基于SEER数据库的原发性纵隔及肺部软组织肉瘤相关生存及预后分析

目的 利用SEER数据库分析影响原发性纵隔及肺部软组织肉瘤预后的相关因素。方法 收集SEER数据库376例患者数据,随机分为训练集（263例）与验证集（113例）。使用Kaplan-Meier法和Cox比例风险回归分析各变量与患者生存及预后的关系,建立列线图预测患者总生存期。采用校准曲线、一致性指数及ROC曲线评价列线图性能。结果 组织学类型、手术、化疗、肿瘤大小、肿瘤分期是影响原发性纵隔及肺部软组织肉瘤预后的因素。建立的列线图模型可以预测其6个月、1年及2年总生存率,校准曲线显示与实测值基本一致,训练集与验证集C指数分别为0.754与0.745,ROC的曲线下面积分别为0.849与0.924,说明具有良好的预测准确度。结论 本研究建立的列线图可以预测原发性纵隔及肺部软组织肉瘤患者6个月、1年及2年总生存率。     

早发型非转移性结直肠癌患者预后预测模型的构建及外部验证

目的:探讨影响早发型非转移性结直肠癌（early-onset non-metastatic colorectal cancer,EONCRC）患者预后的相关独立危险因素,并构建列线图预测EONCRC患者预后。方法:从美国监测、流行病学和结果数据库SEER数据库中收集了9 097例EONCRC患者的数据,患者按照7∶3比例随机分配到训练集(6 369例)和验证集(2 728例)。通过单变量、多变量COX比例风险回归分析确定独立的预后因素,并构建列线图。 使用C指数、ROC曲线和校准曲线评价列线图的区分度、预测效能和校准度。使用新疆军区总医院收治的EONCRC患者临床资料(n=171)对列线图进行了外部验证并对其预后影响因素进行了分析。结果:多因素分析确定了与总生存期有关的8个独立风险因素,分别是组织学分化程度、组织学类型、神经浸润、分期、T分期、手术、化疗和放疗,并将它们纳入列线图。SEER训练集、SEER验证集、外部验证集的C指数值分别为0.765(95%置信区间,0.749~0.781)、0.785(95%置信区间,0.763~0.807)、0.766(95%置信区间,0.713~0.819),校准曲线表明了列线图预测总生存率与实际总生存率具有良好的一致性。ROC曲线显示,列线图可以准确预测EONCRC患者1年(AUC=0.834 9)、3年(AUC=0.794 7)和5年(AUC=0.771 2)的生存率。根据列线图的风险评分将患者分为高风险、中风险和低风险组,在SEER训练集、SEER验证集、外部验证集中,低风险组的5年生存率均最高,其次是中风险组和高危组。结论:本研究确定了EONCRC患者预后相关的8个独立危险因素,列线图能准确预测中国及美国EONCRC患者1年、3年、5年总生存率,对EONCRC患者进行个体化的分层及预后评估,为临床的诊疗提供科学依据。     

基于炎症相关参数建立根治性膀胱切除术术后的列线图预测模型及验证

目的:探讨接受根治性膀胱切除术的膀胱癌患者相关预测因素,建立并验证列线图预测模型。方法:回顾性收集我院2009年01月至2018年01月期间行根治性膀胱切除术患者的实验室检查和病理结果等临床资料,由术前的血常规结果计算中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）和全身免疫炎症指数（SII）。根据约登指数计算SII及NLR的最佳分界值,术后对患者进行随访,使用多因素Cox回归模型分析影响患者术后总生存率的独立危险因素,然后将独立危险因素纳入并构建预测非肌层浸润性膀胱癌（NMIBC）患者3、5年总生存率的列线图,并对模型的预测准确性进行外部验证,通过一致性指数（C指数）和校准曲线来确定列线图的预测精度和一致性。结果:建模组患者中位总生存期（OS）为21个月(1~66个月),1年、3年和5年的OS率分别为85.2%、68.5%和59.1%。多因素分析显示T分期、N分期、SII和NLR是膀胱癌根治性膀胱切除术后患者的独立危险因素。SII的ROC曲线下面积（AUC）大于NLR,差异有统计学意义,SII预测患者总生存率的准确度更高。我们建立了一个预测根治性膀胱切除术后OS的列线图预测模型,C指数为0.87(95%CI 0.83~0.90),并对模型进行外部验证,校正曲线显示预测和观察的3、5年生存率之间有很好的一致性。结论:本研究建立的接受根治性膀胱切除术的膀胱癌患者列线图预测模型对膀胱癌患者总生存率具有较高的预测价值,验证相关指标能有效预测患者的预后。     

