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Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). In addition, in EU countries, nintedanib plus docetaxel is used for patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. Here, we report a case of advanced NSCLC in a patient with IPF successfully treated with nintedanib monotherapy. A 69-year-old man was diagnosed with NSCLC complicated by IPF. After three lines of chemotherapy, he still had progressive disease. Because his IPF had also progressed, requiring supplemental oxygen, we decided to start best supportive care and introduced nintedanib to treat his IPF. One month later, we observed a partial remission of the primary tumor and pleural disseminations without severe adverse events. Nintedanib monotherapy might therefore be an effective therapeutic choice for NSCLC in patients with IPF who are unable to tolerate cytotoxic chemotherapy. KEY POINTS: Efficacy of nintedanib administered in a NSCLC patient with IPF. Nintedanib monotherapy might be a therapeutic option for NSCLC patients with IPF who are unable to tolerate chemotherapy.

Objective Procalcitonin (PCT) has received much attention as a serum marker for bacterial infection. Elevated serum PCT is occasionally seen in severe trauma, heatstroke, and neoplastic diseases, including lung cancer with neuroendocrine component. Results In the present study, we evaluated PCT expression in the specimen of pulmonary neuroendocrine tumors, comparing large cell neuroendocrine carcinoma (LCNEC), carcinoid, and small cell lung carcinoma (SCLC). Pathological specimens of 10 LCNEC, 4 carcinoid, and 7 SCLC cases were evaluated with immunochemical staining of PCT. Clinical characteristics and serum levels of PCT and C-reactive protein were also evaluated. We observed positive PCT expression in 5 (50%) LCNEC and 2 (50%) carcinoid specimens that were surgically resected. Whereas serum PCT levels were not elevated in patients with PCT-positive carcinoid, two out of three LCNEC patients with high PCT expression in the tumor had elevated serum PCT levels that reflected disease progression. In patients with SCLC, PCT was not detected in the tumor or serum. This is the first immunohistochemical study of the PCT expression in the lung tumor specimens. We concluded that, in patients with LCNEC, high serum PCT levels may be indicative of disease activity and serve as a biomarker.

Background We examined cross-sectional associations between depression and both inflammatory markers and fractional exhaled nitric oxide (FeNO). Methods This cross-sectional study is a secondary analysis of the data of the Iwaki Health Promotion Project 2016 (1,148 subjects). We analyzed the subjects' characteristics and laboratory data including plasma interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and FeNO. The subjects with Center for Epidemiologic Studies Depression Scale scores ≥16 were assigned to the depression group. We performed a multivariate logistic regression analysis to determine whether inflammatory markers and FeNO were associated with depression. Results We assessed 1,099 subjects (430 males, 669 females). The depression group was 237 subjects (21.5%) [84 males (19.5%), 153 females (22.9%)]. The non-depression group was 862 subjects (346 males and 516 females). There were no significant differences in IL-6, hs-CRP, or FeNO between both groups. However, the multivariate logistic regression analysis indicated that lower FeNO was significantly associated with depression in males after adjusting for possible confounding factors (age, BMI, comorbidities, high-sensitivity troponin T, FEV1%, asthma, antidepressant use, smoker and alcohol drinker) (per 1 bpm increase, OR: 0.982; 95%CI: 0.967–0.998; p = 0.032). Conclusion Our findings indicate that lower FeNO may be associated with depression in males.

We aimed to evaluate the efficacy and safety of nab-paclitaxel in patients with refractory advanced non-small cell lung cancer who failed previous chemotherapy. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0–2 and adequate organ function. Patients received nab-paclitaxel, 100 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks. The primary endpoint was the overall response rate. Secondary endpoints were the progression-free survival time, overall survival, and the toxicity profile. From July 2013 to July 2015, a total of 31 patients were enrolled. Fourteen patients received nab-paclitaxel as a second-line and 17 received it as an over third-line therapy. Each patient received a median of 5 treatment cycles (range, 1–11). The overall response rate was 19.3% (95% confidence interval, 9.1–36.2%) (complete response (n = 0), partial response (n = 6), stable disease (n = 17), and progressive disease (n = 8)). The median progression-free survival time was 4.5 months (95% confidence interval 3.5–6.3 months), median overall survival time was 15.7 months, and 1-year survival rate was 54.8%. Most common grade 3 or 4 non-hematological toxicities were elevated aspartate transaminase level (3.2%) and sensory neuropathy (9.6%). Neutropenia was the most common grade 3 or 4 adverse events (38.6%), and febrile neutropenia developed in 12.9% patients. No treatment-related deaths were observed in this study. Primary endpoint was met. Single agent nab-paclitaxel showed significant clinical efficacy and manageable toxicities for patients with chemorefractory advanced non-small cell lung cancer even if late line setting. UMIN000011696 . The date of registration was July 11th, 2013.

Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for mutant non-small cell lung cancer (NSCLC), was approved in Japan in 2014. This study evaluated clinical outcomes of afatinib in real-world practice. Medical records of patients who received afatinib for advanced EGFR-mutant NSCLC were retrospectively reviewed. In total, 128 patients were analyzed. Seventy-six patients received afatinib as the first-line setting and 52 as the re-challenge setting (i.e., after failure of prior first-generation TKI). There was no difference in patient characteristics, such as age, sex, and PS, between the first-line and the re-challenge settings. In the first-line setting, the median progression-free survival (PFS) was 17.8 months (95% confidence interval [CI] 13.7-21.5 months). The overall survival (OS) was 39.5 months (95% CI 34.4- not reached). The response rate (RR) was 64.4%. Subset analysis indicated that patients with dose reduction showed longer PFS than those without dose reduction (18.5 months versus 7.9 months) (P = 0.016). In the re-challenge setting, the median PFS was 8.0 months (95% CI 4.9-9.5 months). The RR was 25%. Most common adverse events leading to dose modification or treatment discontinuation included diarrhea, paronychia, and oral mucositis in both settings. Interstitial lung disease occurred in 5.4% (7/128). In the real-world practice in Japan, afatinib showed comparable or better efficacy compared with that shown in previous clinical trials in both the first-line and the re-challenge settings.

Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation. Switching to alectinib may be beneficial in patients demonstrating crizotinib-associated complex renal cysts with systemic inflammation and exhaustion.

Background: The INPULSIS trials revealed that nintedanib reduced the decline in lung function in patients with idiopathic pulmonary fibrosis. We aimed to evaluate the efficacy and safety of nintedanib in Japanese idiopathic pulmonary fibrosis patients in real-world settings. Method: Medical records of idiopathic pulmonary fibrosis patients, who received treatment with nintedanib in five institutions between July 2015 and June 2017, were reviewed. Patients with % forced vital capacity ⩾50% and % predicted diffusing capacity of the lung carbon monoxide ⩾30% were classified as the moderate group and those with more impaired lung functions as the severe group. Result: Among 158 patients analyzed, 132 (84.6%) were classified as the moderate group and 26 (15.4%) as the severe group. In the moderate group, changes in forced vital capacity in 12 months were significantly different between before and after nintedanib administration (−253 ± 163 vs −125 ± 235 mL; p = 0.0027). In contrast, changes in forced vital capacity in 12 months were not significantly changed by nintedanib treatment in the severe group (−353 ± 250 vs −112 ± 341 mL; p = 0.2374). Incidence of acute exacerbation was higher in the severe group than in the moderate group (30.8% vs 18.9%). The overall survival of the moderate and the severe groups was 17.2 and 10.1 months. Conclusion: In real-world practice, nintedanib showed comparable efficacy to those observed in previous trials. In the severe group, the efficacy of nintedanib might be limited.

