Skip to main content
Top
Published in: Clinical and Translational Oncology 6/2015

Open Access 01-06-2015 | Educational Series – Red Series

Giant cell tumour of bone: new treatments in development

Authors: A. López-Pousa, J. Martín Broto, T. Garrido, J. Vázquez

Published in: Clinical and Translational Oncology | Issue 6/2015

Login to get access

Abstract

Giant cell tumour of bone (GCTB) is a benign osteolytic tumour with three main cellular components: multinucleated osteoclast-like giant cells, mononuclear spindle-like stromal cells (the main neoplastic components) and mononuclear cells of the monocyte/macrophage lineage. The giant cells overexpress a key mediator in osteoclastogenesis: the RANK receptor, which is stimulated in turn by the cytokine RANKL, which is secreted by the stromal cells. The RANK/RANKL interaction is predominantly responsible for the extensive bone resorption by the tumour. Historically, standard treatment was substantial surgical resection, with or without adjuvant therapy, with recurrence rates of 20–56 %. Studies with denosumab, a monoclonal antibody that specifically binds to RANKL, resulted in dramatic treatment responses, which led to its approval by the United States Food and Drugs Administration (US FDA). Recent advances in the understanding of GCTB pathogenesis are essential to develop new treatments for this locally destructive primary bone tumour.
Literature
1.
go back to reference Beebe-Dimmer JL, Cetin K, Fryzek JP, Schuetze SM, Schwartz K. The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology and End Results Program (1975–2004). Rare Tumors. 2009;1:e52. doi:10.4081/rt.2009.e52.PubMedCentralPubMed Beebe-Dimmer JL, Cetin K, Fryzek JP, Schuetze SM, Schwartz K. The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology and End Results Program (1975–2004). Rare Tumors. 2009;1:e52. doi:10.​4081/​rt.​2009.​e52.PubMedCentralPubMed
2.
go back to reference 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;57:167–73.PubMed 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;57:167–73.PubMed
3.
go back to reference Liede A, Bach BA, Stryker S, Hernandez RK, Sobocki P, Bennett B, et al. Regional variation and challenges in estimating the incidence of giant cell tumor of bone. J Bone Joint Surg Am. 2014;96(23):1999–2007. doi:10.2106/JBJS.N.00367.PubMed Liede A, Bach BA, Stryker S, Hernandez RK, Sobocki P, Bennett B, et al. Regional variation and challenges in estimating the incidence of giant cell tumor of bone. J Bone Joint Surg Am. 2014;96(23):1999–2007. doi:10.​2106/​JBJS.​N.​00367.PubMed
5.
go back to reference Turcotte RE, Wunder JS, Isler MH, Bell RS, Schachar N, Masri BA, et al. Giant cell tumor of long bone: a Canadian Sarcoma Group study. Clin Orthop. 2002;(397):248–58. Turcotte RE, Wunder JS, Isler MH, Bell RS, Schachar N, Masri BA, et al. Giant cell tumor of long bone: a Canadian Sarcoma Group study. Clin Orthop. 2002;(397):248–58.
8.
go back to reference Campanacci M. Giant-cell tumor and chondrosarcomas: grading, treatment and results (studies of 209 and 131 cases). Recent Results Cancer Res Fortschritte Krebsforsch Prog Dans Rech Sur Cancer. 1976;54:257–61. Campanacci M. Giant-cell tumor and chondrosarcomas: grading, treatment and results (studies of 209 and 131 cases). Recent Results Cancer Res Fortschritte Krebsforsch Prog Dans Rech Sur Cancer. 1976;54:257–61.
10.
13.
go back to reference Okamoto Y, Mathew S, Daw NC, Neel MD, McCarville MB, Dome JS, et al. Giant cell tumor of bone with pulmonary metastases. Med Pediatr Oncol. 2003;41:454–9. doi:10.1002/mpo.10258.PubMed Okamoto Y, Mathew S, Daw NC, Neel MD, McCarville MB, Dome JS, et al. Giant cell tumor of bone with pulmonary metastases. Med Pediatr Oncol. 2003;41:454–9. doi:10.​1002/​mpo.​10258.PubMed
14.
go back to reference Nahal A, Ajlan A, Alcindor T, Turcotte R. Dedifferentiated giant cell tumour of bone in the form of low-grade fibroblastic osteogenic sarcoma: case report of a unique presentation with follow-up. Curr Oncol. 2010;17:71–6.PubMedCentralPubMed Nahal A, Ajlan A, Alcindor T, Turcotte R. Dedifferentiated giant cell tumour of bone in the form of low-grade fibroblastic osteogenic sarcoma: case report of a unique presentation with follow-up. Curr Oncol. 2010;17:71–6.PubMedCentralPubMed
15.
