新辅助化疗对Ⅱ期和Ⅲ期乳腺癌的疗效观察

目的:探讨新辅助化疗分别在Ⅱ期和Ⅲ期乳腺癌中的应用价值.方法:选取1994年9月～1999年9月术前经病理确诊可手术乳腺癌426例,分为新辅助化疗组(A组)和对照组(R组)分析两组的术式选择、局部控制和5年生存率,评价新辅助化疗在Ⅱ、Ⅲ期乳腺癌治疗中的价值.结果:Ⅱ期可保乳率由24.7%提高到44.6%(P=0.000),两组5年总生存率(OS)和无瘤生存率(DFS)无差异(P=0.525、0.581)Ⅲ期A组患者5年OS和DFS(62 9%、58.1%)均高于B组(39.5%、32.6%)(p=0.014、0.010).Ⅱ、Ⅲ期化疗后需植皮术均下降(P=0.000、0.000),3年内复发转移A组均低于B组(P=0.035、0.027).结论:新辅助化疗可提高Ⅱ、Ⅲ期可手术乳腺癌患者的保乳率、减少植皮术、降低局部复发转移;可提高Ⅲ期乳腺癌患者的5年生存率.     

非小细胞肺癌新辅助化疗后的临床病理学研究

目的　研究非小细胞肺癌 (NSCLC)新辅助化疗的临床病理学改变及其与临床疗效评价的一致性 ,探讨NSCLC新辅助化疗的临床应用价值。方法　 84例Ⅰ～Ⅲ期NSCLC患者随机分为综合治疗组和单纯手术组各 42例。综合治疗组术前行MVP方案化疗 2周期 ,分别进行临床评价和病理学评价 ,术后继续化疗 2～ 4周期 ;单纯手术组仅行手术治疗。结果　综合治疗组原发灶的肿瘤细胞在镜下显示不同程度的变性和坏死 ,单纯手术组则无此改变。术前新辅助化疗临床评价和病理学评价有效率均为 5 9.5 % (2 5 /4 2 )。两种评价的一致率为 71.4% (30 /4 2 ,Kappa值 =0 .40 7,P <0 .0 1)。综合治疗组与单纯手术组比较 ,总生存率差异有显著性 (P =0 .0 47) ,经分层分析 ,两组Ⅰ～Ⅱ期患者生存率差异无显著性 (P >0 .0 5 ) ,但Ⅲ期患者生存率差异有显著性 (P =0 .0 37)。结论　伴有纤维化的变性和坏死是原发灶化疗后的主要病理学改变形式。化疗疗效的临床评价能够反映病理学变化。对Ⅲ期NSCLC患者行术前和术后辅助化疗与单纯手术相比有更好的治疗效果     

ⅠB期非小细胞肺癌中K-ras的表达对辅助化疗预后的影响

目的:回顾性研究ⅠB期非小细胞肺癌(non-small cell lung cancer,NSCLC)中K-ras的表达,探讨其与辅助化疗(含铂类的两药方案)预后的关系.方法:75例根治性切除的NSCLC患者分为辅助化疗组和单纯手术组.应用免疫组织化学法检测NSCLC中K-ras的表达情况.全组随访患者的生存情况,并用Cox多因素分析法分析K-ras表达及临床病理参数中的独立预后因素.结果:辅助化疗组和单纯手术组的5年生存率分别为65.6%和56.3%(χ2=3.105,P=0.097);辅助化疗组中,K-ras表达为阳性患者的生存情况明显好于单纯手术组,5年生存率分别为63.5%和50.4%(χ2=5.695,P=0.026);K-ras表达为阴性时辅助化疗组与单纯手术组的患者生存率差异无统计学意义(χ2=2.618,P=0.155).经多因素分析,组织类型、分化程度、K-ras表达和是否化疗均为NSCLC的独立预后因素,相对危险比分别为1.223、2.812、1.779和2.964.结论:K-ras阳性表达时,对ⅠB期NSCLC患者进行辅助化疗,受益明显.     

