骨肉瘤瘤周组织中微小血管瘤栓浸润对患者预后的影响

Prognostic effect of peritumoral vascular invasion of tumor thrombus in osteosarcomas

目的分析骨肉瘤瘤周组织中微小血管瘤栓浸润(peritumoral vascular invasion,PVI)对患者预后的影响。方法回顾性分析2007年至2016年就诊的232例原发性骨肉瘤患者资料,男142例、女90例;年龄(17.9±8.2)岁(范围3~39岁)。PVI阳性22例、阴性210例,死亡94例、存活138例。采用单因素生存分析(Log-rank检验和单因素Cox回归)评估年龄、性别、PVI情况、肿瘤部位、手术方式、对化疗敏感性及化疗方案对骨肉瘤预后的影响,将差异有统计学意义的指标纳入多因素Cox回归模型,最终确定影响骨肉瘤预后的危险因素。PVI情况与五年生存率和复发或转移的发生率之间的关系采用Kaplan-Meier方法评估。结果所有患者均获得随访,随访时间为(7.6±4.5)年(范围0.1~15年)。PVI阳性组与PVI阴性组对化疗的敏感性(χ2=9.52,P=0.002)、化疗方案(χ2=8.87,P=0.012)、手术方式(χ2=13.50,P<0.001)、肿瘤转移率(χ2=8.51,P=0.004)和死亡率(χ2=5.39,P=0.020)的差异有统计学意义。对232例骨肉瘤患者进行单因素生存分析(性别、年龄、PVI情况、肿瘤发生的部位、手术方式、对化疗敏感性及化疗方案),将差异有统计学意义的指标纳入多因素Cox回归模型。结果显示PVI阳性[五年生存率:HR=2.02,95%CI(1.61,2.79),P=0.010;五年复发或转移率:HR=2.25,95%CI(1.55,3.14),P<0.001]、手术方式为截肢手术[五年生存率:HR=1.22,95%CI(0.94,1.78),P=0.037;五年复发或转移率:HR=1.58,95%CI(1.11,2.23),P=0.026]和对化疗敏感性差[五年生存率:HR=2.71,95%CI(1.84,3.98),P=0.001;五年复发或转移率:HR=2.52,95%CI(1.88,3.45),P<0.001]与预后不良相关。Kaplan-Meier曲线显示PVI阳性组的五年生存率为34%,低于PVI阴性组的68%;五年复发或转移率为72%,高于PVI阴性组的38%,差异均有统计学意义(P<0.05)。结论PVI阳性组的五年生存率低于PVI阴性组,五年复发或转移率高于PVI阴性组。新辅助化疗后骨肉瘤手术标本中瘤周组织中是否存在微小血管瘤栓浸润是评估骨肉瘤患者预后的有效指标。

Objective To analyze the value of peritumoral vascular invasion(PVI)on the prognosis of patients with osteosarcoma.Methods A total of 232 patients with primary osteosarcoma from 2007 to 2016 were retrospectively analyzed,including 142 males and 90 females.The average age was 17.9±8.2 years(range,3-39 years).There were 22 positive and 210 negative cases of PVI,94 deaths and 138 survivals.Univariate survival analysis(Log-rank test and univariate Cox regression)was used to evaluate the effects of age,gender,PVI status,tumor location,surgical method,sensitivity to chemotherapy,and chemotherapy regimen on the prognosis of osteosarcoma.The indicators with statistically significant differences were included in the multivariate Cox regression model to finally determine the risk factors affecting the prognosis of osteosarcoma.The relationship between PVI status and 5-year survival and the incidence of recurrence or metastasis was evaluated using the Kaplan-Meier method.Results All patients were followed up for 7.6±4.5 years(range,0.1-15 years).The differences in sensitivity to chemotherapy(χ2=9.52,P=0.002),choice of chemotherapy regimen(χ2=8.87,P=0.012),choice of surgical modality(χ2=13.50,P<0.001),tumor metastasis rate(χ2=8.51,P=0.004)and mortality rate(χ2=5.39,P=0.020)of PVI positive group and PVI negative group had statistically significant differences.Univariate survival analysis was performed on 232 patients with osteosarcoma(gender,age,PVI status,site of tumor development,surgical modality,sensitivity to chemotherapy,and chemotherapy regimen).Indicators with statistically significant differences were included in a multifactorial Cox regression model.The results showed PVI positive[5-year survival rate:HR=2.02,95%CI(1.61,2.79),P=0.010;5-year recurrence or metastasis rate:HR=2.25,95%CI(1.55,3.14),P<0.001],surgical procedure as amputation[5-year survival rate:HR=1.22,95%CI(0.94,1.78),P=0.037;5-year recurrence or metastasis rate:HR=1.58,95%CI(1.11,2.23),P=0.026]and poor sensitivity to chemotherapy[5-year survival rate:HR=2.71,95%CI(1.84,3.98),P=0.001;5-year recurrence or metastasis rate:HR=2.52,95%CI(1.88,3.45),P<0.001]was associated with poor prognosis.Kaplan-Meier curve showed that the 5-year survival rate of PVI positive group was 34%,which was lower than 68%of PVI negative group.The 5-year recurrence or metastasis rate was 72%in the PVI negative group,which was significantly higher than 38%in the PVI negative group(P<0.05).Conclusion The 5-year survival rate of PVI positive group was lower than that of PVI negative group,and the 5-year recurrence or metastasis rate was higher than that of PVI negative group.The presence of microvascular angiosarcoma plugs infiltrating the peritumoral tissue in surgical specimens of osteosarcoma after neoadjuvant chemotherapy is a useful indicator to assess the prognosis of patients with osteosarcoma.