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Published in: World Journal of Surgical Oncology 1/2019

Open Access 01-12-2019 | giant cell tumor | Research

Retrospective analysis of 51 intralesionally treated cases with progressed giant cell tumor of the bone: local adjuvant use of hydrogen peroxide reduces the risk for tumor recurrence

Authors: Georg W. Omlor, Jessica Lange, Marcus Streit, Simone Gantz, Christian Merle, Thomas Germann, Gunhild Mechtersheimer, Jörg Fellenberg, Burkhard Lehner

Published in: World Journal of Surgical Oncology | Issue 1/2019

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Abstract

Background

Giant cell tumor of the bone (GCT) has high local recurrence rates and the prognosis is hard to predict. We therefore retrospectively analyzed clinical outcome and recurrences of 51 GCT cases focusing on the effects of adjuvant local use of hydrogen peroxide.

Methods

The series enclosed 51 advanced GCT cases of the upper and lower extremities (n = 27 Campanacci grade III; n = 24 grade II; n = 39 surgery at our institution, n = 12 elsewhere). Mean follow-up was 88.3 (± 62.0) months. Surgical details, histology, metastases, recurrences, and interview-based data on satisfaction and function including the Musculoskeletal Tumor Society (MSTS) score were evaluated. It was investigated whether hydrogen peroxide was additionally used or not to clean the tumor cavity after curettage as we hypothesized influence on recurrences. To analyze the underlying mechanisms, GCT-derived stromal cell lines were cultured in vitro and tested for cell viability and apoptosis after treatment with hydrogen peroxide. Statistical analysis was performed with Student’s t tests, analysis of variance (ANOVA) with post hoc testing, Mann-Whitney U tests, chi-square tests, Kaplan-Meier analysis, and multivariate Cox regression analysis.

Results

The whole series had 21 recurrences (41%). Eleven recurrences were found (28%) after surgery at our institution. Kaplan-Meier analysis of cumulative recurrence-free survival revealed at 2 years follow-up 69% (72%, only our institution) and at 10 years follow-up 54% (68%, only our institution). Intralesional resection was performed by vigorous curettage, burring, and defect filling with either polymethylmethacrylate bone cement (n = 45) or cancellous bone from the iliac crest (n = 6). Univariate chi-square analysis showed significantly lower recurrence rate after bone cement filling (2.3-fold, p = 0.024). Cleaning of the lesion cavity with hydrogen peroxide significantly reduced recurrence rate (whole collective 2.9-fold, p = 0.004; our institution 2.8-fold, p = 0.04) and significantly increased cumulative recurrence-free survival rate (whole collective at 10 years follow-up 74% versus 31%, p = 0.002; our institution 79% versus 48%, p = 0.02) compared to cases without hydrogen peroxide treatment. In multivariate analysis, significant risk factors for recurrence were pathological fracture (hazard ratio 3.7; p = 0.04), high mitosis rate (hazard ratio 15.6; p = 0.01), and lack of hydrogen peroxide use (hazard ratio 6.0; p = 0.02). In vitro cell culture analyses found apoptotic nature of hydrogen peroxide induced GCT cell death.

