Non-small cell lung cancer in the very young: Higher EGFR/ALK mutation proportion than the elder.

BACKGROUND: This study aimed to analyze pathologic characteristics, treatment, prognosis, and tumor epidermal growth factor receptor/anaplastic large-cell lymphoma kinase (EGFR/ALK) mutation proportion of non-small cell lung cancer (NSCLC) patients aged <40 years at diagnosis. METHODS: We retrospectively reviewed data of NSCLC patients diagnosed at Taipei Veterans General Hospital between June 2007 and December 2014, aged <90 years at the time of the diagnosis. RESULTS: We found 5051 cases of NSCLC, including 168 patients who were <40 years (younger group) and 4883 patients aged 40 to 89 years (older group). We found that the younger group had a significantly higher proportion of the EGFR mutation (22.6% vs 16.2%, p = 0.026) and the ALK mutation (4.2% vs 0.5%, p < 0.001) than the older group. Although the younger group included more stage IV patients (60.1% vs 49.6%, p = 0.002), it had a better overall survival (OS) rate (1 year: 73.7% vs 66.2%, p = 0.043; 5 years: 44.4% vs 33.7%, p = 0.004) (median survival time: 55 vs 26 months, p = 0.002). About the histologic subtype of NSCLC, the younger group presented less frequent cases of squamous cell carcinoma (4.2% vs 16.1%, p < 0.001), whereas the adenocarcinoma subtype was similarly frequent in the two groups (76.8% vs 76.5%, p = 0.924). CONCLUSION: The OS rate in younger NSCLC patients was higher than that in the older NSCLC patients, despite the higher rate of stage IV NSCLC patients in the younger group. This survival benefit is most likely due to the higher proportion of the EGFR and ALK mutations and the corresponding tyrosine kinase inhibitor treatment.

Erlotinib Salvage Therapy in Pulmonary Adenocarcinoma Patients With Disease Progression After Previous EGFR-TKI Treatment.

BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with promising efficacy in treating pulmonary adenocarcinoma. Treatment choices are few when patients with pulmonary adenocarcinoma have failed both EGFR-TKI and chemotherapy. The purpose of this study was to demonstrate the efficacy of erlotinib as salvage treatment for these nonresponsive patients. METHODS: We retrospectively reviewed the chart records of our stage IV pulmonary adenocarcinoma patients who were diagnosed and treated between July 2004 and June 2013. Clinical data, including type of response to treatment, time to disease progression, duration between the end of first-line EGFR-TKI treatment and starting erlotinib treatment, and overall survival time, were collected. RESULTS: A total of 98 patients were enrolled, and all had been treated with EGFR-TKI, either as a first-line therapy or following platinum-based chemotherapy; of them, 60 patients had a response to initial EGFR-TKI treatment. All received erlotinib as salvage treatment after their disease had progressed following EGFR-TKI treatment. Ninety-three (93.3%) patients had also received previous platinum-based chemotherapy. The median progression-free survival with erlotinib as salvage treatment for patients with and without a response to front-line EGFR-TKI was 4.9 and 3.4 months (P=0.869), respectively. The progression-free survival with erlotinib treatment in the sensitizing EGFR mutation group was 4.3 months, and in the EGFR wild-type group it was 2.6 months (P=0.22). CONCLUSIONS: In pulmonary adenocarcinoma patients who had been heavily treated, erlotinib could still be a choice, regardless of the EGFR mutation status, or whether the patients had responded to previous EGFR-TKI treatment.

Amyloidosis and the risk of cancer: a nationwide population-based study.

BACKGROUND: The association between amyloidosis and cancer remains unclear. PARTICIPANTS AND METHODS: Using the Taiwan National Health Insurance Research Database we conducted a population-based cohort study. Patients newly diagnosed with amyloidosis between 1997 and 2009 were enrolled. Patients with antecedent cancer were excluded. Standardized incidence ratios (SIR) of cancers were calculated for the study cohort and compared with cancer incidence among the general population. We used a multivariate Cox regression model to evaluate the predictors of cancer development for patients with amyloidosis. RESULTS: The study included 1,693 subjects with median follow-up of 5.63 years. A total of 68 patients developed cancer. The incidence of kidney cancer (SIR 3.42; 95 % CI 1.11-7.97; p = 0.034) and hematologic malignancies (SIR 3.88; 95 % CI 1.86-7.14; p < 0.001) were significantly higher for patients with amyloidosis. CONCLUSION: This is currently the largest study to evaluate cancer risk among patients with amyloidosis. The results indicate that amyloidosis may be associated with an increased risk of kidney cancer and hematologic malignancies.