go back to reference Wülling M, Engels C, Jesse N, Werner M, Delling G, Kaiser E. The nature of giant cell tumor of bone. J Cancer Res Clin Oncol. 2001;127:467–74.PubMed Wülling M, Engels C, Jesse N, Werner M, Delling G, Kaiser E. The nature of giant cell tumor of bone. J Cancer Res Clin Oncol. 2001;127:467–74.PubMed
17.
go back to reference Wülling M, Delling G, Kaiser E. The origin of the neoplastic stromal cell in giant cell tumor of bone. Hum Pathol. 2003;34:983–93.PubMed Wülling M, Delling G, Kaiser E. The origin of the neoplastic stromal cell in giant cell tumor of bone. Hum Pathol. 2003;34:983–93.PubMed
18.
go back to reference Roessner A, von Bassewitz DB, Schlake W, Thorwesten G, Grundmann E. Biologic characterization of human bone tumors III. Giant cell tumor of bone. A combined electron microscopical, histochemical, and autoradiographical study. Pathol Res Pract. 1984;178:431–40.PubMed Roessner A, von Bassewitz DB, Schlake W, Thorwesten G, Grundmann E. Biologic characterization of human bone tumors III. Giant cell tumor of bone. A combined electron microscopical, histochemical, and autoradiographical study. Pathol Res Pract. 1984;178:431–40.PubMed
20.
go back to reference Itonaga I, Schulze E, Burge PD, Gibbons CLMH, Ferguson D, Athanasou NA. Phenotypic characterization of mononuclear and multinucleated cells of giant cell reparative granuloma of small bones. J Pathol. 2002;198:30–6. doi:10.1002/path.1184.PubMed Itonaga I, Schulze E, Burge PD, Gibbons CLMH, Ferguson D, Athanasou NA. Phenotypic characterization of mononuclear and multinucleated cells of giant cell reparative granuloma of small bones. J Pathol. 2002;198:30–6. doi:10.​1002/​path.​1184.PubMed
21.
go back to reference Miyamoto N, Higuchi Y, Tajima M, Ito M, Tsurudome M, Nishio M, et al. Spindle-shaped cells derived from giant-cell tumor of bone support differentiation of blood monocytes to osteoclast-like cells. J Orthop Res Off Publ Orthop Res Soc. 2000;18:647–54. doi:10.1002/jor.1100180418. Miyamoto N, Higuchi Y, Tajima M, Ito M, Tsurudome M, Nishio M, et al. Spindle-shaped cells derived from giant-cell tumor of bone support differentiation of blood monocytes to osteoclast-like cells. J Orthop Res Off Publ Orthop Res Soc. 2000;18:647–54. doi:10.​1002/​jor.​1100180418.
22.
go back to reference Morgan T, Atkins GJ, Trivett MK, Johnson SA, Kansara M, Schlicht SL, et al. Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB. Am J Pathol. 2005;167:117–28.PubMedCentralPubMed Morgan T, Atkins GJ, Trivett MK, Johnson SA, Kansara M, Schlicht SL, et al. Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB. Am J Pathol. 2005;167:117–28.PubMedCentralPubMed
23.
go back to reference Liao TS, Yurgelun MB, Chang S-S, Zhang H-Z, Murakami K, Blaine TA, et al. Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. J Orthop Res Off Publ Orthop Res Soc. 2005;23:203–9. doi:10.1016/j.orthres.2004.06.018. Liao TS, Yurgelun MB, Chang S-S, Zhang H-Z, Murakami K, Blaine TA, et al. Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. J Orthop Res Off Publ Orthop Res Soc. 2005;23:203–9. doi:10.​1016/​j.​orthres.​2004.​06.​018.
24.
go back to reference Bridge JA, Neff JR, Bhatia PS, Sanger WG, Murphey MD. Cytogenetic findings and biologic behavior of giant cell tumors of bone. Cancer. 1990;65:2697–703.PubMed Bridge JA, Neff JR, Bhatia PS, Sanger WG, Murphey MD. Cytogenetic findings and biologic behavior of giant cell tumors of bone. Cancer. 1990;65:2697–703.PubMed
25.
go back to reference Horton MA, Rimmer EF, Lewis D, Pringle JA, Fuller K, Chambers TJ. Cell surface characterization of the human osteoclast: phenotypic relationship to other bone marrow-derived cell types. J Pathol. 1984;144:281–94. doi:10.1002/path.1711440410.PubMed Horton MA, Rimmer EF, Lewis D, Pringle JA, Fuller K, Chambers TJ. Cell surface characterization of the human osteoclast: phenotypic relationship to other bone marrow-derived cell types. J Pathol. 1984;144:281–94. doi:10.​1002/​path.​1711440410.PubMed
26.