e21078 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced non-small cell lung cell cancer (LA-NSCLC). We previously reported the phase I study of biweekly carboplatin and nab-paclitaxel (nab-PTX) with RT. Recommended dose for phase II study was carboplatin (AUC 4) and nab-PTX (100 mg/m2) (J Clin Oncol 2015 suppl; abstr 7529). Here we report the phase II part designed to assess the efficacy of biweekly carboplatin and nab-PTX with concurrent RT (UMIN000023802). Methods: Patients with inoperable stage Ⅲ NSCLC were treated with carboplatin (AUC 4) and nab-PTX 100 mg/m2 on days 1, 15, and 29. Thoracic radiotherapy was administered from day 1 to a total dose of 60 Gy in 30 fractions. Consolidation chemotherapy after CCRT was 2 cycles of carboplatin (AUC 6) on day 1 and nab-PTX 100 mg/m2 on days 1, 8, and 15. The primary endpoint for the phase II part is 2-year overall survival (OS) rate. Assuming an expected survival rate was 60% and a lower limit was 35% (alfa 0.05, beta 0.2). Secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), OS, and safety profile. Results: A total of 28 patients (median age 66 years, male 94%) were enrolled. Of the evaluable patients (n = 28), the rate of 2-year OS was 67.8% (95% CI: 49.3–82.1). The ORR was 96%, a median follow-up time was 33.2 months. Median PFS was 18.2 months (95% CI 13.1–not reached), and median OS was not reached (95% CI, 25.6–not reached). The most common toxicities of grade 3 or higher were neutropenia (60.5%), anemia (14.2%), thrombocytopenia (7.6%) and pneumonitis (3.6%). Conclusions: This study achieved the primary endpoint. Biweekly carboplatin and nab-PTX with concurrent RT therapy was well tolerated and promising systemic antitumor activity for patients with LA-NSCLC. Clinical trial information: 000023802 .

This phase I trial was conducted to determine the maximum tolerated dose (MTD) and recommended dose of afatinib for phase II trial in elderly patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The study used a standard 3 + 3 dose escalation design. Patients aged 75 years or older with advanced NSCLC harboring EGFR mutations were enrolled. The doses of afatinib, which were given once daily, were planned as follows: level 1, 20 mg/day; level 2, 30 mg/day; level 3, 40 mg/day. Dose-limiting toxicity (DLT) was defined as grade 4 hematologic, persistent grade > 2 diarrhea for > 2 days despite concomitant medications or grade 3 non-hematologic toxicity. DLT was evaluated during day 1-28. Fifteen patients were enrolled. Patient characteristics were: male/female 3/12; median age 79 (range 75-87); PS 0/1, 2/13. Six patients have been treated at levels 1 and 3, and three patients at level 2. At level 1, one of six patients experienced grade 3 rush, grade 3 anorexia, and grade 3 infection as DLTs. At level 2, none of three patients experienced a DLT. At level 3, two patients developed grade 3 diarrhea, one of whom also experienced grade 3 anorexia. Most frequent adverse events of any grade were diarrhea, paronychia, rush, and nausea. Most patients at level 2 and 3 required dose reduction in 3 months. MTD was defined as 40 mg/day, and recommended dose for phase II study in elderly patients was 30 mg/day.

Sarcoidosis is an inflammatory granulomatous disease that is systemic, but bone involvement is uncommon. A 68-year-old man was referred to our hospital complaining of right shoulder pain with numbness. Computed tomography revealed systemic lymphadenopathy and multiple bone lesions. Because malignant lymphoma with a mass lesion protruding into the vertebral canal was considered, he underwent urgent radiotherapy. Thereafter, a needle biopsy of the left parasternal node was performed and showed epithelioid granulomas, confirming a diagnosis of sarcoidosis. Since his neurologic symptoms improved, the patient was not given systemic corticosteroids. Radiotherapy may be useful for local control of bone sarcoidosis.

Immunohistochemical screening of Anaplastic lymphoma kinase (ALK) rearrangement has been regarded essential and routinely carried out to select treatment for lung adenocarcinoma. However, difficulty to approach a tumor by transbronchial lung biopsy (TBLB), it often fails to obtain tumor tissues whereas tumor cells are contained in cytology specimens simultaneously obtained when the bronchoscopy is done. Therefore we evaluated the expression of ALK protein by using immunohistochemistry (IHC) on TBLB specimens and immunocytochemistry (ICC) on brushing smear cytology slides in the same cases, and compared the concordance rate of IHC and ICC results. ICC was carried out on routine Papanicolau-stained slides after cytology diagnosis and decolorization. Results Eighteen patients with adenocarcinoma were extracted in the Hirosaki University Hospital and the Hirosaki National Hospital. IHC and ICC results showed a very high concordance rate: sensitivity of ICC in comparison with IHC was 85.7% (6/7), specificity was 100% (11/11), positive predictive value was 100% (6/6), and negative predictive value was 91.6% (11/12). Detection of ALK rearrangement using ICC on routine Papanicolau cytology slides is considered to be advantageous for lung cancer treatments.

Background We have developed a new bronchoscopy system with two independent lenses at the tip of the device. This enables measurement of object size using the principle of triangulation. This study was performed to assess the accuracy of this system. Methods The accuracy of the bronchoscopy system was confirmed by measuring the diameters of four plastic tubes and 36 airway calibres in 12 surgical patients under general anaesthesia. The measured diameters of the tubes and airway tracts were compared with the manufactured diameters of tubes and those measured by high-resolution computed tomography (HRCT)-based virtual bronchoscopy, respectively. Results Using the new bronchoscope system, tube diameters, 9, 12, 15, and 19 mm, were measured as 9.9 (0.7), 12.8 (1.4), 16.3 (1.6), and 20.1 (2.0) mm, respectively. Airway calibres obtained by a stereovision bronchoscopy and HRCT-based virtual bronchoscopy were 8.66 (4.31) and 9.38 (5.09) mm, respectively. There is a significant correlation between airway calibres with the two measurement methods ( r =0.975, P Conclusions We have confirmed that this new bronchoscopy system could provide relatively accurate quantitative data. This new system may be useful in the clinic to measure airway dimension and lesion sizes such as tumours.

Background: It is important for medical staffs to understand the state of stress of patients with cancer. The authors investigated stress assessment in patients with lung cancer undergoing chemotherapy. Materials and Method: Salivary cortisol and α-amylase were measured as stress markers before and after chemotherapy in 10 patients. Emotional status was assessed using the Profile of Mood States (POMS) questionnaire, and Quality of Life (QOL) was assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire. Results: No significant differences were found between the before and after chemotherapy in salivary levels of cortisol or α-amylase, the POMS and QOL scores. The salivary cortisol levels correlated with the POMS subscales of anger-hostility, and confusion. A negative correlation was observed between the salivary cortisol level and the QOL full score. The FACT-L full score correlated with the POMS subscales of depression-dejection, fatigue, and confusion. Conclusions: Measurements of salivary stress markers are noninvasive and may be useful for assessing the stress state of the patients

Objective: As it is important for medical staff to understand the stress state of patients with cancer, this study investigated the stress state in patients with lung cancer undergoing chemotherapy using salivary biomarkers and questionnaires. Materials and Methods: The subjects included 19 men and 9 women, with a mean age of 66.1 ± 7.1 years who received chemotherapy for lung cancer. Salivary samples of the participants were collected before and the 7 day after chemotherapy. Simultaneously, they completed the POMS (profile of mood states) and QOL (quality of life) questionnaires. The salivary cortisol and secretory IgA as stress markers were measured by enzyme immunoassay. Results: The salivary secretory IgA level was significantly higher at the 7th day after chemotherapy than before chemotherapy (p < 0.05), although the salivary cortisol level did not change. The tension-anxiety score, which is one of POMS subclasses, and total mood disturbance score were lower at day 7 of chemotherapy than before chemotherapy (p < 0.05), although no correlations were observed between POMS scores and salivary markers. However, a negative correlation was observed between the salivary cortisol level and the QOL full score (r= -0.411, p < 0.05). Conclusion: Measurement of salivary stress markers is noninvasive and may be useful for assessing the stress state of the patients.

e21173Background: Afatinib is the second generation epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitor (TKI) for mutant non-small cell lung cancer (NSCLC), and approved in Japan in...

Background: Bronchial asthma (BA) and allergic rhinitis (AR) are thought to share a common pathogenesis. However, reports concerning the comorbidity of the two diseases in a large-scaled population are rare in Japan. In the present study, we performed an analysis on the two diseases using questionnaires that addressed the diagnosis, symptoms and period of occurrence in more than 10,000 patients with BA or AR. Methods: Patients with BA (adult: n = 2,781, childhood: n = 3,283) and AR (n = 3,945) were enrolled in the present study during the 3 months from August 1, 2006 to October 31, 2006. Results: Sixty one percent of the patients with adult BA showed symptoms of AR. Among them, 68% of the patients were diagnosed with AR. Among the patients with childhood BA, 68% showed AR symptoms and 60% were diagnosed with AR. On the other hand, 49% of AR patients showed BA symptoms and 35% of them were diagnosed with BA. The symptoms of both BA and AR in the BA and AR patients were frequent in two seasons, March and April, and September and October. In addition, BA and AR symptoms often co-occurred in the patients with BA and AR. Conclusions: Comorbidity of BA and AR was high in both populations of BA and AR. The symptoms of both BA and AR co-occurred on both a daily and seasonal basis. These results suggested that BA and AR share a common immuno-pathogenesis in the airway and need to be treated as a single airway disease.

