XPG遗传多态位点His46His和His1104Asp与卵巢癌患者铂类药物敏感性关系探讨

目的探讨核苷酸切除修复基因XPG单核苷酸多态性与卵巢癌患者对铂类药物敏感性的关系。方法 2002年6月至2009年6月在广西医科大学附属肿瘤医院以聚合酶链-限制性片段长度多态性(PCR-RFLP)和DNA序列测定方法检测接受含铂类药物化疗的102例卵巢上皮细胞癌患者的XPGHis46His及XPGHis1104Asp的多态基因型,并比较不同基因型与化疗敏感性的关系。结果 His1104Asp多态性在卵巢癌铂类药物化疗敏感组中分布与耐药组差异无统计学意义(P>0.05)。而XPGHis46His在化疗敏感组T/T,T/C,C/C的基因型频率明显高于耐药组(P=0.016),与携带XPG46T/T基因型比较,携带至少一个46C等位基因(即T/C和C/C基因型)的卵巢癌患者对铂类药物化疗敏感性增加3.096倍(95%CI1.330～7.208)。COX风险比例回归模型结果显示XPG遗传多态位点His46His和His1104Asp不是卵巢上皮癌患者的独立预后因素(P<0.05)。结论核苷酸切除修复系统中XPGHis46His遗传多态可能与卵巢癌患者对铂类药物敏感性相关。     

紫杉醇剂量密度方案化疗在上皮性卵巢癌应用的疗效及安全性meta分析

目的:评价紫杉醇剂量密度化疗方案治疗上皮性卵巢癌(EOC)的疗效及安全性。方法:采用计算机检索Cochrane图书馆、Pub Med、Embase、ASCO、中国生物医学文献数据库、中国期刊全文数据库、万方数据库中从建库至2014年12月31日关于紫杉醇周疗治疗上皮性卵巢癌与传统月疗方案比较的临床随机对照试验。由两名评价者独立按Cochrane系统评价手册5.1版推荐的RCT标准评价纳入研究的质量,并采用Cochrane协作网提供的Rev Man 5.3软件进行Meta分析,无进展生存期(PFS)及总生存期(OS)合并统计量为风险比(HR),不良反应合并统计量为相对危险度(RR)。结果:纳入5项随机对照试验共2589例患者。Meta分析结果显示,与传统化疗方案相比,紫杉醇周疗在PFS(HR=0.91,95%CI 0.83~1.01)及OS(HR=1.01,95%CI 0.81~1.25)上并未显示明显优势。安全性分析显示,紫杉醇周疗方案发生贫血的风险较传统方案高(RR=1.32,95%CI 1.00~1.75),但对关节痛/肌痛具有保护作用(RR=0.70,95%CI 0.59~0.83)。结论:目前证据表明,紫杉醇周疗相较于传统3周疗法并未在改善患者OS及PFS上显示明显优势,但由于纳入文献较少,故需对此结论持审慎态度。尚需进一步开展大规模、高质量的临床研究进行证实。由于两种方案的不良反应谱不同,仍可以为临床提供参考意义。     

E-钙粘蛋白基因遗传变异与子宫内膜异位症的关联研究

目的:探讨E-钙粘蛋白(E-cadherin,CDH1)基因遗传变异与子宫内膜异位症(EMS)发病风险的关系。方法:采用病例-对照研究方法,DNA测序技术分析CDH1基因启动子区、所有外显子和3'非翻译区(3'-UTR)SNPs位点,从中筛选出6个候选位点(rs16260、rs28372783、rs1801552、rs1801026、rs8049282、rs13689)。扩大样本,通过聚合酶链反应-连接酶检测反应(PCR-LDR)方法检测651例EMS患者(病例组)和655名健康对照妇女(对照组)6个SNPs位点的基因型频率分布情况。结果:DNA测序结果显示CDH1基因启动子区、所有外显子和3'-UTR的17个SNP位点中15个位点在NCBI数据库中有记载,而2个位点尚无相关记载,位于3'-UTR+759和3'-UTR+1445。统计学分析显示6个候选的SNPs基因型和等位基因在病例组和对照组间的频率分布均无统计学差异(P0.05)。但进一步分层分析显示,rs8049282 C/T多态可能与EMS患者的原发不孕相关,即与CT+TT基因型相比,CC基因型可显著增加EMS患者原发不孕的风险(OR=2.25,95%CI=1.32~3.83)。结论:CDH1基因启动子区、外显子和3'-UTR区的遗传变异可能与中国北方汉族妇女EMS的发病风险无关,但rs8049282 C/T多态可能是EMS患者原发不孕的潜在危险因素。     