食管癌列线图预后预测模型的构建与验证

目的:构建列线图分析食管癌患者的预后因素并且预测其总生存期,协助临床诊疗。方法:从监测、流行病学及预后(Surveillance, Epidemiology, and End Result, SEER)数据库中按照纳入排除标准选择了2000年至2020年间食管癌患者41 783例,以7∶3随机划分为训练队列(29 249例)和内部验证队列(12 534例),从新疆医科大学附属肿瘤医院依据同样标准收集了2010年1月至2022年12月间食管癌患者5 472例,作为外部验证队列。采用单因素、多因素Cox回归分析筛选变量绘制预测食管癌患者1年、3年及5年总生存期的列线图。利用一致性指数(C-index)、时间依赖性ROC曲线下面积(time-dependent AUC)、校准曲线（calibration curve）、决策曲线（decision curve analysis,DCA）、Kaplan-Meier生存分析来评估列线图的判别和校准能力及临床效益。结果：最终纳入8个变量构建列线图。列线图的训练队列、内部验证队列和外部验证队列的一致性指数分别为0.700、0.679和0.644;1年、...     

基于列线图构建和验证肝细胞癌伴门静脉癌栓患者肝切除术后的预后评估模型

目的 分析影响肝细胞癌伴门静脉癌栓（PVTT-HCC）患者肝切除术后预后的影响因素,并基于列线图模型构建和验证预后评估模型。方法 本研究为回顾性队列研究,选择2008年1月—2017年11月在本院行肝切除术的PVTT-HCC患者为研究对象,随访截至2021年1月。主要预测结局为1、3、5年总生存率。按照7∶3的比例将患者随机分为训练集和验证集,在训练集中采用Cox比例风险回归分析影响预后的影响,并基于影响因素构建列线图模型。同时在训练集和验证集中采用C-index评价模型的区分度,一致性曲线评估模型的校准度。结果 共231例患者符合纳入排除标准纳入分析,其中训练集162例,验证集69例。Cox比例风险回归模型显示,AFP≥400 μg/L、AST≥40 U/L、ALP≥80 U/L、肿瘤个数>1个及肿瘤包膜不完整是影响预后的危险因素。在训练集中,列线图模型预测1、3、5年总生存率的C-index分别为0.826（95%CI: 0.791~0.861）、0.818（95%CI：0.782~0.854）、0.781（95%CI：0.742~0.820）,在验证集中分别为0.814（95%CI：0.777~0.851）、0.798（95%CI：0.758~0.837）、0.769（95%CI：0.728~0.810）。校正曲线显示列线图模型在训练集和验证集均有较好的校准度。结论 本研究构建的列线图模型可准确预测PVTT-HCC患者的预后。     