go back to reference Flanagan AM, Nui B, Tinkler SM, Horton MA, Williams DM, Chambers TJ. The multinucleate cells in giant cell granulomas of the jaw are osteoclasts. Cancer. 1988;62:1139–45.PubMed Flanagan AM, Nui B, Tinkler SM, Horton MA, Williams DM, Chambers TJ. The multinucleate cells in giant cell granulomas of the jaw are osteoclasts. Cancer. 1988;62:1139–45.PubMed
27.
go back to reference Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T, et al. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci USA. 1990;87:7260–4.PubMedCentralPubMed Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T, et al. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci USA. 1990;87:7260–4.PubMedCentralPubMed
28.
go back to reference Branstetter DG, Nelson SD, Manivel JC, Blay J-Y, Chawla S, Thomas DM, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18:4415–24. doi:10.1158/1078-0432.CCR-12-0578. Branstetter DG, Nelson SD, Manivel JC, Blay J-Y, Chawla S, Thomas DM, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18:4415–24. doi:10.​1158/​1078-0432.​CCR-12-0578.
29.
go back to reference Atkins GJ, Kostakis P, Vincent C, Farrugia AN, Houchins JP, Findlay DM, et al. RANK Expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. J Bone Miner Res Off J Am Soc Bone Miner Res. 2006;21:1339–49. doi:10.1359/jbmr.060604. Atkins GJ, Kostakis P, Vincent C, Farrugia AN, Houchins JP, Findlay DM, et al. RANK Expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. J Bone Miner Res Off J Am Soc Bone Miner Res. 2006;21:1339–49. doi:10.​1359/​jbmr.​060604.
30.
go back to reference Huang L, Xu J, Wood DJ, Zheng MH. Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: possible involvement in tumor cell-induced osteoclast-like cell formation. Am J Pathol. 2000;156:761–7.PubMedCentralPubMed Huang L, Xu J, Wood DJ, Zheng MH. Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: possible involvement in tumor cell-induced osteoclast-like cell formation. Am J Pathol. 2000;156:761–7.PubMedCentralPubMed
31.
go back to reference Kartsogiannis V, Zhou H, Horwood NJ, Thomas RJ, Hards DK, Quinn JM, et al. Localization of RANKL (receptor activator of NF kappa B ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone. 1999;25:525–34.PubMed Kartsogiannis V, Zhou H, Horwood NJ, Thomas RJ, Hards DK, Quinn JM, et al. Localization of RANKL (receptor activator of NF kappa B ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone. 1999;25:525–34.PubMed
32.
go back to reference Roux S, Amazit L, Meduri G, Guiochon-Mantel A, Milgrom E, Mariette X. RANK (receptor activator of nuclear factor kappa B) and RANK ligand are expressed in giant cell tumors of bone. Am J Clin Pathol. 2002;117:210–6. doi:10.1309/BPET-F2PE-P2BD-J3P3.PubMed Roux S, Amazit L, Meduri G, Guiochon-Mantel A, Milgrom E, Mariette X. RANK (receptor activator of nuclear factor kappa B) and RANK ligand are expressed in giant cell tumors of bone. Am J Clin Pathol. 2002;117:210–6. doi:10.​1309/​BPET-F2PE-P2BD-J3P3.PubMed
33.
go back to reference Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, et al. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol. 1999;145:527–38.PubMedCentralPubMed Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, et al. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol. 1999;145:527–38.PubMedCentralPubMed
34.
go back to reference Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–76.PubMed Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–76.PubMed
35.
go back to reference Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95:3597–602.PubMedCentralPubMed Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95:3597–602.PubMedCentralPubMed
36.
go back to reference Atkins GJ, Haynes DR, Graves SE, Evdokiou A, Hay S, Bouralexis S, et al. Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res Off J Am Soc Bone Miner Res. 2000;15:640–9. doi:10.1359/jbmr.2000.15.4.640. Atkins GJ, Haynes DR, Graves SE, Evdokiou A, Hay S, Bouralexis S, et al. Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res Off J Am Soc Bone Miner Res. 2000;15:640–9. doi:10.​1359/​jbmr.​2000.​15.​4.​640.