外周血循环肿瘤细胞对卵巢癌患者临床病理特征和预后关系的Meta分析

目的:系统性评价外周血循环肿瘤细胞(CTCs)与卵巢癌患者的相关临床病理特征及其预后的相关性。方法:计算机检索PubMed、EMbase、Cochrane图书馆、CNKI及CBM等数据库,收集循环肿瘤细胞(CTCs)与卵巢癌患者预后的相关研究。检索时间从建库至2019年5月30日。由2位独立研究者按纳入及排除标准筛选文献、提取数据以及质量评价等,使用RevMan5.3软件进行Meta分析。结果:共纳入13篇文献。Meta分析结果示,CTCs阳性组与卵巢肿瘤分期(RR=0.54,95%CI为0.31～0.95)及肿瘤分级均呈正相关(RR=0.76,95%CI为0.59～0.98),与肿瘤细胞病理类型无相关性(RR=1.00,95%CI为0.74～1.33)。CTCs阳性组与CTCs阴性组的OS(HR=1.56,95%CI为1.25～1.95)和PFS(HR=1.43,95%CI为1.18～1.75)比较,差异均有统计学意义,提示CTCs阳性组患者的预后差。结论:CTCs可能在卵巢癌患者疾病进展过程中起重要作用,外周血CTCs阳性是卵巢癌患者不良预后的重要危险因素,有望应用于临床成为评估卵巢癌预后的指标。     

初始治疗结束后血清视黄醇结合蛋白水平与卵巢癌预后关系研究

目的探讨初始治疗结束后血清视黄醇结合蛋白(RBP)表达水平与卵巢癌预后的关系。方法收集2015年4月至2019年3月辽宁省肿瘤医院初始治疗结束后并达到临床完全缓解的126例卵巢癌患者。以初始治疗结束后血清RBP表达水平25mg/L为阈值,将患者分为高水平组(RBP≥25mg/L)65例和低水平组(RBP 25mg/L) 61例。对两组患者的无进展生存期(PFS)进行比较,并通过单因素和多因素分析确定卵巢癌预后的风险因素。结果Kaplan-Meier分析显示:初始治疗结束后血清RBP水平减低的患者PFS较长[低水平组(28.6±4.8)个月vs.高水平组(15.4±4.7)个月],差异有统计学意义(P 0.05)。多因素Cox分析显示:初始治疗结束后血清RBP水平25mg/L(HR 0.33,95%CI 0.172～0.654,P=0.041)、病理分期(HR 2.15,95%CI 1.42～0.3.31,P=0.018)、分化程度(HR1.52,95%CI 1.132～1.875,P=0.036)、淋巴结转移(HR 1.41,95%CI 1.251～1.926,P=0.043)是影响卵巢癌预后的独立因素。结论初始治疗结束后血清RBP水平、病理分期、分化程度和淋巴结转移是卵巢癌患者预后的独立影响因素。     

影响复发上皮性卵巢癌化疗疗效的临床病理因素分析

目的:分析影响铂类敏感型及耐药型复发上皮性卵巢癌(EOC)患者预后的相关临床病理因素。方法:回顾分析1985年1月至2011年11月广西医科大学附属肿瘤医院收治的复发EOC患者83例,其中铂类敏感型56例,耐药型27例。采用Kaplan-meier生存率曲线、Log-rank test检验和Cox模型多因素回归分析法分析影响复发EOC患者预后的相关因素。结果:(1)铂类敏感型复发EOC患者的中位无进展生存期(PFS)为11个月(95%CI 9.105～12.895),中位总生存期(OS)为16个月(95%CI 13.144～18.856);铂类耐药型复发EOC患者的中位PFS为8个月(95%CI 4.219～11.781),中位OS为10个月(95%CI 3.824～16.176)。(2)复发后伴有腹水、复发后化疗方案、化疗疗程、化疗效果是影响敏感型复发EOC患者的重要预后因素(P<0.05);无复发生存时间(RFS)、复发后伴有腹水、复发部位、化疗效果是影响耐药型复发EOC患者的重要预后因素(P<0.05)。(3)复发后化疗疗程数、复发后伴有腹水、化疗疗效是影响敏感型复发EOC患者预后的独立危险因素,而复发部位是影响耐药型复发EOC患者预后的独立危险因素。结论:铂类敏感型患者复发后宜选择与一线类似的铂类联合方案化疗,并尽可能化疗至6疗程。复发病灶位于盆腹腔是影响耐药型患者预后的独立危险因素,应积极治疗。     