甲状腺癌患者预后列线图的构建及验证

目的 利用甲状腺癌患者预后独立因素构建预后列线图并进行验证.方法 从美国国立癌症研究所监测、流行病学和最终结果(SEER)数据库收集2004—2015年诊断为甲状腺癌的94216例患者的临床资料,采用随机数字表法分为训练组(n=47108)和内部验证组(n=47108),选取2008—2020年于武汉科技大学附属孝感医院诊断为甲状腺癌的1500例患者作为外部验证组.采用Cox比例风险回归模型分析甲状腺癌患者总生存率的影响因素并构建预后列线图,预测10、15、20年总生存率,计算一致性指数(c-指数),通过校准曲线确定列线图预测的准确性.结果 单因素分析结果显示,年龄、性别、肿瘤直径、区域淋巴结转移状态、远处转移状态、临床TNM分期、病理类型、原发灶手术状态、区域淋巴结手术状态、放疗状态、婚姻状态均可能是甲状腺癌患者总生存率的影响因素(P﹤0.01).多因素分析结果显示,年龄≥55岁、男性、肿瘤直径﹥39 mm、区域淋巴结转移、远处转移、临床TNM分期为Ⅱ/Ⅲ/Ⅳ期、病理类型为髓样癌及未分化癌、原发灶未进行手术、区域淋巴结未手术、未进行放疗、离婚/丧偶均是甲状腺癌患者总生存率的独立危险因素(P﹤0.05).基于影响因素构建10、15、20年总生存率的列线图并进行内外部验证,训练组c-指数为0.855(95％CI:0.846～0.864),内部验证组c-指数为0.851(95％CI:0.842～0.860),外部验证组c-指数为0.812(95％CI:0.759～0.865),校准曲线表明了列线图预测总生存率与实际总生存率具有良好的一致性.结论 甲状腺癌患者总生存率列线图能够比较准确地预测10年总生存率,有助于临床医师对甲状腺癌患者进行个体化的预后评估及治疗策略制订.     

局部晚期鼻咽癌调强放疗后区域复发的列线图模型的建立

[目的]建立预测局部晚期鼻咽癌（nasopharyngeal carcinoma,NPC）患者调强放疗后无区域复发生存期的列线图模型。[方法]回顾性分析2016年6月至2019年6月在江苏省肿瘤医院行调强放疗后的424例局部晚期NPC患者临床资料,随机分为训练集（n=297）和验证集（n=127）。在训练集中,通过Cox回归分析,筛选出影响区域复发的独立危险因素。根据危险因素建立列线图模型并进行危险分层,通过C指数和校准曲线评估列线图。[结果]年龄（≥60岁）、血小板与淋巴细胞比值、全身免疫炎症指数是影响局部晚期NPC患者调强放疗后区域复发的独立危险因素（P均<0.05）。训练组、验证组的C指数分别为0.745(95%CI:0.726～0.764)、0.845(95%CI:0.815～0.869)。校准曲线结果显示符合度较好。此外,列线图对不同风险分层的患者有显著的分辨能力。[结论]本研究建立的列线图模型可以有效预测调强放疗后局部晚期NPC患者的无区域复发生存期。     

胃癌恶性腹水患者的临床特征及预后影响因素分析

目的 研究胃癌恶性腹水患者的临床特征及其预后影响因素。方法 回顾性分析陕西省肿瘤医院2014年1月1日至2019年12月31日收治的124例胃癌恶性腹水患者的临床资料,其中男88例（71.0%）,女36例（29.0%）;<65岁75例(60.5%),≥65岁49例(39.5%)。通过Log rank检验和多因素Cox回归分析,确定影响总生存时间（OS）的独立预后因素,根据预后因素构建预测胃癌恶性腹水患者预后的列线图模型;使用一致性指数（C-index）、受试者工作特征曲线的曲线下面积（AUC）、校准曲线和决策曲线分析法（DCA）对预测模型的性能进行验证。基于患者个体化列线图的总得分,构建胃癌恶性腹水患者的风险分层,分析患者临床特征对预后的影响。结果 124例胃癌恶性腹水患者的中位OS为5.4个月,3、6和12个月生存率分别为72.6%、42.7%和15.3%。单因素分析结果显示,美国东部肿瘤协作组（ECOG）评分、胃癌手术史、是否以腹水起病、腹水颜色、肿瘤分化程度、其他器官转移数目、治疗方式以及血清白蛋白（ALB）、总胆红素（TBIL）和乳酸脱氢酶（LDH）水平与患者的中位OS有...     

