骨巨细胞瘤的肿瘤血运变化与地舒单抗用药时间的相关性研究

Study on the relationship between the changes of tumor blood supply and the treatment time of denosumab in giant cell tumor of bone

目的评价地舒单抗治疗骨巨细胞瘤后,肿瘤血运随时间的变化特点以及与用药时间的相关性。方法收集2015年1月至2017年12月接受地舒单抗治疗的骨巨细胞瘤患者38例。地舒单抗120mg皮下注射,每4周1次,初次用药后第8天和第15天各增加1次用药。患者在地舒单抗用药前和用药后不同时间(第1、3、6个月)分别接受相同肿瘤部位的增强CT检查,测量平扫CT值和增强CT值,并计算肿瘤部位的CT强化率。分析肿瘤的CT强化率随用药时间的变化特点。结果地舒单抗用药前病灶的平扫和增强CT值的平均值分别为(42.5±9.9)HU和(95.6±24.4)HU,平均强化率为2.25±0.62。用药前骶骨或骨盆病灶的强化率显著高于肢体病灶的CT强化率(P=0.007)。用药后第1、3、6个月的肿瘤平均强化率分别为1.64±0.42,1.43±0.40和1.38±0.36。用药后平均每月CT强化率降低情况如下:用药第1个月平均降低0.61(27.1%),第2~3个月平均每月降低0.105(4.65%),第4~6个月平均每月降低0.025(1.15%)。用药3个月以后,病灶的强化率无显著降低(P>0.05)。用药后第1、3、6个月的骶骨或骨盆与肢体骨肿瘤的平均强化率分别为1.75±0.42和1.28±0.23(P=0.005),1.49±0.41和1.34±0.32(P=0.226),1.41±0.35和1.33±0.30(P=0.229)。用药1个月后CT强化率的降低程度与初始CT强化率显著相关(r=0.619,P=0.000)。患者在接受治疗后,疼痛VAS评分显著降低(P=0.000),MSTS功能评分显著提高(P=0.000)。5例患者出现轻度低钙血症,未出现其他不良反应。结论术前应用地舒单抗辅助治疗骨巨细胞瘤,可以降低肿瘤组织的血运。在用药初期血运降低最为显著,随着用药时间的延长,血运的降低程度逐渐缩小。不建议在术前应用地舒单抗时间过长。

Objective To evaluate the time-dependent characteristics of tumor blood supply of giant cell tumor of bone after denosumab treatment and the correlation between the treatment time and the characteristics.Methods Thirty-eight cases of giant cell tumor of bone treated with denosumab were enrolled from January 2015 to December 2017.The dosage of denosumab was 120 mg subcutaneously injected once every 4 weeks,and the supplement dosage was on the 8th and 15th day after the initial application.The patients received contrast-enhanced CT examination of the same tumor site before and after the treatment(the 1st,3rd and 6th months)of denosumab.The values of plain and contrast-enhanced CT were measured,and the enhancement rate of the tumor site was calculated.The changing characteristics of CT enhancement rate of tumor with time were analyzed.Results The plain and enhanced CT values of tumor before denosumab treatment were(42.5±9.9)HU and(95.6±24.4)HU respectively,with an average enhancement rate of 2.25±0.62.The enhancement rate of sacral or pelvic lesions was significantly higher than that of limb lesions(P=0.007).The mean enhancement rates of the tumors were 1.64±0.42,1.43±0.40 and 1.38±0.36 in the first,the third and the sixth month after treatment.After treatment,the average monthly CT enhancement rate decreased as follows:0.61(27.1%)in the first month,0.105(4.65%)in the second to the third month,and it decreased by 0.025(1.15%)in the fourth to the sixth month.The enhancement rate of tumor was no longer significantly reduced 3 months post-treatment.The mean enhancement rates of sacral or pelvic and limb bone tumors post-treatment were 1.75±0.42 and 1.28±0.23(P=0.005)in the first month,1.49±0.41 and 1.34±0.32(P=0.226)in the third month,and 1.41±0.35 and 1.33±0.30(P=0.229)in the sixth month.There was a significant correlation between the reduction of CT enhancement rate in the first month and the initial CT enhancement rate(r=0.619,P=0.000).The VAS score of pain decreased significantly(P=0.000)and the MSTS function score increased significantly(P=0.000)after treatment.Mild hypocalcemia happened in 5 cases,and no other adverse effect was observed.Conclusion The preoperative application of denosumab in the treatment of giant cell tumor of bone can reduce the blood supply of tumor.The decrease of blood supply is the most significant at the beginning of the treatment.With the prolongation of the treatment time,the decrease of blood supply gradually decreases.It is not recommended to apply denosumab too long before operation.