Effects of Genetic Polymorphisms in the ABCB1 Gene onClinical Outcomes in Patients with Gastric Cancer Treated bySecond-line Chemotherapy

Objective: Tumor cells that overexpress P-glycoprotein (Pgp) may be resistant to several anticancer agentsdue to altered pharmacokinetics and reduced intracellular concentrations of the anticancer agents. Pgp is encodedby the ATP binding cassette gene B1 (ABCB1). To our knowledge, only one previous report has evaluated theeffect of ABCB1 gene polymorphisms on clinical outcomes of gastric cancer. The purpose of this analysis was toevaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advancedgastric cancer (AGC) treated with second-line chemotherapy. Methods: We retrospectively analyzed the impactof ABCB1 gene polymorphisms (ABCB1 3435C>T) on clinical outcomes in 100 patients with AGC who receivedsecond-line chemotherapy. Results: Median overall survival (OS) since the initiation of second-line chemotherapywas 6.0 months (95% confidence interval [CI], 4.8 to 8.0 months), and median progression-free survival (PFS)was 2.7 months (95% CI, 2.1 to 3.4 months). In a multivariate analysis of PFS, a 3435 CC polymorphism (n =45) was significantly associated with longer PFS compared with the CT/TT type polymorphism (n = 55), withborderline significance (PFS of 3.2 months vs. 2.2 months, respectively; HR 1.50; 95% CI, 0.98-2.30; P = 0.061).ABCB1 3435 C>T polymorphisms were not associated with OS. No interaction was seen between ABCB1polymorphisms and treatment regimens. Conclusion: Genetic polymorphisms of ABCB1 3435C>T might havea possible impact on clinical outcomes of second-line chemotherapy in AGC. Further prospective evaluationusing a larger sample size is required.     

Associations of ABCB1 and XPC Genetic Polymorphisms with Susceptibility to Colorectal Cancer and Therapeutic Prognosis in a Chinese Population

Associations between ABCB1 and XPC genetic polymorphisms and risk of developing colorectal cancer (CRC)as well as clinical outcomes in CRCs with chemotherapy were investigated. A case-control study was performedon the ABCB1 C3435T, G2677T/A and XPC Lys939Gln polymorphisms in 428 CRC cases and 450 hospitalbased,age and sex frequency-matched controls using polymerase chain reaction-restriction fragment lengthpolymorphism (PCR-RFLP) assays. We observed that the ABCB1 3435CT or CC+CT variants were significantlylinked with increasing risk of developing CRC (adjusted OR (95% CI): 1.814 (1.237-2.660), P=0.0022; adjustedOR (95% CI): 1.605 (1.117-2.306), P=0.0102, respectively). Moreover, the distribution frequency of XPC ACgenotype or AC+CC genotypes also showed a tendency towards increasing the suscepbility for CRC (P=0.0759and P=0.0903, respectively). Kaplan-Meier curves showed that the ABCB1 C3435T variant was associated witha tendency toward longer progression-free survival (PFS) (n=343, Log-rank test: P=0.063), and the G2677T/Avariant genotypes (GT+TT+GA+AA) with a tendency for longer OS in postoperative oxaliplatin-based patients(n=343, Log-rank test: P=0.082). However, no correlation of the XPC Lys939Gln polymorphism was found withPFS and OS in patients with postoperative oxaliplatin-based chemotherapy (n=343). Our study indicated thatABCB1 polymorphisms might be candidate pharmacogenomic factors for the prediction of CRC susceptibility,but not for prognosis with oxaliplatin chemosensitivity in CRC patients.     

Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study).

BACKGROUND: This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric cancer patients. PATIENTS AND METHODS: From June 1996 to June 2001, 228 stage IB-IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy. RESULTS: A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.051). The most common grade 3-4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal. CONCLUSIONS: In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.     

