Prognostic role of the ABO blood types in Chinese patients with curatively resected non-small cell lung cancer: a retrospective analysis of 1601 cases at a single cancer center.

BACKGROUND: A positive association between the ABO blood types and survival has been suggested in several malignancies. The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1, 2005 and December 31, 2009. The relationship between the ABO blood types and survival was investigated. In addition, univariate and multivariate analyses were performed. RESULTS: Group 1 (patients with the blood type O or B) had significantly prolonged overall survival (OS) compared with group 2 (patients with the blood type A or AB), with a median OS of 74.9 months versus 61.5 months [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.72-0.96; P = 0.015]. Additionally, group 1 had significantly longer disease-free survival (DFS; HR 0.86; 95% CI 0.76-0.98; P = 0.022) and locoregional relapse-free survival (LRFS; HR 0.79; 95% CI 0.64-0.98; P = 0.024) than group 2. The association was not significantly modified by other risk factors for NSCLC, including smoking status, pathologic tumor-node-metastasis stage, pT category, pN category, and chemotherapy. CONCLUSIONS: There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC. Patients with the blood type O or B had significantly prolonged OS, DFS, and LRFS compared with those with the blood type A or AB.

A randomized phase 2 trial of erlotinib versus pemetrexed as second-line therapy in the treatment of patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma.

BACKGROUND: The current study was undertaken to investigate the efficacy and safety of erlotinib versus pemetrexed as second-line therapy for patients with advanced epidermal growth factor receptor (EGFR) wild-type and EGFR fluorescence in situ hybridization (FISH)-positive lung adenocarcinoma. METHODS: In this open-label, randomized, phase 2 study, patients with EGFR wild-type and EGFR FISH-positive adenocarcinoma who had developed disease progression after 1 prior platinum-based chemotherapy were randomly assigned (1:1) to receive erlotinib or pemetrexed until the time of disease progression or death, unacceptable toxicity, or a request for discontinuation by the patient. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 123 patients were enrolled (61 in the erlotinib arm and 62 in the pemetrexed arm). The median PFS was 4.1 months (95% confidence interval [95% CI], 1.6 months-6.6 months) in the erlotinib group versus 3.9 months (95% CI, 2.7 months-5.1 months) in the pemetrexed group. The difference in PFS between the 2 treatment groups was not significant (hazard ratio, 0.92; 95% CI, 0.62-1.37 [P= .683]). The objective response rate appeared to be higher among patients receiving erlotinib compared with those receiving pemetrexed (19.7% vs 8.1%; P= .062). The 3 most commonly recorded adverse events were rash (54.1%), fatigue (19.7%), and diarrhea (16.4%) in the erlotinib group and fatigue (25.8%), nausea (24.2%), and anorexia (14.5%) in the pemetrexed group. CONCLUSIONS: There were no significant differences noted with regard to efficacy between erlotinib and pemetrexed in the second-line setting for patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma. Both regimens appear to be effective treatment options for these patients.

Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in resected stage IIIA-N2 non-small cell lung cancer harbouring EGFR mutations: a randomized, phase II study.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown. METHODS: In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5), administered every 21 days for 4 cycles, followed with or without gefitinib (250 mg/day) for 6 months. The primary end point was disease-free survival (DFS). RESULTS: From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95 % confidence interval (CI) 0.16-0.85; P = 0.014; median, 39.8 vs. 27.0 months]. The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and 54.2 % in the PC alone group. The rates of 2-year overall survival (OS) were 92.4 % in the PC-gefitinib group and 77.4 % in the PC alone group (HR, 0.37; 95 % CI 0.12-1.11, P = 0.076). The most common adverse event was rash (43.3 %, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated. CONCLUSIONS: The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.

Tyrosine-protein phosphatase non-receptor type 12 expression is a good prognostic factor in resectable non-small cell lung cancer.

Tyrosine-protein phosphatase non-receptor type 12 (PTPN12) has been considered to be a tumor suppressor in human cancer, but its clinical and prognostic significance in non-small cell lung cancer (NSCLC) has not been well elucidated.A retrospective analysis of 215 patients with surgically resected NSCLCs from Sun Yat-Sen University Cancer Center between April 2002 and March 2005 was performed using immunohistochemistry and Western Blot to analyze PTPN12 expression. The association between PTPN12 expression and patient survival was investigated.Western Blots showed that the expression level of PTPN12 were higher in normal paracancerous lung tissues than in NSCLC tissues. High PTPN12 expression was less common in the presence than in the absence of visceral pleural invasion (p=0.038). Patients with PTPN12-high tumors had a longer disease-free survival (DFS) (P<0.001) and overall survival (OS) (p<0.001), especially for those with non-squamous cell carcinoma (non-SCC) (DFS, p<0.001; OS, p<0.001). Multivariate analysis confirmed that PTPN12 positivity was associated with increased survival duration (DFS, p<0.001; OS, p<0.001), independent of prognostic indicator.High PTPN12 expressive levels are associated with favorable survival duration in patients with NSCLC, especially those with non-SCC. Our study suggests that PTPN12 expression is a valuable prognostic biomarker for NSCLC patients.