新辅助化疗在Ⅲa期非小细胞肺癌治疗中的应用

目的探讨新辅助化疗对Ⅲa期非小细胞肺癌(non-smallcelllungcancer,NSCLC)手术切除率和术后生存率的影响。方法1999年1月至2005年1月收治的293例ⅢaNSCLC患者随机分为新辅助化疗组(136例)及单纯手术组(157例),对两组病人的临床资料进行统计学分析。结果新辅助化疗近期疗效总有效率53.1%;外科手术切除率较单纯手术组高,差异显著(P<0.05);术后1、3年生存率均较单纯手术组高,差异显著(P<0.05)。结论进行新辅助化疗可显著提高Ⅲa期肺癌患者手术切除率,延长患者生存期。     

新辅助化疗治疗Ⅲ期非小细胞肺癌的临床评价

目的　评价新辅助化疗 (术前诱导化疗 )在治疗ⅢA 期非小细胞肺癌 (NSCLC)中的应用价值。方法　将 10 2例Ⅲ A 期NSCLC患者随机分为 2个组 :新辅助化疗组 5 1例 ,诱导化疗后行手术治疗 ,其中 3 0例术前接受支气管动脉灌注 (BAI)化疗 ,2 1例术前接受全身化疗。单一手术组 5 1例 ,确诊后直接行手术治疗。结果　新辅助化疗组总有效率 (CR PR )为 49.0 % (2 5 / 5 1) ,化疗不良反应患者可耐受。新辅助化疗组手术切除率和完全性切除率为 92 .2 %和 5 4.9% ,明显高于单一手术组 (72 .5 %和 3 5 .3 % ,P<0 .0 5 )。新辅助化疗组患者 (3 4例 )平均中位生存期为 2 5个月 ,2年生存率为 5 5 .9% (19/ 3 4)。单一手术组患者 (3 2例 )平均中位生存期为 13个月 ,2年生存率为 2 8.1% (9/ 3 2 )。 2组比较有显著性差异 (P <0 .0 5 )。结论　对ⅢA 期NSCLC患者进行新辅助化疗可提高手术切除率 ,延长患者中位生存期 ,提高患者 2年生存率。     

完全性切除非小细胞肺癌围术期化疗的随机研究

目的:探讨围术期化疗对NSCLC生存率预后因素的影响。方法:1995年2月至2003年12月Ⅰ-ⅢA期根治性手术NSCLC的随机多中心研究分为术前先行化疗和先行手术两组,术后除部分I期外均作术后辅助化疗,以Kaplan-Meier曲线统计累积生存率及LogRank检验,Cox单因素和多因素分析生存率影响因素并计算风险比(HR)。结果:全组337例,术前先行化疗组169例,先行手术组168例。先手术组的累积年生存率优于先化疗组,如5年生存率为47.85%∶36.52%,MST为56.63月∶39.14月(P=0.03);Cox多因素分析显示术前化疗、年龄、性别、病理类型与年生存率不相关(P>0.05),期别及术后化疗和生存率显著相关(P<0.01);Ⅱ期术前先化疗组累积年生存率、MST在Cox单因素分析中明显差于先手术组,如5年生存率为28.50%∶58.91%,MST为35.38月∶60 月(P=0.02);Ⅰ、Ⅲ期中未见两组生存率有统计学差别。两组NSCLC的疾病无进展生存期(PFS)无统计学差异(P=0.10);Cox多因素分析提示期别及术后化疗次数和PFS显著相关(P<0.01),HR分别为2.08和0.86;Ⅱ期先化疗组的年PFS明显低于先手术组(P=0.03),而Ⅰ期、ⅢA期的两组的PFS无明显差别(P>0.05)。术后化疗<3周期的有121例,≥3周期的有216例,年生存率、MST以≥3周期优于<3周期者(P=0.04)。Ⅰ期行术后化疗未见生存收益(P>     