Conclusions

The present series proved for the first time that additional cleaning of the tumor cavity with hydrogen peroxide before defect filling significantly reduced recurrence rate and significantly increased recurrence-free survival in advanced but intralesionally treated GCT cases.
Literature
1.
go back to reference Werner M. Giant cell tumour of bone: morphological, biological and histogenetical aspects. Int Orthop. 2006;30:484–9.CrossRef Werner M. Giant cell tumour of bone: morphological, biological and histogenetical aspects. Int Orthop. 2006;30:484–9.CrossRef
2.
go back to reference Jeys LM, Suneja R, Chami G, Grimer RJ, Carter SR, Tillman RM. Impending fractures in giant cell tumours of the distal femur: incidence and outcome. Int Orthop. 2006;30:135–8.CrossRef Jeys LM, Suneja R, Chami G, Grimer RJ, Carter SR, Tillman RM. Impending fractures in giant cell tumours of the distal femur: incidence and outcome. Int Orthop. 2006;30:135–8.CrossRef
3.
go back to reference Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69:106–14.CrossRef Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69:106–14.CrossRef
4.
go back to reference Muheremu A, Niu X. Pulmonary metastasis of giant cell tumor of bones. World J Surg Oncol. 2014;12:261.CrossRef Muheremu A, Niu X. Pulmonary metastasis of giant cell tumor of bones. World J Surg Oncol. 2014;12:261.CrossRef
5.
go back to reference 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;134:969–78.CrossRef 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;134:969–78.CrossRef
6.
go back to reference Wijsbek AE, Vazquez-Garcia BL, Grimer RJ, Carter SR, Abudu AA, Tillman RM, Jeys L. Giant cell tumour of the proximal femur: is joint-sparing management ever successful? Bone Joint J. 2014;96:127–31.CrossRef Wijsbek AE, Vazquez-Garcia BL, Grimer RJ, Carter SR, Abudu AA, Tillman RM, Jeys L. Giant cell tumour of the proximal femur: is joint-sparing management ever successful? Bone Joint J. 2014;96:127–31.CrossRef
7.
go back to reference Errani C, Tsukamoto S, Mavrogenis AF. How safe and effective is denosumab for bone giant cell tumour? Int Orthop. 2017;41:2397–400.CrossRef Errani C, Tsukamoto S, Mavrogenis AF. How safe and effective is denosumab for bone giant cell tumour? Int Orthop. 2017;41:2397–400.CrossRef
8.
go back to reference Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T. Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. World J Surg Oncol. 2018;16:160.CrossRef Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T. Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. World J Surg Oncol. 2018;16:160.CrossRef
9.
go back to reference Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018;16:191.CrossRef Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018;16:191.CrossRef
10.
go back to reference Wang H, Wan N, Hu Y. Giant cell tumour of bone: a new evaluating system is necessary. Int Orthop. 2012;36:2521–7.CrossRef Wang H, Wan N, Hu Y. Giant cell tumour of bone: a new evaluating system is necessary. Int Orthop. 2012;36:2521–7.CrossRef
11.
go back to reference Lun DX, Hu YC, Yang XG, Wang Z, Yu XC, Wu SJ, Ye ZM, Wang H. Development and proposal of a scoring system for giant cell tumour of the bone around the knee. Int Orthop. 2018;42:203–13.CrossRef Lun DX, Hu YC, Yang XG, Wang Z, Yu XC, Wu SJ, Ye ZM, Wang H. Development and proposal of a scoring system for giant cell tumour of the bone around the knee. Int Orthop. 2018;42:203–13.CrossRef
12.
go back to reference Oh JH, Yoon PW, Lee SH, Cho HS, Kim WS, Kim HS. Surgical treatment of giant cell tumour of long bone with anhydrous alcohol adjuvant. Int Orthop. 2006;30:490–4.CrossRef Oh JH, Yoon PW, Lee SH, Cho HS, Kim WS, Kim HS. Surgical treatment of giant cell tumour of long bone with anhydrous alcohol adjuvant. Int Orthop. 2006;30:490–4.CrossRef
13.
go back to reference Malek F, Krueger P, Hatmi ZN, Malayeri AA, Faezipour H, O’Donnell RJ. Local control of long bone giant cell tumour using curettage, burring and bone grafting without adjuvant therapy. Int Orthop. 2006;30:495–8.CrossRef Malek F, Krueger P, Hatmi ZN, Malayeri AA, Faezipour H, O’Donnell RJ. Local control of long bone giant cell tumour using curettage, burring and bone grafting without adjuvant therapy. Int Orthop. 2006;30:495–8.CrossRef