原发性肝癌射频消融术后复发预测模型的建立及评价

目的 构建和评价用于预测原发性肝癌（primary liver cancer,PLC）患者射频消融（radiofrequency ablation,RFA） 术后无瘤生存率的列线图模型。 方法 回顾性分析2009年6月至2017年5月于广西医科大学附属肿瘤医院接受射频消融治疗的213例PLC患者的临床资料。ＰＬＣ患者被随机分为训练组（n=133）和验证组（n=80）。采用Cox回归模型分析射频消融术后复发的因素,并建立复发的列线图模型。通过校准曲线评估模型的预测符合度,Kaplan-Meier 曲线评估模型的实用性,一致性指数（C-index）评估模型的准确度。结果 训练组1年、3年、5年无瘤生存率分别为65.25%、40.91%、26.99%,验证组分别为66.29%、48.10%、24.59%,两组生存曲线比较差异无统计学意义（P=0.785）。Cox回归分析结果显示,肿瘤数目（HR=1.921, 95%CI：1.136~3.251）、丙肝抗体阳性（HR=4.545,95%CI：1.700~12.149）、HBV-DNA≥10² IU/mL（HR=1.993,95%CI：1.209~3.284）及血清前白蛋白（HR=0.996,95%CI：0.993~0.999）为无瘤生存率的影响因素。基于肿瘤数目、HBV-DNA和血清前白蛋白等因素建立列线图模型,训练组和验证组的 C-index 分别为 0.649（95%CI：0.588~0.710）、0.641（95%CI：0.556~0.724）,校准图形中标准曲线与预测校准曲线贴合良好。采用列线图将患者分为高风险组和低风险组,高风险组无瘤生存率低于低风险组（P<0.05）。结论 基于肿瘤数目、HBV-DNA和血清前白蛋白等因素建立的列线图测模型可预测PLC射频消融术后的无瘤生存率,对患者辅助治疗具有一定指导价值。     

基于SEER数据库绘制列线图分析软骨肉瘤患者预后相关因素

目的:分析软骨肉瘤流行病学特征及影响预后的相关因素,并且绘制列线图来个体化预测患者远期生存率。方法:收集SEER数据库2004至2015年诊断的1 453例软骨肉瘤患者的临床数据,回顾性分析软骨肉瘤患者流行病学特征及影响患者预后的相关危险因素,使用随机数字表法将所有纳入对象以7∶3分为建模组（1 017例）和验证组（436例）并构建列线图进行内部验证,预测软骨肉瘤患者3年、5年的生存率,使用多因素COX风险比例模型来确定独立因素,采用一致性指数(C-index)及校准曲线评估该预测模型的准确性。结果:软骨肉瘤患者男女性别比为:1.23∶1,年龄≥50岁患者占比为55.7%,最常见的发病部位是下肢骨,多因素分析提示,影响软骨肉瘤患者预后的因素包括年龄、性别、肿瘤原发部位、肿瘤大小、病理分级、AJCC TNM分期、手术方式、是否化疗、肿瘤大小;建模组与验证组1、3、5年ROC曲线AUC值分别为:0.87、0.838、0.807,0.864、0.754、0.755;列线图C-index指数为:0.805。结论:列线图可以准确预测软骨肉瘤患者生存率,具有较好的预测精度,有助于对患者进行个性化的预后评估和指导临床决策。     

Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic,castration-resistant prostate cancer

Purpose

We conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms.

Experimental design

Twenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 10⁷ dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis.

Results

No serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13–0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17–0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS.

Conclusions

In patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.     

