非小细胞肺癌根治性化放疗前外周血CK19 mRNA表达的初步研究

目的研究根治性化放疗的非小细胞肺癌(NSCLC)患者放疗前以CK19 mRNA表达为标志的外周血微转移的临床意义。方法应用巢式RT-PCR方法,检测106例NSCLC患者根治性化放疗前外周血微转移标志物CK19 mRNA的表达,并研究其与临床病理特征相关性和预后意义。结果外周血微转移阳性率为63%(67/106)。外周血微转移与N分期(X~2=10.41,P=0.001)、病理类型(X~2=5.22,P=0.022)和病理分级相关(X~2=7.82,P=0.020),但与性别(X~2=2.70,P=0.100)、T分期(X~2=0.01,P=0.941)、TNM分期(X~2=5.32,P=0.070)、体重减轻(X~2=0.71,P=0.399)和KPS评分(X~2=0.23,P=0.629)无相关性。外周血微转移阳性和阴性3年远处转移率分别为70%和63%(X~2=0.34,P=0.559);3年局部复发率分别为69%和57%(X~2=0.61,P=0.435);所有患者中位生存期和3年总生存率分别为17个月和24%;外周血微转移阳性和阴性中位生存期分别为16、20个月,3年总生存率分别为21%和28%(X~2=0.61,P=0.435)。结论NSCLC根治性化放疗前外周血微转移与N分期、病理类型和病理分级密切相关,但无预后意义。     

非小细胞肺癌根治性化放疗前后外周血微转移的检测及其预后

目的探讨根治性化放疗治疗非小细胞肺癌（NSCLC）患者外周血微转移的预后意义。方法应用巢式CK19 RT-PCR方法,动态检测67例NSCLC患者根治性化放疗前后外周血微转移,研究其与临床病理特征的相关性和预后价值。结果治疗前和治疗后,微转移阳性分别为44例（65．7％）和22例（32．8％）;治疗前,微转移表达与N分期（P=0．014）相关;治疗后,微转移表达与N分期（P=0．032）、病理类型（P=0．019）、体重减轻（P=0．01）和KPS评分（P=0．027）相关;治疗前微转移阳性和阴性的4年远处转移率分别为78．3％和70．4％（P=0．544）,治疗后分别为100％和62．9％（P〈0．001）。治疗前微转移阳性和阴性患者的中位生存期分别为13．8个月和17．6个月, 4年生存率分别为18．2％和17．4％（P=0．619）。治疗后微转移阳性和阴性患者的中位生存期分别为7．8个月和27．6个月,4年生存率分别为0和26．4％（P〈0．001）。多因素分析显示,治疗后微转移阳性是一独立不良预后因素（P=0．000）。结论根治性化放疗后,外周血微转移的检测有预后价值;与微转移阳性相比,阴性患者预后好。     

Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis

We investigated whether detection of cytokeratin-positive (CK+) cells in the peripheral blood (PB) of breast cancer patients before chemotherapy could be a prognostic factor. Blood from a total of 92 breast cancer patients was evaluated for the presence of CK+ cells. Blood samples were collected before chemotherapy. Patients entered in the study included: neoadjuvant (n = 25), adjuvant (n = 42) and metastatic (n = 25). Blood samples (10 ml) were centrifuged using a double density-gradient to recovering the mononuclear cell (MNC) and granulocyte cell (GC) fractions. Subsequently, positive immunomagnetic cell separation was carried out to isolating CK+ cells. The enriched cell fraction was cytocentrifuged and then immunocytochemically labeled using an anti-cytokeratin antibody. Our results indicated that breast tumor cells sediment with both MNC and GC fractions. We therefore recommend examination of both fractions in all enrichment protocols. CK+ cells in PB were identified in 57 of 92 (62%) patients when MNC and GC fractions were assessed (range = 1-61 cells, median = 8). No CK+ cells were detected in blood samples of 16 healthy donors. There were significant differences in the presence of CK+ cells according to estrogen receptor expression (p = 0.049), and lymph node status (p = 0.033), but not to the age, menopausal status, type of patient (neoadjuvant, adjuvant or metastatic), TNM stage, histological type, progesterone receptor expression, c-erbB2 expression, p53 expression or Ki67 expression. Regarding the relationship between tumor size (T) and the presence of CK+ cells, a borderline significant trend was observed (p = 0.07). The median follow-up of the patients was 21 months and statistical analysis (Kaplan-Meier analysis) showed that using the method we present, the detection of CK+ cells in PB before starting the chemotherapy in breast cancer patients was significantly correlated with both progression-free survival (p = 0.058) and overall survival (p = 0.003). In conclusion, the present study suggests that detection of CK+ cells in PB before chemotherapy might identify breast cancer patients with poor prognosis.     

Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy

Expression of excision repair cross-complementation group 1 (ERCC1), p53, or thioredoxin (TRX) is reported to be correlated with resistance to platinum-based drugs. The authors evaluated whether ERCC1, p53, or TRX expression could predict progression-free and/or overall survival in relapsed non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Immunohistochemistry was used to examine the expression of these three proteins in resected lung tumor samples obtained from 67 patients treated with platinum-based chemotherapy against recurrent tumors after curative resection. Immunostaining for ERCC1, p53, and TRX was positive in 29, 35, and 24 patients, respectively. Patients negative for ERCC1 had a significantly longer median progression-free (44 vs 26 weeks, P = 0.0075) and overall (73 vs 44 weeks, P = 0.0006) survival than those positive for ERCC1. Patients negative for p53 expression had a significantly longer median overall (70 vs 62 weeks, P = 0.0289), but not progression-free (37.5 vs 36 weeks, P = 0.2465), survival than those positive for p53 expression. From multivariate analysis, negative ERCC1 expression (hazard ratio [HR] = 1.3740, P = 0.0147) was a significantly favorable factor for progression-free survival, and negative ERCC1 expression (HR = 1.6533, P = 0.0018) and better performance status (HR = 1.9117, P = 0.0017) were significantly favorable factors for overall survival. This retrospective study indicates that immunostaining for ERCC1 may be useful for predicting survival in NSCLC patients receiving platinum-based chemotherapy against recurrent tumors after curative resection and can provide critical information for planning personalized chemotherapy.     

Differential efficacy of docetaxel according to non-small cell lung cancer histology and the therapeutic effect of epidermal growth factor receptor tyrosine kinase inhibitors

The active mutation of epidermal growth factor receptor (EGFR) and clinical characteristics are significant biomarkers for chemotherapy selection in non-small cell lung cancer (NSCLC). Although docetaxel is a key agent in second-line therapy for NSCLC, predictive biomarkers for assessing its efficacy have yet to be determined. To assess the clinical efficacy of docetaxel in second-line therapy for NSCLC according to NSCLC histology and the therapeutic effect of EGFR-tyrosine kinase inhibitors (EGFR-TKIs), we retrospectively reviewed 454 NSCLC patients treated with docetaxel between April 2002 and April 2009. In total, 239 patients with advanced NSCLC treated with docetaxel as second-line therapy following failure of platinum-based chemotherapy were analyzed in this study. A total of 59 (25%) patients had squamous cell carcinoma. The overall response rate and median progression-free survival time in the squamous cell group were significantly inferior to those in the non-squamous cell group (p=0.031 and p=0.005, respectively). Following the failure of docetaxel, 91 non-squamous patients were treated with EGFR-TKIs. The patients that achieved clinical benefit from EGFR-TKIs (n=32) demonstrated a significantly better response rate and longer progression-free survival compared to the other group (p<0.001 and p=0.027, respectively). In the univariate and multivariate analysis, the favorable therapeutic effect of EGFR-TKIs had an independent effect on progression- free survival (HR 1.484, p=0.0464). In conclusion, this retrospective study suggests that non-squamous histology and favorable therapeutic effect from EGFR-TKIs are useful markers for predicting the efficacy of docetaxel in second-line therapy for NSCLC.     

