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To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10(-12)); however, this association did not achieve genome-wide significance (p ≤ 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.

Introduction: The primary objective of this study was to compare the response rates of elderly, chemonaive patients with advanced non-small cell lung cancer (NSCLC) treated with daily oral erlotinib versus oral vinorelbine., Methods: Chemonaive Taiwanese patients aged 70 years or older who had advanced NSCLC were randomized to receive either oral erlotinib 150 mg (E) daily or oral vinorelbine 60 mg/m (V) on days 1 and 8 every 3 weeks., Results: From February 2007 to July 2008, 116 patients were enrolled and 113 were included in the intent-to-treat population: 57 patients in the E group and 56 patients in the V group. Objective response rates were 22.8% (13 of 57) in E and 8.9% (5 of 56) in V (p = 0.0388). Median progression-free survival (PFS) was 4.57 months in E and 2.53 months in V (p = 0.0287), with an 80.6% increase in median PFS for E compared with V. Median survival time was 11.67 months in E and 9.3 months in V (p = 0.6975). Toxicities were generally mild in both groups. Median PFS was longest for epidermal growth factor receptor gene (EGFR)-mutated patients in the E group, followed by EGFR-mutated patients in V, EGFR wild type in E, and EGFR wild type in V (p = 0.0034). Overall survival was longer for EGFR-mutated patients than for EGFR wild-type patients (p < 0.0001)., Conclusions: Erlotinib is highly effective compared with oral vinorelbine in elderly, chemonaive, Taiwanese patients with NSCLC. EGFR-mutated patients had better survival than those with EGFR wild-type disease, regardless of the treatment received.

Introduction: Erlotinib is an epidermal growth factor receptor tyrosine kinase inhibitor that significantly increases survival for patients with previously treated advanced non-small cell lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors have been reported to be particularly effective in Asian patients and may have a distinct safety profile in this population compared with non-Asian patients. We report safety and efficacy data from a subpopulation of East/South-East (E/SE) Asian patients enrolled in a global, open-label, phase IV trial of erlotinib (Tarceva Lung Cancer Survival Treatment study)., Methods: Patients who had previously failed on chemotherapy or radiotherapy, or were unsuitable for these treatments, were treated with oral erlotinib (150 mg/d) until disease progression or unacceptable toxicity., Results: Best response data were available for 1118 E/SE Asian and 4276 non-E/SE Asian patients. The overall response rates were 27% versus 10%, respectively (p < 0.0001). The disease control rates were 78% versus 66%, respectively (p < 0.0001). Survival data were available for 1242 E/SE Asian and 5338 non-E/SE Asian patients. The median progression-free survival times were 5.78 months versus 2.92 months, respectively (hazard ratio = 0.66, p < 0.0001). The median overall survival times were 14.7 months versus 6.8 months, respectively (hazard ratio = 0.57, p < 0.0001). One-year survival rates were 58.3% and 32.7%, respectively. Safety data were available for 1242 E/SE Asian patients. Seventeen percent of these patients experienced one or more erlotinib-related adverse event (AE) (other than the most frequently occurring AEs prespecified in the protocol) and 2% experienced an erlotinib-related serious AE. Dose reductions were reported for 171 (14%) patients., Conclusion: Erlotinib is an effective and well-tolerated treatment for Asian patients with advanced non-small cell lung cancer.

Introduction: It was found that second-line or thereafter therapies for patients with non-small cell lung cancer (NSCLC) who failed previous chemotherapy yielded a modest survival benefit. However, whether elderly patients (> or =70 years) benefit and are as suitable for salvage therapy as nonelderly patients (<70 years) are unknown. Whether epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is more favorable than chemotherapeutic agents as a salvage therapy agent in elderly patients with NSCLC is also undetermined., Methods: We retrospectively reviewed and updated the data of our patients with NSCLC who received second-line salvage therapies, classified them into elderly and nonelderly groups, and compared the efficacy, toxicities, and survival of the patients., Results: Four hundred sixty-one cases were reviewed. The nonelderly group had a similar response rate, control rate, and median survival time than the elderly group (p = 0.2, p = 0.9, and p = 0.5, respectively). The median progression-free time was numerically longer in the elderly than the nonelderly patients (p = 0.08). The nonelderly group had statistically insignificantly less hematologic toxicities than the elderly group, but more nausea and vomiting. In addition, the use of EGFR-TKI salvage therapy, compared with salvage chemotherapies in the elderly group, resulted in a similar disease control rate and median survival time and more favorable toxicity profiles., Conclusions: There were no differences in the efficacy of salvage chemotherapies and EGFR-TKI therapy, in terms of response rate, control rate, and overall survival, in elderly and nonelderly patients, and the therapies had acceptable toxicities. Age itself should not preclude patients with NSCLC from second-line salvage therapy.

