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Kosuke Tanaka,
Akito Hata,
Reiko Kaji,
Shiro Fujita,
Takehiro Otoshi,
Daichi Fujimoto,
Takahisa Kawamura,
Koji Tamai,
Jumpei Takeshita,
Takeshi Matsumoto,
Kazuya Monden,
Kazuma Nagata,
Kyoko Otsuka,
Atsushi Nakagawa,
Ryo Tachikawa,
Kojiro Otsuka,
Keisuke Tomii,
Nobuyuki Katakami
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ABSTRACT: BACKGROUND:: EGFR gene mutation is independently associated with a favorable response in non-small-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs), regardless of sex or smoking history. Squamous cell carcinoma patients harboring EGFR mutations show a significantly worse response to EGFR-TKIs compared with adenocarcinoma patients. We hypothesized that the serum cytokeratin 19 fragment (CYFRA 21-1) is associated with the efficacy of EGFR-TKIs in EGFR-mutated NSCLC patients. METHODS:: We retrospectively screened 160 NSCLC patients harboring EGFR mutations, who had received either gefitinib, or erlotinib between 1992 and 2011. Patients were screened for clinical characteristics, the efficacy of EGFR-TKI, and tumor markers (carcinoembryonic antigen [CEA]/CYFRA 21-1) at the initial diagnosis. RESULTS:: Of 160 eligible patients treated with EGFR-TKIs, 77 patients with high CYFRA 21-1 level (>2 ng/ml) showed significantly shorter progression-free survival (PFS) than the 83 patients with normal CYFRA 21-1 level (median PFS, 7.5 versus 13.3 months; p < 0.001). No significant difference in PFS was observed between the high-CEA group (>5 ng/ml) and the normal-CEA group (median PFS, 8.6 versus 11.2 months; p = 0.242). A multivariate analysis revealed that high CYFRA 21-1 level is independently associated with PFS (hazard ratio, 1.27; p = 0.002). No significant difference in overall survival was observed between the high- and the normal-CYFRA 21-1 groups (median overall survival, 24.8 versus 39.1 months; p = 0.104). CONCLUSIONS:: Patients with a high CYFRA 21-1 level have significantly shorter PFS. CYFRA 21-1 is not a prognostic but a predictive marker of EGFR-TKI treatment in EGFR-mutated NSCLC patients.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2013; · 4.55 Impact Factor
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Daichi Fujimoto,
Keisuke Tomii,
Takehiro Otoshi,
Takahisa Kawamura,
Koji Tamai,
Junpei Takeshita, Kosuke Tanaka,
Takeshi Matsumoto,
Kazuya Monden,
Kazuma Nagata,
Kyoko Otsuka,
Atsushi Nakagawa,
Akito Hata,
Ryo Tachikawa,
Kojiro Otsuka,
Hiroshi Hamakawa,
Nobuyuki Katakami,
Yutaka Takahashi,
Yukihiro Imai
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ABSTRACT: INTRODUCTION: Interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis, has been shown to be associated with lung carcinogenesis. However, an association between epidermal growth factor receptor (EGFR) mutation status and preexisting ILD in patients with lung adenocarcinoma is unknown. METHODS: Between January 2008 and April 2012, we analyzed 602 patients with lung adenocarcinoma. EGFR mutation status was analyzed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, and preexisting ILD was diagnosed based on clinical features, chest high-resolution computed tomography (HRCT) findings, and histological findings. RESULTS: There were 555 patients with pulmonary adenocarcinoma with tumor EGFR mutation data available for analysis. Of them, 31 patients (6%) had preexisting ILD, and EGFR mutations were detected in 246 of the 555 patients (46%). In the comparison between patients with EGFR mutations and those with wild-type EGFR, there was a significant inverse association between occurrence of tumors with EGFR mutations and ILD (1/246 vs. 30/309, P<0.001). Based on the multivariate analysis of age, gender, smoking status, Eastern Cooperative Oncology Group Performance Status, stage, and ILD, EGFR mutations were found to be independently associated with females (OR, 1.58; 95% CI, 1.01-2.46; P=0.048), never-smokers (OR, 3.31; 95% CI, 2.12-5.20; P<0.001), and the absence of ILD (OR, 17.41; 95% CI, 3.54-315.34; P<0.001). CONCLUSIONS: This study showed that patients with pulmonary adenocarcinoma and ILD had a lower probability of carrying tumor EGFR mutations.