39.
go back to reference Gorunova L, Vult von Steyern F, Storlazzi CT, Bjerkehagen B, Follerås G, Heim S, et al. Cytogenetic analysis of 101 giant cell tumors of bone: nonrandom patterns of telomeric associations and other structural aberrations. Genes Chromosomes Cancer. 2009;48:583–602. doi:10.1002/gcc.20667.PubMed Gorunova L, Vult von Steyern F, Storlazzi CT, Bjerkehagen B, Follerås G, Heim S, et al. Cytogenetic analysis of 101 giant cell tumors of bone: nonrandom patterns of telomeric associations and other structural aberrations. Genes Chromosomes Cancer. 2009;48:583–602. doi:10.​1002/​gcc.​20667.PubMed
40.
go back to reference Bardi G, Pandis N, Mandahl N, Heim S, Sfikas K, Willén H, et al. Chromosomal abnormalities in giant cell tumors of bone. Cancer Genet Cytogenet. 1991;57:161–7.PubMed Bardi G, Pandis N, Mandahl N, Heim S, Sfikas K, Willén H, et al. Chromosomal abnormalities in giant cell tumors of bone. Cancer Genet Cytogenet. 1991;57:161–7.PubMed
41.
go back to reference Haque AU, Moatasim A. Giant cell tumor of bone: a neoplasm or a reactive condition? Int J Clin Exp Pathol. 2008;1:489–501.PubMedCentralPubMed Haque AU, Moatasim A. Giant cell tumor of bone: a neoplasm or a reactive condition? Int J Clin Exp Pathol. 2008;1:489–501.PubMedCentralPubMed
42.
go back to reference Langer F, Pritzker KP, Gross AE, Shapiro II. Giant cell tumor associated with trauma. Clin Orthop. 1982;(164):245–8. Langer F, Pritzker KP, Gross AE, Shapiro II. Giant cell tumor associated with trauma. Clin Orthop. 1982;(164):245–8.
44.
go back to reference Byers VS, Levin AS, Johnston JO, Hackett AJ. Quantitative immunofluorescence studies of the tumor antigen-bearing cell in giant cell tumor of bone and osteogenic sarcoma. Cancer Res. 1975;35:2520–31.PubMed Byers VS, Levin AS, Johnston JO, Hackett AJ. Quantitative immunofluorescence studies of the tumor antigen-bearing cell in giant cell tumor of bone and osteogenic sarcoma. Cancer Res. 1975;35:2520–31.PubMed
45.
go back to reference James IE, Dodds RA, Olivera DL, Nuttall ME, Gowen M. Human osteoclastoma-derived stromal cells: correlation of the ability to form mineralized nodules in vitro with formation of bone in vivo. J Bone Miner Res Off J Am Soc Bone Miner Res. 1996;11:1453–60. doi:10.1002/jbmr.5650111012. James IE, Dodds RA, Olivera DL, Nuttall ME, Gowen M. Human osteoclastoma-derived stromal cells: correlation of the ability to form mineralized nodules in vitro with formation of bone in vivo. J Bone Miner Res Off J Am Soc Bone Miner Res. 1996;11:1453–60. doi:10.​1002/​jbmr.​5650111012.
47.
go back to reference 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;158:331–4. doi:10.2214/ajr.158.2.1729794.PubMed 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;158:331–4. doi:10.​2214/​ajr.​158.​2.​1729794.PubMed
48.
go back to reference Alberghini M, Kliskey K, Krenacs T, Picci P, Kindblom L, Forsyth R, et al. Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone. Virchows Arch Int J Pathol. 2010;456:97–103. doi:10.1007/s00428-009-0863-2. Alberghini M, Kliskey K, Krenacs T, Picci P, Kindblom L, Forsyth R, et al. Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone. Virchows Arch Int J Pathol. 2010;456:97–103. doi:10.​1007/​s00428-009-0863-2.
49.
go back to reference McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant-cell tumor of bone. J Bone Joint Surg Am. 1986;68:235–42.PubMed McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant-cell tumor of bone. J Bone Joint Surg Am. 1986;68:235–42.PubMed
50.
go back to reference Saiz P, Virkus W, Piasecki P, Templeton A, Shott S, Gitelis S. Results of giant cell tumor of bone treated with intralesional excision. Clin Orthop. 2004;424:221–6.PubMed Saiz P, Virkus W, Piasecki P, Templeton A, Shott S, Gitelis S. Results of giant cell tumor of bone treated with intralesional excision. Clin Orthop. 2004;424:221–6.PubMed
51.