Efficacy of carboplatin–taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials

BackgroundDocetaxel is associated with prolonged survival in castration-resistant prostate cancer (CRPC). Platinum compounds have modest but distinct single-agent activity. Carboplatin may have greatest potential for benefit when combined with taxanes. We investigated whether there is a subset of patients with CRPC for whom the efficacy of combination taxane–estramustine–carboplatin (TEC) chemotherapy may be greatest.Patients and methodsIndividual patient data (n = 310) were obtained from seven trials using TEC chemotherapy. Prostate-specific antigen (PSA) response was defined as ≥50% post-therapy decline from baseline. Overall survival was defined from baseline to death from any cause. Logistic and Cox regression were used to investigate heterogeneity in outcome to TEC by patient and disease characteristics. Predicted survival probabilities were calculated from the Halabi Cancer and Leukemia Group B (CALGB) nomogram.ResultsThe pooled PSA response proportion was 69% [95% confidence interval (CI) 56% to 80%]. There was no evidence of differential PSA response by disease characteristics. Established prognostic factors were associated with survival. The pooled 12-month survival estimate of 79% (95% CI 71% to 84%) was higher than the median 59% 12-month nomogram-predicted survival.ConclusionsTEC chemotherapy has significant clinical activity in CRPC. A randomized, controlled trial evaluating the addition of carboplatin to taxane-based chemotherapy is needed to elucidate the value of carboplatin in CRPC.     

Metronomic Oral Cyclophosphamide Chemotherapy Possibly Contributes to Stabilization of Disease in Patients With Metastatic Castration-Resistant Prostate Cancer: A Prospective Analysis of Consecutive Cases

Introduction/BackgroundCastration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes.Patients and MethodsTwenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively.ResultsA total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities.ConclusionMetronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.     

A prognostic nomogram for colorectal cancer liver metastases after percutaneous thermal ablation

Purpose: To assess the efficacy of percutaneous thermal ablation in treating colorectal cancer liver metastases (CRCLM), and to propose a prognostic nomogram for overall survival (OS).

Materials and methods: Seventy-one patients with CRCLM undergoing thermal ablation at our institute from 2009 to 2013 were identified and analysed to formulate a prognostic nomogram. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the nomogram. The nomogram was compared with two current prognostic nomograms for patients with CRCLM who had undergone hepatectomy (Kattan) and selective internal radiation therapy (Fendler). Predictive validity was assessed in the validation cohort of 25 patients who had undergone thermal ablation from 2014 to 2016.

Results: The median OS in the primary cohort was 26.4?months, whereas the 1-, 3- and 5-year OS rates were 72.2%, 37.2% and 17%, respectively. The median progression-free survival was 4.2?months. After univariate and multivariate analysis, a prognostic nomogram was formulated based on four predictors, including the number of tumours, maximum diameter of the tumour, CA19–9 level and ablation margin. The C-index of the nomogram was 0.815. Based on the patients of this study, the C-index was significantly higher than that of the Fendler nomogram (C-index, 0.698) and Kattan nomogram (C-index, 0.514, p?Conclusions: Thermal ablation was an effective therapy for CRCLM. Moreover, the nomogram was effective and simple for CRCLM patients undergoing thermal ablation.     

