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

Gonzalo Luengo-Alonso, Maria Mellado-Romero, Shai Shemesh, Luis Ramos-Pascua, Juan Abelardo Augusto Pretell

Research output: Contribution to journalReview article

1 Citation (Scopus)

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.

Original languageEnglish (US)
JournalArchives of Orthopaedic and Trauma Surgery
DOIs
StatePublished - Jan 1 2019

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Giant Cell Tumor of Bone
Therapeutics
Giant Cell Tumors
Recurrence
Pain
Denosumab
Neoplasm Metastasis
Bone and Bones
Neoplasms
Muscle Fatigue
Neoadjuvant Therapy
PubMed
Observational Studies
Monoclonal Antibodies
Demography

Keywords

  • Denosumab
  • Fatigue
  • Local recurrence
  • Metastasis
  • Systematic review

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Denosumab treatment for giant-cell tumor of bone : a systematic review of the literature. / Luengo-Alonso, Gonzalo; Mellado-Romero, Maria; Shemesh, Shai; Ramos-Pascua, Luis; Pretell, Juan Abelardo Augusto.

In: Archives of Orthopaedic and Trauma Surgery, 01.01.2019.

Research output: Contribution to journalReview article

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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.",
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T2 - a systematic review of the literature

AU - Luengo-Alonso, Gonzalo

AU - Mellado-Romero, Maria

AU - Shemesh, Shai

AU - Ramos-Pascua, Luis

AU - Pretell, Juan Abelardo Augusto

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N2 - 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.

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KW - Fatigue

KW - Local recurrence

KW - Metastasis

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