ERCC1对顺铂同期放化疗治疗局部晚期鼻咽癌疗效的预测

目的 探讨核苷酸切除修复交叉互补基因1（ERCC1）表达水平对局部晚期鼻咽癌应用顺铂同期放化疗的疗效预测作用。方法回顾性分析本院2001年1月至2009年1月行顺铂同期放化疗的205例局部晚期鼻咽癌患者,根据治疗结果分为治疗敏感组和治疗抵抗组。采用免疫组织化学法检测鼻咽癌组织中ERCC1的表达并分析ERCC1表达与治疗有效率、5年无病生存率和5年生存率的关系。结果在205例鼻咽癌组织中,110例（53.7％）ERCC1高表达,95例（46.3％）ERCC1低表达。ERCC1高表达组的有效率（RR）为97.3％（107／110）,ERCC1低表达组为100.0％（95／95）,差异无统计学意义（P＞0.05）。治疗敏感组的ERCC1低表达率与高表达率分别为61.4％和38.6％,而治疗抵抗组分别为35.9％和64.1％,两组表达的差异有统计学意义（P=0.000）。ERCC1低表达和高表达组的中位生存期分别为61.3个月和49.7个月（P=0.013）,5年无病生存率分别为61.5％和36.2％（P=0.054）,5年生存率分别为63.4％和38.5％（P=0.037）。Cox多因素分析显示,ERCC1表达、PS评分及分期为影响预后的独立因素。结论 ERCC1可以作为局部晚期鼻咽癌的疗效预测指标,ERCC1高表达的患者预后差。     

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.     

ERCC1 Expression in Metastatic Triple Negative Breast Cancer Patients Treated with Platinum-Based Chemotherapy

Background: Possible targeted therapies for metastatic triple negative breast cancer (TNBC) include cytotoxic chemotherapy that causes interstrand breaks (platinum-based drugs). The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway, removing platinum-induced DNA adducts and contributing to cisplatin resistance. Detecting ERCC1 overexpression is important in considering treatment options for metastatic TNBC, including individualized approaches to therapy, and may facilitate improved responses or reduction of unnecessary toxicity. We hypothesized that assigning cisplatin based on pretreatment ERCC1 expression would improve response and survival. This study was conducted to assess the impact of ERCC1 expression on PFS, OS and response rates in metastatic triple negative breast cancer patients treated with platinum-based chemotherapy. Methods: From June 2012 to November 2013, 52 metastatic triple negative breast cancer patients were enrolled. ERCC1 protein expression was detected from pretreatment biopsies by Immunohistochemistry. All patients received cisplatin plus paclitaxel. The primary end point was the impact of ERCC1 expression on PFS and OS. Results: 34 patients (65.4%) showed positive ERCC1 expression while 18 (34.6%) proved negative. Positive ERCC1 expression was associated with short PFS (median, 5 months vs. 7 months; P = 0.043), short OS (median, 9 months vs. 11 months; P = 0.033) and poor response to cisplatin based chemotherapy (P = 0.046). Conclusions: This prospective study further validated ERCC1 as a reliable biomarker for customized chemotherapy in metastatic triple negative breast cancer patients. High expression of ERCC1 was thereby fond to be significantly associated with poor outcome in patients treated with platinum based chemotherapy.     

Expression of ERCC1 predicts clinical outcome in locoregionally advanced nasopharyngeal carcinoma treated with cisplatin-based induction chemotherapy

The aim of the present study was to evaluate the correlation between excision repair cross-complementation group 1 (ERCC1) protein with the clinical outcome of nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based induction chemotherapy. One hundred one Stage III-IVB nonkeratinizing NPC patients who were treated with cisplatin (DDP)+fluorouracil (5-Fu) induction chemotherapy were recruited. Pre-treatment tumor biopsy specimens were analyzed for ERCC1 by immunohistochemistry. The relationship of ERCC1 expression and chemotherapy response and survival of these NPC patients was analyzed. The objective response to induction chemotherapy of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 88.2% vs. 72% (P=0.041). The 5-year distant failure-free survival (D-FFS) of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 73.5% vs. 51.3% (P=0.037). ERCC1 expression was a significant prognostic factor for overall survival and D-FFS using Cox regression analysis. High tumor ERCC1 expression predicts low chemotherapy response and poor survival mainly caused by more metastasis in locoregionally advanced NPC treated with cisplatin-based induction chemotherapy.     

