BACKGROUND:We investigated the risk of central nervous system (CNS) failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in Korean patients with nonsmall-cell lung cancer (NSCLC) METHODS: We retrospectively evaluated the pattern of disease progression of 287 advanced NSCLC patients who were treated with gefitinib or erlotinib. Patients whose best tumor response was complete response, partial response, or stable disease (90 days) were classified into the group receiving clinical benefit with these drugs. RESULTS: The clinical benefit group had a higher incidence of CNS failure as an initial progression, compared with the non-clinical benefit group (26% vs 4%; P < .001). Isolated CNS failure was also more frequent in the clinical benefit group than in the non-clinical benefit group (13% vs 1%; P < .001). In a multivariate analysis, clinical benefit with EGFR-TKIs significantly increased the risk of isolated CNS failure, with an adjusted hazard ratio of 10.9 (95% confidence interval [CI], 1.4-29.1, P ¼ .01). In patients with isolated CNS failure, the median time from initial intracranial failure to extracranial failure was 9.9 months (95% CI, 1.9-21.9 months) and to death was 12.9 months (95% CI, 3.3-22.5 months). CONCLUSIONS: The CNS was frequently the initial failure site after clinical benefit with EGFR-TKIs in Korean NSCLC patients. Patients with isolated CNS failure showed durable extracranial control after cranial progression. A role for close surveillance of the CNS during EGFR-TKI treatment or prophylactic measures appears worthy of further study in these patients. Cancer 2010;116:1336-43.

BackgroundInterferon-γ release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory.MethodsWe conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009.ResultsOf 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (κ = 0.38), but moderate agreement was observed for the immunocompetent group (κ = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia.ConclusionIn immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.

Purpose: We investigated the prognostic effect of incorporating metabolic assessment by 18 F-fluoro-2-deoxyglucose uptake on positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) into a conventional staging system in small-cell lung cancer (SCLC). Experimental Design: Seventy-six consecutive patients with pathologically proven SCLC were enrolled. All patients underwent standard treatment after pretreatment Results: Patients with high meanSUV max were significantly related with the established poor prognostic factors, such as higher lactate dehydrogenase (P = 0.04) and extensive disease (ED; P = 0.01). Furthermore, in multivariate analysis, patients with high meanSUV max were associated with poor survival outcomes compared with patients with low meanSUV max [adjusted hazard ratio, 3.74; 95% confidence interval (95% CI), 1.67-8.37; P = 0.001, for death and adjusted hazard ratio, 2.25; 95% CI, 1.21-4.17; P = 0.01for recurrence/progression]. In subgroup analysis, limited disease (LD) with high meanSUV max showed significantly shorter overall survival than LD with low meanSUV max [high versus low meanSUV max , 20.1 months (95% CI, 7.9-23.2) versus 35.3 months (95% CI, 27.6-42.9); P = 0.02]. ED with high meanSUV max had significantly shorter overall survival than ED with low meanSUV max [high versus low meanSUV max , 9.5 months (95% CI, 4.9-13.9) versus 17.7 months (95% CI, 12.0-20.1); P = 0.007]. These findings were replicated in progression-free survival analysis. Conclusions: In SCLC, tumor metabolic activity as assessed by FDG-PET is a significant prognostic factor and identifies subgroups of patients at higher risk of death in both LD and ED SCLC.

Activating mutations within the EGFR TK domain can be used to predict the risk of recurrence in curatively resected pulmonary adenocarcinoma.

For specimens such as pleural effusion, in which the bacillary load is very low, the clinical utility of PCR testing seems highly limited.

This study compared the results of a tuberculin skin test (TST) and a whole-blood interferon-gamma release assay (IGRA) to screen latent tuberculosis (TB) infection (LTBI) according to risk of TB exposure in South Korea. A cross-sectional comparison of 82 healthcare workers (HCWs) was performed from June 2009 to January 2010. Participants were grouped according to their risk for TB exposure: group 1, frequent and direct contact with active TB patients (n = 35); group 2, no known history of direct contact with active TB patients (n = 47). For the TST (10-mm induration cut-off), the positive response rate was 42.9% in group 1 and 34.0% in group 2 (p = 0.42). For the IGRA, the positive response rate was 40% in group 1 and 10.6% in group 2 (p = 0.002). Results obtained from the TST and the IGRA were not in significant agreement. The working duration of HCWs in TB-related departments was the only significant risk factor for LTBI (odds ratio 1.03; p = 0.031). Further, the IGRA can more accurately discriminate LTBI compared to the TST, based on the risk of TB exposure. These results suggest that the IGRA is diagnostically useful for LTBI in South Korean HCWs.

Human papillomavirus (HPV) infection is a co-carcinogen of lung cancer and contributes to its pathogenesis. To evaluate the prevalence of HPV infection, polymerase chain reaction (PCR) was employed to detect HPV 16, 18, and 33 DNA in tumor tissues of 112 patients with non-small cell lung cancer (NSCLC) who underwent curative surgery from Jan. 1995 to Dec. 1998 at Severance Hospital, Seoul, Korea. The patients consisted of 90 men and 22 women. Nineteen patients were under 50 years old (17%), and 92 patients (82%) were smokers. Fifty-three patients had adenocarcinomas, while 59 patients had non-adenocarcinomas. Early stage (I and II) cancer was found in 64 patients (57.1%) and advanced stage (III and IV) found in 48 (42.9%). The prevalence of HPV 16, 18, and 33 were 12 (10.7%), 11 (9.8%), and 37 (33.0%), respectively. Smoking status, sex, and histologic type were not statistically different in the presence of HPV DNA. The presence of HPV 16 was more common in younger patients and HPV 18 was more common in advanced stage patients. This study showed that the prevalence rate of HPV 16 and 18 infections in NSCLC tissue was low, suggesting HPV 16 and 18 infections played a limited role in lung carcinogenesis of Koreans. However, the higher prevalence of HPV 33 infections in Korean lung cancer patients compared to other Asian and Western countries may be important and warrants further investigation.