Mallick A, Chawla SP. Giant Cell tumor of bone: an update. Curr Oncol Rep. 2021;23(5):51.
  • Palmerini E, Seeger LL, Gambarotti M, et al. Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab. BMC Cancer. 2021;21(1):89.
  • Borkowska AM, Szumera-Ciećkiewicz A, Szostakowski B, Pieńkowski A, Rutkowski PL. Denosumab in giant cell tumor of bone: multidisciplinary medical management based on pathophysiological mechanisms and real-world evidence. Cancers (Basel). 2022;14(9):2290.
Year 2024, , 225 - 228, 28.05.2024
https://doi.org/10.38053/acmj.1466741

Abstract

References

  • Mendenhall WM, Zlotecki RA, Scarborough MT, Gibbs CP,Mendenhall NP. Giant cell tumor of bone. Am J Clin Oncol. 2006;29(1):96-99.
  • Verschoor AJ, Bovée J, 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):570-574.
  • Larsson SE, Lorentzon R, Boquist L. Giant-cell tumor of bone. A demographic, clinical, and histopathological study of all cases recorded in the Swedish Cancer Registry for the years 1958 through 1968. J Bone Joint Surg Am. 1975;57(2):167-173.
  • del Carmen Baena-Ocampo L, Ramirez-Perez E, Linares-Gonzalez LM, Delgado-Chavez R. Epidemiology of bone tumors in Mexico City: retrospective clinicopathologic study of 566 patients at a referral institution. Ann Diagn Pathol. 2009;13(1):16-21.
  • Szendröi M. Giant-cell tumour of bone. J Bone Joint Surg Br. 2004;86(1):5-12.
  • Balke M, Schremper L, Gebert C, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol. 2008;134(9):969-978.
  • Chrcanovic BR, Gomes CC, Gomez RS. Central giant cell lesion of the jaws: an updated analysis of 2270 cases reported in the literature. J Oral Pathol Med. 2018;47(8):731-739.
  • Cowan RW, Singh G. Giant cell tumor of bone: a basic science perspective. Bone. 2013;52(1):238-246.
  • Dougall WC, Glaccum M, Charrier K, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999;13(18):2412-2424.
  • Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309-319.
  • Xiong J, Piemontese M, Thostenson JD, Weinstein RS, Manolagas SC, O’Brien CA. Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone. 2014;66:146-154.
  • Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18(16):4415-4424.
  • Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11(3):275-280.
  • Chawla S, Henshaw R, Seeger L, 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):901-908.
  • Palmerini E, Chawla NS, Ferrari S, et al. Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): for how long? Eur J Cancer. 2017;76:118-124.
  • Ueda T, Morioka H, Nishida 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):2149-2154.
  • Errani C, Tsukamoto S, Mavrogenis AF. How safe and effective is denosumab for bone giant cell tumour? Int Orthop. 2017;41(11):2397-2400.
  • Prosser GH, Baloch KG, Tillman RM, Carter SR, Grimer RJ. Does curettage without adjuvant therapy provide low recurrence rates in giant-cell tumors of bone? Clin Orthop Relat Res. 2005;435:211-218.
  • Errani C, Tsukamoto S, Leone G, 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.
  • Borkowska A, Goryń T, Pieńkowski A, et al. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone. Oncol Lett. 2016;12(6):4312-4318.
  • Deventer N, Budny T, Gosheger G, et al. Giant cell tumor of bone: a single center study of 115 cases. J Bone Oncol. 2022;33:100417.
  • Rutkowski P, Gaston L, Borkowska A, 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(9):1384-1390.
  • Chawla S, Blay JY, Rutkowski P, et al. Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(12):1719-1729.
  • Basu Mallick A, Chawla SP. Giant Cell tumor of bone: an update. Curr Oncol Rep. 2021;23(5):51.
  • Palmerini E, Seeger LL, Gambarotti M, et al. Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab. BMC Cancer. 2021;21(1):89.
  • Borkowska AM, Szumera-Ciećkiewicz A, Szostakowski B, Pieńkowski A, Rutkowski PL. Denosumab in giant cell tumor of bone: multidisciplinary medical management based on pathophysiological mechanisms and real-world evidence. Cancers (Basel). 2022;14(9):2290.
There are 26 citations in total.

Details

Primary Language English
Subjects Clinical Oncology, Orthopaedics
Journal Section Research Articles
Authors

Arif Akyıldız 0000-0002-4452-2076

Rashad Ismayılov 0000-0002-7093-2722

Denizcan Güven 0000-0002-6924-9467

Elvin Chalabiyev 0000-0001-6470-6043

Najmaddin Abdurrahimli 0000-0002-5694-5527

Sercan Aksoy 0000-0003-4984-1049

Publication Date May 28, 2024
Submission Date April 9, 2024
Acceptance Date May 1, 2024
Published in Issue Year 2024

Cite

AMA Akyıldız A, Ismayılov R, Güven D, Chalabiyev E, Abdurrahimli N, Aksoy S. Adjuvant denosumab treatment in patients with resectable high-risk giant cell tumor of bone. Anatolian Curr Med J / ACMJ / acmj. May 2024;6(3):225-228. doi:10.38053/acmj.1466741

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