High Mutagen Sensitivity in Peripheral Blood Lymphocytes Predicts Poor Overall and Disease-Specific Survival in Patients with Stage III Non–Small Cell Lung Cancer Treated with Radiotherapy and Chemotherapy

High Mutagen Sensitivity in Peripheral Blood Lymphocytes Predicts Poor Overall and Disease-Specific Survival in Patients with Stage III Non–Small Cell Lung Cancer Treated with Radiotherapy and Chemotherapy
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外周血淋巴细胞的高诱变剂敏感性预示接受放疗和化疗的 III 期非小细胞肺癌患者总体生存率和疾病特异性生存率较差

DOI:
10.1158/1078-0432.ccr-04-2176
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发表时间:
2005
影响因子:
11.5
通讯作者:
Xifeng Wu
Xifeng Wu
中科院分区:
医学1区
文献类型:
--
作者:
Joe Y. Chang;R. Komaki;R. Sasaki;Z. Liao;C. Stevens;Charles Lu;F. Fossella;P. Allen;J. Cox;M. Spitz;Xifeng Wu

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目的:研究博来霉素敏感性试验(一种体外外周血淋巴细胞试验)是否可以预测接受确定性放疗和化疗的不可手术的III期非小细胞肺癌(NSCLC)患者的结局。实验设计:我们确定了102例无法手术的III期NSCLC细胞肺癌患者接受了明确的放疗和化疗。用拟放射性诱变剂博来霉素处理患者的预处理外周血淋巴细胞培养物。通过计数50个中期分裂相的染色单体断裂数来确定博莱霉素敏感性指数。分析博来霉素敏感性(表示为每个细胞的平均断裂)和临床结果之间的相关性。结果如下:高博莱霉素敏感性(定义为平均>1.02个染色单体断裂/细胞,代表博莱霉素敏感性的第三四分位数)预测疾病特异性生存率和总生存率较差。博莱霉素高敏感性患者的6年疾病特异性生存率为27%,而无此类敏感性患者的6年疾病特异性生存率为46%(P = 0.0094)。在调整吸烟状况、年龄和辐射剂量后,这种关联仍然具有统计学意义。博莱霉素高敏感性患者的6年总生存率为19%,而非高敏感性患者的6年总生存率为29%(P = 0.0193)。博莱霉素高敏感性患者的局部区域控制和无病生存率有下降的趋势。两组之间无远处转移生存率或放射治疗相关并发症无差异。结论:在接受放疗和化疗的III期NSCLC患者中,博来霉素高敏感性与总生存率和疾病特异性生存率差相关。博莱霉素敏感性可能作为这组患者临床结局不良的生物标志物。
Purpose: To investigate whether the bleomycin sensitivity assay, an in vitro peripheral blood lymphocyte assay, can predict outcome in patients with inoperable stage III non–small-cell lung cancer (NSCLC) treated with definitive radiotherapy and chemotherapy. Experimental Design: We identified 102 patients with inoperable stage III NSCLC cell lung cancer treated with definitive radiotherapy and chemotherapy. The patients' pretreatment peripheral blood lymphocyte cultures were treated with the radiomimetic mutagen bleomycin. An index of bleomycin sensitivity was determined by counting the number of chromatid breaks in 50 metaphases. The correlation between bleomycin sensitivity (expressed as mean breaks per cell) and clinical outcome was analyzed. Results: High bleomycin sensitivity (defined as a mean of >1.02 chromatid breaks/cell, representing the third quartile of bleomycin sensitivity) predicted poor disease-specific survival and overall survival. The 6-year disease-specific survival was 27% in patients with high bleomycin sensitivity compared with 46% in patients without such sensitivity (P = 0.0094). The association remained statistically significant when adjusted for smoking status, age, and radiation dose. The 6-year overall survival was 19% for patients with high bleomycin sensitivity and 29% for those without (P = 0.0193). There was a trend toward worse local regional control and worse disease-free survival among patients with high bleomycin sensitivity. There was no difference between the two groups in distant metastasis-free survival or radiation treatment-related complications. Conclusions: High bleomycin sensitivity correlated with poor overall survival and disease-specific survival in these patients with stage III NSCLC treated with radiotherapy and chemotherapy. Bleomycin sensitivity may function as a biomarker for poor clinical outcome for this group of patients.
DOI: 10.1093/jnci/94.14.1091
发表时间: 2002-07
期刊: Journal of the National Cancer Institute
影响因子: --
作者:
C. Bosken;Q. Wei;C. Amos;M. Spitz
通讯作者: C. Bosken;Q. Wei;C. Amos;M. Spitz
淋巴细胞染色体不稳定性:口腔癌前病变易感性的潜在指标。
DOI: --
发表时间: 2002
期刊: Cancer research.
影响因子: --
作者:
Wu,Xifeng;Lippman,ScottM;Lee,JJack;Zhu,Yong;Wei,QVictoria;Thomas,Margaret;Hong,WaunKi;Spitz,MargaretR
通讯作者: Spitz,MargaretR
DOI: 10.1093/carcin/21.4.551
发表时间: 2000-04-01
期刊: CARCINOGENESIS
影响因子: 4.7
作者:
Lunn, RM;Helzlsouer, KJ;Bell, DA
通讯作者: Bell, DA
DOI: 10.1200/jco.2004.08.067
发表时间: 2004-07-01
影响因子: 45.3
作者:
Gurubhagavatula, S;Liu, G;Christiani, DC
通讯作者: Christiani, DC
博来霉素诱导的染色体断裂作为肺癌的风险标记:一项针对人群和医院对照的病例对照研究。
DOI: 10.1093/carcin/24.2.269
发表时间: 2003
期刊: Carcinogenesis
影响因子: 4.7
作者:
Zheng,Yun-Ling;Loffredo,ChristopherA;Yu,Zhipeng;Jones,RaymondT;Krasna,MarkJ;Alberg,AnthonyJ;Yung,Rex;Perlmutter,Donna;Enewold,Lindsey;Harris,CurtisC;Shields,PeterG
通讯作者: Shields,PeterG