Meta-analysis of Six Randomized Control Trials of Chemotherapy Plus Anti-HER Monoclonal Antibody for Advanced Gastric and Gastroesophageal Cancer

Background: A meta-analysis was performed to examine the benefit/risk ratio for the addition of anti-HER MoAbs to chemotherapy in patients with advanced gastric and gastroesophageal cancer from six andomized phase II/III trials. Materials and Methods: We searched relative trials from Pubmed, EMBASE, Cochrane library databases, China National Knowledge Infrastructure databases, Google Scholar and the NIH ClinicalTrials. Primary outcomes were overall response rate (ORR), progression-free survival (PFS), overall survival (OS). Secondary outcomes were toxicities. All analyses were performed using STATA 12.0. Results: This meta-analysis included six randomized controlled trials (RCTs) with 2, 297 patients and we demonstrated that the anti-HER MoAbs arm did have a positive effect on ORR in the anti-HER MoAbs arm (OR 1.28, 95% CI 1.00-1.64, p=0.01). There was an increasing benefit regarding OS (HR 0.74, 95% CI 0.60-0.88, p<0.05) and PFS (HR 0.72, 95% CI 0.60-0.84, p<0.05) in the anti-HER2 subgroup, but a reduction of OS (HR 1.11, 95% CI 0.87-1.36, p<0.05) and PFS (HR 1.13, 95% CI 0.98 -1.28, P<0.05) in anti-EGFR subgroup. Some grade 3-4 toxicity had a significantly higher incidence in the anti-HER MoAbs arm. There was no significant publicationbias for all endpoints. Conclusions: The addition of trstuzumab MoAb to chemotherapy for gastric and gastroesophageal cancer significantly improved outcome of OS and PFS endpoints, while other MoAbs led to no improvement in results. Some adverse events were increased in anti-HER MoAbs arm compared with the control.     

The ERCC1 C118T Polymorphism Predicts Clinical Outcomes of Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Meta-analysis Based on 22 Studies

Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1)C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-basedchemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, weperformed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in thisclinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategywas used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) wereused to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs forprogression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRCpatients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118Tpolymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian andCaucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter inpatients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratifiedanalysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS,HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS,HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, wefailed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity.Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoingoxaliplatin-based chemotherapy.     

Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients.

BACKGROUND: The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. METHODS: This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). RESULTS: Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) < or = 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42-6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69-3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04-2.58, P = 0.032). CONCLUSIONS: Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis.     

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphismregarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapyhas been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performeda meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation andoptimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligiblestudies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) wereused to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-freesurvival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusioncriteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response tooxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFSand OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Glnallele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratifiedanalysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47;OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI:1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRCundergoing oxaliplatin-based chemotherapy.     

First‐Line Treatment Patterns and Clinical Outcomes in Patients With HER2‐Positive and Hormone Receptor‐Positive Metastatic Breast Cancer From registHER

Background.

Limited data are available describing the natural history of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC). We examined first-line treatment patterns and clinical outcomes in patients with HER2-positive, HR-positive MBC in a real-world setting.

Methods.

registHER is a prospective, observational cohort of 1,023 patients with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up time: 27 months). Demographics, first-line treatment patterns, and clinical outcomes were examined for 530 HER2-positive, HR-positive patients. Progression-free survival (PFS) and overall survival (OS) times were examined. Multivariate analyses adjusted for baseline demographic and prognostic factors.

Results.

HER2-positive, HR-positive patients receiving first-line trastuzumab plus hormonal therapy had significantly longer PFS times than patients who received hormonal therapy only (13.8 vs. 4.8 months; adjusted hazard ratio [HR]: 0.37, 95% confidence interval [CI]: 0.22–0.60); a nonsignificant reduction in OS time was observed (adjusted HR: 0.55, 95% CI: 0.27–1.14). Compared with patients who received first-line trastuzumab plus chemotherapy, patients who received first-line trastuzumab plus chemotherapy and hormonal therapy had longer median PFS times (20.4 months vs. 9.5 months; adjusted HR: 0.53, 95% CI: 0.42–0.68); a statistically significant reduction in risk of death was observed (adjusted HR: 0.50, 95% CI: 0.36–0.70). Sequential use of chemotherapy and hormonal therapy was associated with improved OS times when compared with concurrent use (adjusted PFS HR: 0.81, 95% CI: 0.54–1.21; adjusted OS HR: 0.48, 95% CI: 0.26–0.89).

Conclusions.