ⅢC～Ⅳ期上皮性卵巢癌预后影响因素分析

目的:探讨ⅢC～Ⅳ期上皮性卵巢癌患者预后的影响因素,为临床诊疗提供数据支持。方法:回顾分析广西医科大学附属肿瘤医院129例ⅢC～Ⅳ期上皮性卵巢癌患者的临床资料,包括年龄、临床分期、组织病理学类型与分级、手术残余病灶直径和术后化疗周期数等。分析评价各因素对ⅢC～Ⅳ期上皮性卵巢癌预后的影响。结果:单因素分析显示,年龄、手术残余病灶直径、术后化疗周期数与患者预后密切相关,临床分期、病理学类型与组织学分级对预后无显著影响。应用COX回归模型进行多因素分析,患者年龄≥50岁(RR=0.493,95%CI:0.308～0.790)、手术残余病灶直径≥1 cm(RR=2.527,95%CI:1.585～4.028)及术后化疗周期数6次(RR=2.294,95%CI:1.464～3.593)为ⅢC～Ⅳ期上皮性卵巢癌患者预后的独立危险因素。结论:对于ⅢC～Ⅳ期上皮性卵巢癌患者,年龄越大、手术残余病灶直径越大、术后化疗周期数越少,预后越差。     

VEGF基因多态性与不明原因复发性自然流产发生风险相关性的meta分析

目的:评价血管内皮生长因子(VEGF)基因的多态位点与不明原因复发性自然流产发生风险的相关性。方法:检索Pubmed数据库、Medline数据库、Cochrane图书馆数据库、中国知网(CNKI)、维普中文科技期刊数据库、万方数据库、中国生物医学文献数据库中有关VEGF基因多态性与不明原因复发性自然流产的病例-对照研究,对纳入的研究进行质量评价,采用Rev Man5.3软件进行数据分析。结果:最终纳入11篇文献对VEGF基因的-634G/C(rs2010963)、+936C/T(rs3025039)、-2578C/A(rs699947)及-1154G/A(rs1570360)4个位点进行评价,累计病例组1945例,对照组2074例。Meta分析结果显示,在VEGF基因的-634G/C位点,基因型CC发生复发性自然流产的风险高于基因型GG[P=0.03,OR=1.29,95%CI(1.03,1.63)];携带等位基因C妇女的发病风险高于携带等位基因G[P=0.02,OR=1.14,95%CI(1.02,1.27)]。+936C/T位点的CT、TT基因型及携带T等位基因发生复发性自然流产的风险高于CC基因型及携带C等位基因的女性[CT vs CC基因型:P0.0001,OR=1.40,95%CI(1.18,1.65),TT vs CC基因型:P=0.02,OR=1.72,95%CI(1.11,2.66),T vs C等位基因:P0.00001,OR=1.52,95%CI(1.30,1.78)];两组的-1154G/A、-2578C/A各基因型比较,差异均无统计学意义(P0.05)。结论:VEGF基因-634G/C(rs2010963)、+936C/T(rs3025039)位点的单核苷酸多态性与不明原因的复发性流产发生可能相关。     