The association between tumor epidermal growth factor receptor (EGFR) mutation and multiple primary malignancies in patients with adenocarcinoma of the lungs.

OBJECTIVES: An increased incidence of multiple primary malignancies has been found in recent decades. However, the nature of the association between the epidermal growth factor receptor (EGFR) mutation status and multiple primary malignancies in patients with adenocarcinoma of the lungs is not clearly understood at this time. METHODS: We retrospectively reviewed the data of our patients with adenocarcinoma of the lungs, and evaluated the association between the tumor EGFR mutation status and multiple primary malignancies. RESULTS: From December 2008 to November 2011, 655 pulmonary adenocarcinoma patients with tumor EGFR mutation data were available for analysis. Of them, 359 had EGFR mutations (including 336 classic EGFR mutations), 63 had double primary malignancies, and 7 had triple primary malignancies. Patients with classic EGFR mutations had a higher incidence of multiple primary malignancies than those without (P=0.042). Multiple primary malignancies occurred more frequently in patients with exon 19 mutations (including insertions, point mutations, or deletions) or exon 19 deletions than in patients without (P=0.037 and 0.032, respectively). Patients with any EGFR mutations or classic EGFR mutations survived longer than those who did not (P<0.001 and <0.001, respectively). Patients with multiple primary malignancies survived for a longer period than those without (P=0.006). CONCLUSIONS: Multiple primary malignancies occurred more frequently in patients with classic EGFR mutations, especially those with exon 19 deletions.

Latent TB infection in newly diagnosed lung cancer patients - A multicenter prospective observational study.

OBJECTIVES: Lung cancer and tuberculosis (TB) share common risk factors and are associated with high morbidity and mortality. Coexistence of lung cancer and TB were reported in previous studies, with uncertain pathogenesis. The association between lung cancer and latent TB infection (LTBI) remains to be explored. METHODS: Newly diagnosed, treatment-naïve lung cancer patients were prospectively enrolled from four referral medical centers in Taiwan. The presence of LTBI was determined by QuantiFERON-TB Gold In-Tube (QFT-GIT). Demographic characteristics and cancer-related factors associated with LTBI were investigated. The survival status was also analyzed according to the status of LTBI. RESULTS: A total of 340 lung cancer patients were enrolled, including 96 (28.2%) LTBI, 214 (62.9%) non-LTBI, and 30 (8.8%) QFT-GIT results-indeterminate cases. Non-adenocarcinoma cases had higher proportion of LTBI than those of adenocarcinoma, especially in patients with younger age. In multivariate analysis, COPD (OR 2.41, 95% CI 1.25-4.64), fibrocalcified lesions on chest radiogram (OR 2.73, 95% CI 1.45-5.11), and main tumor located in typical TB areas (OR 2.02, 95% CI 1.15-3.55) were independent clinical predictors for LTBI. Kaplan-Meier survival analysis demonstrated patients with indeterminate QFT-GIT results had significantly higher 1-year all-cause mortality than those with LTBI (p<0.001) and non-LTBI (p=0.003). In multivariate analysis, independent predictors for 1-year all-cause mortality included BMI<18.5 (HR 2.09, 95% CI 1.06-4.14, p=0.033), advanced stage of lung cancer (RR 7.76, 95% CI 1.90-31.78, p=0.004), and indeterminate QFT-GIT results (RR 2.40, 95% CI 1.27-4.54, p=0.007). CONCLUSIONS: More than one-quarter of newly diagnosed lung cancer patients in Taiwan have LTBI. The independent predictors for LTBI include COPD, fibrocalcified lesions on chest radiogram, and main tumor located in typical TB areas. The survival rate is comparable between LTBI and non-LTBI cases. However, indeterminate QFT-GIT result was an independent predictor for all-cause mortality in lung cancer patients.

Erlotinib in patients with advanced lung squamous cell carcinoma.