Lung cancer (Amsterdam, Netherlands) 02/2013; · 3.14 Impact Factor
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Kazuma Nagata,
Keisuke Tomii,
Kojiro Otsuka,
Ryo Tachikawa,
Atsushi Nakagawa,
Kyoko Otsuka,
Junpei Takeshita, Kosuke Tanaka,
Takeshi Matsumoto,
Kazuya Monden,
Takahisa Kawamura,
Koji Tamai
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ABSTRACT: SUMMARY AT A GLANCEY: The purpose of this study was to evaluate the diagnostic and prognostic role of serum procalcitonin in patients with acute exacerbation of interstitial pneumonia. We found that serum procalcitonin was a useful marker in discriminating from bacterial pneumonia. However, serum procalcitonin was not useful as a prognostic marker. ABSTRACT: Background and objective: Acute exacerbation of interstitial pneumonia (AE-IP) is defined as a life-threatening deterioration of IP without identifiable cause. We evaluated the diagnostic and prognostic role of serum procalcitonin (PCT) in AE-IP. Methods: Twenty consecutive patients admitted for AE-IP between May 2010 and April 2012 were evaluated. Controls consisted of 13 consecutively admitted patients with Acute Respiratory Distress Syndrome due to bacterial pneumonia (BP-ARDS), and 24 with bacterial pneumonia with stable IP ('BP with IP'). Serum PCT was measured at baseline, day 2, 4, and 8 in patients with AE-IP, and at baseline in controls. Results: Serum PCT levels in AE-IP were significantly lower than in BP-ARDS (mean±SD, 0.62±1.30-versus-30.14±22.76 ng/ml; p<0.0001) or 'BP with IP' (mean±SD, 0.62±1.30-versus-8.31±14.83 ng/ml; p<0.05). Thus, serum PCT discriminated well between AE-IP and BP-ARDS or 'BP with IP' (area under the curve 0.99 and 0.85, respectively). However, there were no significant differences in serum PCT between 30-day survivors or non-survivors. Serum PCT tended to be reduced in both patient groups. Conclusions: Serum PCT is a useful marker for discriminating between AE-IP and bacterial pneumonia. However, serum PCT is not useful as a prognostic marker for survival. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.
Respirology 11/2012; · 2.42 Impact Factor
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ABSTRACT: The 2008 American Thoracic Society Project concluded that idiopathic nonspecific interstitial pneumonia (NSIP), once regarded as a "provisional" diagnosis, can be considered a distinct clinical entity. However, an increasing number of recent reports have shown a likely link between the entity of idiopathic NSIP and autoimmune diseases. Similarly, IgG4-related disease is being increasingly reported, and some of the lung lesions, at least radiologically, look like NSIP. A case of IgG4-related interstitial lung disease without other systemic manifestations of IgG4-related disease is reported. The existence of IgG4-related disease should, therefore, be taken into consideration as a possible differential diagnosis from NSIP. The cause of IgG4-related disease remains unknown, but we emphasize the importance of a clinically novel interstitial lung disease.
Chest 07/2012; 142(1):228-30. · 5.25 Impact Factor
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ABSTRACT: A well-validated instrument that is simple to use is needed to assess health-related quality of life in patients with interstitial lung disease (ILD). The COPD assessment test (CAT) is a recently introduced, short and simple questionnaire for COPD patients, which shows good and valid measurement properties. This study was conducted to evaluate the validity of the CAT in patients with ILD.
Patients with ILD (n = 55) completed the CAT and the St. George's Respiratory Questionnaire (SGRQ). These patients also completed the Medical Research Council (MRC) dyspnoea scale, the Leicester Cough Questionnaire (LCQ), and the hospital anxiety and depression scale; performed 6-min walk tests and pulmonary function tests; and provided samples for arterial blood gas analysis.
There was a very strong correlation between the CAT score and the SGRQ total score (r = 0.93, P < 0.0001). The CAT score was also significantly correlated with the SGRQ symptoms score (r = 0.74, P < 0.0001), the SGRQ activity score (r = 0.87, P < 0.0001) and the SGRQ impact score (r = 0.89, P < 0.0001). Stepwise multiple regression analysis demonstrated that the MRC and LCQ scores contributed most to both the CAT score and the SGRQ total score.
The CAT is a short and simple questionnaire that shows good and valid measurement properties for assessing the health status of patients with ILD.
Respirology 01/2012; 17(3):506-12. · 2.42 Impact Factor