外泌体生物标志物在卵巢癌诊断及预后评估方面的价值——系统评价

目的:系统评价外泌体生物标志物在卵巢癌诊断和预后评估方面的价值。方法:计算机检索中国知网、维普、万方、PubMed、EMBASE、Web of Knowledge和Cochrane Library数据库,搜集外泌体在卵巢癌诊断和预后方面的相关研究,检索时间均从建库至2019年12月20日。由2名研究者按照纳入与排除标准筛选文献、提取资料和评价纳入研究的质量。在诊断方面,比较卵巢癌患者和非卵巢癌对照人群外泌体生物标志物的表达情况。在预后方面,评价外泌体生物标志物表达与卵巢癌患者总生存期(OS)、无进展生存期(PFS)之间的相关性。结果:共纳入文献10篇。利用外泌体提取试剂盒是分离纯化外泌体的最常见方法,透射电子显微镜观察形态和检测外泌体标志蛋白是鉴定外泌体的基本方法。①诊断方面,血清来源外泌体内含miR-200a、miR-145显示出较高的诊断价值(miR-200a的AUC为0.91,敏感度和特异度分别为83.9%和90.0%;miR-145的AUC为0.91,敏感度和特异度分别为91.7%和75.0%)。血浆来源外泌体内含纤维蛋白原α链(FGA)、凝溶胶蛋白(GSN)、纤维蛋白原γ链(FGG)也具有一定的诊断价值(FGA、GSN、FGG的AUC分别为0.85、0.83和0.74)。②预后评估方面,血清来源外泌体内含miR-373、miR-200b、miR-200c高表达与卵巢癌患者的OS明显缩短密切相关(HR分别为2.1、2.7和2.4,95%CI分别为1.0～4.3、1.3～5.7和1.2～4.9);miR-200c的高表达与卵巢癌患者PFS缩短也密切相关(HR=2.0,95%CI:1.1～3.6)。血清来源外泌体内含长链非编码RNA反义缺氧诱导因子(lncRNA aHIF)的高表达与卵巢癌患者OS缩短密切相关(HR=3.70,95%CI:1.83～7.50)。结论:外泌体生物标志物可用于卵巢癌患者的早期诊断和预后评估。     

淋巴结阳性率在ⅠB～ⅡA期宫颈癌患者中的临床意义

目的:研究淋巴结阳性比率(LNR)对IB~IIA期宫颈癌患者无进展生存期(PFS)及总生存期(OS)的影响。方法:回顾分析2010年1月~2015年12月我院收治的102例经根治性子宫切除±双侧卵巢切除+盆腔淋巴结清扫±腹主动脉淋巴结清扫术的淋巴结转移阳性的102例IB~IIA期宫颈癌患者的临床资料。采用单因素和多因素分析LNR、分期、病理类型、组织学分级、肿瘤大小、辅助治疗对PFS及OS的影响。结果:单因素分析显示,LNR、分期对PFS、OS有显著影响。多因素分析显示,LNR10%的患者PFS更差(HR=0.151,P=0.047,95%CI为0.023~0.974);而LNR10%患者的OS与LNR≤10%者比较,差异无统计学意义。结论:LNR可以作为判断IB~IIA期宫颈癌患者PFS的一项独立危险因素。     

nm23 gene polymorphisms are associated with survival of patients with epithelial ovarian cancer but not with susceptibility to disease

Objective

nm23, a tumor metastasis suppressor gene, has been linked to protection against tumorigenesis and tumor metastasis. This study evaluated whether genetic variants in the nm23 gene were associated with susceptibility to epithelial ovarian cancer (EOC) or the clinical outcome of patients.

Methods

A case-control study was performed with 302 patients with epithelial ovarian cancer and 302 control women. According to the genotypes, the outcome in 213 EOC patients was compared. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier plots and Cox models adjusted for clinical factors.

Results

The case-control analysis showed that the rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter were not associated with the risk of developing EOC. In contrast, survival analysis showed that the rs2302254 C/T polymorphism was related to the prognosis of EOC patients. Compared with patients carrying the C/C genotype, patients carrying the T/T genotype had a shorter median PFS and median OS by Kaplan-Meier plots and Cox models adjusted for clinical factors. For rs16949649 T/C polymorphisms, Kaplan-Meier analysis indicated that patients carrying the homozygous C/C genotype had shorter PFS and OS than those carrying the T allele (T/T + T/C genotype). The Cox proportional hazard model analysis suggested that this relationship was only retained in OS when adjusted for clinical factors.

Conclusion

Our studies suggest that rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter may influence the prognosis of patients with epithelial ovarian cancer.     

晚期卵巢癌新辅助化疗的Meta分析

目的:评价新辅助化疗对晚期卵巢癌患者总生存期及无进展生存期的影响,探讨新辅助化疗在晚期卵巢癌的应用价值。方法:计算机检索PubMed数据库、Med-line数据库、EMbas数据库、Cochrane Library数据库、万方数据库、中国学术文献总库(CNKI)、中国生物医学文献数据库(CBM),手工检索《中华妇产科杂志》,《中国实用妇科与产科杂志》,《实用妇产科杂志》,《生殖与避孕》,《现代妇产科进展》5本妇产科杂志。语言种类为中文和英文,网上检索时间不限。试验组行新辅助化疗,即以铂类为基础的化疗后行细胞减灭术;对照组行传统治疗,即细胞减灭术后行规范性化疗。结果:共纳入3篇文献,提取数据后,Review Manager5.0软件进行Meta分析,两组的总生存期合并后的RR值为0.96(95%CI,0.90～1.03),两组的无进展生存期合并后的RR值为1.00(95%Cl 0.93～1.09),森林图菱形均与垂直线相交。结论:新辅助化疗并未改善晚期卵巢癌患者的预后。     

