Postoperative Outcomes with and without Neoadjuvant Denosumab in Grade-III Giant Cell Tumor of the Proximal Femur: A Comparative Retrospective Study

Abstract

Objective

To retrospectively compare the impact of using neoadjuvant denosumab for Campanacci grade-III giant cell tumor (GCT) of the proximal femur involving the hip joint.

Methods

We retrospectively reviewed 18 cases of Campanacci grade-III GCT of the proximal femur receiving surgery between January 2014 and December 2019 from our hospital. One group of 10 patients received weekly neoadjuvant denosumab 120 mg for 4 weeks, while the other group of 8 patients did not receive denosumab before surgery. Two patients were subjected to intralesional curettage while the others received resection and hip arthroplasty. Comparisons were made using unpaired t-test and Fisher's exact test. Functional outcomes were assessed by revised Musculoskeletal Tumor Society (MSTS) score and Harris Hip Score (HHS) at 6 weeks, 6 months, and 12 months of follow-up, as well as incidence of recurrence.

Results

The comparison of the mean MSTS scores of the denosumab and non-denosumab groups was as follows: 24.0 ± 6.5 versus 20.0 ± 6.0 (p = 0.04) at 6 weeks respectively; 26.0 ± 5.0 versus 23.0 ± 0.67 (p = 0.04) at 6 months respectively; and 28.8 ± 1.7 versus 29.5 ± 0.33 (p = 0.35) at 12 months respectively. The comparison of HHSs between the denosumab and non-denosumab groups was as follows: 61.02 ± 7.36 versus 48.52 ± 3.97 (p = 0.03) at 6 weeks respectively; 81.1 ± 2.97 versus 79.15 ± 3.24 (p = 0.82) at 6 months respectively; and 89.84 ± 3.75 versus 90.05 ± 3.00 (p = 0.38) at 12 months respectively. There was no recurrence.

Conclusion

Denosumab was clinically effective in improving the short-term functional outcomes, but long-term functional outcomes remained similar between the groups. We did not find an increased recurrence rate in the denosumab group.

Resumo

Objetivo

Comparar retrospectivamente o impacto do uso de denosumabe neoadjuvante em tumores de células gigantes (TCG) de grau III de Campanacci no fêmur proximal com acometimento da articulação do quadril.

Métodos

Avaliamos retrospectivamente 18 casos de TCG de grau III de Campanacci do fêmur proximal que foram submetidos à cirurgia entre janeiro de 2014 e dezembro de 2019 em nosso hospital. Um grupo de 10 pacientes receberam denosumabe neoadjuvante em dose de 120 mg uma vez por semana por 4 semanas, enquanto outro grupo, com 8 pacientes, não recebeu denosumabe antes da cirurgia. Dois pacientes foram submetidos à curetagem intralesional e os demais, à ressecção e artroplastia de quadril. As comparações foram feitas usando o teste t não pareado e o teste exato de Fisher. Os resultados funcionais foram avaliados pelo escore revisto da Musculoskeletal Tumor Society (MSTS) e pelo escore de quadril de Harris (Harris Hip Score, HSS) em 6 semanas, 6 meses e 12 meses de acompanhamento. A incidência de recidiva também foi determinada.

Resultados

A comparação das médias dos escores MSTS entre os grupos com e sem denosumabe foi de 24,0 ± 6,5 versus 20,0 ± 6,0 (p = 0,04) em 6 semanas, respectivamente; 26,0 ± 5,0 versus 23,0 ± 0,67 (p = 0,04) em 6 meses, respectivamente; e 28,8 ± 1,7 versus 29,5 ± 0,33 (p = 0,35) em 12 meses, respectivamente. A comparação das médias das pontuações no HSS entre os grupos com e sem denosumabe foi de 61,02 ± 7,36 versus 48,52 ± 3,97 (p = 0,03) em 6 semanas, respectivamente; 81,1 ± 2,97 versus 79,15 ± 3,24 (p = 0,82) em 6 meses, respectivamente; e 89,84 ± 3,75 versus 90,05 ± 3,00 (p = 0,38) em 12 meses, respectivamente. Não houve recidiva.

Conclusão

O denosumabe foi clinicamente eficaz na melhora dos desfechos funcionais em curto prazo, mas os desfechos funcionais em longo prazo foram semelhantes entre ambos os grupos. Não observamos aumento na taxa de recidiva no grupo com denosumabe.

Keywords

bone neoplasms - denosumab - giant cell tumor - hip - proximal femoral fractures

Palavras-chave

denosumab - fraturas proximais do fêmur - neoplasias ósseas - quadril - tumores de células gigantes

Authors' Contributions

Each author contributed individually and significantly to the development of this article: MUA and SMEA: conceptualization, data collection, writing – review & editing, study design, data interpretation, and writing – original draft; BS: conceptualization, data collection, and writing – review & editing; and HK and AA: study design, data interpretation, and writing – original draft. All authors approved the final draft and stand accountable for the validity of the data.

Work developed at the Trauma & Orthopedic Departments, Dr. Ruth KM Pfau Civil Hospital, Karachi, Pakistan.