These real-world data in patients with HER2-positive/HR-positive MBC provide evidence that, with or without chemotherapy, dual targeting of HRs and HER2 receptors is associated with significantly prolonged PFS and OS times.     

食管癌术后辅助治疗的Meta分析

[目的]探讨食管癌术后辅助治疗的价值.[方法]收集1995年至2011年期间发表的关于食管癌术后辅助治疗的随机对照研究文章,利用Stata12.0软件进行Meta分析.[结果]与单纯手术相比,术后辅助化疗患者的3年无进展生存率相对危险度(RR)为1.225 (95％CI:1.012～1.482,P=0.037),差异有统计学意义.而3、5年总生存率的RR值分别为0.899(95％CI:0.797～1.016,P=0.087),1.183(95％CI:0.97～1.442,P=0.098),差异无统计学意义.同样,与单纯手术相比,术后辅助放疗患者的3年总生存率的RR值为0.935 (95％CI:0.879～0.994,P=0.033),差异有统计学意义.而5年总生存率的RR值为0.988(95％CI:0.821～1.188,P=0.897),差异无统计学意义.Begg's与Egger试验检测P值均大于0.05,不存在发表偏倚.[结论]术后辅助化疗能延长食管癌患者术后的3年无进展生存率,术后辅助放疗不利于延长食管癌患者的3年总生存率.     

Activity of first-line epirubicin and paclitaxel in metastatic breast cancer is independent of type of adjuvant therapy

To evaluate the impact of prior adjuvant chemotherapy on response rate (RR), progression-free (PFS) and overall survival (OS) of metastatic breast cancer patients treated with epirubicin/paclitaxel (ET) regimens. In all, 291 patients enrolled in five studies in metastatic breast cancer were analysed: 101 (35%) were chemonaive, 109 (37%) had received adjuvant CMF and 81 (28%) adjuvant anthracyclines. Response rate to ET was 66%. Response rate was 63% for cyclophosphamide plus methotrexate plus 5-fluorouracil (CMF), 67% for prior anthracyclines and 68% in chemonaive patients (P=0.5). By multivariate analysis, adjusted odds ratio for response was 0.81 (95% CI: 0.37-1.79) for CMF and 0.92 (95% CI 0.43-2.01) for anthracyclines (P=0.86). The CR rates were 14% for both CMF and anthracyclines and 22% for chemonaive patients (P=0.2). By multivariate analysis, the relative odds of CR for CMF or anthracyclines were 0.40 and 0.39 as compared to chemonaive patients (P=0.036). The median PFS was 11.0 months for prior CMF, 10.2 months for anthracyclines and 12.5 months in chemonaive patients (P=0.33). In multivariate Cox's model, a nonsignificant increase in the risk of progression was seen in patients treated with adjuvant CMF or anthracyclines. The median OS was 23.8 months for CMF, 20.2 months for anthracyclines and 27.5 months in chemonaive patients (P=0.61). The same, nonsignificant, association was seen in multivariate analysis. The ET regimens provide satisfactory results in metastatic breast cancer, regardless of previous adjuvant chemotherapy.     

Prognostic and clinical significance of subcellular CDC27 for patients with rectal adenocarcinoma treated with adjuvant chemotherapy

Rectal adenocarcinoma (READ) constitutes one-third of newly diagnosed colorectal cancer cases. Surgery, chemotherapy and concurrent chemoradiotherapy are the main treatments to improve patient outcomes for READ. However, patients with READ receiving these treatments eventually relapse, leading to a poor survival outcome. The present study collected surgical specimens from patients with READ and determined that cytoplasmic cell division cycle 27 (CDC27) expression was associated with the risk of lymph node metastasis and distant metastasis. Nuclear CDC27 expression was negatively associated with 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates. Multivariate Cox proportional regression analysis showed that nuclear CDC27 was an independent prognostic factor in the patients with READ, especially in those treated with adjuvant chemotherapy. High nuclear CDC27 expression was significantly associated with poorer 5-year DFS (HR, 2.106; 95% CI, 1.275-3.570; P=0.003) and 5-year OS (HR, 2.369; 95% CI, 1.270-4.6810; P=0.005) rates. The data indicated that cytoplasmic CDC27 expression could affect tumor progression and that it plays an important role in metastasis. Nuclear CDC27 expression was markedly associated with poorer survival outcomes and was an independent prognostic factor in patients with postoperative adjuvant chemotherapy-treated READ. Thus, CDC27 expression serves as a potential prognostic marker for rectal tumor progression and chemotherapy treatment.     

