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Purpose: Sonic hedgehog (Shh) signaling pathway is known to play a crucial role in carcinogenesis in various malignancies, including lung cancer regarding tumorigenesis, angiogenesis, and cellular differentiation. The aim of this study was to investigate the value of components of Shh pathway as a prognostic marker in extensive stage small cell lung cancer (ES-SCLC) patients. Materials and Methods: We retrospectively analyzed data of 36 patients who were diagnosed with ES-SCLC between 2008 and 2012 at a single center. We performed immuo-histochemistry for glioma-associated oncogene homolog zinc finger protein 1 (Gli1), patched, Shh, and Ptch-mediated repression of smoothened (Smo) proteins using formalin-fixed, paraffin-embedded tissue derived from primary tumors. We then conducted survival analysis to evaluate the prognostic impact of these markers. Results: All 36 patients received platinum-based doublet chemotherapy. The median progression free survival and median overall survival were 6.9 months [95% confidence interval (CI), 6.5-7.3] and 11.7 months (95% CI, 9.1-14.3), respectively. The overall response rate was 84%. Of the 36 tissue specimens examined, over-expression of Gli1, Patched, Shh, and Smo was found in 12 (33.3%), five (13.9%), five (13.9%), and six (16.7%) cases, respectively. We found that high expression of Shh was associated with worse progression free survival (6.3 vs. 7.6 months, p=0.005) and overall survival (9.2 vs. 12.0 months, p=0.039) by both univariate and multivariate analyses, whereas other markers were not related to patient prognosis. Conclusion: A high proportion of small cell lung cancer tumors express proteins related to Shh pathway, and over-expression of Shh is correlated with poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the prognostic value of 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG PET) in patients with resectable pancreatic cancer. Materials and Methods: We retrospectively reviewed the medical records of pancreatic cancer patients who underwent curative resection, which included 64 consecutive patients who had preoperative FDG PET scans. For statistical analysis, the maximal standardized uptake value (SUVmax) of primary pancreatic cancer was measured. Survival time was estimated by the Kaplan-Meier method, and Cox's proportional hazard model was used to determine whether SUVmax added new predictive information concerning survival together with known prognostic factors. p<0.05 indicated statistical significance. Results: Overall survival (OS) and disease-free survival (DFS) were respectively 42.9 months (27.6-58.2; 95% CI) and 14.9 months (10.1-19.7; 95% CI). When subjects were divided into two groups according to SUVmax with a cutoff value of 3.5, the high SUVmax group (n=32; SUVmax >3.5) showed significantly shorter OS and DFS than the low SUVmax group. Multivariate analysis of OS and DFS showed that both high SUVmax and poor tumor differentiation were independent poor prognostic factors. Conclusion: Our study showed that degree of FDG uptake was an independent prognostic factor in pancreatic cancer patients who underwent curative resection. [ABSTRACT FROM AUTHOR]

Adenocarcinoma arising from the ampulla of Vater is a rare disease and has limited data regarding outcome of chemotherapy. The ampulla of Vater is a heterogeneous junctional structure located at the union of the common bile duct, the pancreatic duct, and the small intestine. Thus, ampullary adenocarcinoma is classified as either intestinal type or pancreatobiliary type. We investigated the efficacy of the XELOX (capecitabine plus oxaliplatin) chemotherapy in patients with recurrent or metastatic ampullary adenocarcinoma, and analyzed the histopathologic features and outcomes. From November 2009 to December 2011, 21 patients were treated with XELOX regimen. XELOX was administered in outpatient clinic every 3 weeks according to the following protocol: oral administration of capecitabine 750 mg/m² twice a day on days 1-14 and intravenous injection of oxaliplatin 130 mg/m² on day 1. With follow-up of median 16.6 months, median time to progression (TTP) was 7.6 months (95% confidence interval [CI], 6.7-8.5), and median overall survival was 19.7 months (95% CI, 14.8-23.6). Two patients (9%) achieved complete response and 6 patients (29%) showed partial response. In subgroup analysis with tissue specimens obtained from 17 patients, median TTP was longer among patients with the intestinal-type adenocarcinoma (n = 7), compared to those with the pancreatobiliary type (n = 10) (13.1 vs. 6.4 months, P = 0.038). The most common grade 3-4 adverse event was neutropenia (27%), and most events were mild. XELOX chemotherapy shows favorable efficacy with manageable toxicity for advanced intestinal-type ampullary adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. Materials and Methods: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. Results: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G→A or C→T) rather than a transversion mutation (G→T or G→C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. Conclusion: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations. [ABSTRACT FROM AUTHOR]

Purpose: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. Materials and Methods: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. Results: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. Conclusion: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung. [ABSTRACT FROM AUTHOR]

Purpose: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. Materials and Methods: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. Results: SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. Conclusion: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with geitinib or erlotinib. Materials and Methods: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving geitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. Results: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. Conclusion: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving geitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: Anaplastic thyroid cancer is known to have a poor prognosis due to its aggressive and rapid metastasis with median survival of less than 6 months. Multimodal treatment involving surgery and chemoradiotherapy has been used to improve the survival of patients. Here, we retrospectively review of treatment outcome of 13 consecutive patients who were treated at a single center. Materials and Methods: We retrospectively reviewed medical records of 13 anaplastic thyroid cancer patients who received multidisciplinary treatment between 2006 and 2010. Kaplan-Meier survival curve was used to analyze progression-free survival and overall survival of patients. Results: The median patient age at diagnosis was 69 years, and six patients had stage IVc diseases. Eight patients received primary surgery followed by radiotherapy or concurrent chemoradiotherapy (CCRT). Five patients received weekly doxorubicin-based definitive CCRT, but only one patient's condition remained stable, while the rest experienced rapid disease progression. The median progression-free survival was 2.8 months (95% CI, 1.2-4.4 months), and the median overall survival was 3.8 months (95% CI, 3.0-4.6 months). Conclusion: Patients with anaplastic thyroid cancer showed poor prognosis despite multimodality treatment. Therefore, identification of novel therapeutic targets is warranted to take an effective mode of treatment. [ABSTRACT FROM AUTHOR]

The strategies of incorporating monoclonal antibodies (MoABs) have now proved efficacy in the first-line treatment of advanced non-small cell lung cancer (NSCLC). These include targeting the vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR). Bevacizumab is a MoAB targeting the vascular endothelial growth factor (VEGF), an important mediator of new blood vessel formation. Cetuximab is a MoAB directed at EGFR. Binding cetuximab to EGFR blocks signal transduction and promotes receptor internalization and degradation. In this review, we present current data of bevacizumab and cetuximab for the first line treatment of advanced NSCLC. We also refer to their potential for Asian patients with advanced NSCLC in the first-line setting. [ABSTRACT FROM AUTHOR]