Patients with ERCC1-negative locally advanced esophageal cancers may benefit from preoperative chemoradiotherapy

PURPOSE: To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer. EXPERIMENTAL DESIGN: Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression. RESULTS: Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score >1; 71 patients, 47%) and ERCC1-negative (score 相似文献   

ERCC1和RRM1蛋白表达与局部晚期宫颈癌含奈达铂同步放化疗疗效的关系

目的 探讨核苷酸切除修复交叉互补基因1（ERCC1）和核苷酸还原酶M1亚基（RRM1）的表达与局部晚期宫颈癌含奈达铂同步放化疗疗效的关系。方法 回顾性分析我院2009年2月至2012年11月接受含奈达铂同步放化疗方案治疗的宫颈癌患者72例,根据疗效分为治疗敏感组和治疗抵抗组。采用免疫组织化学法检测治疗前活检组织中ERCC1、RRM1的表达情况,分析两者表达与临床病理参数、疗效及预后的关系,并采用受试者工作特征曲线（ROC）评价ERCC1、RRM1水平在局部晚期宫颈癌含奈达铂同步放化疗疗效预测中的价值。结果 宫颈癌组织中ERCC1、RRM1均呈高表达,ERCC1、RRM1的高表达率分别为54.2％和59.7％,高于正常组织的35.9％和37.5％,差异有统计学意义（P＜0.05）;治疗敏感组的ERCC1、RRM1高表达率分别为42.9％和47.6％,低于治疗抵抗组的70.0％和76.7％,差异有统计学意义（P＜0.05）,且ERCC1及RRM1预测宫颈癌放化疗疗效的曲线下面积（AUC）、灵敏度和特异度分别为0.915、92.1％、86.2％和0.944、87.3％、91.0％;ERCC1表达与FIGO分期、分化程度及盆腔淋巴结肿大有关,RRM1表达与分化程度、盆腔淋巴结肿大有关,以上差异均有统计学意义（P＜0.05）;ERCC1高表达者的中位无进展生存期为27.5个月,与低表达者的28.6个月比较,差异无统计学意义（P＞0.05）;RRM1高表达者的中位无进展生存期为20.0个月,低于低表达者的37.5个月（P＜0.05）。结论 宫颈癌组织中ERCC1、RRM1呈高表达,且两者表达水平均与疗效、分化程度及盆腔淋巴结肿大有关,RRM1表达亦与预后有关,两者可用于局部晚期宫颈癌含奈达铂同步放化疗疗效的预测。     

ERCC1 expression as a prognostic marker in N2(+) nonsmall-cell lung cancer patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy

BACKGROUND.: Excision repair cross-complementation Group 1 (ERCC1) overexpression is associated with resistance to cisplatin-based chemotherapy in patients with nonsmall-cell lung cancer (NSCLC). A preliminary study also suggested that ERCC1 expression is associated with radioresistance in lung cancer cells. The aim of this study was to evaluate the clinical implications of ERCC1 expression in stage IIIA N2-positive NSCLC patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery. METHODS.: Sixty-eight patients with mediastinoscopy-proven N2-positive NSCLC were enrolled between August 1997 and September 2003. ERCC1 expression was assessed by immunohistochemistry from pretreatment mediastinoscopic biopsy specimens. RESULTS.: ERCC1 expression was positive in 31 of 68 specimens (46%). Among 14 patients who obtained pathologic complete response, 6 were positive for ERCC1 expression and 8 were negative (P = .818). On univariate analysis, with median follow-up of 61.8 months (range, 34.3-108.8 months), progression-free survival was 15.9 months for ERCC1-positive and 29.5 months for ERCC1-negative patients (P = .062), and there was a statistically significant difference in overall survival between ERCC1-negative tumors and ERCC1-positive tumors (89.2 vs 26.0 months, P = .014). On multivariate analysis, ERCC1 negativity (P = .041) and achieving mediastinal nodal clearance (downstage to pathological N0 or N1) after neoadjuvant CCRT followed by surgery (P = .005) were significant independent prognostic factors for the prolongation of survival. CONCLUSIONS.: These results suggest that N2-positive NSCLC patients with ERCC1 negative tumors show a survival benefit from neoadjuvant CCRT with a platinum-containing regimen. Cancer 2008. (c) 2008 American Cancer Society.     

Endostar,an Antiangiogenesis Inhibitor,Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p = 0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p = 0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.Key words: Cervical cancer, Antiangiogenesis, Radiation therapy, Concurrent chemotherapy, Randomized controlled trial     

Endostar,an Antiangiogenesis Inhibitor,Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.     