新辅助化疗前后乳腺癌患者外周血细胞角蛋白19表达变化及其临床意义

目的探讨细胞角蛋白（CK）19在乳腺癌新辅助化疗前后表达的变化及其临床意义。方法采用实时定量RT-PCR技术检测86例乳腺癌患者新辅助化疗前后外周血CK19 mRNA的表达变化,将30例乳腺良性疾病患者和20例健康体检志愿者作为对照。对非正态分布或方差不齐的数据采用Wilcoxon非参数秩和检验,用中位数±百分位数之差[M（Q_R）]表示,计数资料组间采用χ~2检验。结果新辅助化疗前乳腺癌患者外周血中CK19 mRNA阳性表达率为32.56%（28/86）,与腋窝淋巴结转移、临床分期有关（分别P〈0.001）;而新辅助化疗后阳性表达率为13.95%（12/86）,化疗前后CK19mRNA表达差异具有统计学意义（P=0.004）;新辅助化疗后CK19 mRNA阳性表达的患者中,57.14%（16/28）获得临床完全缓解成部分缓解,低于CK19 mRNA阴性患者的93.10%（54/58）,差异有统计学意义（P〈0.001）,这提示CK19 mNRA表达水平变化可能与新辅助化疗疗效有关。结论 CK19可作为新辅助化疗疗效判定的早期预测指标之一。     

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

检测CK19 mRNA、CEA mRNA诊断非小细胞肺癌外周血微转移

目的 探讨检测细胞角蛋白(cytokeratin 19，CK19)mRNA、癌胚抗原(cancer embryonic antigen，CEA)mRNA诊断非小细胞肺癌(non-small cell lung cancer，NSCLC)患者外周血微转移的临床意义。方法 应用RT-PCR法检测35例NSCLC患者外周血中的CK19mRNA、CEAmRNA，并以20例良性病变、20例健康人作对照。结果 35例NSCLC患者外周血CK19mRNA、CEAmRNA阳性表达率分别为40％和57％，两者均阳性者40％，两者均阴性者43％；肺良性疾病患者20例，CK19mRNA阳性2例(10％)，无CEAmRNA阳性者；20例健康对照2个指标检测结果均为阴性。随访发现CK-19mRNA阳性、CEAmRNA阳性和二者均阴性患者的远处转移率分别为50％、56％和27％。结论CEAmRNA和CK19mRNA是检测肺癌患者外周血微转移的良好标志物，检测外周血微转移有助于预测肺癌患者预后。     

Influence of tumor volume on survival in patients irradiated for non-small-cell lung cancer

PURPOSE: To investigate the importance of CT-defined total tumor volume (TTV) on overall survival (OS) in patients with unresectable or medically inoperable non-small-cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Between 1991 and 1998, 150 evaluable patients with Stage I-IIIB NSCLC were treated with three-dimensionally planned conformal radiotherapy and curative intent at Duke University Medical Center. On the treatment-planning CT, the primary tumor and nodal volumes were identified and subsequently combined to form the TTV. The TTV was compared with the stage and outcome with respect to OS, local progression-free survival, and distant failure-free survival using the Kruskall-Wallis analysis of variance and Kaplan-Meier actuarial method. To account for the potentially confounding effects of therapeutic and patient-specific covariates on survival, the Cox proportional hazard regression model was used. RESULTS: The TTVs in patients with Stage I disease (median 19 cm3) were smaller than in patients with Stage II (median 80 cm3) or Stage III (median 97 cm3; p <0.001) disease. The Stage II TTVs were not significantly different from those of Stage III (post-hoc test according to Bonferroni). Prolonged OS was independently associated with a small TTV (<80 vs. >80 cm3 [median]; p = 0.01), young age (<60 vs. > or =60 years; p = 0.03), high Karnofsky performance status (< o r =70 vs. >70; p = 0.04), and female gender (p = 0.04). Both stage (p = 0.7) and T stage (p = 0.06) were of less importance for OS than was the TTV, according to multivariate modeling. Increased local progression-free survival (p = 0.001) and distant failure-free survival (p = 0.03) were independently associated with a small TTV (i.e., <80 cm3). The results were unchanged if the TTV was analyzed as a continuous variable. CONCLUSION: A strong independent association between a small CT-defined TTV and prolonged survival in patients with NSCLC selected for curative/definitive RT was found. Future therapeutic studies in NSCLC should consider stratifying/adjusting for differences in TTV to avoid confounding effects on survival from variations in the TTV at baseline.     