A retrospective analysis of neoadjuvant platinum-based chemotherapy versus up-front surgery in advanced ovarian cancer

Abstract.   Steed H, Oza AM, Murphy J, Laframboise S, Lockwood G, De Petrillo D, Sturgeon J, Rosen B. A retrospective analysis of neoadjuvant platinum-based chemotherapy versus up-front surgery in advanced ovarian cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 47–53.
The objective of this study is to compare progression-free survival (PFS) and overall survival (OS) of ovarian cancer patients treated with neoadjuvant chemotherapy and surgery to primary surgery and postoperative chemotherapy. Retrospective analysis from 1998 to 2003 of 116 patients with ovarian cancer was performed. Fifty women diagnosed by positive cytology received three cycles of carboplatin and paclitaxel. Thirty-six patients subsequently underwent cytoreductive surgery and completed three further cycles postoperatively. The OS and PFS were compared in 66 women treated with primary surgery and postoperative chemotherapy. A statistically significant difference was observed for OS ( P = 0.03, HR = 1.85, CI = 1.06–3.23) and PFS ( P = 0.04, HR = 1.61, CI = 1.03–2.53) favoring the primary surgery group. Due to the small numbers, age, grade, stage, pleural effusions, and histologic cell type were controlled for separately in the bivariate analyses. Controlling for stage made the results weaker. A matched subgroup survival analysis was performed on patients who had surgery following neoadjuvant chemotherapy. After matching for stage and grade and controlling age and pleural effusions ( N = 28 matched pairs), there was no statistical difference for OS ( P = 0.95, HR = 1.04, CI = 0.33–3.30) or PFS ( P = 0.79, HR = 1.11, CI = 0.98–1.04). It is concluded that primary surgery should be considered in all patients. Neoadjuvant chemotherapy may be an alternative in a subset of women with the intent to also perform interval debulking.     

A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer

Ovarian cancer is the fourth leading cause of cancer death among women in the United States. First-line chemotherapy offered to patients with ovarian cancer generally consists of an intravenous (IV) platinum plus taxane regimen and has remained virtually unchanged for the past 10 years. A number of recently completed phase III randomized trials in the United States have reported improved progression-free survival (PFS) and/or overall survival (OS) with the intraperitoneal (IP) administration of cisplatin. The purpose of this study was to pool the published data to perform a meta-analysis of randomized trials of IP cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This study was initiated to obtain a more valid estimate of the therapeutic impact of IP treatment for these patients. A search strategy was initiated that searched published findings of randomized trials of IP cisplatin therapy from multiple sources from January 1990 through January 2006. Six randomized trials of 1716 ovarian cancer patients were identified and included in this analysis. The pooled hazard ratio (HR) for PFS of IP cisplatin as compared to IV treatment regimens is 0.792 (95% CI: 0.688-0.912, P= 0.001), and the pooled HR for OS is 0.799 (95% CI: 0.702-0.910, P= 0.0007). These findings strongly support the incorporation of an IP cisplatin regimen to improve survival in the front-line treatment of stage III, optimally debulked ovarian cancer.     

新辅助化疗在晚期卵巢上皮性癌综合治疗中的临床研究

目的探讨新辅助化疗(NACT)在晚期卵巢上皮性癌(卵巢癌)治疗中的临床意义。方法回顾性分析四川省肿瘤医院1999年1月至2008年12月收治的晚期卵巢癌(FIGOⅢ、Ⅳ期)患者161例,其中73例接受新辅助化疗+手术治疗+化疗(研究组),88例行初次肿瘤细胞减灭术+化疗(传统组)。结果研究组肿瘤手术切除率(即理想减瘤率)77.1%,传统组为56.8%,差异有统计学意义(P=0.012)。研究组术中失血量、术中输血量、术中补液量、腹水量和手术时间与传统组比较,差异均有统计学意义(P<0.05)。研究组平均无进展生存期(PFS)和总体生存期(OS)分别为22.7(7～63.5)个月和33.5(13.8～92.3)个月,传统组分别为21.7(4.3～61.2)个月和32.1(12.4～114.9)个月,两组比较差异无统计学意义(分别为P=0.082和P=0.293)。研究组和传统组5年生存率分别为17.8%和11.4%,差异无统计学意义(P=0.503)。结论行新辅助化疗+手术治疗+化疗治疗晚期卵巢上皮性癌的PFS、OS与仅行初次肿瘤细胞减灭术+化疗相似,但前者能明显提高肿瘤的手术切除率、减少术中出血量,同时并没有增加手术的并发症。     

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian,fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study

IntroductionCabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer.MethodsThis was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m² given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens.ResultsMedian PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77–1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17–4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24–2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm.ConclusionsMedian PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.     