外科治疗局部晚期非小细胞肺癌的疗效分析

目的:分析有手术适应症的Ⅲb期非小细胞肺癌(NSCLC)患者的外科治疗的疗效,寻找提高疗效的策略.方法:1988年至1997年96例Ⅲb期NSCLC患者接受了外科手术治疗.根据是否接受术前新辅助化疗分为单纯手术组(47例)和术前新辅助化疗组(49例),比较两组的手术性质及治疗结果.结果:术前新辅助化疗组的肉眼下手术完全切除率(46.9%)和1、3、5年生存率(42.5%、弘.7%、24.5%)均明显高于单纯手术组(23.4%和36.2%、21.3%、12.8%,P＜0.05).结论:局部晚期非小细胞肺癌Ⅲb期患者术前接受新辅助化疗较单纯手术可提高外科治疗的疗效,值得在临床上推广.     

检测P53蛋白表达在Ⅲ期非小细胞肺癌新辅助化疗中的意义

背景与目的新辅助化疗能有效提高Ⅲ期非小细胞肺癌(NSCLC)患者的生存率,其主要体现在有效化疗的患者身上,P53在其中的临床意义未见有相关报道。本研究旨在探讨Ⅲ期NSCLC患者中P53蛋白表达与新辅助化疗敏感性及预后的关系,同时探讨P53蛋白表达与CT检查在判断新辅助化疗疗效中的相关性。方法51例行新辅助化疗患者为试验组,49例同期未行新辅助化疗者为对照组,应用免疫组化法检测两组P53蛋白表达。试验组患者于新辅助化疗前后均行CT检查。结果(1)对照组P53蛋白阳性表达率48.98%,中位生存时间18个月,试验组P53蛋白阳性表达率49.02%,中位生存时间19个月,二者无显著差别(P>0.05)。(2)试验组中P53阳性者中位生存时间13个月,阴性者中位生存时间31个月,二者有显著差别(P<0.05)。(3)胸部CT检查示新辅助化疗有效率为43.14%(22/51),同时CT为有效同时P53蛋白表达为阴性者18例,CT为无效同时P53表达为阳性者2例,P53表达与CT所示有效率具有相关性(r=0.537,P<0.01)。结论(1)检测P53蛋白表达有助于预测Ⅲ期NSCLC新辅助化疗疗效。(2)P53蛋白表达与胸部CT检查的化疗有效率相关。     

新辅助化疗对165例Ⅲa期非小细胞肺癌患者术后生存的影响分析

 目的 探讨新辅助化疗对Ⅲa期非小细胞肺癌（NSCLC）生存率的影响，评价其安全性及可行性。方法 回顾性分析该院2000年1月至2004年1月外科完全性切除Ⅲa期NSCLC 165例临床资料，以新辅助化疗组（A组）与直接手术组（B组）进行对照。Life-Table法比较两组1、3、5年生存率差异，Kaplan-Meier法比较累计生存率及中位生存时间；COX多因素回归模型Condition-Forward法分析影响生存的主要因素。结果 两组患者术后1、3、5年生存率A组 80 %、30 %、13 %，B组 87 %、40 %、16 %；术后平均生存时间分别为25.5、29.4个月；中位生存期分别为20.0、25.0个月；差异有统计学意义（P＜0.05）。COX多因素分析表明病理类型、纵隔淋巴结转移状况、术前辅助化疗是影响Ⅲa期NSCLC预后的因素（P＜0.05）。结论 新辅助化疗+手术可延长生存期，新辅助化疗在一定程度上增加手术难度,但是安全可行的。     