52.
go back to reference Kivioja AH, Blomqvist C, Hietaniemi K, Trovik C, Walloe A, Bauer HCF, et al. 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 Kivioja AH, Blomqvist C, Hietaniemi K, Trovik C, Walloe A, Bauer HCF, et al. 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/​1745367071001481​5.PubMed
53.
go back to reference Boons HW, Keijser LCM, Schreuder HWB, Pruszczynski M, Lemmens JAM, Veth RPH. Oncologic and functional results after treatment of giant cell tumors of bone. Arch Orthop Trauma Surg. 2002;122:17–23.PubMed Boons HW, Keijser LCM, Schreuder HWB, Pruszczynski M, Lemmens JAM, Veth RPH. Oncologic and functional results after treatment of giant cell tumors of bone. Arch Orthop Trauma Surg. 2002;122:17–23.PubMed
56.
go back to reference Labs K, Perka C, Schmidt RG. Treatment of stages 2 and 3 giant-cell tumor. Arch Orthop Trauma Surg. 2001;121:83–6.PubMed Labs K, Perka C, Schmidt RG. Treatment of stages 2 and 3 giant-cell tumor. Arch Orthop Trauma Surg. 2001;121:83–6.PubMed
57.
go back to reference Saini R, Bali K, Bachhal V, Mootha AK, Dhillon MS, Gill SS. En bloc excision and autogenous fibular reconstruction for aggressive giant cell tumor of distal radius: a report of 12 cases and review of literature. J Orthop Surg. 2011;6:14. doi:10.1186/1749-799X-6-14. Saini R, Bali K, Bachhal V, Mootha AK, Dhillon MS, Gill SS. En bloc excision and autogenous fibular reconstruction for aggressive giant cell tumor of distal radius: a report of 12 cases and review of literature. J Orthop Surg. 2011;6:14. doi:10.​1186/​1749-799X-6-14.
58.
go back to reference Futani H, Okumura Y, Fukuda Y, Fukunaga S, Hasegawa S, Yoshiya S. Giant cell tumor of the sternum: a case report and review of the literature. Anticancer Res. 2008;28:4117–20.PubMed Futani H, Okumura Y, Fukuda Y, Fukunaga S, Hasegawa S, Yoshiya S. Giant cell tumor of the sternum: a case report and review of the literature. Anticancer Res. 2008;28:4117–20.PubMed
60.
go back to reference Blackley HR, Wunder JS, Davis AM, White LM, Kandel R, Bell RS. Treatment of giant-cell tumors of long bones with curettage and bone-grafting. J Bone Joint Surg Am. 1999;81:811–20.PubMed Blackley HR, Wunder JS, Davis AM, White LM, Kandel R, Bell RS. Treatment of giant-cell tumors of long bones with curettage and bone-grafting. J Bone Joint Surg Am. 1999;81:811–20.PubMed
61.
go back to reference Liu HS, Wang JW. Treatment of giant cell tumor of bone: a comparison of local curettage and wide resection. Chang Yi Xue Za Zhi Chang Ji Nian Yi Yuan Chang Gung Med J Chang Gung Meml Hosp. 1998;21:37–43. Liu HS, Wang JW. Treatment of giant cell tumor of bone: a comparison of local curettage and wide resection. Chang Yi Xue Za Zhi Chang Ji Nian Yi Yuan Chang Gung Med J Chang Gung Meml Hosp. 1998;21:37–43.
65.
go back to reference Lee FY, Montgomery M, Hazan EJ, Keel SB, Mankin HJ, Kattapuram S. Recurrent giant-cell tumor presenting as a soft-tissue mass. A report of four cases. J Bone Joint Surg Am. 1999;81:703–7.PubMed Lee FY, Montgomery M, Hazan EJ, Keel SB, Mankin HJ, Kattapuram S. Recurrent giant-cell tumor presenting as a soft-tissue mass. A report of four cases. J Bone Joint Surg Am. 1999;81:703–7.PubMed
66.
go back to reference 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. 2005;(435):211–8. 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. 2005;(435):211–8.
67.
go back to reference 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;134:969–78. doi:10.1007/s00432-008-0370-x.PubMed 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;134:969–78. doi:10.​1007/​s00432-008-0370-x.PubMed
68.
go back to reference Kafchitsas K, Habermann B, Proschek D, Kurth A, Eberhardt C. Functional results after giant cell tumor operation near knee joint and the cement radiolucent zone as indicator of recurrence. Anticancer Res. 2010;30:3795–9.PubMed Kafchitsas K, Habermann B, Proschek D, Kurth A, Eberhardt C. Functional results after giant cell tumor operation near knee joint and the cement radiolucent zone as indicator of recurrence. Anticancer Res. 2010;30:3795–9.PubMed
69.
