Abu-Zaid Ahmed, Alaqaili Sadiq Issa, Ahmad Syed Osama, Bin Hazzaa Ibrahim, Alharbi Hani
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Gulf J Oncolog. 2019 May;1(30):67-75.
Giant cell tumor of bone (GCTB) is a biologically benign osteolytic tumor that affects the metaphyseal/epiphyseal portions of bones. Histologically, GCTB is composed of osteoclast-like multinucleated giant cells that express receptor activator of nuclear factor kappa B (RANK), and neoplastic mesenchymal stromal cells that express RANK ligand (RANKL). The pathogenesis of GCTB is primarily attributable to the RANK-RANKL interaction, resulting in the activation of osteoclasts and the resultant osteolytic phenotype. Denosumab is a monoclonal antibody targeted against RANKL. In 2013, it was approved by the United States Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is inoperable, or initial surgery is expected to culminate in substantial morbidity. The aim of this study is to narratively review the current literature on the role of preoperative denosumab followed by surgery in the management of patients with GCTB. In brief, caution should be exercised in the interpretation of existing data on preoperative denosumab in the management of GCTB patients, owing to some critical limitations, for example, short follow-up and only a minority of patients have undergone intralesional surgery following denosumab therapy. All in all, administration of preoperative denosumab is associated with clinical, radiological, and histopathological therapeutic benefits. It is also associated with tolerability, safety, surgical downstaging and less morbid salvageable procedures. Preoperative denosumab does not seem to reduce the likelihood of local recurrence after intralesional therapy; a planned randomized phase III clinical trial (JCOG 1610) will holistically address this concern. Furthermore, more than ten cases of denosumab-related malignant transformation of GCTB have been reported in literature. Lastly, large-sized phase III randomized clinical trials with long-term follow-up data are warranted to withdraw concrete conclusions and recommendations.
骨巨细胞瘤（GCTB）是一种生物学行为上为良性的溶骨性肿瘤，累及骨骼的干骺端/骨骺部分。组织学上，GCTB由表达核因子κB受体激活剂（RANK）的破骨细胞样多核巨细胞和表达RANK配体（RANKL）的肿瘤性间充质基质细胞组成。GCTB的发病机制主要归因于RANK-RANKL相互作用，导致破骨细胞活化并产生溶骨表型。地诺单抗是一种靶向RANKL的单克隆抗体。2013年，它被美国食品药品监督管理局（FDA）批准用于治疗无法手术的成人和骨骼成熟的青少年GCTB患者，或预期初次手术会导致严重并发症的患者。本研究的目的是叙述性综述关于术前使用地诺单抗然后进行手术在GCTB患者管理中的作用的当前文献。简而言之，由于一些关键局限性，例如随访时间短且只有少数患者在接受地诺单抗治疗后进行了病灶内手术，在解释现有关于术前使用地诺单抗治疗GCTB患者的数据时应谨慎。总而言之，术前使用地诺单抗与临床、影像学和组织病理学治疗益处相关。它还与耐受性、安全性、手术降期以及较少并发症的挽救性手术相关。术前使用地诺单抗似乎并未降低病灶内治疗后局部复发的可能性；一项计划中的随机III期临床试验（JCOG 1610）将全面解决这一问题。此外，文献中已报道了十多例与地诺单抗相关的GCTB恶性转化病例。最后，需要有长期随访数据的大型III期随机临床试验才能得出具体结论和建议。