Ⅲ期非小细胞肺癌术后辅助化疗疗效分析

目的评价Ⅲ期非小细胞肺癌(NSCLC)切除术后辅助化疗疗效,并对影响术后辅助化疗的因素进行初步分析。方法回顾性分析本院268例切除术后的Ⅲ期NSCLC,有94例于术后3~4周开始接受化疗(辅助化疗组),其中予以CAP方案化疗42例;EP方案化疗34例;NP方案化疗18例。在化疗组中化疗3~4周期56例;化疗4~6周期38例。另174例患者术后未行化疗(单纯手术组)。结果辅助化疗组和单纯手术组的5年生存率分别为27.6%和16.6%(P<0.05),差别有统计学意义。在辅助化疗组中行CAP、EP、NP方案化疗组的5年生存率分别为26.1%、26.4%和27.7%(P>0.05),而在化疗组中化疗3~4周期和化疗5~6周期患者的5年生存率分别为26.7%和28.8%(P>0.05)。结论对切除术后Ⅲ期NSCLC患者进行3~4周期,以顺铂为基础的化疗方案的辅助化疗,可以提高长期生存率。     

多基因表达对IIIA期非小细胞肺癌术后转移及生存期的影响

目的前瞻性探讨抑癌基因p53,癌基因K-ras、HER2, 血管内皮生长因子(VEGF),表皮生长因子受体(EGFR),粘连因子CD44,金属蛋白酶MMP9等蛋白表达对ⅢA期非小细胞肺癌(NSCLC)术后复发转移和生存期的影响.方法采用免疫组织化学方法检测32例ⅢA期非小细胞肺癌手术标本中上述蛋白表达.结果 p53、K-ras、VEGF、EGFR、CD44、MMP9和HER2蛋白表达率分别为62.5%(20/32)、34.3%(11/32)、25.0%(8/32)、46.9%(15/32)、78.1% (25/32)、50%(16/32)和43.8%(14/32).K-ras,EGFR蛋白表达与疾病进展时间(time to progression,TTP)有关(P=0.030, P=0.008).多变量Cox回归分析,K-ras,HER2蛋白表达是影响生存期的独立影响因素.Kaplan-M 生存分析显示K-ras,HER2 阳性组生存期明显短于阴性组(P=0.042,P=0.039).结论对于ⅢA期NSCLC,上述7种因子阳性表达率很高.K-ras,EGFR蛋白表达阳性患者术后更易发生远处转移, K-ras,HER2表达是影响生存期的独立影响因素.     

Randomized controlled trial of neoadjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IIIA non-small cell lung cancer in China

Aim:   The aim of this study was to evaluate the efficacy of cisplatin plus vinorelbine as a regimen of neoadjuvant chemotherapy on the improvement of surgical resectability and survival in Chinese patients with stage IIIA non-small cell lung cancer (NSCLC).
Methods:   Fifty-six patients with stage IIIA NSCLC were randomly assigned to undergo either surgery preceded by two cycles of chemotherapy with cisplatin plus vinorelbine (the neoadjuvant chemotherapy arm) or immediate surgery (the primary surgery arm). The patients who had a complete resection received two to four cycles of chemotherapy, and those with incomplete resection received radiotherapy followed by two cycles of chemotherapy after surgery.
Results:   The overall response rate to neoadjuvant chemotherapy was 53.6%, with a complete response of 7.1%. A pathological complete response was seen in two patients (8%). The complete resection rates were 78.6% in the neoadjuvant chemotherapy arm and 60.7% in the primary surgery arm. The median overall survival and median disease-free survival was 30 months and 24 months, respectively, in the neoadjuvant chemotherapy arm as compared to 16 months and 11 months in the primary surgery arm ( P  = 0.04 and P  = 0.048). The 3-year and 5-year survival rate was 49.7% and 31.9%, respectively, for the neoadjuvant chemotherapy arm and 29.2% and 3.6% for the primary surgery arm.
Conclusion:   Neoadjuvant chemotherapy with cisplatin plus vinorelbine regimen is effective and tolerable and can improve the overall survival and disease-free survival time in Chinese patients with stage IIIA NSCLC.     