go back to reference Zhen W, Yaotian H, Songjian L, Ge L, Qingliang W. Giant-cell tumour of bone. The long-term results of treatment by curettage and bone graft. J Bone Joint Surg Br. 2004;86:212–6.PubMed Zhen W, Yaotian H, Songjian L, Ge L, Qingliang W. Giant-cell tumour of bone. The long-term results of treatment by curettage and bone graft. J Bone Joint Surg Br. 2004;86:212–6.PubMed
70.
go back to reference Malawer MM, Bickels J, Meller I, Buch RG, Henshaw RM, Kollender Y. Cryosurgery in the treatment of giant cell tumor. A long-term followup study. Clin Orthop. 1999;(359):176–88. Malawer MM, Bickels J, Meller I, Buch RG, Henshaw RM, Kollender Y. Cryosurgery in the treatment of giant cell tumor. A long-term followup study. Clin Orthop. 1999;(359):176–88.
71.
go back to reference Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, et al. The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. J Bone Joint Surg Br. 2010;92:1475–9.PubMed Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, et al. The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. J Bone Joint Surg Br. 2010;92:1475–9.PubMed
72.
go back to reference Jones KB, DeYoung BR, Morcuende JA, Buckwalter JA. Ethanol as a local adjuvant for giant cell tumor of bone. Iowa Orthop J. 2006;26:69–76.PubMedCentralPubMed Jones KB, DeYoung BR, Morcuende JA, Buckwalter JA. Ethanol as a local adjuvant for giant cell tumor of bone. Iowa Orthop J. 2006;26:69–76.PubMedCentralPubMed
73.
go back to reference Eckardt JJ, Grogan TJ. Giant cell tumor of bone. Clin Orthop. 1986;(204):45–58. Eckardt JJ, Grogan TJ. Giant cell tumor of bone. Clin Orthop. 1986;(204):45–58.
74.
go back to reference Nicholson NC, Ramp WK, Kneisl JS, Kaysinger KK. Hydrogen peroxide inhibits giant cell tumor and osteoblast metabolism in vitro. Clin Orthop. 1998;347:250–60.PubMed Nicholson NC, Ramp WK, Kneisl JS, Kaysinger KK. Hydrogen peroxide inhibits giant cell tumor and osteoblast metabolism in vitro. Clin Orthop. 1998;347:250–60.PubMed
75.
go back to reference Ward WG Sr, Li G 3rd. Customized treatment algorithm for giant cell tumor of bone: report of a series. Clin Orthop. 2002;(397):259–70. Ward WG Sr, Li G 3rd. Customized treatment algorithm for giant cell tumor of bone: report of a series. Clin Orthop. 2002;(397):259–70.
76.
77.
go back to reference Dürr HR, Maier M, Jansson V, Baur A, Refior HJ. Phenol as an adjuvant for local control in the treatment of giant cell tumour of the bone. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 1999;25:610–8. doi:10.1053/ejso.1999.0716. Dürr HR, Maier M, Jansson V, Baur A, Refior HJ. Phenol as an adjuvant for local control in the treatment of giant cell tumour of the bone. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 1999;25:610–8. doi:10.​1053/​ejso.​1999.​0716.
78.
go back to reference Trieb K, Bitzan P, Lang S, Dominkus M, Kotz R. Recurrence of curetted and bone-grafted giant-cell tumours with and without adjuvant phenol therapy. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2001;27:200–2. doi:10.1053/ejso.2000.1086. Trieb K, Bitzan P, Lang S, Dominkus M, Kotz R. Recurrence of curetted and bone-grafted giant-cell tumours with and without adjuvant phenol therapy. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2001;27:200–2. doi:10.​1053/​ejso.​2000.​1086.
79.
go back to reference McCarthy EF. Giant-cell tumor of bone: an historical perspective. Clin Orthop. 1980;(153):14–25. McCarthy EF. Giant-cell tumor of bone: an historical perspective. Clin Orthop. 1980;(153):14–25.
80.
go back to reference Malone S, O’Sullivan B, Catton C, Bell R, Fornasier V, Davis A. Long-term follow-up of efficacy and safety of megavoltage radiotherapy in high-risk giant cell tumors of bone. Int J Radiat Oncol Biol Phys. 1995;33:689–94. doi:10.1016/0360-3016(95)00159-V.PubMed Malone S, O’Sullivan B, Catton C, Bell R, Fornasier V, Davis A. Long-term follow-up of efficacy and safety of megavoltage radiotherapy in high-risk giant cell tumors of bone. Int J Radiat Oncol Biol Phys. 1995;33:689–94. doi:10.​1016/​0360-3016(95)00159-V.PubMed
81.
go back to reference Micke O, Bruns F, Eich HT, Muecke R, Buentzel J, Willich N, et al. Radiation therapy for giant cell tumors of bone: Long-term results of a multicenter study in Germany. Int J Radiat Oncol Biol Phys. 2005;63:S108. doi:10.1016/j.ijrobp.2005.07.183. Micke O, Bruns F, Eich HT, Muecke R, Buentzel J, Willich N, et al. Radiation therapy for giant cell tumors of bone: Long-term results of a multicenter study in Germany. Int J Radiat Oncol Biol Phys. 2005;63:S108. doi:10.​1016/​j.​ijrobp.​2005.​07.​183.