Purpose Amrubicin, a new anthracycline agent, and topotecan are both active for previously treated small-cell lung cancer (SCLC). No comparative study of these agents has been reported. This randomized phase II study was conducted to select amrubicin or topotecan for future evaluation. Patients and Methods Patients with SCLC previously treated with platinum-containing chemotherapy were randomly assigned to receive amrubicin (40 mg/m2 on days 1 through 3) or topotecan (1.0 mg/m2 on days 1 through 5). Patients were stratified by Eastern Cooperative Oncology Group performance status (0, 1, or 2) and type of relapse (chemotherapy sensitive or refractory). The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival, and toxicity profile. Results From February 2004 to July 2007, 60 patients were enrolled, and 59 patients (36 patients with sensitive and 23 patients with refractory relapse) were assessable for efficacy and safety evaluation. Neutropenia was severe, and one treatment-related death owing to infection was observed in the amrubicin arm. ORRs were 38% (95% CI, 20% to 56%) for the amrubicin arm and 13% (95% CI, 1% to 25%) for the topotecan arm. In sensitive relapse, ORRs were 53% for the amrubicin arm and 21% for the topotecan arm. In refractory relapse, ORRs were 17% for the amrubicin arm and 0% for the topotecan arm. Median PFS was 3.5 months for patients in the amrubicin arm and 2.2 months for patients in the topotecan arm. Multivariate analysis revealed that amrubicin has more influence than topotecan on overall survival. Conclusion Amrubicin may be superior to topotecan with acceptable toxicity for previously treated patients with SCLC. Further evaluation of amrubicin for relapsed SCLC is warranted.

The aim of this study was to investigate the clinical outcome of stereotactic body radiotherapy (SBRT) of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system. The subjects were 19 patients who had localized lung tumor (11 primaries, 8 metastases) between May 2003 and October 2005. Treatment was conducted on 19 lung tumors by fixed multiple noncoplanar conformal beams with a standard linear accelerator. The isocentric dose was 54 Gy in nine fractions. The median overall treatment time was 15 days (range 11–22 days). All patients were immobilized by a thermo-shell and a custom-made headrest during the treatment. The crude local tumor control rate was 95% during the follow-up of 9.4–39.5 (median 17.7) months. In-field recurrence was noted in only one patient at the last follow-up. The Kaplan-Meier overall survival rate at 2 years was 89.5%. Grade 1 radiation pneumonia and grade 1 radiation fibrosis were observed in 12 of the 19 patients. Treatment-related severe early and late complications were not observed in this series. The stereotactic body radiotherapy of 54 Gy in nine fractions achieved acceptable tumor control without any severe complications. The results suggest that SBRT can be one of the alternatives for patients with localized lung tumors.

Background Lung cancers with anaplastic lymphoma kinase rearrangements are highly sensitive to anaplastic lymphoma kinase tyrosine kinase inhibition, underscoring the notion that such cancers are addicted to anaplastic lymphoma kinase activity. Several anaplastic lymphoma kinase inhibitors have been identified and are being evaluated in clinical trials. However patients with poor performance status (3 or 4) were not involved in these clinical trials, it has been unclear to use anaplastic lymphoma kinase–tyrosine kinase inhibitors for these patients. Here, we report an anaplastic lymphoma kinase-positive non small cell lung cancer patient with performance status 4, who was successfully treated with alectinib. Case presentation We report on a 52-year-old patient diagnosed as non small cell lung cancer harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene. His performance status was 4 because of severe respiratory failure. We treated this patient with alectinib as the first line therapy. Dramatic response was obtained and his performance status improved from 4 to 1 without severe adverse events. Conclusion Alectinib is a therapeutic option for the anaplastic lymphoma kinase positive patients with poor performance status.