巢式PCR检测CK19 mRNA和LUNX mRNA诊断肺癌淋巴结微转移

目的：探讨非小细胞肺癌（non-small cell lung cancer，NSCLC）淋巴结微转移的基因诊断方法，并分析CK19 mRNA、LUNX mRNA作为肺癌微转移检测分子标记物的可行性。方法：采用巢式RT—PCR技术检测39例NSCLC患者的149枚淋巴结和20例肺良性病变患者的47枚淋巴结中的细胞角蛋白19（CK19 mRNA）、肺特异性X蛋白（LUNX mRNA）的表达。结果：39例NSCLN患者的149枚淋巴结中，46枚（30．9％）淋巴结存在CK19 mRNA阳性表达，56枚（37．6％）存在LUNX mRNA阳性表达，常规病理组织学检出20枚（13．4％）有癌转移，巢式RT—PCR方法和常规病理方法比较差异有统计学意义（P〈0．01）；20例肺良性病变患者的47枚淋巴结中CK19 mRNA和LUNX mRNA表达均为阴性，与肺癌组比较均有统计学意义（P〈0．01）。淋巴结微转移与病理类型、细胞分化程度和临床分期有密切关系（P〈0．05）。结论：CK19 mRNA、LUNX mRNA可作为检测NSCLC患者淋巴结微转移的分子标记物，联合检测可能有助于早期诊断肺癌转移，从而指导临床个体化治疗。     

Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.     

Prognostic Factors for Lymph Node Negative Stage I and IIA Non-small Cell Lung Cancer: Multicenter Experiences

Background: Surgery is the only curative treatment for operable non-small lung cancer (NSCLC) and theimportance of adjuvant chemotherapy for stage IB patients is unclear. Herein, we evaluated prognostic factorsfor survival and factors related with adjuvant treatment decisions for stage I and IIA NSCLC patients withoutlymph node metastasis. Materials and Methods: We retrospectively analyzed 302 patients who had undergonecurative surgery for prognostic factors regarding survival and clinicopathological factors related to adjuvantchemotherapy. Results: Nearly 90% of the patients underwent lobectomy or pneumonectomy with mediastinallymph node resection. For the others, wedge resection were performed. The patients were diagnosed as stageIA in 35%, IB in 49% and IIA in 17%. Histopathological type (p=0.02), tumor diameter (p=0.01) and stage(p<0.001) were found to be related to adjuvant chemotherapy decisions, while operation type, lypmhovascularinvasion (LVI), grade and the presence of recurrence were important factors in predicting overall survival (OS),and operation type, tumor size greater than 4 cm, T stage, LVI, and visceral pleural invasion were related withdisease free survival (DFS). Multivariate analysis showed operation type (p<0.001, hazard ratio (HR):1.91) andthe presence of recurrence (p<0.001, HR:0.007) were independent prognostic factors for OS, as well visceralpleural invasion (p=0.01, HR:0.57) and LVI (p=0.004, HR:0.57) for DFS. Conclusions: Although adjuvantchemotherapy is standard for early stage lymph node positive NSCLC, it has less clear importance in stage Iand IIA patients without lymph node metastasis.     

Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival

ABSTRACT: INTRODUCTION: Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. METHODS: Bone marrow and peripheral blood were collected before NACT (BM1: n=231/PB1: n=219), at surgery (BM2: n=69/PB2: n=71), and after 12 months from start of NACT (BM3: n=162/PB3: n=141). Patients were included from 1997 to 2003 and followed until 2009 (or ten years follow-up). DTC- and CTC-status were determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. The prognostic significance of DTCs/CTCs was assessed by univariate and multivariable Cox-regression analyses. RESULTS: Before NACT, DTCs and CTCs were detected in 21.2% and 4.9% of the patients, respectively. At surgery, 15.9% and 1.4% had DTC- and CTC-presence, compared to 26.5% and 4.3% at 12 months from start of NACT. Of patients for whom DTC results both before NACT and at 12 months were available, concordant results were observed in 68%, and 14 out of 65 had positive DTC-status at both time points. Presence of [greater than or equal to]1 DTC 12 months from start of NACT, but not at other time points, predicted reduced disease-free survival (DFS; HR 2.3, p= 0.003), breast cancer-specific survival (BCSS; HR 3.0, p<0.001) and overall survival (OS; HR 2.8, p<0.001). Before NACT, presence of [greater than or equal to]3 DTCs was also associated with unfavorable outcome. In addition, reduced BCSS was observed for CTC-positive patients (HR 2.2, p=0.046). In multivariable analysis, DTC status (相似文献   

Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up

We performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.     

Bone marrow cytokeratin 19 mRNA level is an independent predictor of relapse-free survival in operable breast cancer patients

Purpose To study the prognostic significance of elevated cytokeratin 19 (CK19) mRNA levels in the bone marrow (BM) of operable breast cancer patients. Patients and Methods From 1998 to 2000, BM was collected from 195 consecutive breast cancer patients immediately prior to surgery and from 34 healthy volunteers. The patients received surgical and adjuvant treatment according to national guidelines at the time. We analyzed the level of CK19 mRNA in the BM samples from patients and normal controls using a real-time RT-PCR assay. The associations with known prognostic factors and the impact of pathological CK19 mRNA levels on patients’ prognosis were investigated. Results Using the 99 percentile of the normal control group as a cut-off, 24 (12%) of the 195 patients and 1 (3%) of the 34 volunteers were diagnosed as CK19 mRNA positive. There was no correlation between CK19 BM status and the clinicopathological factors tested. During a median follow-up of 72 months, 7 (29%) of the 24 CK19 mRNA BM positive patients experienced systemic relapse compared to 20 (12%) of the 171 in the CK19 mRNA negative group. The patients with CK19 mRNA-positive BM had significantly shorter systemic recurrence-free survival (P = 0.01) and overall recurrence-free survival (P = 0.005). Multivariate Cox regression showed CK19 mRNA BM status to be an independent predictor of relapse. Conclusion Detection of CK19 mRNA in the BM of breast cancer patients by real-time RT-PCR is an independent predictor of relapse-free survival in operable breast cancer patients. This work was supported by the Norwegian Cancer Society.     

Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

Background: The efficacy of erlotinib is controversial in patients with unknown EGFR mutational status.The aim of this study was to identify the clinicopathological factors that are predictive of erlotinob treatmentoutcomes for NSCLC patients with unknown EGFR mutational status. Materials and Methods: A retrospectiveanalysis of 109 patients with advanced NSCLC who had previously failed at least one line of chemotherapy andreceived subsequent treatment with erlotinib (150 mg/day orally) was performed. A Cox proportional hazardmodel for univariate and multivariate analyses was used to identify the baseline clinical parameters correlatingwith treatment outcome, expressed in terms of hazard ratios (HRs) and 95% confidence intervals. Results: Themedian treatment duration was 15 weeks (range, 4-184). The disease control rate was 55%, including diseasestability for ≥3 months for 40% of the patients. Median progression-free survival and median overall survival(OS) were 4.2 and 8.5 months, respectively. The Cox model indicated that an Eastern Cooperative OncologyGroup performance status (ECOG PS) ≥2 (HR 3.82; p<0.001), presence of intra-abdominal metastasis (HR 3.42;p=0.002), 2 or more prior chemotherapy regimens (HR 2.29; p=0.021), and weight loss >5% (HR 2.05; p=0.034)were independent adverse prognostic factors for OS in NSCLC patients treated with erlotinib. Conclusions: Thisstudy suggests that NSCLC patients should be enrolled in erlotinib treatment after a first round of unsuccessfulchemotherapy to improve treatment success, during which they should be monitored for intra-abdominalmetastasis and weight loss.