82.
go back to reference Hug EB, Muenter MW, Adams JA, de Vries A, Rosenberg AE, Munzenrider JE. 3-D-conformal radiation therapy for pediatric giant cell tumors of the skull base. Strahlenther Onkol Organ Dtsch Röntgenges Al. 2002;178:239–44. Hug EB, Muenter MW, Adams JA, de Vries A, Rosenberg AE, Munzenrider JE. 3-D-conformal radiation therapy for pediatric giant cell tumors of the skull base. Strahlenther Onkol Organ Dtsch Röntgenges Al. 2002;178:239–44.
83.
go back to reference Roeder F, Timke C, Zwicker F, Thieke C, Bischof M, Debus J, et al. Intensity modulated radiotherapy (IMRT) in benign giant cell tumors–a single institution case series and a short review of the literature. Radiat Oncol Lond Engl. 2010;5:18. doi:10.1186/1748-717X-5-18. Roeder F, Timke C, Zwicker F, Thieke C, Bischof M, Debus J, et al. Intensity modulated radiotherapy (IMRT) in benign giant cell tumors–a single institution case series and a short review of the literature. Radiat Oncol Lond Engl. 2010;5:18. doi:10.​1186/​1748-717X-5-18.
84.
go back to reference Brien EW, Mirra JM, Kessler S, Suen M, Ho JK, Yang WT. Benign giant cell tumor of bone with osteosarcomatous transformation (“dedifferentiated” primary malignant GCT): report of two cases. Skeletal Radiol. 1997;26:246–55.PubMed Brien EW, Mirra JM, Kessler S, Suen M, Ho JK, Yang WT. Benign giant cell tumor of bone with osteosarcomatous transformation (“dedifferentiated” primary malignant GCT): report of two cases. Skeletal Radiol. 1997;26:246–55.PubMed
86.
go back to reference Layalle I, Flandroy P, Trotteur G, Dondelinger RF. Arterial embolization of bone metastases: is it worthwhile? J Belge Radiol. 1998;81:223–5.PubMed Layalle I, Flandroy P, Trotteur G, Dondelinger RF. Arterial embolization of bone metastases: is it worthwhile? J Belge Radiol. 1998;81:223–5.PubMed
88.
91.
go back to reference Emori M, Kaya M, Sasaki M, Wada T, Yamaguchi T, Yamashita T. Pre-operative selective arterial embolization as a neoadjuvant therapy for proximal humerus giant cell tumor of bone: radiological and histological evaluation. Jpn J Clin Oncol. 2012;42:851–5. doi:10.1093/jjco/hys090.PubMed Emori M, Kaya M, Sasaki M, Wada T, Yamaguchi T, Yamashita T. Pre-operative selective arterial embolization as a neoadjuvant therapy for proximal humerus giant cell tumor of bone: radiological and histological evaluation. Jpn J Clin Oncol. 2012;42:851–5. doi:10.​1093/​jjco/​hys090.PubMed
92.
go back to reference Lin PP, Guzel VB, Moura MF, Wallace S, Benjamin RS, Weber KL, et al. Long-term follow-up of patients with giant cell tumor of the sacrum treated with selective arterial embolization. Cancer. 2002;95:1317–25. doi:10.1002/cncr.10803.PubMed Lin PP, Guzel VB, Moura MF, Wallace S, Benjamin RS, Weber KL, et al. Long-term follow-up of patients with giant cell tumor of the sacrum treated with selective arterial embolization. Cancer. 2002;95:1317–25. doi:10.​1002/​cncr.​10803.PubMed
96.
go back to reference Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res Off J Am Soc Bone Miner Res. 2004;19:1059–66. doi:10.1359/JBMR.040305. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res Off J Am Soc Bone Miner Res. 2004;19:1059–66. doi:10.​1359/​JBMR.​040305.
97.
go back to reference Body J-J, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2006;12:1221–8. doi:10.1158/1078-0432.CCR-05-1933. Body J-J, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2006;12:1221–8. doi:10.​1158/​1078-0432.​CCR-05-1933.