Objective To clarify the clinical significance of vascular endothelial growth factor (VEGF) in Japanese patients with small cell lung cancer (SCLC).Materials and Methods We measured serum VEGF levels using an enzyme-linked immunosorbent assay in 45 patients with SCLC before treatment and in 38 patients with benign pulmonary disease and in 32 healthy subjects (71 non-malignant subjects). VEGF immunostaining was performed in tissue biopsies obtained from 23 SCLC patients during bronchoscopic examination.Results Median serum VEGF level was 332 pg/ml in patients with SCLC and 160 pg/ml in non-malignant subjects, respectively. The 95% cut-off level to exclude non-malignant subjects was 500 pg/ml. An elevated VEGF level (>500 pg/ml) was found more frequently in patients with extensive disease of SCLC than in those with the limited disease (p

The purpose of this study was to determine the safety and efficacy of nedaplatin and paclitaxel when given concurrently with radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC).Nedaplatin was administered at a fixed dose of 20 mg/m(2), and paclitaxel was administered at a starting dose of 30 mg/m(2) with an incremental increase of 5 mg/m(2) until dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered once a week for 6 weeks. The RT was given at a single daily dose of 2 Gy for 5 days per week. The pharmacokinetics of nedaplatin and paclitaxel were investigated.Overall, 20 patients were recruited and assigned to three different treatment groups: group 1 (paclitaxel 30 mg/m(2)), group 2 (paclitaxel 35 mg/m(2)) and group 3 (paclitaxel 40 mg/m(2)). Pulmonary toxicity was the main toxicity which occurred in 16 of 20 patients. In group 3, grades 3 and 4 pulmonary toxicity occurred in two of six patients and grade 3 esophagitis in one patient. The maximum tolerated dose of paclitaxel in this study was 40 mg/m(2) and the recommended dose of paclitaxel was therefore 35 mg/m(2). Four complete and 11 partial responses were observed, resulting in a 75% overall response rate. The area under the concentration-time curve of paclitaxel in group 3 was significantly higher than that in group 1.Nedaplatin 20 mg/m(2) and paclitaxel 35 mg/m(2) could be safely administered for NSCLC with concurrent thoracic RT, and this regimen was effective. The most important DLT was pulmonary toxicity.

Background: Airway eosinophilia is one of the hallmarks of asthma. Eotaxin may play an important role in eosinophil recruitment. Objectives: To examine the relationship between eotaxin levels in the sputum and eosinophilic inflammation. Methods: The sputum was obtained from 11 non-smokers, 14 smokers and 13 asthmatic patients using a sputum induction method. Eotaxin and interleukin (IL)-5 levels in the sputum were determined by ELISA and immunocytochemical analysis. Results: Asthmatic patients had eosinophilia and smokers showed neutrophilia in their sputum. The eotaxin level in the sputum was significantly higher in smokers (median 412.5, range 91.1–872.2 pg/ml) and asthmatic patients (351.0, 185.0–928.0 pg/ml) compared with non-smokers (123.2, 0–369.0 pg/ml; both p < 0.05). IL-5 was detected in the sputum of 1 non-smoker, none of the smokers and 4 asthmatic patients. The percentage of eotaxin-positive cells was higher in smokers and asthmatic patients than in non-smokers, but the percentage of IL-5-positive cells was significantly higher only in asthmatic patients (p < 0.05). Conclusions: These findings suggest that the elevated eotaxin level in the sputum does not always accompany the increase in eosinophils, and cooperation with another cytokine such as IL-5 may be required for the recruitment of eosinophils.

