Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field.Urothelial carcinoma is a very heterogeneous disease and responses to system...Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field.Urothelial carcinoma is a very heterogeneous disease and responses to systemic therapies,and outcomes after radical cystectomy are difficult to predict.Advances in molecular biology such as next generation sequencing and whole genome or transcriptomic analysis provide promising platforms to achieve a full understanding of the biology behind the disease and can identify emerging predictive biomarkers.Moreover,the ability to categorize patients’risk of recurrence after curative treatment,or even predict benefit from a conventional or targeted therapies,represents a compelling challenge that may reshape both selection for tailored treatment and disease monitoring.Progress has been made but currently no molecular biomarkers are used in the clinical setting to predict response to systemic agents in either neoadjuvant or adjuvant settings highlighting a relevant unmet need.Here,we aim to present the emerging role of molecular biomarkers in predicting response to systemic agents in urothelial carcinoma.展开更多
目的:探索国际转移肾癌数据库联盟(International mRCC Database Consortium,IMDC)危险分层以外可以独立预测减瘤性肾切除术后患者总体死亡风险的因素,并构建联合预测模型,以指导手术适应证选择。方法:回顾性分析来自国际减瘤性肾切除...目的:探索国际转移肾癌数据库联盟(International mRCC Database Consortium,IMDC)危险分层以外可以独立预测减瘤性肾切除术后患者总体死亡风险的因素,并构建联合预测模型,以指导手术适应证选择。方法:回顾性分析来自国际减瘤性肾切除术临床研究协作组(International Consortium of Clinical Research on Cytoreductive Nephrectomy)全球13个医学中心减瘤性肾切除术治疗转移性肾癌264例患者资料,中位年龄63岁,男性占比73.9%,66.7%的患者合并肺转移,26.5%的患者合并骨转移,寡转移患者占比73.3%,IMDC中高危占比63.3%。基于Cox多因素分析结果构建减瘤性肾切除术后患者总体死亡风险的临床预测模型,并计算IMDC模型和联合模型的C-index值。基于纳入模型的变量系数间比例关系进行半定量赋值,绘制新模型不同分值患者队列的生存曲线并进行log-rank检验,分析新纳入变量在IMDC危险分层不同亚组的预测价值。计算新模型预测3年死亡风险的时依性ROC曲线下面积。结果:开放手术占比68.9%,术后病理学肿瘤最大径中位9(7.1,12.3) cm,透明细胞癌占81.8%,手术切缘阳性率6.1%,清扫淋巴结阳性率47.7%,二期手术行转移灶切除比例为8.3%。中位随访27.5(15.1,46.4)个月,随访期内死亡110例,总体死亡率41.7%。Cox多因素回归结果显示,IMDC危险分层和寡转移状态(Oligo-metastasis,影像学评估转移病灶数不超过5个,HR=2.089,96%CI:1.390~3.139,P<0.001)是患者术后总体死亡风险的独立预测因素。IMDC模型C-index值为0.598,IMDC-Olig联合模型C-index值为0.645。IMDC不同危险分层的亚组分析显示,在IMDC中危组和高危组,是否为寡转移两组患者术后总体死亡风险差异均有统计学意义(P<0.05,高危组差异仅限于1年生存率),IMDC低危组两者差异无统计学意义(P>0.05)。结论:IMDC-Olig模型可以很好地对IMDC中高危组患者基于总体死亡风险进行再分层,可作为手术适应证选择的重要参考。展开更多
文摘Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field.Urothelial carcinoma is a very heterogeneous disease and responses to systemic therapies,and outcomes after radical cystectomy are difficult to predict.Advances in molecular biology such as next generation sequencing and whole genome or transcriptomic analysis provide promising platforms to achieve a full understanding of the biology behind the disease and can identify emerging predictive biomarkers.Moreover,the ability to categorize patients’risk of recurrence after curative treatment,or even predict benefit from a conventional or targeted therapies,represents a compelling challenge that may reshape both selection for tailored treatment and disease monitoring.Progress has been made but currently no molecular biomarkers are used in the clinical setting to predict response to systemic agents in either neoadjuvant or adjuvant settings highlighting a relevant unmet need.Here,we aim to present the emerging role of molecular biomarkers in predicting response to systemic agents in urothelial carcinoma.
文摘目的:探索国际转移肾癌数据库联盟(International mRCC Database Consortium,IMDC)危险分层以外可以独立预测减瘤性肾切除术后患者总体死亡风险的因素,并构建联合预测模型,以指导手术适应证选择。方法:回顾性分析来自国际减瘤性肾切除术临床研究协作组(International Consortium of Clinical Research on Cytoreductive Nephrectomy)全球13个医学中心减瘤性肾切除术治疗转移性肾癌264例患者资料,中位年龄63岁,男性占比73.9%,66.7%的患者合并肺转移,26.5%的患者合并骨转移,寡转移患者占比73.3%,IMDC中高危占比63.3%。基于Cox多因素分析结果构建减瘤性肾切除术后患者总体死亡风险的临床预测模型,并计算IMDC模型和联合模型的C-index值。基于纳入模型的变量系数间比例关系进行半定量赋值,绘制新模型不同分值患者队列的生存曲线并进行log-rank检验,分析新纳入变量在IMDC危险分层不同亚组的预测价值。计算新模型预测3年死亡风险的时依性ROC曲线下面积。结果:开放手术占比68.9%,术后病理学肿瘤最大径中位9(7.1,12.3) cm,透明细胞癌占81.8%,手术切缘阳性率6.1%,清扫淋巴结阳性率47.7%,二期手术行转移灶切除比例为8.3%。中位随访27.5(15.1,46.4)个月,随访期内死亡110例,总体死亡率41.7%。Cox多因素回归结果显示,IMDC危险分层和寡转移状态(Oligo-metastasis,影像学评估转移病灶数不超过5个,HR=2.089,96%CI:1.390~3.139,P<0.001)是患者术后总体死亡风险的独立预测因素。IMDC模型C-index值为0.598,IMDC-Olig联合模型C-index值为0.645。IMDC不同危险分层的亚组分析显示,在IMDC中危组和高危组,是否为寡转移两组患者术后总体死亡风险差异均有统计学意义(P<0.05,高危组差异仅限于1年生存率),IMDC低危组两者差异无统计学意义(P>0.05)。结论:IMDC-Olig模型可以很好地对IMDC中高危组患者基于总体死亡风险进行再分层,可作为手术适应证选择的重要参考。