【摘要】 目的 探讨前瞻性应用唑来膦酸（ZOL）早期干预实体瘤骨转移、骨相关事件（SREs）的疗效和生存期。方法 2016年1月～2020年12月入组165例患者，中位年龄52岁。按简单随机方法分为：观察组为治疗结束即使用ZOL，对照组为同期治疗结束的、不使用ZOL、定期随访的患者。对两组患者的疗效、生存进行分析，对具体应用ZOL的次数与疗效、生存的关系等进行分层分析。结果 观察组骨转移3例（1.8%）、对照组26例（15.8%），差异有统计学意义（χ~2=10.792, P <0.05）；观察组SREs 2例（1.2%），对照组19例（11.5%），差异有统计学意义（χ~2=8.284, P <0.05）。两组患者的总生存期（OS）和中位生存期（MST）差异无统计学意义（χ~2=1.347, P> 0.05）；两组1～5年的无骨转移进展生存期（TTPS）和中位进展生存期（MPST）比较，差异有统计学意义（χ~2=4.155, P=0.040）。观察组是否发生骨转移与使用ZOL的次数无明显关系（χ~2=2.505, P> 0.05）。使用ZOL后仍发生骨转移的患者与未发生骨转移患者的生存比较：1～5年的OS和MST相比，差异无统计学意义（χ~2=0.002, P> 0.05）；两组1～5年的TTPS和MPST相比，差异无统计学意义（χ~2=1.709, P> 0.05）。观察组使用ZOL次数的多少对生存的影响：使用ZOL次数较少（1～3次）、中量（4～6次）与较多（7次以上）三组相比，差异无统计学意义（χ~2=2.892, P> 0.05），但少和中量的OS、TTPS曲线分开明显。Cox回归模型多因素分析，性别、年龄、分期、使用ZOL后是否出现骨转移、使用ZOL次数未影响OS及TTPS。结论 实体瘤尚未骨转移患者，经使用ZOL早期干预后，观察组的骨转移、SREs明显低于对照组，TTPS延长；分层分析：发生骨转移与使用ZOL次数、对生存的影响尚需进一步观察，可能使用次数较多者对生存有益。ZOL早期干预实体瘤骨转移、SREs具明显优势。更多还原

【Abstract】 Objective To explore the efficacy, survival period of prospective application of zoledronic acid(ZOL) in early intervention of bone metastasis and bone related events(SREs) in solid tumors. Methods From January 2016 to December 2020, 165 patients with a median age of 52 years were enrolled.According to a simple randomized method,the observation group was treated with ZOL immediately after treatment, and the control group was treated with ZOL at the end of the same period, without using ZOL, and with regular follow-up.The curative effect and survival of the two groups were analyzed, and the relationship between the times of specific application of ZOL and curative effect and survival was analyzed hierarchically. Results There were 3 cases of bone metastases(1.8%) in the observation group and 26 cases(15.8%) in the control group,the difference was statistically significant （χ~2 = 10.792, P < 0.05）, 2 cases(1.2%) in the observation group and 19 cases(11.5%) in the control group （χ~2 = 8.284, P < 0.05）,the difference was statistically significant. There was no statistically significant difference（χ~2= 1.347, P > 0.05）between OS and MST of the two groups,there was a statistically significant difference in TTPS and MPST between the two groups for 1 ～ 5 years（χ~2 = 4.155, P = 0.040）.There was no significant relationship between the occurrence of bone metastasis and the number of times ZOL was used in the observation group（χ~2= 2.505, P > 0.05）.Survival comparison between patients who still have bone metastasis after using ZOL and patients who do not have bone metastasis: there was no statistically significant difference between the two groups in OS and MST for 1 ～ 5 years（χ~2= 0.002, P > 0.05）; there was no statistically significant difference between the two groups in TTPS and MPST for 1 ～ 5 years（χ~2= 1.709, P > 0.05）.The effect of the number of times ZOL was used on survival in the observation group: there was no statistically significant difference between the three groups with less(1 ～ 3 times), moderate(4 ～ 6 times), and more(7 times or more) ZOL use（χ~2= 2.892, P > 0.05）, but the OS and TTPS curves for less and moderate amounts are significantly separated.Cox regression model multivariate analysis showed that gender, age, stage, whether bone metastasis occurred after ZOL use, and the number of times ZOL use did not affect OS and TTPS.Conclusion After early intervention with ZOL in patients with solid tumors without bone metastasis, the bone metastasis and SREs in the observation group were significantly lower than those in the control group, and the TTPS was prolonged.Stratified analysis: the occurrence of bone metastasis, the number of times ZOL is used, and the impact on survival need to be further observed. It is possible that those who use ZOL more frequently are beneficial to survival. ZOL has obvious advantages in early intervention of solid tumor bone metastasis and SREs.ZOL has obvious advantages in early intervention of bone metastasis and SREs of solid tumors.更多还原