复发上皮性卵巢癌化疗疗效的Meta分析

目的：系统评价不同化疗方案治疗复发上皮性卵巢癌（EOC）的临床疗效差异及毒副反应等。方法：按Cochrane系统评价方法,计算机检索PubMed、Embase、Medline、Cochrane Library、循证医学数据库（EBMR）、中国生物医学文献数据库（CBM）、中国期刊全文数据库（CJFD）、中国知网（CNKI）等数据库,并手工检索相关领域杂志。检索期限自1995年1月1日-2011年12月31日。查找复发性EOC治疗中评价了两种化疗方案对患者无进展生存期（PFS）、整体生存时间（OS）、缓解人数、完全缓解人数、3-4度血液学毒性反应、非血液学毒性反应等的随机对照试验（RCT）,由2位研究者按照纳入排除标准筛选文献、评价质量并提取资料后,采用RevMan5.1软件进行Meta分析。结果：共纳入14个研究（7个评价治疗敏感型复发EOC,7个评价治疗耐药型复发EOC）。Meta分析结果显示,卡铂联合化疗较单一卡铂可以改善敏感型复发EOC患者的OS（OR=0.50,95%CI：0.32-0.78,P=0.002）及缓解率（OR=1.87,95%CI：1.38-2.55,P＜0.0001）,但无助于改善PFS（OR=1.19,95%CI：0.60-2.33,P=0.62）,会增加3-4度白细胞降低的风险（OR=7.82,95%CI：4.00-15.30,P＜0.00001）。两项研究提示拓扑替康可以改善耐药型复发EOC的OS,吉西他滨与脂质体阿霉素相比并不增加改善耐药型复发EOC的缓解率（OR=1.29,95%CI：0.67-2.46,P=0.45）,但增加3-4度中性粒细胞降低的风险（OR=2.97,95%CI：1.70-5.17,P=0.0001）。结论：卡铂联合化疗可以改善敏感型复发EOC患者的OS及缓解率,化疗过程中要注意监测血液学毒性反应。拓扑替康可以改善耐药型复发EOC的OS但无助于改善PFS,可以作为今后治疗耐药型复发EOC的研究方向。尚需更多设计严格的高质量RCT研究加以证实。     

The prognostic value of vascular endothelial growth factor in ovarian cancer: A systematic review and meta-analysis

ObjectiveThe prognostic role of vascular endothelial growth factor (VEGF) in ovarian cancer remains inconclusive. This meta-analysis aimed to explore the association between VEGF overexpression and survival outcomes in ovarian cancer patients.MethodsStudies were identified from PubMed and EMBASE searches performed on January 2nd, 2011. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) in serum and tumor tissue studies.ResultsSixteen studies with 1111 patients were analyzed. Elevated serum VEGF was significantly associated with poor PFS [HR 2.46, 95% CI (1.84, 3.29)] and OS [HR 2.21, 95% CI (1.57, 3.13)]. No significant heterogeneity existed in serum studies. Similarly, tissue VEGF overexpression was associated with poor PFS [HR 1.63, 95% CI (1.09, 2.42)] and OS [HR 1.70, 95% CI (1.01, 2.87)]. However, significant heterogeneity was found in tissue studies, with I² of 44% for PFS and 64% for OS. Studies were stratified into subgroups by International Federation of Gynecology and Obstetrics (FIGO) stages. Subgroup analyses showed that high tissue VEGF was significantly associated with shorter PFS [HR 5.34, 95% CI (1.95, 14.59)] and OS [HR 6.13, 95% CI (2.47, 15.26)] in studies where predominantly early-stage patients were included, but not in studies with a majority of advanced-stage patients. Subgroup analysis was not performed in serum studies because all those studies enrolled more patients in advanced stages than early stages.ConclusionsOverexpression of VEGF in primary tumor and serum associates with poor PFS and OS for patients with ovarian cancer. The association between high tissue VEGF level and poor prognosis exists in early stage patients, but not in advanced stage patients.