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Metastatic giant cell tumour of bone: a narrative review of management options and approaches.

ABSTRACT: Giant cell tumour of bone (GCTB) is a locally aggressive bone neoplasm with a rare tendency to metastasise, most commonly to the lungs. The management of metastatic GCTB (metGCTB) is controversial due to its unpredictable behaviour. Asymptomatic patients should be monitored radiologically and undergo treatment only when disease progression occurs. Surgery is recommended for resectable metGCTB. Denosumab, a monoclonal antibody which inhibits receptor activator of nuclear factor-κB ligand, is recommended for unresectable metGCTB with evidence from phase II trials demonstrating its safety and efficacy. Relapse after denosumab withdrawal may occur and prolonged treatment may be associated with serious adverse events, thus further research is warranted to inform a maintenance regimen with reduced dosing and frequency. Combined denosumab and bisphosphonate therapy has the potential to achieve sustained disease control or remission in unresectable metGCTB without requiring long-term treatment and should be evaluated in prospective trials. Various novel agents have demonstrated in vitro and anecdotal efficacy and warrant further evaluation.

SUBMITTER: Xu R

PROVIDER: S-EPMC9303226 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Metastatic giant cell tumour of bone: a narrative review of management options and approaches.

Xu Ruiwen R Choong Peter F M PFM

ANZ journal of surgery 20220210 4

Giant cell tumour of bone (GCTB) is a locally aggressive bone neoplasm with a rare tendency to metastasise, most commonly to the lungs. The management of metastatic GCTB (metGCTB) is controversial due to its unpredictable behaviour. Asymptomatic patients should be monitored radiologically and undergo treatment only when disease progression occurs. Surgery is recommended for resectable metGCTB. Denosumab, a monoclonal antibody which inhibits receptor activator of nuclear factor-κB ligand, is reco ...[more]

PMID: 35143093

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Project description:The rare benign giant cell tumour of bone (GCTB) is defined by an almost unique mutation in the H3.3 family of histone genes H3-3A or H3-3B; however, the same mutation is occasionally found in primary malignant bone tumours which share many features with the benign variant. Moreover, lung metastases can occur despite the absence of malignant histological features in either the primary or metastatic lesions. Herein we investigated the genetic events of 17 GCTBs including benign and malignant variants and the methylation profiles of 122 bone tumour samples including GCTBs. Benign GCTBs possessed few somatic alterations and no other known drivers besides the H3.3 mutation, whereas all malignant tumours harboured at least one additional driver mutation and exhibited genomic features resembling osteosarcomas, including high mutational burden, additional driver event(s), and a high degree of aneuploidy. The H3.3 mutation was found to predate the development of aneuploidy. In contrast to osteosarcomas, malignant H3.3-mutated tumours were enriched for a variety of alterations involving TERT, other than amplification, suggesting telomere dysfunction in the transformation of benign to malignant GCTB. DNA sequencing of the benign metastasising GCTB revealed no additional driver alterations; polyclonal seeding in the lung was identified, implying that the metastatic lesions represent an embolic event. Unsupervised clustering of DNA methylation profiles revealed that malignant H3.3-mutated tumours are distinct from their benign counterpart, and other bone tumours. Differential methylation analysis identified CCND1, encoding cyclin D1, as a plausible cancer driver gene in these tumours because hypermethylation of the CCND1 promoter was specific for GCTBs. We report here the genomic and methylation patterns underlying the rare clinical phenomena of benign metastasising and malignant transformation of GCTB and show how the combination of genomic and epigenomic findings could potentially distinguish benign from malignant GCTBs, thereby predicting aggressive behaviour in challenging diagnostic cases. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Project description:Background and objectiveGiant mediastinal tumors are represented by well-defined histological variants originating from different structures and compartments while their clinical presentation may be similar and characterized by the same set of symptoms, the well-known mediastinal syndrome (MS). In 80% of cases the MS is caused by malignant neoplasms, such as lung tumors, in 10-18% of cases by hematological neoplasms and in 2-3% by benign causes. In this review we investigated the medical treatment of main giant mediastinal tumors, focusing our interest on the objective response rate (ORR), as it represents the most suitable parameter to predict the volumetric reduction of the neoplasm and, consequently, the regression of their most severe complication, the MS. We will also cover the supportive and symptomatic treatment of MS.MethodsWe performed a deep analysis of the recent international literature published on PUBMED, UpToDate and Medline. The literature search was undertaken from origin until November 30th, 2021, and we only considered publications in English.Key content and findingsConsidering the variety of pathologies that can occur in the mediastinum, a rapid histological characterization of the neoplasm is mandatory. In fact, the treatment of these neoplasms includes different approaches, sometimes used in combination, which include chemotherapy, radiotherapy, and surgery. The vena cava syndrome (VCS), due to its high mortality, is considered an oncological emergency and, therefore, requires effective treatments carried out urgently, evaluated in multidisciplinary meeting.ConclusionsThe treatment of MS includes both antiblastic treatments and therapies directed to the symptoms. Among the former, chemotherapy, target therapy, radiation and surgery may be used, according to the etiology of MS. Among the latters, supportive therapies, interventional radiology procedures such as stenting may help manage this syndrome, despite the prognosis is poor in most cases and linked to the histology of the tumor, which therefore represents the most important prognostic factor.

Dataset Information

Metastatic giant cell tumour of bone: a narrative review of management options and approaches.

Publications

Metastatic giant cell tumour of bone: a narrative review of management options and approaches.

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