Epidermal growth factor receptor (EGFR) is an independent adverse prognostic factor in esophageal adenocarcinoma patients treated with cisplatin-based neoadjuvant chemotherapy

Neoadjuvant platin-based therapy is accepted as a standard therapy for advanced esophageal adenocarcinoma (EAC). Patients who respond have a better survival prognosis, but still a significant number of responder patients die from tumor recurrence. Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet. We investigated the epidermal growth factor receptor (EGFR) in prognosis and chemotherapy resistance in these patients. Two EAC patient cohorts, either treated by neoadjuvant cisplatin-based chemotherapy followed by surgery (n=86) or by surgical resection (n=46) were analyzed for EGFR protein expression and gene copy number. Data were correlated with clinical and histopathological response, disease-free and overall survival.In case of EGFR overexpression, the prognosis for neoadjuvant chemotherapy responders was poor as in non-responders. Responders had a significantly better disease-free survival than non-responders only if EGFR expression level (p=0.0152) or copy number (p=0.0050) was low. Comparing neoadjuvantly treated patients and primary resection patients, tumors of non-responder patients more frequently exhibited EGFR overexpression, providing evidence that EGFR is a factor for indicating chemotherapy resistance.EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders. Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy.     

Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival.

The prognostic role of epidermal growth factor receptor (EGFR) and HER2-neu remains controversial in patients with non-small cell lung cancer (NSCLC). We studied the association between the mRNA expression of EGFR, HER2-neu, and survival in primary tumor and matching nonmalignant tissues from 83 patients with NSCLC. Analysis was performed using a quantitative real-time PCR system (Taqman). EGFR and HER2-neu mRNA expression was detectable in all (100%) specimens analyzed. Twenty-nine (34.9%) patients had high HER2-neu expression, and 28 (33.7%) patients had high EGFR expression. A high HER2-neu and EGFR coexpression was detectable in 14 (16.9%) patients. High HER2-neu expression was associated with inferior survival (P = 0.004), whereas high EGFR expression showed a trend toward inferior survival (P = 0.176). The impact of HER2-neu and EGFR coexpression on patients' survival was additive (P = 0.003). Multivariate analysis determined high HER2-neu expression (P = 0.041), and high EGFR/HER2-neu coexpression (P = 0.030) as significant and independent unfavorable prognostic factors. These findings indicate that HER2-neu and EGFR play a crucial role in the biological behavior of NSCLCs. Testing of molecular marker coexpression (EGFR and HER2-neu) improves the estimation of prognosis and appears to define low- and high-risk groups for treatment failure in curatively resected NSCLC.     

EGFR与HER2对非小细胞肺癌的预后观察

目的:探讨传统的非小细胞肺癌预后因素与表皮生长因子等生物学新预后因素结合对非小细胞肺癌的预后作用.方法:复习116例非小细胞肺癌手术病例临床病理资料及随访资料,观察常规HE染色切片判断血管浸润及淋巴管浸润,用免疫组化法测定病灶的EGFR、HER2的表达,再用Cox模型进行生存分析.结果:NSCLC组EGFR、HER2、BVI、LVI的阳性表达率分别为42.24%、43.10%、44.83%、31.90%.BVI阴、阳性组术后生存期比较P=0.006,无瘤生存期比较P=0.001;LVI阴、阳性组术后生存期、无瘤生存期比较P分别为0.239和0.048;EGFR阴、阳性组术后生存期、无瘤生存期比较P分别为0.117及0.217;HER2阴、阳性组术后生存期、无瘤生存期比较P分别为0.073和0.053.进入影响生存期多因素模型的为N分期、HER2、TNM分期及手术方式(P分别为0.006、0.01、0.019和0.022).结论:13项临床病理和生物因素结合起来进行多变量Cox回归分析,影响生存期的因素为:N分期、HER2、TNM分期及手术方式.影响无瘤生存期的因素为:BVI、TNM分期和N分期.     

Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.     

The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes.