14.
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 Relat Res. 2004;424:221–6.CrossRef 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 Relat Res. 2004;424:221–6.CrossRef
15.
go back to reference Turcotte RE, Wunder JS, Isler MH, Bell RS, Schachar N, Masri BA, Moreau G, Davis AM. Giant cell tumor of long bone: a Canadian Sarcoma Group study. Clin Orthop Relat Res. 2002;397:248–58.CrossRef Turcotte RE, Wunder JS, Isler MH, Bell RS, Schachar N, Masri BA, Moreau G, Davis AM. Giant cell tumor of long bone: a Canadian Sarcoma Group study. Clin Orthop Relat Res. 2002;397:248–58.CrossRef
16.
go back to reference Errani C, Ruggieri P, Asenzio MA, 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.CrossRef Errani C, Ruggieri P, Asenzio MA, 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.CrossRef
17.
go back to reference Kivioja AH, Blomqvist C, Hietaniemi K, Trovik C, Walloe A, Bauer HC, Jorgensen PH, Bergh P, Folleras 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.CrossRef Kivioja AH, Blomqvist C, Hietaniemi K, Trovik C, Walloe A, Bauer HC, Jorgensen PH, Bergh P, Folleras 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.CrossRef
18.
go back to reference Li D, Zhang J, Li Y, Xia J, Yang Y, Ren M, Liao Y, Yu S, Li X, Shen Y, Zhang Y, Yang Z. Surgery methods and soft tissue extension are the potential risk factors of local recurrence in giant cell tumor of bone. World J Surg Oncol. 2016;14:114.CrossRef Li D, Zhang J, Li Y, Xia J, Yang Y, Ren M, Liao Y, Yu S, Li X, Shen Y, Zhang Y, Yang Z. Surgery methods and soft tissue extension are the potential risk factors of local recurrence in giant cell tumor of bone. World J Surg Oncol. 2016;14:114.CrossRef
19.
go back to reference Gao ZH, Yin JQ, Xie XB, Zou CY, Huang G, Wang J, Shen JN. Local control of giant cell tumors of the long bone after aggressive curettage with and without bone cement. BMC Musculoskelet Disord. 2014;15:330.CrossRef Gao ZH, Yin JQ, Xie XB, Zou CY, Huang G, Wang J, Shen JN. Local control of giant cell tumors of the long bone after aggressive curettage with and without bone cement. BMC Musculoskelet Disord. 2014;15:330.CrossRef
20.
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.CrossRef 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.CrossRef
21.
go back to reference Zuo D, Zheng L, Sun W, Fu D, Hua Y, Cai Z. Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis. World J Surg Oncol. 2013;11:156.CrossRef Zuo D, Zheng L, Sun W, Fu D, Hua Y, Cai Z. Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis. World J Surg Oncol. 2013;11:156.CrossRef
22.
go back to reference Algawahmed H, Turcotte R, Farrokhyar F, Ghert M. High-speed burring with and without the use of surgical adjuvants in the intralesional management of giant cell tumor of bone: a systematic review and meta-analysis. Sarcoma. 2010. https://doi.org/10.1155/2010/586090. Algawahmed H, Turcotte R, Farrokhyar F, Ghert M. High-speed burring with and without the use of surgical adjuvants in the intralesional management of giant cell tumor of bone: a systematic review and meta-analysis. Sarcoma. 2010. https://​doi.​org/​10.​1155/​2010/​586090.
23.
go back to reference Becker WT, Dohle J, Bernd L, Braun A, Cserhati M, Enderle A, Hovy L, Matejovsky Z, Szendroi M, Trieb K, Tunn PU. Local recurrence of giant cell tumor of bone after intralesional treatment with and without adjuvant therapy. J Bone Joint Surg Am. 2008;90:1060–7.CrossRef Becker WT, Dohle J, Bernd L, Braun A, Cserhati M, Enderle A, Hovy L, Matejovsky Z, Szendroi M, Trieb K, Tunn PU. Local recurrence of giant cell tumor of bone after intralesional treatment with and without adjuvant therapy. J Bone Joint Surg Am. 2008;90:1060–7.CrossRef
24.
go back to reference Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res. 1993;286:241–6. Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res. 1993;286:241–6.