弥漫大B细胞淋巴瘤患者体质量指数对预后影响的Meta分析

目的:系统评价体质量指数（BMI）对弥漫大B细胞淋巴瘤（DLBCL）患者预后的影响。方法:计算机检索PubMed、Medline、Web of Science等数据库,按照纳入及排除标准筛选关于BMI与DLBCL患者预后关系的临床研究文献,采用RevMan 5.3软件对各研究的总生存（OS）、无进展生存（PFS）的风险比（ HR）及95%置信区间（95% CI）等数据进行分析,同时评估纳入文献质量、偏倚风险及异质性。 结果:共12篇文献纳入研究。Meta分析结果显示,与正常体质量（BMI 18.5~24.9 kg/m 2）患者相比,超重（BMI 25.0~29.9 kg/m 2）患者OS和PFS时间更长,但差异均无统计学意义（OS： HR=0.93,95% CI 0.78~1.11, P=0.42;PFS： HR=0.89,95% CI 0.67~1.20, P=0.45）;低体质量（BMI<18.5 kg/m 2）患者（OS： HR=1.97,95% CI 1.41~2.74, P<0.01;PFS： HR=1.89,95% CI 1.19~3.03, P<0.01）和肥胖（BMI≥30.0 kg/m 2）患者OS和PFS时间更短,但后者差异无统计学意义（OS： HR=1.15,95% CI 0.88~1.51, P=0.31;PFS： HR=1.32,95% CI 0.90~1.94, P=0.15）。漏斗图对称,纳入文献无发表偏倚。 结论:一定范围内BMI升高是DLBCL患者预后的保护性因素。     

Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial

Patients with metastatic triple-negative breast cancer (TNBC) typically have a poor prognosis and limited treatment options. To determine the impact of combining bevacizumab with second-line chemotherapy in patients with metastatic TNBC, we performed an exploratory subgroup analysis of the randomized phase 3 RIBBON-2 trial. RIBBON-2 enrolled patients with metastatic breast cancer that had progressed on first-line non-bevacizumab-containing chemotherapy. After selection of chemotherapy (taxane, gemcitabine, capecitabine, or vinorelbine), patients were randomized 2:1 to receive chemotherapy with either bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Of 684 patients treated in RIBBON-2, 159 (23%) had TNBC. Baseline characteristics were reasonably balanced in the two treatment groups. The majority received taxane chemotherapy. The hazard ratio (HR) for PFS was 0.494 [95% confidence interval (CI) 0.33-0.74; P = 0.0006]. Median PFS was 6.0 months with bevacizumab-chemotherapy versus 2.7 months with chemotherapy alone. Median OS was 17.9 versus 12.6 months, respectively (HR 0.624, 95% CI 0.39-1.007; P = 0.0534). ORR was 41 versus 18%, respectively (P = 0.0078). The safety profile was consistent with the overall study population and previous phase 3 trials of bevacizumab. Patients with metastatic TNBC derived significant PFS and response benefits from the combination of bevacizumab with second-line chemotherapy. Despite the small sample size and immature data, there was a trend toward improved OS.     

Randomized phase III clinical trial evaluating weekly cisplatin for advanced epithelial ovarian cancer

This randomized, open label, phase III clinical trial (1988-1992) compared the efficacy and safety of a dose-dense regimen of single-agent cisplatin with a standard 3-weekly schedule in first-line chemotherapy for advanced epithelial ovarian cancer. Two hundred eighty-five patients were randomly assigned to the experimental dose-dense arm (cisplatin 50 mg/m(2) weekly × nine cycles) or to the control (standard treatment) arm (cisplatin 75 mg/m(2), administered on day 1 every 21 days × six cycles). The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), overall response to chemotherapy, and toxicity. Toxicity and response to treatment were compared with the χ(2) test using trend or exact correction. PFS and OS were estimated by Kaplan-Meier analyses and treatment hazard ratios (HRs) with the Cox proportional hazards model. All statistical tests were two-sided. After a median follow-up of 16.8 years, no differences were observed between the two treatments in PFS (experimental arm: 17.2 months; control arm: 18.1 months; HR = 1.08, 95% confidence interval [CI] = 0.83 to 1.40; P = .57) and in OS (experimental arm: 35 months; control arm: 32 months; HR = 0.97, 95% CI = 0.75 to 1.26; P = .97). Thus, increasing dose intensity of cisplatin does not improve PFS or OS compared with standard chemotherapy.     