基于SEER数据库构建1~2枚淋巴结阳性且乳房全切的老年早期乳腺癌患者不同腋窝手术方式的生存预测模型

背景与目的：指南推荐1~2枚前哨淋巴结阳性的保乳并计划行全乳放疗的T1-2期乳腺癌患者可以豁免腋窝淋巴结清扫。探讨1~2枚淋巴结阳性且乳房全切的老年早期乳腺癌患者的预后危险因素,并构建不同腋窝处理手术方式下的生存预测模型。方法：从SEER数据库收集2010—2015年期间65岁及以上、T 1-2 期、1~2枚淋巴结阳性且乳房全切的乳腺癌患者并随机分为验证集和训练集。对训练集进行单因素及多因素COX比例风险回归分析筛选出影响总生存的独立预后因素,利用R软件构建预测患者3年和5年总生存率的列线图,利用一致性指数（C指数）和校正曲线对预测模型进行内部（训练集）和外部（验证集）验证。结果：共纳入4 863例患者,中位随访42个月,训练集（3 647例）和验证集（1 216例）的基线分布符合简单随机分组。将多因素COX回归分析筛选出的年龄、种族、婚姻状态、组织学分级、分子分型、T分期、腋窝手术方式、是否放化疗共9个总生存的独立风险因素（P<0.05）用于构建列线图预测模型。训练集（即内部验证）和验证集（即外部验证）的C指数分别为0.710（95% CI：0.689~0.731）和0.728（95 % CI：0.691~0.765）,两组的校正曲线均靠近45°参考线,表明列线图具有良好的预测能力。结论：本研究构建的列线图预测模型具有良好的预测价值,有利于指导临床对患者进行个体化治疗。     

Consolidative Radiotherapy in Oligometastatic Lung Cancer: Patient Selection With a Prediction Nomogram

BackgroundPatients with stage IV oligometastatic (≤ 3 sites) non–small-cell lung cancer have a progression-free survival (PFS) and overall survival benefit when all sites of metastatic disease and the primary tumor are treated radically with consolidative radiotherapy (cRT). However, the optimal selection of patients most likely from cRT is yet to be defined.Patients and MethodsPatients with metastatic non–small-cell lung cancer treated with definitive radiotherapy to all metastatic sites and primary tumor (2008-2019) were retrospectively identified. Univariable Cox proportional-hazards model was used to compare outcomes with demographic and clinical characteristics. A predictive nomogram model for selection of patients most likely to benefit from cRT was constructed.ResultsThere were 91 patients identified with a total of 114 metastases treated. Median PFS from the start of cRT was 10.9 months (95% confidence interval [CI], 8.1-16.6), while the median survival time was 37.0 months (95% CI, 31.3-NR). On univariable modeling, patients with squamous histology (hazard ratio, 4.16; 95% CI, 1.99-8.71; P < .001) and those treated with non–stereotactic body radiotherapy hypofractionated therapy (hazard ratio, 5.43; 95% CI, 2.10-14.01; P < .001) had worse overall survival, while patients with targetable mutations (hazard ratio, 0.49; 95% CI, 0.25-0.98; P = .04) had a longer survival. Using a predictive nomogram model, patients with a solitary site of metastasis, targetable mutations, intracranial disease, and metachronous timing of oligometastases had a larger PFS benefit from cRT.ConclusioncRT is associated with favorable outcomes in PFS and overall survival. These results may aid in patient counseling, selection for aggressive local therapy, and stratification in future prospective clinical trials.     

Multi-institutional Analysis of the Clinical and Genomic Characteristics of Black Patients with Metastatic Hormone-Sensitive Prostate Cancer

BackgroundThe outcomes of metastatic hormone-sensitive prostate cancer (mHSPC) have significantly improved through treatment intensification, yet Black representation in those studies is suboptimal.MethodsA multi-institutional, retrospective analysis of Black men with mHSPC was conducted, focusing on baseline demographics, treatment patterns, genomic profiles, clinical outcomes including prostate-specific antigen response, time to castrate-resistant prostate cancer (CRPC), and subsequent treatments.ResultsA total of 107 patients, median age 64 years, 62% with de novo metastases at diagnosis and 64% with high-volume disease, were included. Twenty-nine patients (27%) were treated with androgen deprivation therapy (ADT) with and without first generation anti-androgens, while 20%, 38% and 5% received chemotherapy, abiraterone, and enzalutamide, respectively. At time of data cut-off, 57 (54%) patients had developed CRPC, with a median time to CRPC of 25.4 months (95% CI 20.3-30.4). The median time to CRPC was 46.3 months (18.9-73.7) and 23.4 months (18.6-28.2) for patients who received ADT with or without first-generation anti-androgens and treatment intensification, respectively. The 2-year survival rate was 93.3%, and estimated median overall survival of was 74.9 months (95% CI, 68.7-81.0). Most patients (90%) underwent germline testing; the most frequent known alterations were found within the DNA repair group of genes. Somatic testing revealed pathogenic alterations of interest, notably TP53 (24%) and CDK12 (12%).ConclusionIn our cohort, Black men with mHSPC presented with a high proportion of de novo metastases and high-volume disease. Treatment outcomes were very favorable with ADT-based regimens. The genomic landscape suggests different molecular profile relative to White patients with potential therapeutic implications.     