PURPOSE: Gene expression analysis identifies several breast cancer subtypes. We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes. EXPERIMENTAL DESIGN: We used immunohistochemical profiles [human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-negative for HER2+/estrogen receptor-negative (ER-), hormone receptor and HER2- for basal-like, hormone receptor-positive for luminal] to subtype a prospectively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based (doxorubicin plus cyclophosphamide, AC) chemotherapy. We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease-free survival and overall survival. RESULTS: Of the 107 patients tested, 34 (32%) were basal-like, 11 (10%) were HER2+/ER-, and 62 (58%) were luminal. After neoadjuvant AC, 75% received subsequent chemotherapy and all received endocrine therapy if hormone receptor-positive. The chemotherapy regimen and pretreatment stage did not differ by subtype. Clinical response to AC was higher among the HER2+/ER- (70%) and basal-like (85%) than the luminal subtypes (47%; P < 0.0001). Pathologic complete response occurred in 36% of HER2+/ER-, 27% of basal-like, and 7% of luminal subtypes (P = 0.01). Despite initial chemosensitivity, patients with the basal-like and HER2+/ER- subtypes had worse distant disease-free survival (P = 0.04) and overall survival (P = 0.02) than those with the luminal subtypes. Regardless of subtype, only 2 of 17 patients with pathologic complete response relapsed. The worse outcome among basal-like and HER+/ER- subtypes was due to higher relapse among those with residual disease (P = 0.003). CONCLUSIONS: Basal-like and HER2+/ER- subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers. Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype. The poorer prognosis of basal-like and HER2+/ER- breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved.     

Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients.

PURPOSE: In non-small-cell lung cancer (NSCLC), response to tyrosine kinase inhibitors (TKIs) is significantly associated with the presence of increased copy number and/or activating mutations of the epidermal growth factor receptor gene (EGFR). Preclinical data indicate that HER2, a member of the EGFR family, could enhance TKI sensitivity. PATIENTS AND METHODS: HER2 gene copy numbers per cell were evaluated by fluorescent in situ hybridization (FISH) in 102 NSCLC patients treated with gefitinib, and previously evaluated for EGFR status by FISH, immunohistochemistry, and presence of mutations. RESULTS: Patients with HER2 high copy number (high polysomy and gene amplification [HER2 FISH positive]) represented 22.8% of patients, and compared with patients with no or low gain (HER2 FISH negative), had significantly better objective response (OR, 34.8% v 6.4%; P = .001), disease control rate (DCR, 56.5% v 33.3%; P = .04), time to progression (TTP, 9.05 v 2.7 months; P = .02), and a trend toward longer overall survival (OS, 20.8 v 8.4 months; P = .056). HER2 protein expression investigated by immunohistochemistry was positive in only five of 72 (7%) patients analyzed and all 89 patients tested by DNA sequencing were negative for mutations in HER2 exon 20. Patients with HER2 FISH-positive tumors displaying increased expression of EGFR protein, gene gain, or mutations (EGFR positive) had a significantly better OR, DCR, TTP, and OS than patients negative for both receptors. CONCLUSION: Increased copy number of the HER2 gene is associated with gefitinib sensitivity in EGFR-positive patients, supporting use of HER2 FISH analysis for selection of patients for TKI therapy.     

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.     

ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer

The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients). The relations between the ERCC1 or BRCA1 protein expression and the clinical outcomes of the patients were then examined. The rates of radiological response and pathological effectiveness were significantly higher among patients with ERCC1-negative tumors, compared with those with positive tumors in the neoadjuvant chemotherapy group (radiological response rates; 100% vs. 42.8%, P=0.013; pathological effectiveness; 100% vs. 47.1%, P=0.038), but no associations were observed in the neoadjuvant chemoradiotherapy group. Regarding survival, no significant differences in overall survival or disease-free survival were observed between patients with ERCC1-negative and positive tumors in both the neoadjuvant chemotherapy and chemoradiotherapy groups. In summary, we showed that a ERCC1-negative protein status was significantly related to tumor responsiveness to neoadjuvant chemotherapy with cisplatin and irinotecan, but such a status was not a clear prognostic predictor to cisplatin-based neoadjuvant therapy in NSCLC patients. Further study is needed to clarify the value of molecular predictors for customizing therapy for patients with NSCLC.