BACKGROUND Transforming growth factor-β1 (TGF- β1) is a multifunctional factor and is known to affect tumor growth in malignant tumors. The effects of TGF-β1 on angiogenesis, stromal formation, and immune function suggest its possible involvement in tumor progression. The authors examined whether TGF-β1 levels may be correlated with angiogenesis, clinicopathologic factors, and survival in patients with surgically resected lung carcinoma. METHODS TGF-β1 protein was extracted from 53 nonsmall cell lung carcinoma tissue samples (19 squamous cell carcinomas, 33 adenocarcinomas, and 1 adenosquamous cell carcinoma), and its level was measured by enzyme-linked immunosorbent assay. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD31 immunostaining. RESULTS The protein level of TGF-β1 was 289 picograms per milligram of protein (pg/mg protein), ranging from 94 pg/mg protein to 584 pg/mg protein. The TGF-β1 protein level was significantly higher in patients with lymph node metastasis compared with patients who were without lymph node metastasis (P = 0.02), and the TGF-β1 protein level was significantly higher in patients with Stage III disease (TNM classification) compared with patients who had Stage I and II disease (P = 0.03). There was no significant correlation between the TGF-β1 protein level and any of the other clinicopathologic factors that were considered. A significant positive correlation between TGF-β1 protein level and MVD was noted (P < 0.01). Furthermore, in patients with adenocarcinoma, a significant correlation between TGF-β1 protein level and prognosis was detected by multivariate analysis (P = 0.028). CONCLUSIONS TGF-β1 seems to affect tumor angiogenesis and to play an important role in tumor progression in patients with nonsmall cell lung carcinoma. Furthermore, the TGF-β1 protein level may be an independent predictor of survival in patients with adenocarcinoma of the lung. Cancer 2001;91:964–71. © 2001 American Cancer Society.

気管支結石症の2症例を提示する.症例1は46歳女性.乾性咳嗽を主訴に受診し,胸部X線上右中下葉の含気の低下, CTで中間幹に石灰化腫瘤.気管支鏡下に9mmの結石を摘出し,結石下の瘢痕性狭窄部にレーザー治療を行った.症例2は48歳男性.咳嗽を主訴.胸部X線上右S3の肺炎像, CTで右B3aに石灰化結節を認めた.気管支鏡にて8mmの結石を摘出した. 2症例ともに可動性があり,気管支鏡下に治療が可能であった.

癌性胸膜炎に対するCisplatin (CDDP) の胸腔内投与物質としての有用性を評価するために, 1) CDDPの家兎胸膜刺激作用, 2) 癌性胸膜炎患者におけるCDDPの体内動態, 3) その臨床効果について検討した. その結果, CDDPは強い胸膜刺激作用を持ち, 比較的長時間胸腔内に維持できる薬剤であると考えられた. また臨床的にも奏効率73%, 平均生存期間220.3日と, 従来癌性胸膜炎に用いられてきた胸腔内投与物質と比較しても遜色のないものであった.

Summary Background Diagnosing tuberculous pleural effusion (pTB) is often difficult because the culturing of tubercle bacilli results in a negative test in the majority of cases. Serological tests for the detection of antibodies to tuberculous glycolipid (TBGL) and lipoarabinomannan (LAM) have been introduced for the diagnosis of pulmonary tuberculosis. We examined the levels of these antibodies, adenosine deaminase (ADA) and interferon- γ (IFN- γ ) in the pleural effusion and compared their diagnostic values in pTB. Methods We studied 65 patients with pleural effusion. Of those, 19 patients were diagnosed as having pTB according to our broad case definition. The etiologies in the other 46 patients were malignant effusion, transdative effusion and miscellaneous diseases. Determiner TBGL antibody ® (D-TBGL-Ab) and MycoDot ® were used for the detection of anti-LAM and anti-TBGL antibodies, respectively, in the pleural effusion. Results The sensitivity of ADA was 78.9% (15/19) and the specificity 97.8% (45/46). The sensitivity of IFN- γ was 84.2% (16/19) and the specificity 93.5% (43/46). The sensitivities of D-TBGL-Ab and MycoDot ® were both 52.6% (10/19) and their specificities were 95.7% (44/46) and 97.8% (45/46), respectively. When DTBGL-Ab (cutoff point: 2.0U/ml) and ADA activity (cutoff point: 57IU/l) were combined, the sensitivity was 94.7% (18/19) and the specificity 93.5% (43/46). Conclusions In the diagnosis of pTB, D-TBGL-Ab and MycoDot ® each have low sensitivity but high specificity. When D-TBGL-Ab is used in combination with ADA, the sensitivity and specificity are both >90%. We conclude that D-TBGL-Ab and ADA in combination are useful in the diagnosis of pTB.

7520 Background: When this trial was planned, A was believed to be a promising new anthracycline agent for sensitive-relapsed SCLC. While re-challenge of P that had been used for the first-line tre...

