乳腺癌脑转移患者的预后因素及生存预测列线图构建:一项单中心大样本回顾性研究OACSTPCD
Prognostic factors and construction of a survival prediction nomogram for patients with breast cancer brain metastasis:A single-center,large-sample retrospective study
背景 随着乳腺癌(breast cancer,BC)治疗手段的进步,越来越多患者整体生存期延长,随之而来的是乳腺癌脑转移(breast cancer brain metastasis,BCBM)的增加,但BCBM患者的预后整体仍然较差.目的 分析BCBM患者的预后因素,建立预测BCBM患者预后的临床列线图模型并评估其效能.方法 纳入2001年1月-2021年6月于本中心诊断的BCBM患者,收其集临床病理特征,通过Cox回归分析确定患者预后因素,并建立预后预测列线图以预测BCBM患者6个月、1年、2年的生存率,通过ROC曲线和校准曲线对列线图的预测效能和校准度进行评价,采用Bootstrap方法进行内部验证.结果 总计纳入700例患者,确诊BC时的平均年龄为43.77岁,中位总生存期为11(95%CI:9.8~12.2)个月.多因素Cox回归显示,BCBM患者较差预后与诊断BC时年龄>48岁(HR=1.30,95%CI:1.09~1.56,P=0.003)、诊断BCBM时KPS<80(HR=1.34,95%CI:1.13~1.60,P=0.001)、分型为三阴性乳腺癌(HR 阳性/HER2 阴性:HR=0.77,95%CI:0.60~0.98;HER2 阳性:HR=0.62,95%CI:0.50~0.77;P<0.001)、首发转移部位非脑(HR=1.83,95%CI:1.44~2.32,P<0.001)、脑转移灶数目≥3 个(HR=1.44,95%CI:1.20~1.72,P<0.001)、同时出现脑膜转移(HR=1.53,95%CI:1.12~2.08,P=0.008)、诊断BCBM 后未接受放疗(HR=1.31,95%CI:1.10~1.57,P=0.003)、伴随肝转移(HR=1.28,95%CI:1.07~1.52,P=0.006)及伴随肺转移(HR=1.19,95%CI:1.00~1.42,P=0.049)独立关联.基于Cox回归构建预测BCBM患者生存率的列线图,其预测6个月、12个月、24个月生存的曲线下面积(area under curve,AUC)分别为0.723、0.720、0.798,内部验证显示模型预测各时间段平均AUC均>0.7,预测6个月、1年、2年生存的平均AUC及95%CI分别为:0.725(0.723~0.727),0.723(0.721~0.725),0.759(0.757~0.761).校准曲线及决策曲线显示该模型具有良好精确度和临床获益.结论 本研究开发了一种性能良好的预测BCBM患者预后的列线图.诊断BC时的年龄、诊断BCBM时的KPS、分子亚型、首发转移部位、脑转移灶数目是否≥3个、是否伴随脑膜转移、是否接受放疗、是否伴随肝转移及是否伴随肺转移为BCBM患者预后的独立影响因素.
Background With the prolonged overall survival of breast cancer(BC)patients,the incidence of breast cancer brain metastasis(BCBM)is gradually increasing.However,the prognosis of BCBM patients remains significantly poor.Objective To analyze prognostic factors of patients with BCBM,establish and evaluate a clinical nomogram for predicting prognosis of BCBM patients.Methods Clinical data about patients diagnosed with BCBM at our center from January 2003 to June 2021 were retrospectively collected.Prognostic factors were determined using Cox regression analysis,and a prognostic nomogram model was developed to predict the survival of BCBM patients at 6 months,1 year,and 2 years.The predictive performance and calibration of the nomogram were evaluated using ROC curves and calibration plots,with internal validation performed using bootstrap methods.Results A total of 700 patients were enrolled.The mean age at diagnosis of BC was 43.77 years,and the median overall survival of patients was 11 months(95%CI:9.8-12.2 months).Multivariable Cox regression analysis revealed that poor prognosis in BCBM patients was independently associated with older age(>48 years)at BC diagnosis(HR=1.30,95%CI:1.09-1.56,P=0.003),Karnofsky Performance Status(KPS)<80 at BCBM diagnosis(HR=1.34,95%CI:1.13-1.60,P=0.001),triple-negative breast cancer(HR-positive/HER2-negative:HR=0.77,95%CI:0.60-0.98;HER2-positive:HR=0.62,95%CI:0.50-0.77;P<0.001),non-brain site of first metastasis(HR=1.83,95%CI:1.44-2.32,P<0.001),number of brain metastases ≥ 3(HR=1.44,95%CI:1.20-1.72,P<0.001),leptomeningeal metastasis(HR=1.53,95%CI:1.12-2.08,P=0.008),not receiving radiotherapy after BCBM diagnosis(HR=1.31,95%CI:1.10-1.57,P=0.003),liver metastasis(HR=1.28,95%CI:1.07-1.52,P=0.006)and lung metastasis(HR=1.19,95%CI:1.00-1.42,P=0.049).A prognostic nomogram of BCBM patients was constructed,with area under the curve(AUC)values of 0.723,0.720,and 0.798 at 6 months,12 months,and 24 months,respectively.Internal validation demonstrated an average AUC>0.7 for each time period,the average AUCs and 95%CIs for predicting patients'survival at 6 months,1 year and 2 years were 0.725(0.723-0.727),0.723(0.721-0.725)and 0.759(0.757-0.761),respectively.Calibration and decision curves indicated great accuracy and clinical utility of the model.Conclusion We have developed a prognostic nomogram with good performance for survival in BCBM patients.Age at BC diagnosis,KPS at BCBM diagnosis,molecular subtype,first metastatic site,number of brain metastases,presence of leptomeningeal metastasis,receipt of radiotherapy,presence of liver metastasis and lung metastasis are independent prognostic factors for breast cancer patients with brain metastasis.
吴子声;王涛;李峰;张会强;周金妹;吴雪雪;陈佳欣;杨斯茗;张少华;江泽飞
解放军医学院,北京 100853||解放军总医院第五医学中心肿瘤医学部,北京 100071解放军总医院第五医学中心肿瘤医学部,北京 100071||安徽医科大学,安徽合肥 230031||南方医科大学第二临床医学院,广东广州 510515解放军总医院第五医学中心肿瘤医学部,北京 100071北京生物医学工程研究所,北京 100071
临床医学
乳腺癌脑转移预后列线图生存率
breast cancerbrain metastasesprognosisnomogramssurvival rate
《解放军医学院学报》 2024 (005)
493-502 / 10
评论