地诺单抗治疗复发或难治骨巨细胞瘤疗效和安全性的初步观察

发布时间：2018-09-03 17:04

【摘要】：目的评价地诺单抗(denosumab)治疗骨巨细胞瘤(giant cell tumor,GCT)的短期疗效和安全性。方法回顾性分析2014年2月至12月,于我院接受地诺单抗治疗的25例GCT患者,其中男12例,女13例,平均年龄33.7(18~58)岁。所有患者均有明确GCT病理诊断,5例病理提示为GCT中的恶性。16例(治疗用药组)有影像学可评估病灶;9例(预防用药组)用药前已经接受外科治疗,体内无影像学可评估病灶,但因为外科边界不满意或病理提示恶性变,应用地诺单抗作为预防性治疗。全部患者每4周接受120 mg地诺单抗皮下注射,第8天和第15天增加2次负荷剂量。安全性评估指标主要包括药物副反应(临床症状和实验室检查异常)。疗效评估包括:治疗用药组(16例)应用实体瘤疗效评价标准(response evaluation criteria in solid tumors,RECIST);预防用药组(9例)观察指标为无事件生存率(event free survival,EFS)。除CT和MRI等常规影像学评估外,部分患者接受了二次活检手术和PET-CT检查,2例恶性GCT患者用药前进行了肿瘤组织核因子κB活化剂受体配体(receptor activator of nuclear factor-κB ligand,RANKL)表达水平的检测。结果以初次用药为随访开始时间,末次随访时间为2015年3月1日。平均随访时间6(4~12)个月。用药期间无死亡病例,患者均按计划用药,平均用药次数7.4(6~17)次,依从性好。副反应包括骨痛(4例)、低钙血症(3例)、发热(3例)、肿瘤破溃形成窦道(2例)、疲劳骨折(1例)。未见下颌骨坏死。治疗用药组16例中,RECIST评估显示:完全缓解1例、部分缓解8例、疾病稳定6例、疾病进展1例。3例接受二次活检手术,组织学均未见残留巨细胞瘤成分;1例复查PET-CT可见SUVmax摄取降至正常肌肉组织水平;2例用药前进行了肿瘤组织RANKL表达水平的检测,结果显示RANKL表达水平与疗效相关。预防用药组(9例)4个月和6个月的EFS均为100%。结论地诺单抗对于复发难治的GCT患者是一种安全有效的治疗手段,恶性GCT和伴发肺转移的病例也应考虑接受地诺单抗治疗。在评估地诺单抗疗效时,应在RECIST标准基础上结合活检和PET-CT结果。肿瘤组织RANKL表达水平与疗效具有相关性。
[Abstract]:Objective to evaluate the short-term efficacy and safety of (denosumab) in the treatment of giant cell tumor of bone (giant cell tumor,GCT). Methods from February to December, 2014, 25 patients with GCT were treated with dinomab in our hospital, including 12 males and 13 females, with an average age of 33.7 (1858) years. All the patients had definite pathological diagnosis of GCT. 5 cases were diagnosed as malignant in GCT. 16 cases (treatment group) had imaging to evaluate the lesions. 9 cases (prophylactic group) had received surgical treatment before medication, and no imaging could be used to evaluate the lesions in vivo. However, due to unsatisfactory surgical boundaries or pathological indications of malignancy, desnoxumab was used as a prophylactic treatment. All patients were subcutaneously injected with 120 mg desaminotumab every 4 weeks, and the loading dose was increased twice on day 8 and day 15. Safety assessment indicators mainly include adverse drug reactions (clinical symptoms and laboratory abnormalities). The evaluation of curative effect included: treatment group (16 cases) were treated with solid tumor evaluation standard (response evaluation criteria in solid tumors,RECIST), prophylactic drug group (9 cases) were observed as event free survival rate (event free survival,EFS). In addition to routine imaging evaluation such as CT and MRI, the expression of (receptor activator of nuclear factor- 魏 B ligand,RANKL, a receptor ligand of nuclear factor 魏 B activator, was detected in 2 patients with malignant GCT before treatment by secondary biopsy and PET-CT examination. Results the initial medication was used as the starting time, and the last time was March 1, 2015. The mean follow-up time was 6 (4 / 12) months. There were no death cases during the treatment, the patients were treated according to the plan, the average number of times was 7.4 (6 / 17), and the compliance was good. Side effects included bone pain (4 cases), hypocalcemia (3 cases), fever (3 cases), tumor rupture and formation of sinus tract (2 cases) and fatigue fracture (1 case). No osteonecrosis of the mandible was seen. The evaluation of RECIST showed that 1 case had complete remission, 8 cases had partial remission, 6 cases had stable disease, and 1 case had disease progression. Histologically, no residual giant cell tumor components were found in 1 case. PET-CT showed that SUVmax uptake decreased to normal muscle tissue level in 2 cases. The expression of RANKL in tumor tissue was detected in 2 cases before medication. The results showed that the expression level of RANKL was correlated with the curative effect. The EFS of preventive medication group (9 cases) was 100 at 4 months and 6 months. Conclusion Dinocumab is a safe and effective treatment for patients with refractory GCT and malignant GCT and patients with pulmonary metastasis should also be considered for treatment. In assessing the efficacy of dinolumab, biopsy and PET-CT results should be combined on the basis of RECIST criteria. The expression of RANKL in tumor tissue was correlated with the therapeutic effect.
【作者单位】：北京大学人民医院骨与软组织肿瘤治疗中心;
【分类号】：R738.1

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