98.
go back to reference Chawla S, Henshaw R, Seeger L, Choy E, Blay J-Y, 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;14:901–8. doi:10.1016/S1470-2045(13)70277-8.PubMed Chawla S, Henshaw R, Seeger L, Choy E, Blay J-Y, 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;14:901–8. doi:10.​1016/​S1470-2045(13)70277-8.PubMed
99.
100.
101.
go back to reference Chakarun CJ, Forrester DM, Gottsegen CJ, Patel DB, White EA, Matcuk GR Jr. Giant cell tumor of bone: review, mimics, and new developments in treatment. Radiogr Rev Publ Radiol Soc N Am Inc. 2013;33:197–211. doi:10.1148/rg.331125089. Chakarun CJ, Forrester DM, Gottsegen CJ, Patel DB, White EA, Matcuk GR Jr. Giant cell tumor of bone: review, mimics, and new developments in treatment. Radiogr Rev Publ Radiol Soc N Am Inc. 2013;33:197–211. doi:10.​1148/​rg.​331125089.
102.
go back to reference Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E. Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:e200–2. doi:10.1200/JCO.2012.46.4255. Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E. Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:e200–2. doi:10.​1200/​JCO.​2012.​46.​4255.
103.
go back to reference Kaban LB, Mulliken JB, Ezekowitz RA, Ebb D, Smith PS, Folkman J. Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a. Pediatrics. 1999;103:1145–9.PubMed Kaban LB, Mulliken JB, Ezekowitz RA, Ebb D, Smith PS, Folkman J. Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a. Pediatrics. 1999;103:1145–9.PubMed
104.
go back to reference Kaban LB, Troulis MJ, Ebb D, August M, Hornicek FJ, Dodson TB. Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2002;60:1103–11 discussion 1111–1113. Kaban LB, Troulis MJ, Ebb D, August M, Hornicek FJ, Dodson TB. Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2002;60:1103–11 discussion 1111–1113.
106.
go back to reference Cheng YY, Huang L, Lee KM, Xu JK, Zheng MH, Kumta SM. Bisphosphonates induce apoptosis of stromal tumor cells in giant cell tumor of bone. Calcif Tissue Int. 2004;75:71–7. doi:10.1007/s00223-004-0120-2.PubMed Cheng YY, Huang L, Lee KM, Xu JK, Zheng MH, Kumta SM. Bisphosphonates induce apoptosis of stromal tumor cells in giant cell tumor of bone. Calcif Tissue Int. 2004;75:71–7. doi:10.​1007/​s00223-004-0120-2.PubMed
111.
112.
go back to reference Agarwal A, Larsen BT, Buadu LD, Dunn J, Crawford R, Daniel J, et al. Denosumab chemotherapy for recurrent giant-cell tumor of bone: a case report of neoadjuvant use enabling complete surgical resection. Case Rep Oncol Med. 2013;2013:496351. doi:10.1155/2013/496351.PubMedCentralPubMed Agarwal A, Larsen BT, Buadu LD, Dunn J, Crawford R, Daniel J, et al. Denosumab chemotherapy for recurrent giant-cell tumor of bone: a case report of neoadjuvant use enabling complete surgical resection. Case Rep Oncol Med. 2013;2013:496351. doi:10.​1155/​2013/​496351.PubMedCentralPubMed
113.
114.
go back to reference Li GN, Wang SP, Xue X, Qu XJ, Liu HP. Monoclonal antibody-related drugs for cancer therapy. Drug Discov Ther. 2013;7:178–84.PubMed Li GN, Wang SP, Xue X, Qu XJ, Liu HP. Monoclonal antibody-related drugs for cancer therapy. Drug Discov Ther. 2013;7:178–84.PubMed
117.
go back to reference Smith LT, Mayerson J, Nowak NJ, Suster D, Mohammed N, Long S, et al. 20q11.1 amplification in giant-cell tumor of bone: array CGH, FISH, and association with outcome. Genes Chromosomes Cancer. 2006;45:957–66. doi:10.1002/gcc.20354.PubMed Smith LT, Mayerson J, Nowak NJ, Suster D, Mohammed N, Long S, et al. 20q11.1 amplification in giant-cell tumor of bone: array CGH, FISH, and association with outcome. Genes Chromosomes Cancer. 2006;45:957–66. doi:10.​1002/​gcc.​20354.PubMed
Metadata
Title
Giant cell tumour of bone: new treatments in development
Authors
A. López-Pousa
J. Martín Broto
T. Garrido
J. Vázquez
Publication date
01-06-2015
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 6/2015
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1268-5

Other articles of this Issue 6/2015

Clinical and Translational Oncology 6/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine