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Abstract：
Giant cell tumour of bone (GCTB) is a rare tumour, generally managed with surgery. Treatment of the very rare unresectable advanced/metastatic GCTB is challenging and denosumab is the only current available medical option, an anti-RANKL monoclonal antibody inhibiting osteolysis. An uncommon but severe and treatment-limiting adverse event of denosumab is the osteonecrosis of the jaw (ONJ). The clinical management of GCTB patients stopping denosumab for medication-related (MR)-ONJ and the possible reintroduction of denosumab after MR-ONJ resolution is matter of debate. We performed a retrospective study to describe the incidence, clinical features and outcome of MR-ONJ in unresectable GCTB patients treated with denosumab at our Institution.
Retrospective, single-institutional study.
Adult patients receiving denosumab as antineoplastic therapy for GCTB and experiencing MR-ONJ at Fondazione IRCCS Istituto Nazionale Tumori of Milan between January 2008 and July 2019.
Incidence, time of onset and clinical features of MR-ONJ.
29 patients with locally advanced and/or metastatic GCTB treated with denosumab were identified. At a median follow-up of 70 months (range 1-125), 4 (13.8%) patients experienced MR-ONJ while on treatment, after 125, 119, 85 and 41 months of denosumab, respectively. All patients showed an ongoing tumour stabilisation with denosumab at the MR-ONJ onset and in all cases denosumab was stopped. All four patients were treated with ozone therapy. Two are waiting for surgery, two were already operated on. Both of them experienced disease progression and were thus rechallenged with denosumab. One is still on therapy after 25 months. The other had an MR-ONJ relapse after 39 months and was treated again with ozone therapy and surgery. She is under surveillance, GCTB being currently stable.
A clinical algorithm of denosumab rechallenge after complete resolution of MR-ONJ in progressing GCTB patients should be prospectively validated.
Retrospective, single-institutional study.
Adult patients receiving denosumab as antineoplastic therapy for GCTB and experiencing MR-ONJ at Fondazione IRCCS Istituto Nazionale Tumori of Milan between January 2008 and July 2019.
Incidence, time of onset and clinical features of MR-ONJ.
29 patients with locally advanced and/or metastatic GCTB treated with denosumab were identified. At a median follow-up of 70 months (range 1-125), 4 (13.8%) patients experienced MR-ONJ while on treatment, after 125, 119, 85 and 41 months of denosumab, respectively. All patients showed an ongoing tumour stabilisation with denosumab at the MR-ONJ onset and in all cases denosumab was stopped. All four patients were treated with ozone therapy. Two are waiting for surgery, two were already operated on. Both of them experienced disease progression and were thus rechallenged with denosumab. One is still on therapy after 25 months. The other had an MR-ONJ relapse after 39 months and was treated again with ozone therapy and surgery. She is under surveillance, GCTB being currently stable.
A clinical algorithm of denosumab rechallenge after complete resolution of MR-ONJ in progressing GCTB patients should be prospectively validated.
摘要：
骨巨细胞瘤（GCTB）是一种罕见的肿瘤，通常通过手术管理。治疗非常罕见的不可切除的晚期/转移性GCTB具有挑战性，而denosumab是目前唯一可用的医疗选择。抗RANKL单克隆抗体抑制骨溶解。denosumab的一种罕见但严重且治疗限制性的不良事件是颌骨坏死（ONJ）。GCTB患者因药物相关（MR）-ONJ而停止denosumab的临床管理以及MR-ONJ解决后可能重新引入denosumab是有争议的。我们进行了一项回顾性研究来描述发病率，在我们机构接受denosumab治疗的无法切除的GCTB患者中MR-ONJ的临床特征和结局。
回顾,单机构研究。
2008年1月至2019年7月，在米兰的FondazioneIRCCSIstitutoNazionaleTumori接受denosumab作为GCTB的抗肿瘤治疗并经历MR-ONJ的成年患者。
入射,MR-ONJ的发病时间和临床特征。
确定了29例用地诺单抗治疗的局部晚期和/或转移性GCTB患者。中位随访时间为70个月（范围1-125），4例（13.8%）患者在治疗期间经历了MR-ONJ，在Denosumab的125、119、85和41个月之后，分别。在MR-ONJ发作时，所有患者均显示denosumab持续稳定肿瘤，并且在所有情况下都停止了denosumab。所有四名患者均接受臭氧治疗。两个在等手术,两个已经手术了。他们俩都经历了疾病进展，因此被denosumab再次挑战。25个月后仍在接受治疗。另一个在39个月后MR-ONJ复发，再次接受臭氧治疗和手术治疗。她被监视着,GCTB目前稳定。
进展性GCTB患者MR-ONJ完全消退后denosumab再激发的临床算法应进行前瞻性验证。
回顾,单机构研究。
2008年1月至2019年7月，在米兰的FondazioneIRCCSIstitutoNazionaleTumori接受denosumab作为GCTB的抗肿瘤治疗并经历MR-ONJ的成年患者。
入射,MR-ONJ的发病时间和临床特征。
确定了29例用地诺单抗治疗的局部晚期和/或转移性GCTB患者。中位随访时间为70个月（范围1-125），4例（13.8%）患者在治疗期间经历了MR-ONJ，在Denosumab的125、119、85和41个月之后，分别。在MR-ONJ发作时，所有患者均显示denosumab持续稳定肿瘤，并且在所有情况下都停止了denosumab。所有四名患者均接受臭氧治疗。两个在等手术,两个已经手术了。他们俩都经历了疾病进展，因此被denosumab再次挑战。25个月后仍在接受治疗。另一个在39个月后MR-ONJ复发，再次接受臭氧治疗和手术治疗。她被监视着,GCTB目前稳定。
进展性GCTB患者MR-ONJ完全消退后denosumab再激发的临床算法应进行前瞻性验证。
