266例四肢骨肉瘤患者的临床疗效分析

Clinical efficacy analysis of 266 cases with extremitiesosteosarcoma

目的近二十年来,骨肉瘤患者的五年生存率始终未得到明显提升。文中基于四肢骨肉瘤治疗的长期随访结果,探讨规范性化疗和手术技术的联合应用对生存率、手术安全性以及术后肿瘤的局部复发和远处转移率的影响。方法收集2000年1月1日至2015年1月1日东部战区总医院骨科首诊时确诊的282例四肢高度恶性骨肉瘤患者。根据纳入标准和排除标准,最终纳入患者266例。规范化的综合治疗模式包括术前、术后新辅助化疗及手术治疗。手术治疗包括截肢手术(39例)和保肢手术(227例)。随访63~240个月,平均随访时间115.84个月(9.65年)。根据随访结果,分析术前Enneking分期、化疗规范情况、肿瘤坏死率、复发及转移情况等因素对患者预后的影响。并应用多因素Cox回归模型计算不同年龄、性别、化疗后肿瘤坏死率、手术方式、局部复发及远处转移的HR及95%可行区间。结果至随访截止,存活165例,总生存率为62.03%;无病存活148例,无病生存率为55.64%。Enneking分期与患者的复发率、转移率及死亡率显著相关(P<0.05)。肿瘤坏死率≥90%患者的中位生存期明显高于肿瘤坏死率<90%者(42个月vs 20个月,P<0.01)。保肢患者的术后切口感染发生率明显高于截肢患者(P=0.031);同时,保肢或截肢手术方式的选择与患者的复发率、转移率及死亡率无显著相关性(P>0.05)。肺转移患者109例(40.98%);转移发生在综合治疗模式开始后1-2年44例(41.90%);共死亡100例(37.59%),死亡时间为肺转移后6~16个月。多因素Cox比例风险回归分析显示,化疗后的肿瘤坏死率≥90%及复发和转移是影响总生存率的危险因素(P=0.005、0.004、0.003)。结论四肢骨肉瘤患者保肢手术后带来的并发症问题明显多于截肢手术,但对于患者预后的影响差异不大。化疗后肿瘤坏死率的高低直接影响患者的生存率,出现远处转移或复发的骨肉瘤患者预后往往不佳。

Objective In the past 20 years,the five-year survival rate of patients with osteosarcomahas not been significantly improved.This study is based on the long-term follow-up data of patients with extremities osteosarcoma,to investigate the effects of the combined application of standardized chemotherapy and new surgical techniques on survival rate,surgical safety,and recurrence and metastasis rate of postoperative tumors.Methods Collected 282 patients with high-grade malignant extremityosteosarcoma from January 1,2000 to January 1,2015 in Jinling Hospital.According to the inclusion and exclusion criteria,266 patients were finally included.The standardized comprehensive treatment model includes preoperative and postoperative neoadjuvant chemotherapy and surgical treatment.Surgical treatment included amputation(39 cases)and limb salvage(227 cases).Follow-up time was from 63 months to 240 months,with an average follow-up time of 115.84 months(9.65 years).According to the follow-up results,preoperative Enneking stage,chemotherapy,tumor necrosis rate,surgical selection,recurrence+metastasis and other factors that effectson the prognosis of patients were analyzed.The multivariate Cox regression model was used to calculate the HR and 95%feasible interval for different ages,genders,tumor necrosis rate after chemotherapy,surgical methods,local recurrence and distant metastasis or not.Results By the end of follow-up,165 cases survived,with an overall survival rate of 62.03%;148 cases survived without disease,with a disease-free survival rate of 55.64%.Enneking staging was significantly related to the recurrence rate,metastasis rate and mortality of patients(P<0.05).The median survival of patients with tumor necrosis rate≥90%was significantly higher than that of patients with tumor necrosis rate<90%(42 months vs 20 months,P<0.01).The incidence of postoperative wound infection in limb salvage patients was significantly higher than that in amputation patients(P=0.031).Moreover,the choice of limb salvage or amputation was not significantly correlated with the recurrence rate,metastasis rate,and mortality of patients(P>0.05).There were 109 patients with lung metastasis(40.98%);44 patients(41.90%)with metastasis occurred 1-2 years after the start of the comprehensive treatment mode;Among them,100 patients(37.59%)died,and the time of death was 6 to 16 months after lung metastasis.The multivariate Cox proportional hazardregression analysis revealed that the tumor necrosis rate≥90%,recurrence and metastasis were independent prognostic factors(P=0.005,P=0.004 and P=0.003).Conclusion The complications of limb salvage surgery were significantly more than those of amputation,but there was no significant differences in the prognosis.The survival rate was directly influenced by the tumor necrosis rate after chemotherapy,andthe prognosis was bad when there was distant metastasis or recurrence.