Development of Disseminated Tuberculosis with Intestinal Involvement due to Adalimumab Administration Despite Latent Tuberculosis Treatment.

Treatment of latent tuberculosis infection (LTBI) reduces the probability of reactivation of tuberculosis associated with anti-tumor necrosis factor (TNF) α inhibitors, but no chemoprophylaxis is completely protective. We herein report a woman with rheumatoid arthritis who developed disseminated tuberculosis with intestinal involvement during adalimumab administration despite LTBI treatment. Tuberculosis reactivation was not detected in sputum or urine but was detected from the terminal ileal mucosa. Detection of intestinal tuberculosis is rare in patients being treated with anti-TNFα therapy after LTBI treatment. As anti-TNFα inhibitors have become more common, the rate of reactivation of tuberculosis, including intestinal tuberculosis, has increased in patients being treated for LTBI.

[Basaloid Squamous Cell Carcinoma;Report of a Case].

We report a resected case of basaloid squamous cell carcinoma (BSC). BSC is a rare type of malignant lung tumor. A 79-year-old woman had a 13 mm tumor in the left upper lobe on chest computed tomography (CT). On fluorodeoxyglucose-position emission tomography (FDG-PET), the tumor showed the accumulation of FDG with an SUVmax of 14.7. A left upper lobectomy with lymph node dissection was performed by video-assisted thoracoscopic surgery. The pathological diagnosis was BSC (pT2aN0M0, stage IB). There was no recurrence following lung cancer resection for 12 months. BSC is generally poor prognosis.

[Fetal Adenocarcinoma of the Lung].

We report a resected case of fetal adenocarcinoma. Fetal adenocarcinoma is a rare type of malignant lung tumor. A 53-year-old man had a 25 mm tumor in the right upper lobe on chest computed tomography. On fluorodeoxyglucose-positron emission tomography( FDG-PET), the tumor showed the accumulation of FDG with a standardized uptake value( SUV) max of 5.63. He underwent bronchoscopic examination, but a diagnosis was not established. We suspected that the tumor was primary lung cancer or metastatic lung tumor of rectal cancer which was resected prior to the treatment for pulmonary lesion. A right upper lobectomy with lymph node dissection was performed and the pathological diagnosis was high-grade fetal adenocarcinoma, stage IB (pT2aN0M0). The patient was treated with postoperative adjuvant chemotherapy. There has been no recurrence after surgery resection for 9 months.

Pemetrexed monotherapy for chemo-naïve elderly (aged ≥80) patients with non-squamous non-small cell lung cancer: results from combined analysis of two single arm phase II studies (HANSHIN002 and 003).

PURPOSE: The aim of this retrospective study was to evaluate via combined analysis the efficacy and safety of pemetrexed monotherapy for chemo-naïve elderly patients aged ≥80 with non-squamous non-small cell lung cancer (NSCLC). METHODS: We conducted a combined analysis from two phase II studies of pemetrexed for chemo-naïve elderly (aged ≥75) (n = 47) and performance status 2 (n = 28) patients with advanced non-squamous NSCLC. Population aged ≥80 (80+ Group) was compared to those aged 70-79 (70's Group). RESULTS: We analyzed a total of 66 patients (37 70s and 29 80+ Groups) after exclusion of 4 ineligible and 5 aged ≤69 patients. Overall response rate, disease control rate, median progression-free survival, and median overall survival of 70s vs. 80+ Groups were 13.5 vs. 13.8% [p = not significant (NS)], 67.6 vs. 58.6% (p = 0.608), 3.7 months vs. 4.2 months (p = 0.5588) and 18.5 vs. 13.5 months (p = 0.2621), respectively. Non-hematological and hematological toxicities ≥grade 3 of 70s vs. 80+ Groups were 24 vs. 35% (p = 0.4192) and 49 vs. 52% (p = NS), respectively. Dose reduction and/or delay due to toxicities of 70s vs. 80+ Groups was 19 vs. 28% (p = 0.7784). Febrile neutropenia and interstitial lung disease were not observed. Treatment-related death (bacterial pneumonia) was confirmed in one (3%) of 29 80+ Group patients. CONCLUSIONS: Pemetrexed monotherapy demonstrated similar efficacy and safety between aged ≥80 and aged 70-79 populations. It could be a therapeutic option in clinical practice for elderly non-squamous NSCLC patients aged ≥80 without indications of carboplatin-based combination regimens or docetaxel monotherapy.

Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases.

AIM: The aim of the present study was to investigate the prognostic impact of central nervous system metastases (CNS) after acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in EGFR-mutant non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We defined CNS-collapse as death due to uncontrolled and progressive CNS metastases. Post-progression survival (PPS) after initial TKI failure and T790M status were retrospectively compared in 92 patients with or without CNS collapse. RESULTS: The median PPS in 32 patients with CNS-collapse (16.7 months) was significantly shorter than that of 60 without (26.8 months) (p=0.0002). T790M was detected in four (12%) out of the 32 CNS-collapse patients and in 26 (43%) out of 60 without (p=0.0026). Median PPS in 39 patients with leptomeningeal metastases (LM) (11.4 months) was significantly shorter versus 53 without (26.8 months) (p=0.0006). The median PPS was 25.1 months in 40 patients with brain metastases and 11.2 months in 52 without (p=0.0387). T790M was detected in 4/5 resected brain tumors (80%) and in 1/26 cerebrospinal fluid (CSF) samples (4%) (p=0.0008). CONCLUSION: CNS-collapse represented poorer prognosis, which was associated with T790M-negative status and LM. Controlling CNS metastases, especially LM, is important to achieve longer survival.

Bevacizumab plus weekly paclitaxel with or without carboplatin for previously-treated non-squamous non-small cell lung cancer.

AIM: The aim of this retrospective study was to evaluate bevacizumab combined with weekly paclitaxel with and without carboplatin in pre-treated patients with non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Between November 2009 and October 2011, 43 pre-treated patients with non-squamous NSCLC received bevacizumab (15 mg/kg, day 1) plus weekly paclitaxel (60-80 mg/m(2), days 1, 8, 15) with carboplatin (area under the curve=4-5, day 1) (n=36), or bevacizumab plus weekly paclitaxel (n=7) alone every four weeks. RESULTS: The response rate and disease control rates were 48.8% (21/43) and 86.0% (37/43), respectively. Median progression-free survival was 5.7 months, and overall survival was 14.5 months. Grade 3/4 neutropenia was observed in 37.2% of patients and peripheral neurotoxicity in 0%. No bevacizumab-related death was observed. CONCLUSION: Even for heavily pre-treated patients, bevacizumab plus weekly paclitaxel with or without carboplatin was effective and tolerable in non-squamous NSCLC.

Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: Comparison between T790M mutation-positive and mutation-negative populations.

BACKGROUND: The secondary epidermal growth factor receptor (EGFR) mutation Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Recent reports have demonstrated that the emergence of T790M predicts a favorable prognosis and indolent progression. However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M mutation. METHODS: The study investigated 78 EGFR-mutant patients who had undergone rebiopsy after TKI failure. The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used in EGFR mutational analyses. Various patient characteristics and postprogression survivals (PPSs) after initial TKI failure were retrospectively compared in patients with and without T790M. RESULTS: The T790M mutation was identified in 4 (17%) of 24 central nervous system lesions, and in 22 (41%) of 54 other lesions (P = .0417). No other characteristics had a statistical association with T790M prevalence. Median PPS was 31.4 months in 26 patients with T790M, and 11.4 months in 52 patients without T790M (P = .0017). In the multivariate analysis, statistically significant factors for longer PPS included T790M-positive, good performance status, and no carcinomatous meningitis. CONCLUSIONS: The emergence of T790M in central nervous system lesions was rare, compared with other lesions. Patients with T790M after TKI failure appear to have better prognoses than those without T790M. TKI rechallenge or continuous administration beyond progression may be effective after initial TKI failure.

Cytokeratin 19 fragment predicts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor in non-small-cell lung cancer harboring EGFR mutation.

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.

Preexisting interstitial lung disease is inversely correlated to tumor epidermal growth factor receptor mutation in patients with lung adenocarcinoma.

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.