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Erschienen in: Archives of Orthopaedic and Trauma Surgery 10/2019

15.03.2019 | Orthopaedic Surgery

Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature

verfasst von: Gonzalo Luengo-Alonso, Maria Mellado-Romero, Shai Shemesh, Luis Ramos-Pascua, Juan Pretell-Mazzini

Erschienen in: Archives of Orthopaedic and Trauma Surgery | Ausgabe 10/2019

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Abstract

Background

Denosumab is a human monoclonal antibody (mAb) that specifically inhibits tumor-associated bone lysis through the RANKL pathway and has been used as neoadjuvant therapy for giant-cell tumor of bone (GCTB) in surgical as well as non-surgical cases. The purpose of this systematic review of the literature, therefore, is to investigate: (1) demographic characteristics of patients affected by GCTBs treated with denosumab and the clinical impact, as well as, possible complications associated with its use (2) oncological outcomes in terms of local recurrence rate (LRR) and development of lung metastasis, and (3) characteristics of its treatment effect in terms of clinical, radiological, and histological response.

Methods

A systematic review of the literature was conducted using PubMed, EMBASE, and COCHRANE search including the following terms and Boolean operators: “Denosumab” AND “primary bone tumor”, “denosumab” AND “giant cell tumor”, “denosumab” AND “treatment”, and finally, “denosumab” AND “giant cell tumor” AND “treatment” since 2000. After applying inclusion and exclusion criteria, a total of 19 articles were included. The quality of the included studies was assessed using STROBE for the assessment of observational studies.

Results

A total of 1095 patients were included across all 19 studies. Across all the studies included, there were 615 females and 480 males. The mean patient age was 33.7 ± 8.3 years when starting the denosumab treatment. The pooled weighted local recurrence rate was 9% (95% CI 6–12%) and the pooled weighted metastases rate was 3% (95% CI 1–7%). The most common adverse event was fatigue and muscular pain. Radiologic response was estimated to occur in 66–100% of the patients. A significant reduction in pain under denosumab treatment was reported in seven studies and additional improvement in function and mobility was reported by several authors. Only two studies reported musculoskeletal tumor society (MSTS) scores which were better after denosumab treatment.

Conclusions

The use of denosumab as an adjuvant treatment of GCTB has shown a positive but variable histological response with consistent radiological changes and several types of adverse effects. There is a positive clinical response in terms of pain relief with decrease on the morbidity of surgical procedures to be performed. Finally, oncological outcomes are disparate with neither effect on metastatic disease nor local recurrence rates.

Level of evidence

IV.
Literatur
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Zurück zum Zitat Fletcher CDM, Unni KK, Mertens F, World Health Organization, International Agency for Research on Cancer (2002) Pathology and genetics of tumours of soft tissue and bone. IARC Press, Geneva, p 427 Fletcher CDM, Unni KK, Mertens F, World Health Organization, International Agency for Research on Cancer (2002) Pathology and genetics of tumours of soft tissue and bone. IARC Press, Geneva, p 427
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Zurück zum Zitat Rekhi B, Verma V, Gulia A, Jambhekar NA, Desai S, Juvekar SL et al (2017) Clinicopathological features of a series of 27 cases of post-denosumab treated giant cell tumors of bones: a single institutional experience at a Tertiary Cancer Referral Centre, India. Pathol Oncol Res 23(1):157–164. https://doi.org/10.1007/s12253-016-0123-0 CrossRef Rekhi B, Verma V, Gulia A, Jambhekar NA, Desai S, Juvekar SL et al (2017) Clinicopathological features of a series of 27 cases of post-denosumab treated giant cell tumors of bones: a single institutional experience at a Tertiary Cancer Referral Centre, India. Pathol Oncol Res 23(1):157–164. https://​doi.​org/​10.​1007/​s12253-016-0123-0 CrossRef
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Zurück zum Zitat Wang B, Chen W, Xie X, Tu J, Huang G, Zou C et al (2017) Development and validation of a prognostic index to predict pulmonary metastasis of giant cell tumor of bone. Oncotarget 8(64):108054–63. Available from: http://www.oncotarget.com/fulltext/22478. Accessed 27 Nov 2018 Wang B, Chen W, Xie X, Tu J, Huang G, Zou C et al (2017) Development and validation of a prognostic index to predict pulmonary metastasis of giant cell tumor of bone. Oncotarget 8(64):108054–63. Available from: http://​www.​oncotarget.​com/​fulltext/​22478. Accessed 27 Nov 2018
Metadaten
Titel
Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature
verfasst von
Gonzalo Luengo-Alonso
Maria Mellado-Romero
Shai Shemesh
Luis Ramos-Pascua
Juan Pretell-Mazzini
Publikationsdatum
15.03.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Orthopaedic and Trauma Surgery / Ausgabe 10/2019
Print ISSN: 0936-8051
Elektronische ISSN: 1434-3916
DOI
https://doi.org/10.1007/s00402-019-03167-x

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