不同治疗方式对术后伴中危因素Ⅰ-ⅡA期宫颈癌预后影响

目的 比较不同治疗方式对伴中危因素的Ⅰ-ⅡA期宫颈癌患者的生存差异,探讨早期宫颈癌术后伴中危因素患者的最佳治疗模式。方法 回顾分析2007-2016年间收治的包含中危因素的323例宫颈癌术后患者,比较观察(NT)、单纯化疗(CT)、放疗(RT)及同步放化疗(CCRT)方式对生存的影响。Kaplan-Meier法生存分析,Logrank检验差异,Cox模型行预后因素分析。结果 全组的5年PFS、OS为79.0%、84.8%。单因素及多因素分析肿瘤大小>4 cm、治疗方式是影响PFS的因素(P=0.017、0.002),危险因素个数、治疗方式是影响OS的因素(P=0.042、0.000)。全组中RT及CCRT均可改善患者预后(P=0.007、0.000)。亚组分析中任意1个中危因素(低危组),CT能够延长5年PFS (P=0.026),在改善5年OS上相近(P=0.692);与NT及CT相比,RT及CCRT均能改善患者预后(P=0.006、0.000),但RT与CCRT相近(P=0.820、0.426)。≥2个中危因素(高危组)中,与CT相比,CCRT能提高患者的5年PFS (P=0.006),但不能延长患者5年OS (P=0.107);RT与CCRT比较,CCRT均可改善患者的预后(P=0.028、0.039)。结论 仅有1个中危因素时,RT也能改善预后;伴有≥2个中危因素时,CCRT更能改善患者的预后。     

Different relation between ERCC1 overexpression and treatment outcomes of two platinum agents in advanced biliary tract adenocarcinoma patients

Purpose

The aim of this study is to evaluate the effect of excision repair cross-complementation group 1 (ERCC1) expression on treatment outcomes in advanced biliary tract adenocarcinoma (ABTA) patients treated with platinum-based chemotherapy.

Methods

One hundred and six patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions in South Korea between January 2002 and September 2008. Of 106 patients, 93 were assessed by immunohistochemistry from tissue specimens. Sixty-five patients were treated with cisplatin-based regimens and the other 28 treated with oxaliplatin-based ones.

Results

For total study population, no significant differences were noted in progression-free survival (PFS) and overall survival (OS) between ERCC1-negative and ERCC1-positive patients, respectively (4.2 vs. 2.9?months, p?=?0.116; 7.0 vs. 7.8?months, p?=?0.143). In patients treated with cisplatin-based regimens, median PFS and OS were significantly longer in ERCC1-negative group than in ERCC1-positive group, respectively (4.6 vs. 1.9?months, p?=?0.014; 9.1 vs. 7.9?months, p?=?0.017). Disease control rate (DCR) was better in patients with ERCC1 negative than in patients with ERCC1 positive (p?=?0.048). On the other hand, in patients treated with oxaliplatin-containing regimens, median PFS and OS tended to be longer in ERCC1-positive group, but these did not reach statistical significances. Response rate was better in patients with ERCC1 positive (p?=?0.005).

Conclusions

ERCC1 shows a significant prognostic value in ABTA patients treated with cisplatin. A survival benefit was observed in ERCC1-negative patients from cisplatin-containing chemotherapy but not from oxaliplatin-containing ones. The action mechanism of ERCC1 on cisplatin may be different from that on oxaliplatin.     

Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy

To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1-118 and XPD 751 polymorphisms were significant (P=0.02 and P=0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance (P=0.008). In the univariate analysis for PFS, ERCC1-118 and XPD 751 were significant (P=0.003 and P=0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P=0.02). Finally, ERCC1-118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P=0.006 and P=0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P=0.022 and P=0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments.     

核苷酸切除修复交叉互补基因1 mRNA表达与非小细胞肺癌铂类化疗患者预后的相关性

目的 探讨核苷酸切除修复交叉互补基因1(ERCC1)mRNA表达与非小细胞肺癌(NSCLC)铂类化疗患者临床病理特征的关系及其预后意义.方法 采用实时荧光定量逆转录聚合酶链反应(RT-PCR)方法,检测NSCLC石蜡包埋组织中ERCC1 mRNA的表达水平,并比较其表达水平与NSCLC铂类化疗患者临床病理特征和生存时间之间的关系.结果 61例NSCLC患者中,ERCC1 mRNA的中位表达量为0.48.ERCC1 mRNA表达与NSCLC患者临床病理特征无关.ERCC1mRNA低表达(<0.35)患者经铂类药物化疗后的无进展生存时间为14.3个月,而高表达者为8.0个月,差异有统计学意义(P=0.028).ERCC1 mRNA低表达(<0.28)患者的总生存时间为28.4个月,而高表达者为12.9个月,差异有统计学意义(P=0.0064).Cox多因素回归分析显示,ERCC1 mRNA表达水平是影响NSCLC患者预后的独立因素.结论 ERCC1 mRNA的表达水平可以作为以铂类为基础药物化疗的NSCLC患者预后的独立预测因素,ERCC1 mRNA低表达的NSCLC患者经铂类化疗后,总生存时间明显延长,为制定NSCLC个体化的化疗方案提供了重要信息.     

Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome

INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.     

Impact of ERCC1 expression on treatment outcome in small-cell lung cancer patients treated with platinum-based chemotherapy

IntroductionThe excision repair cross-complementing 1 (ERCC1) protein is an extensively investigated molecular marker because it may decrease sensitivity to platinum-based chemotherapy. Low ERCC1 expression has already been correlated with better treatment efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy. However, the data on a prognostic and/or predictive value of ERCC1 in small-cell lung cancer (SCLC) are still very limited.MethodsThis retrospective pilot study evaluated the impact of ERCC1 expression levels on response to first-line platinum-based chemotherapy with or without radiotherapy and survival outcomes of 77 SCLC patients. ERCC1 protein expression was determined immunohistochemically in primary tumour tissue.ResultsERCC1 protein expression was positive in 40/77 (51.9%) of our patients. No significant association was found between ERCC1 protein expression and response rate to first-line platinum-based chemotherapy, progression-free survival (PFS), or overall survival (OS), either in the overall population or in patients stratified by disease stage.ConclusionsIn our limited group of 77 SCLC patients, ERCC1 protein expression was not found to correlate with either response rate to platinum-based chemotherapy or survival outcomes. Multi-centric prospective trials using a validated method of ERCC1 determination are mandatory in order to obtain a definitive answer on the predictive value of ERCC1 in SCLC.     

基于IMRT的Ⅱ期鼻咽癌同期放化疗与单纯放疗远期疗效比较

目的 评价以IMRT为基础的不同治疗模式对Ⅱ期鼻咽癌患者预后的影响。方法 回顾分析123例Ⅱ期鼻咽癌患者的临床资料,其中单纯放疗81例,同期放化疗42例。Kaplan-Meier计算生存率并Logrank检验。结果 全组5年OS、LRFS、DMFS、PFS分别为96.7%、94.7%、93.1%、87.8%。单纯放疗组与同期放化疗组相比,5年OS (98.7%:92.9%,P=0.569)、LRFS (94.8%:94.5%,P=0.770)、DMFS (94.5%:90.2%,P=0.408)、PFS (90.6%:82.2%,P=0.340)均无明显差异。T₂N₁期患者两组5年各项生存率仍无明显差异(P=0.929、0.967、0.917、0.492)。急性不良反应方面同期放化疗组中性粒细胞减少、白细胞减少、血红蛋白减少和放射性黏膜反应发生率明显升高(P=0.000、0.000、0.012、0.010),而两组晚期不良反应发生率相近(P=0.823、0.622、0.113)。结论 对Ⅱ期患者同期化疗的加入并未改善患者预后,但急性不良反应明显增加。     

Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy

BackgroundExpression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but little is known about factors predictive of efficacy in patients with locally advanced non-small cell lung cancer (NSCLC). We investigated the predictive relevance of PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy (CCRT).MethodsWe retrospectively reviewed 74 consecutive patients with stage III NSCLC who had received CCRT. PD-L1 expression and CD8+ TIL density were evaluated by immunohistochemical analysis.ResultsUnivariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression-free survival (PFS) and OS, whereas PD-L1 expression was not correlated with PFS and OS. Sub-analysis revealed that the PD-L1+/CD8 low group had the shortest PFS (8.6 months, p = 0.02) and OS (13.9 months, p = 0.11), and that the PD-L1-/CD8 high group had the longest prognosis (median PFS and OS were not reached) by Kaplan-Meier curves of the four sub-groups.ConclusionsAmong stage III NSCLC patients who received CCRT, there was a trend for poor survival in those who expressed PD-L1. Our analysis indicated that a combination of lack of PD-L1 expression and CD8+ TIL density was significantly associated with favourable survival in these patients. It is proposed that PD-L1 expression in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III NSCLC.     

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.     

Excision repair cross complementation group 1 immunohistochemical expression predicts objective response and cancer-specific survival in patients treated by Cisplatin-based induction chemotherapy for locally advanced head and neck squamous cell carcinoma.

PURPOSE: To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatin-based induction chemotherapy. EXPERIMENTAL DESIGN: The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 immunohistochemical expression. RESULTS: Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1 at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1 expression. ERCC1 and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value. CONCLUSION: Our results suggest that those patients characterized by low ERCC1 expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1 expression.