Efficacy of estramustine phosphate according to risk classification of castration-resistant prostate cancer

Treatment options for patients who progressed to castration-resistant prostate cancer (CRPC) are very limited. The purpose of this study was to assess the efficacy of estramustine phosphate (EMP) in patients with CRPC, grouped according to the risk classification advocated by Armstrong et al. and to identify candidates for EMP treatment. Between March 2003 and July 2010, 82 patients with CRPC were treated with 280 or 560?mg EMP per os daily until disease progression or occurrence of unacceptable adverse events. Prostate-specific antigen (PSA) response and overall survival were evaluated according to risk classification. 52 (67%) patients achieved PSA decline. Rates of PSA decline in the good-, intermediate-, and poor-risk groups were 77, 71, and 25%, respectively, significantly higher in the good- and intermediate-risk groups than the poor-risk group (p?=?0.03). The median overall survival times in good-, intermediate-, and poor-risk groups were 21, 19, and 9?months, respectively (p?=?0.005 for good vs intermediate, p?=?0.001 for intermediate vs poor). When the intermediate-risk group was divided into two subgroups by PSA doubling time (PSADT), men with PSADT?≥?2?months achieved higher PSA response rate (88%) and longer survival (22?months) than those with PSADT?相似文献   

Lenalidomide Monotherapy in Chemotherapy-Naive,Castration-Resistant Prostate Cancer Patients: Final Results of a Phase II Study

BackgroundWe investigated the activity of lenalidomide, which has antiangiogenic, antineoplastic, and immunomodulatory properties, in chemotherapy-naive, castration-resistant prostate cancer (CRPC) patients.PatientsPatients received 25 mg/d lenalidomide for 21 days in 28-day cycles, until disease progression or unacceptable toxicity developed. Endpoints included overall response rate and clinical benefit (overall response + stable disease), toxicity, time to radiographic progression, and time to prostate-specific antigen (PSA) progression, overall survival, and quality of life.ResultsThirty-two patients were enrolled in the study; of these, 77% (n = 25) had Gleason scores ≥ 7. The median age was 74 years (58-89 y), the median PSA level was 66 ng/mL (2-919 ng/mL), and 5 of 32 patients (17%) had liver or lung involvement. The median number of lenalidomide cycles was 3 (1-16 cycles). Stable disease was seen in 20 patients, for a clinical benefit rate of 63%. The median time to radiographic progression was 4 months (2-16 mo); the median overall survival was 20 months. Of 27 PSA-evaluable patients, 13 (48%) had a decline in PSA level; 3 (11%) had > 50% PSA decrease; the median time to PSA progression was 3 months (2-9 mo). Grade 3/4 hematologic toxicities were the most common adverse events without adverse impact on quality of life. Serious adverse events occurred in 14 patients (44%), including 1 patient (3%) with a rash definitely related to lenalidomide.ConclusionLenalidomide monotherapy demonstrates modest activity in chemotherapy-naive CRPC.     

A phase 2 study of estramustine,docetaxel, and bevacizumab in men with castrate‐resistant prostate cancer

BACKGROUND:

The use of docetaxel prolongs survival for patients with castrate‐resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC.

METHODS:

This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m² docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate‐specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression‐free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival.

RESULTS:

Seventy‐nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty‐three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty‐four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity.

CONCLUSIONS:

The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing. Cancer 2011. © 2010 American Cancer Society.