Expression of Cystatin SN significantly correlates with recurrence, metastasis, and survival duration in surgically resected non-small cell lung cancer patients.

Cystatin SN has been considered to be involved in human cancer, but its clinical significance in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to evaluate the clinical value of Cystatin SN expression in patients with surgically resected NSCLCs. A retrospective analysis of 174 patients with surgically resected NSCLCs from April 2002 to March 2005 was performed with immunohistochemistry and fluorescence in situ hybridization to analyze the protein expression and amplification of Cystatin SN. The associations between Cystatin SN expression and recurrence, metastasis, and survival were investigated. In recurrence and metastasis analysis, compared with low-Cystatin SN expression NSCLCs, high expression tumors were more likely to recur and metastasize (P < 0.001). Disease-free survival (DFS) and overall survival (OS) were significantly prolonged in the low-Cystatin SN expression subgroup compared with the high-Cystatin SN expression subgroup (DFS, P < 0.001; OS, P = 0.001). A multivariate analysis confirmed that high expression of Cystatin SN was associated with poor survival (DFS, P = 0.001; OS, P = 0.006) and was an independent prognostic indicator. The present study indicates that high expression of Cystatin SN is a significant prognostic indicator of a higher rate of recurrence, metastatic risk, and poor survival in patients with surgically resected NSCLCs.

Meta-analysis of EGFR tyrosine kinase inhibitors compared with chemotherapy as second-line treatment in pretreated advanced non-small cell lung cancer.

BACKGROUND: Since efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy in the treatment of patients with pretreated advanced non-small cell lung cancer (NSCLC) remain controversial, we performed a meta-analysis to compare them. METHODS: An internet search of several databases was performed, including PubMed, Embase, and the Cochrane database. Randomized trials that compared an EGFR-TKI with chemotherapy in the second-line setting were included. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3-4 toxicities. The PFS, OS for the EGFR mutation-positive (EGFR M+) and EGFR mutation-negative (EGFR M-) subgroups were pooled. The pooled hazard ratios (HRs) and odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated on the STATA software. RESULTS: Our meta-analysis combined 3,825 patients from 10 randomized trials. Overall, EGFR-TKIs and second-line chemotherapy have equivalent efficacy in terms of PFS (HR, 1.03; 95%CI, 0.87-1.21; P = 0.73; I2 = 78.7%, Pheterogeneity<0.001), OS (HR, 1.00; 95%CI, 0.92-1.08; P = 0.90; I2 = 0.0%, Pheterogeneity = 0.88), and ORR (OR, 1.34; 95%CI, 0.86-2.08; P = 0.20; I2 = 73.1%, Pheterogeneity<0.001). However, subgroup analysis based on EGFR mutation status showed that second-line chemotherapy significantly improved PFS (HR, 1.35; 95%CI, 1.09-1.66; P = 0.01; I2 = 55.7%, Pheterogeneity = 0.046) for EGFR M- patients, whereas OS was equal (HR, 0.96; 95%CI, 0.77-1.19; P = 0.69; I2 = 0.0%, Pheterogeneity = 0.43); EGFR-TKIs significantly improved PFS (HR, 0.28; 95%CI, 0.15-0.53; P<0.001; I2 = 4.1%, Pheterogeneity = 0.35) for EGFR M+ patients, whereas OS was equal (HR, 0.86; 95%CI, 0.44-1.68; P = 0.65; I2 = 0.0%, Pheterogeneity = 0.77). Compared with chemotherapy, EGFR-TKIs led to more grade 3-4 rash, but less fatigue/asthenia disorder, leukopenia and thrombocytopenia. CONCLUSIONS: Our analysis suggests that chemotherapy in the second-line setting can prolong PFS in EGFR M- patients, whereas it has no impact on OS. EGFR-TKIs seem superior over chemotherapy as second-line therapy for EGFR M+ patients. Our findings support obtaining information on EGFR mutational status before initiation of second-line treatment.