Purpose: This phase II single arm, open label study was designed to evaluate the efficacy and toxicity of oral gefitinib (250mg) daily in previously untreated patients with advanced non-small-cell lung cancer (NSCLC)., Methods: Eligible patients had stage IIIB or IV NSCLC with adequate organ functions, and were chemonaïve. All eligible patients were treated with oral administration of 250mg of gefitinib until intolerable toxicity, disease progression or death occurred. Responses were assessed after every 8 weeks of therapy., Results: For a total of 53 patients, the objective response rate (ORR) was 32.1% and overall disease control rate (DCR) was 52.8%. Median overall and progression-free survivals (PFS) were 9.4 (95% CI, 8.8-13.3) and 3.2 months (95% CI, 1.1-5.2) months, and 1-year survival rate was 41.5%. Patients with adenocarcinoma (n=35) had a higher response rate. Adenocarcinoma, female gender (n=24), and response to gefitinib were predictive factors for better survival. The most commonly seen adverse events (AEs) were skin toxicity (54.7%), diarrhea (43.4%) and nail change (16.9%). Most AEs were mild to moderate and considered manageable. Drug-related interstitial pneumonia was clinically diagnosed in four cases (7.5%)., Conclusions: Oral gefitinib, as compared to conventional chemotherapy, has comparable effect but less toxicity as a first-line treatment in Chinese patients who have advanced NSCLC, especially in those with adenocarcinoma histology. A further phase III prospective study comparing gefitinib to standard chemotherapy to define the efficacy of gefitinib is appropriate in advanced NSCLC patients.

We here report a case of squamous cell carcinoma of the lung, with an unusually fast tumor growth rate, so fast that its early detection was impossible even with two sequential chest roentgenograms taken only 36 days apart. Literature related to the concept of cell growth kinetics was reviewed, and the tumor volume doubling time that characterizes any measurable tumor was calculated for our case accordingly, based on the single lesion found on the plain chest film, with the best possible estimation of its volume. We concluded that, to the best of our knowledge, a squamous cell carcinoma of the lung that grew so fast (with a tumor doubling time less than 7.5 days) has not yet been reported to date; neither has a bronchogenic carcinoma of any cell type been reported with such a presentation. Given that a patient aged 81 belonged to a group usually with slower growth in tumor cell kinetics, the behavior of his tumor was indeed uncommon.

A 77-year-old man presented with painful swelling of his Port-A-Cath insertion site soon after flushing with normal saline. No discomfort or abnormality was found during the saline flush. A chest roentgenogram showed that the disconnected catheter had separated from the disc and was absent from its original location. The disconnected catheter was found embolized, by chest roentgenogram and CT scan, to the right atrium and hepatic vein. The patient was treated successfully with an X-ray guided extraction of the catheter. The possibility of catheter disconnection with embolization should be considered and a chest roentgenogram performed immediately in cases of rapid swelling of subcutaneous tissue around the port chamber after fluid infusion.

Tracheal bronchus is a rarely found congenital bronchial anomaly. It usually originates from the right lateral wall of the trachea at the level < 2 cm above the tracheal bifurcation. The patients usually are asymptomatic, but some may experience recurrent pneumonia, chronic bronchitis, or bronchiectasis. It is very rare for a malignant tumor to grow from this aberrant bronchus. There are only four cases of lung cancer developing from the tracheal bronchus reported in the world literature, and we present a fifth case.

A clinical review with an analysis of prognostic factors, including clinical characteristics, histological classifications, presenting symptoms/signs and treatment modalities, was conducted in 67 patients with primary malignant neoplasms of the trachea who were seen at the Veterans General Hospital-Taipei between 1979 and 1994. The incidence of tracheal cancer was 140 times less than lung cancer during this period. Delayed diagnosis of more than 6 months after onset of symptoms occurred in one-third of the patients owing to lack of specific symptoms/signs indicative of tracheal disease. Epidermoid carcinoma was the most frequent histological type encountered and accounted for half of the cases. Surgical resection was the first choice of treatment for all patients if the disease was locally confined, except for small cell carcinoma and lymphoma. Radiotherapy was given if the patient was not suitable for surgery. Single and multivariate analyses showed that clinical symptoms and signs were not related to prognosis, except for general malaise and acute respiratory failure. Patients suffering from adenoid cystic carcinoma and mucoepidermoid carcinoma had a better prognosis than other histological diagnoses. Whether the patient received radiotherapy or not proved to be a significant prognostic factor in the patients. Patients with tracheal cancers had a poorer prognosis than those with lung cancer.