26.
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 Relat Res. 1998;347:250–60.CrossRef Nicholson NC, Ramp WK, Kneisl JS, Kaysinger KK. Hydrogen peroxide inhibits giant cell tumor and osteoblast metabolism in vitro. Clin Orthop Relat Res. 1998;347:250–60.CrossRef
27.
go back to reference Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, Wunder JS. The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. J Bone Joint Surg Br. 2010;92:1475–9.CrossRef Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, Wunder JS. The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. J Bone Joint Surg Br. 2010;92:1475–9.CrossRef
28.
go back to reference Lujic N, Sopta J, Kovacevic R, Stevanovic V, Davidovic R. Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67. Int Orthop. 2016;40:2393–9.CrossRef Lujic N, Sopta J, Kovacevic R, Stevanovic V, Davidovic R. Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67. Int Orthop. 2016;40:2393–9.CrossRef
29.
go back to reference Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ. Giant cell tumor of bone. J Am Acad Orthop Surg. 2013;21:118–26.CrossRef Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ. Giant cell tumor of bone. J Am Acad Orthop Surg. 2013;21:118–26.CrossRef
31.
go back to reference Matsumoto Y, Okada Y, Fukushi J, Kamura S, Fujiwara T, Iida K, Koga M, Matsuda S, Harimaya K, Sakamoto A, Iwamoto Y. Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone. J Orthop Surg Res. 2010;5:85.CrossRef Matsumoto Y, Okada Y, Fukushi J, Kamura S, Fujiwara T, Iida K, Koga M, Matsuda S, Harimaya K, Sakamoto A, Iwamoto Y. Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone. J Orthop Surg Res. 2010;5:85.CrossRef
32.
go back to reference Rutkowski P, Gaston L, Borkowska A, Stacchiotti S, Gelderblom H, Baldi GG, Palmerini E, Casali P, Gronchi A, Parry M, Campanacci DA, Scoccianti G, Wagrodzki M, Ferrari S, Dijkstra S, Pieńkowski A, Grimer R. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - multicenter analysis outside clinical trial. Eur J Surg Oncol. 2018. https://doi.org/10.1016/j.ejso.2018.03.020. Rutkowski P, Gaston L, Borkowska A, Stacchiotti S, Gelderblom H, Baldi GG, Palmerini E, Casali P, Gronchi A, Parry M, Campanacci DA, Scoccianti G, Wagrodzki M, Ferrari S, Dijkstra S, Pieńkowski A, Grimer R. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - multicenter analysis outside clinical trial. Eur J Surg Oncol. 2018. https://​doi.​org/​10.​1016/​j.​ejso.​2018.​03.​020.
33.
go back to reference Palmerini E, Chawla NS, Ferrari S, Sudan M, Picci P, Marchesi E, Leopardi MP, Syed I, Sankhala KK, Parthasarathy P, Mendanha WE, Pierini M, Paioli A, Chawla SP. Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): for how long? Eur J Cancer. 2017;76:118–24.CrossRef Palmerini E, Chawla NS, Ferrari S, Sudan M, Picci P, Marchesi E, Leopardi MP, Syed I, Sankhala KK, Parthasarathy P, Mendanha WE, Pierini M, Paioli A, Chawla SP. Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): for how long? Eur J Cancer. 2017;76:118–24.CrossRef
34.
go back to reference Jamshidi K, Gharehdaghi M, Hajialiloo SS, Mirkazemi M, Ghaffarzadehgan K, Izanloo A. Denosumab in patients with giant cell tumor and its recurrence: a systematic review. Arch Bone Jt Surg. 2018;6:260–8.PubMedPubMedCentral Jamshidi K, Gharehdaghi M, Hajialiloo SS, Mirkazemi M, Ghaffarzadehgan K, Izanloo A. Denosumab in patients with giant cell tumor and its recurrence: a systematic review. Arch Bone Jt Surg. 2018;6:260–8.PubMedPubMedCentral
Metadata
Title
Retrospective analysis of 51 intralesionally treated cases with progressed giant cell tumor of the bone: local adjuvant use of hydrogen peroxide reduces the risk for tumor recurrence
Authors
Georg W. Omlor
Jessica Lange
Marcus Streit
Simone Gantz
Christian Merle
Thomas Germann
Gunhild Mechtersheimer
Jörg Fellenberg
Burkhard Lehner
Publication date
01-12-2019
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2019
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-019-1613-9

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