PURPOSE: Erlotinib had proved efficacy in patients with advanced non-small cell lung cancer, especially adenocarcinoma. The aim of this study was to evaluate the efficacy of erlotinib in patients with advanced lung squamous cell carcinoma (LSQC). METHODS: We retrospectively reviewed medical records and serial chest images of consecutive patients who were diagnosed with advanced LSQC and had been treated with erlotinib monotherapy. The primary objective was to evaluate the treatment efficacy and to correlate with patients' clinical characteristics. RESULTS: Totally 55 patients were analyzed (42 men and 13 women, median age of 71 years). In 37 patients who had measurable lesions, 6 had partial response and 13 had stable disease, yielding an overall response rate of 16.2% and disease control rate of 51.4%. In all patients, the median progression-free survival (PFS) and overall survival (OS) were 2.0 months (95% confidence interval, 1.5-2.4 months) and 10.4 months (95% confidence interval, 0.6-20.2 months), respectively. The PFS and OS were significantly longer in patients who had good clinical response (either the tumor achieved partial response or the patients had disease controlled for more than 6 months) than those who did not (median PFS, 13.0 vs. 1.6 months; median OS, 28.3 vs. 4.9 months; both P values <0.01). Patients who never smoked seemed to have better clinical response and longer survival than those who had smoking history (P = 0.077 and 0.086, respectively). CONCLUSIONS: Erlotinib could provide some clinical benefit to patients with advanced LSQC.

Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an effective treatment for advanced non-small cell lung cancer. The objective of the present study was to compare the efficacy of gefitinib and erlotinib in patients with pulmonary adenocarcinoma, whose tumor EGFR mutation status was known. Pulmonary adenocarcinoma patients who began receiving gefitinib or erlotinib treatment from January 2005 to December 2010, and whose tumor EGFR mutation status had been determined, were included. Clinical data, type of treatment response and survival time data were collected. Of the 224 patients enrolled, 124 received gefitinib treatment and 100 received erlotinib treatment. Of these patients, 146 individuals had tumors with EGFR-activating mutations (exon 19 deletions and/point mutation of L858R in exon 21) and 78 did not. There was no difference in treatment response whether or not the patients had tumors with EGFR-activating mutations at the time they received gefitinib or erlotinib treatment. The median progression-free survival (PFS) of the gefitinib and erlotinib groups was 7.6 and 7.9 months, respectively (p=0.4731). PFS was significantly longer for patients without EGFR-activating mutations who received erlotinib treatment (n=48; median, 4.5 months) than for those who received gefitinib treatment (n=30; median, 2.3 months), with a hazard ratio of 0.58 (95% CI, 0.35-0.96; p=0.0339). Patients whose tumors had EGFR-activating mutations displayed no difference in PFS with either gefitinib (n=94; median, 10.5 months) or erlotinib treatment (n=52; median, 10.4 months). In conclusion, PFS showed no difference with either agent in patients whose tumors had EGFR-activating mutations, but was significantly longer in patients whose tumors did not have EGFR-activating mutations when receiving erlotinib treatment.

Middle lobe syndrome as the pulmonary manifestation of primary Sjögren's syndrome.

Middle lobe syndrome - recurrent atelectasis and/or bronchiectasis involving the right middle lobe and/or lingula - has, up to now, not been reported as the pulmonary manifestation of primary Sjögren's syndrome. We describe a patient in whom lymphocytic bronchiolitis in the atelectatic lobes was proved histologically from two separate transbronchial biopsies. The atelectasis responded well to glucocorticoid treatment, suggesting that the peribronchiolar lymphocytic infiltrates may have played an important role in the development of middle lobe syndrome in this patient.

Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis.

Antituberculosis drug-induced hepatitis is one of the most prevalent drug-induced liver injuries. Isoniazid is the major drug incriminated in this hepatotoxicity. Isoniazid is mainly metabolized to hepatotoxic intermediates by N-acetyltransferase (NAT). However, the association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is debatable. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2 in 224 incident tuberculosis patients who received antituberculosis treatment. Antituberculosis drug-induced hepatitis was diagnosed based on a positive isoniazid rechallenge test and exclusion of viral hepatitis. Acetylator status was determined by genotyping NAT2 in patients using a polymerase chain reaction with restriction fragment length polymorphism. Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. Thirty-three patients (14.7%) were diagnosed with antituberculosis drug-induced hepatitis. Slow acetylators had a higher risk of hepatotoxicity than rapid acetylators (26.4% vs. 11.1%, P =.013). Among patients with hepatotoxicity, slow acetylators had significantly higher serum aminotransferase levels than rapid acetylators. Logistic regression showed that slow-acetylator status (odds ratio [OR], 3.66; 95% CI, 1.58-8.49; P =.003) and age (OR, 1.09; 95% CI, 1.04-1.14; P <.001) were the only 2 independent risk factors for antituberculosis drug-induced hepatitis. In conclusion, slow-acetylator status of NAT2 is a significant susceptibility risk factor for antituberculosis drug-induced hepatitis. Additionally, slow acetylators are prone to develop more severe hepatotoxicity than rapid acetylators. Regular monitoring of serum aminotransferase levels is mandatory in patients receiving antituberculosis treatment, especially in slow acetylators.