TOP2A与胃癌术后辅助化疗及表柔比星疗效的关系

目的 探讨拓扑异构酶ⅡA（TOP2A）与胃癌术后辅助化疗及表柔比星疗效的关系。方法 筛选D2根治术后接受了辅助化疗的胃腺癌患者,采用免疫组化染色检测其石蜡包埋的肿瘤组织中TOP2A蛋白的表达,分析TOP2A与患者无病生存期（DFS）及总生存期（OS）的关系,并亚组分析TOP2A与含表柔比星方案辅助化疗疗效的关系。结果 109例患者入选,其中接受含表柔比星方案辅助化疗的患者44例。TOP2A表达水平与胃癌各临床病理特征均无关（P＞0.05）。Kaplan Meier生存分析显示,TOP2A蛋白低表达患者的3年无病生存率和3年生存率均显著高于高表达者（79.8 ％ vs. 57.1％和88.0％ vs. 65.0％;P均＜0.05）。在接受含表柔比星方案辅助化疗的胃癌患者中,TOP2A蛋白低表达者的3年无病生存率显著高于高表达者（83.3％ vs. 50.0％,P＜0.05）,而3年生存率的差异无统计学意义（91.7％ vs. 62.2％,P=0.068）。多因素Cox比例风险回归模型显示,组织学分级Ⅲ级（HR=3.02,95％CI：1.41～6.46;P=0.004）和TOP2A蛋白高表达（HR=3.51,95％CI：1.06～11.58;P=0.039）是影响胃癌OS的独立风险因素。结论 TOP2A可能与胃癌术后辅助化疗及表柔比星疗效有关,是疗效预测潜在的分子标志。     

胃癌术后辅助放化疗与辅助化疗比较的荟萃分析

目的 采用偱证医学荟萃分析的方法比较胃癌术后辅助放化疗与辅助化疗间的疗效差异。方法 计算机检索PubMed、EMbase、Cochrane图书馆、万方、维普、CNKI及中国生物医学等数据库,搜集有关胃癌术后辅助放化疗和辅助化疗比较的临床对照研究资料,汇总数据采用RevMan 5.2.5和Stata 12.0软件进行分析。两组间差异采用优势比(OR)及95%可信区间(95% CI)描述。结果 根据纳入和排除标准,最终纳入12个包括1674例患者的临床对照研究资料。荟萃分析结果显示,与胃癌术后辅助化疗相比,辅助放化疗的3、5年生存率更高(OR=2.96,95% CI= 1.75~5.03,P=0.000;OR=1.45,95% CI=1.06~1.99,P=0.020),辅助放化疗的局部复发率更低(OR=0.50,95% CI=0.34~0.72,P=0.000),但远处转移率两组相似(OR=0.79,95% CI=0.58~1.07,P=0.130)。结论 现有研究结果的荟萃分析显示,与胃癌术后辅助化疗相比,胃癌术后辅助放化疗是一种较为安全和有效的治疗方法。     

Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group.

PURPOSE: The multidrug resistance protein 1 (MRP1) is expressed in human breast cancer cells and may contribute to the clinical drug resistance of breast cancer patients. Therefore, we determined the impact of MRP1 expression on the clinical outcome of adjuvant therapy in patients with early-stage breast cancer. PATIENTS AND METHODS: Immunostaining for MRP1 was performed on tissue sections from 516 premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease. Statistical analyses were performed to assess the effect of MRP1 expression on survival and to test for interaction between MRP1 expression and treatment. RESULTS: MRP1 expression independently predicted shorter relapse-free survival (RFS) and overall survival (OS) in patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] = 1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P = .02), but it did not predict shorter RFS and OS in patients who received tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR = 0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1 expression and treatment were statistically significant for both RFS (P = .04) and OS (P = .006). CONCLUSION: Our data suggest that MRP1 expression plays an important role in the clinical resistance to adjuvant CMF chemotherapy but does not seem to affect response to adjuvant endocrine treatment with tamoxifen plus goserelin. Thus, MRP1 may be a useful marker for the selection of patients with early-stage breast cancer for the appropriate adjuvant therapy after prospective confirmatory evaluation.     