Publication History

Received: 11 September 2024

Accepted: 13 March 2025

Article published online:
10 July 2025

• References

• 1 Sahito B, Ali SME, Farooqui SF, Abro A, Ahmed J, Younis. Resection and reconstruction with and without neoadjuvant denosumab in campanacci grade III giant cell tumors of proximal humerus: a retrospective comparative study. Eur J Orthop Surg Traumatol 2023; 33 (01) 81-88
• 2 Olivera P, Perez E, Ortega A, Terual R, Gomes C, Moreno LF. et al. Estrogen receptor expression in giant cell tumors of the bone. Hum Pathol 2002; 33 (02) 165-169
• 3 Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am 1987; 69 (01) 106-114
• 4 Sahito B, Ali SME, Qamar J, Katto MS, Ahmed MW, Jamil M. A Comparison of Outcomes of ‘Extensor Carpi Ulnaris Tenodesis’ versus ‘No Tenodesis’ after Resection of the Distal Ulna in Patients with Giant Cell Tumor. J Hand Surg Asian Pac Vol 2022; 27 (01) 110-116
• 5 Rutkowski P, Gaston L, Borkowska A, Stacchiotti S, Gelderblom H, Baldi GG. 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 (09) 1384-1390
• 6 Khan SA, Kumar A, Inna P, Bakhshi S, Rastogi S. Endoprosthetic replacement for giant cell tumour of the proximal femur. J Orthop Surg (Hong Kong) 2009; 17 (03) 280-283
• 7 Gosal GS, Boparai A, Makkar GS. Long-Term Outcome of Endoprosthetic Replacement for Proximal Femur Giant Cell Tumor. Niger J Surg 2015; 21 (02) 143-145
• 8 Wijsbek AE, Vazquez-Garcia BL, Grimer RJ. et al. Giant cell tumour of the proximal femur: Is joint-sparing management ever successful?. Bone Joint J 2014; 96-B [phone]
• 9 Iamthanaporn K, Chareancholvanich K, Pornrattanamaneewong C. Reasons for revision of failed hemiarthroplasty: Are there any differences between unipolar and bipolar?. Eur J Orthop Surg Traumatol 2018; 28 (06) 1117-1123
• 10 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 (04) 260-268
• 11 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 tumor of bone. Ann Surg Oncol 2015; 22 (09) 2860-2868
• 12 Alaqaili SI, Abduljabbar AM, Altaho AJ, Khan AA, Alherabi JA. Malignant Sarcomatous Transformation of Benign Giant Cell Tumor of Bone after Treatment with Denosumab Therapy: A Literature Review of Reported Cases. Cureus 2018; 10 (12) e3792
• 13 Sano K, Suehara Y, Okubo T, Sasa K, Kurihara T, Akaike K. et al. Preoperative denosumab treatment with curettage may be a risk factor for recurrence of giant cell tumor of bone. J Orthop Surg (Hong Kong) 2020; 28 (02) 2309499020929786
• 14 Errani C, Tsukamoto S, Leone G, Akahane M, Cevolani L, Tanzi P. et al. Higher local recurrence rates after intralesional surgery for giant cell tumor of the proximal femur compared to other sites. Eur J Orthop Surg Traumatol 2017; 27 (06) 813-819
• 15 Lau BC, Scribani M, Lassiter T, Wittstein J. Correlation of Single Assessment Numerical Evaluation Score for Sport and Activities of Daily Living to Modified Harris Hip Score and Hip Outcome Score in Patients Undergoing Arthroscopic Hip Surgery. Am J Sports Med 2019; 47 (11) 2646-2650
• 16 Petranova T, Sheytanov I, Monov S, Nestorova R, Rashkov R. Denosumab improves bone mineral density and microarchitecture and reduces bone pain in women with osteoporosis with and without glucocorticoid treatment. Biotechnol Biotechnol Equip 2014; 28 (06) 1127-1137
• 17 Chen X, Li H, Zhu S, Wang Y, Qian W. Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis. BMC Musculoskelet Disord 2020; 21 (01) 256
• 18 Agarwal MG, Gundavda MK, Gupta R, Reddy R. Does Denosumab Change the Giant Cell Tumor Treatment Strategy? Lessons Learned From Early Experience. Clin Orthop Relat Res 2018; 476 (09) 1773-1782
• 19 Sahito B, Ali SME, Kumar D, Kumar J, Hussain N, Lakho T. Role of denosumab before resection and reconstruction in giant cell tumors of bone: a single-centered retrospective cohort study. Eur J Orthop Surg Traumatol 2022; 32 (03) 567-574
• 20 Müller DA, Beltrami G, Scoccianti G, Campanacci DA, Franchi A, Capanna R. Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series. World J Surg Oncol 2016; 14 (01) 281
• 21 Cheng H, Chen BP, Soleas IM, Ferko NC, Cameron CG, Hinoul P. Prolonged Operative Duration Increases Risk of Surgical Site Infections: A Systematic Review. Surg Infect (Larchmt) 2017; 18 (06) 722-735
• 22 Teo BJX, Yeo W, Chong HC, Tan AHC. Surgical site infection after primary total knee arthroplasty is associated with a longer duration of surgery. J Orthop Surg (Hong Kong) 2018; 26 (02) 2309499018785647