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Denosumab-treated Giant Cell Tumors of Bone: A Clinicopathologic Analysis of 35 Cases From the French Group of Bone Pathology.

Denosumab治疗的骨巨细胞瘤: 法国骨病理学组 35 例临床病理分析。

  • 影响因子:6.06
  • DOI:10.1097/PAS.0000000000001388
  • 作者列表:"Treffel M","Lardenois E","Larousserie F","Karanian M","Gomez-Brouchet A","Bouvier C","Le Loarer F","Aubert S","de Pinieux G","Audard V","Rios M","Sirveaux F","Vignaud JM","Gauchotte G","Marie B
  • 发表时间:2020-01-01
Abstract

:Denosumab, an antibody directed against receptor activator of nuclear factor-κB ligand (RANKL), has recently been introduced in the treatment strategy of giant cell tumor of bone. In this study, we assessed the tumor changes induced by denosumab in a national multicentric series of 35 cases (French Bone Pathology Group network-ResOs). Tissue specimens collected before and after denosumab treatment were investigated for RANKL, H3.3 G34W, p63, and Ki-67 expression, and for H3F3A mutation. These parameters were put in correspondance with clinical and radiologic presentation to identify prognostic factors, and more specifically, predictive markers of an optimal histologic response to denosumab, identified as a ≥50% loss in giant cells with fibrosis and ossification. The main changes in posttreatment specimens showed an induction of ossification (P=2.10), an increased fibrosis (P=3.10), and a major decrease in giant cells (P=6.10). No significant change in mononuclear tumor cell density and in patterns of expression of RANKL (P=0.061) and H3.3 G34W was observed (P=0.061). An optimal histologic response to denosumab treatment was associated with an enhanced progression-free survival (P=0.010 in univariate analyses; P=0.040 in multivariate analyses). The initial number of giant cells was predictive of the histologic response to treatment (P=0.016). In summary, denosumab treatment induced radical changes in the tumor. The histologic response, despite the absence of objective regression of the mononuclear cells, was associated with an enhanced progression-free survival. Greater numbers of giant cells represented the only predictive indication of an optimal histologic response to denosumab treatment.

摘要

: Denosumab是一种针对核因子-κ b受体活化因子配体 (RANKL) 的抗体,最近被引入骨巨细胞瘤的治疗策略。在这项研究中,我们评估了denosumab在 35 例国家多中心系列 (法国骨病理学组网络-ResOs) 中诱导的肿瘤变化。研究denosumab治疗前后收集的组织标本RANKL、H3.3 G34W、p63 和Ki-67 表达以及H3F3A突变。这些参数与临床和放射学表现相对应,以确定预后因素,更具体地说,是denosumab最佳组织学反应的预测标志物。确定为纤维化和骨化的巨细胞丢失 ≥ 50%。治疗后标本的主要变化显示诱导骨化 (P = 2.10),纤维化增加 (P = 3.10),巨细胞大量减少 (P = 6.10)。未观察到单核肿瘤细胞密度和RANKL (P = 0.061) 和H3.3 G34W (P = 0.061) 表达模式的显著变化。Denosumab治疗的最佳组织学反应与无进展生存期增强相关 (单变量分析P = 0.010; 多变量分析P = 0.040)。巨细胞的初始数量可预测治疗的组织学反应 (P = 0.016)。总之,denosumab治疗诱导了肿瘤的根治性变化。尽管没有单核细胞的客观消退,但组织学反应与无进展生存期增强相关。更多数量的巨细胞代表了denosumab治疗最佳组织学反应的唯一预测指标。

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发表时间:2020-03-01
DOI:10.1177/1078155219842277
作者列表:["Gyori DJ","Bullington SM","Crawford BS","Vernon VP"]

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骨肿瘤方向

骨肿瘤是发生于骨骼或其附属组织的肿瘤。有良性,恶性之分,良性骨肿瘤易根治,预后良好,恶性骨肿瘤发展迅速,预后不佳,死亡率高。

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