Effect of body mass index on survival of patients with stage I non-small cell lung cancer

Background:Body mass index (BMI) has a U-shaped association with lung cancer risk.However,the effect of BMI on prognosis is controversial.This retrospective study aimed to investigate the effect of BMI on the survival of patients with stage I non-small cell lung cancer (NSCLC) after surgical resection.Methods:In total,624 consecutive stage I NSCLC patients who underwent radical resection were classified into four groups according to their BMI:underweight (BMI ＜ 18.5 kg/m2),normal weight (BMI =18.5-22.4 kg/m2),overweight (BMI =22.5-28.0 kg/m2),and obese (BMI ＞ 28.0 kg/m2).The effect of BMI on progression-free survival (PFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazards model.Postoperative complications in each group were analyzed using the Chi square test or Fisher's exact test.Results:A univariate analysis showed that PFS and OS were longer in the overweight group than in other groups (both P ＜ 0.05).A multivariate analysis showed that OS was longer in the overweight group than in other groups (compared with the other three groups in combination:hazard ratio [HR] =1.87,95％ confidence interval [CI] 1.30-2.68,P =0.003;compared with the underweight group:HR =2.24,95％ CI 1.18-4.25,P =0.013;compared with the normal weight group:HR =1.58,95％ CI 1.07-2.33,P =0.022;compared with the obese group:HR =2.87,95％ CI 1.48-5.59,P =0.002),but PFS was similar among the groups (HR =1.28,95％ CI 0.97-1.68,P =0.080).A subgroup analysis showed an association between being overweight and prolonged OS in patients at stage T1a (P =0.024),T1 b (P =0.051),and T2a (P =0.02),as well as in patients with a non-smoking history (P =0.001).Overweight patients had lower rates of postoperative complications,such as respiratory failure (compared with the underweight and obese groups:P =0.014),myocardial infarction (compared with the obese group:P=0.033),and perioperative death (compared with the other three groups:P=0.016).Conclusions:Preoperative BMI is an independent prognostic factor for stage I NSCLC patients after resection,with overweight patients having a favorable prognosis.     

血小板-淋巴细胞比值在鼻咽癌预后预测中的作用：Meta分析

背景与目的：已发现血小板-淋巴细胞比值（platelet-to-lymphocyte ratio,PLR）可预测鼻咽癌的临床结果。然而,先前关于PLR与鼻咽癌预后的报道不一致。根据Meta分析提供更准确的预后评估。方法：检索了PubMed、Web of Science和Scopus数据库确定评估治疗前PLR在鼻咽癌中的预后作用的研究。终点是总生存期（overall survival,OS）、无进展生存期（progression-free survival,PFS）、疾病特异性生存率（disease-specific survival,DSS）、无远处转移生存期（distant metastasis-free survival,DMFS）。提取风险比（hazard ratio,HR）和95%置信区间（confidence interval,CI）,并根据异质性检验选用固定效应模型或随机效应模型估计每个终点的合并HR。结果：共纳入10项研究,涉及4 655例鼻咽癌患者。Meta分析汇总结果显示,升高的治疗前PLR与鼻咽癌患者较差的OS（HR=1.92,95% CI：1.73~2.14,P＜0.01）、PFS（HR=1.56,95% CI：1.19~2.06,P=0.002）及DSS（HR=1.65,95% CI：1.19~2.27,P=0.002）相关,但与DMFS无显著相关性（HR=1.69,95% CI：0.97~2.96,P=0.06）。结论：升高的治疗前PLR可以预测鼻咽癌患者更差的OS、PFS和DSS,而对DMFS没有预测价值。