Background Thymic carcinoma is a rare neoplasm of the thymus. Systemic chemotherapy is an important therapeutic modality for thymic carcinoma. However, no standard chemotherapy for this carcinoma has yet been established. The usefulness of second-line or later-line chemotherapy has remained unclear. A case of relapsed thymic carcinoma that was successfully treated by S-1 as second-line chemotherapy is reported herein. Case presentation A 73-year-old man diagnosed as having thymic carcinoma was treated with three cycles of first-line chemotherapy with ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) and additional radiotherapy (50 Gy). Since his serum cytokeratin 19 fragment level increased suddenly after 3 months of stable disease, he was considered to have progressive disease, and was given S-1 as chemotherapy. Two months later, he had partial response, and the S-1 treatment has been continued since July 2009. Progression-free survival of greater than 4 years was obtained with S-1. Conclusion A case of relapsed thymic carcinoma that was treated with S-1, and continues to show a long progression-free survival with good quality of life on treatment is described. S-1 might be an active agent against relapsed thymic carcinoma.

Background Lung cancer is the leading cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitor (TKI) is used for the patients with EGFR-mutant lung cancer. Recently, phase III studies in the patients with EGFR-mutant demonstrated that EGFR-TKI monotherapy improved progression-free survival compared with platinum-doublet chemotherapy. The echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion oncogene represents one of the newest molecular targets in non-small cell lung cancer (NSCLC). Patients who harbor EML4-ALK fusions have been associated with a lack of EGFR or KRAS mutations. Case presentation We report a 39-year-old patient diagnosed as adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene. We treated this patient with erlotinib as the third line therapy, but no clinical benefit was obtained. Conclusion We experienced a rare case with EGFR mutation and EML4-ALK. Any clinical benefit using EGFR-TKI was not obtained in our case. The therapeutic choice for the patients with more than one driver mutations is unclear. We needs further understanding of the lung cancer molecular biology and the biomarker infomation.

Pier Giuseppe Agostoni, Milano Marina Aiello, Parma Nicolino Ambrosino, Gussago Eleftherios Anevlavis, Nea Ionia Veena B. Antony, Indianapolis, Ind. Lorenzo Appendini, Veruno Hormoz Ashtyani, Hackensack, N.J. I. Azziz, Edmunds Philip Bardin, Clayton, Melbourne Harry Bassaris, Patra Eric Bateman, Groote Schuur, Cape Town Robert P. Baughman, Cincinnati, Ohio Egmont Baumgartner, Hall, Tirol F. Xaver Baur, Hamburg Robert Berent, Wels Sten Erik Bergstrom, Huddinge Andrea Bianco, Napoli Sebastiano Bianco, Milano Roland Bittner, Berlin Francesco Blasi, Milano Annette Boehler, Zurich Thomas Boehm, Zurich Josef R.M. Bolitschek, Linz T. Bombeli, Zurich Louis-Philippe Boulet, Sainte-Foy Henri Bounameaux, Geneve Demosthenes E. Bouros, Athens Homer A. Boushey, San Francisco, Calif. Lennart Braback, Sundsvall Thomas Brack, Zurich Aidan Bradford, Dublin Christian Brambilla, Grenoble Antonio Braschi, Pavia Otto M. Braun, Horn O. Brandli, Faltigberg Vita Brusasco, Genova Martin H. Brutsche, Basel Jean-Luc Burgaud, Sophia Antipolis Andrew Bush, London Cecilia Calabrese, Napoli Philippe Camus, Dijon Pier Aldo Canessa, Sarzana, La Spezia Laura Carrozzi, Pisa Antonio Castagnaro, Mantova Sergio Cavaliere, Brescia M. Cazzola, Napoli I. Cerveri, Pavia Pascal Chanez, Montpellier Neil S. Cherniack, Newark, N.J. Alfredo Chetta, Parma Gianfranco Chiari, Parma Luke Clancy, Dublin Enrico Clini, Gaiato dei Pavullo Henri Colt, La Jolla, Calif. J.H. Coote, Birmingham Giuseppe M. Corbo, Roma Antonio Corrado, Firenze Paolo Coruzzi, Parma U. Costabel, Essen J. Costello, London Nunzio Crimi, Catania Isidor Dab, Bruxelles Roberto Dal Negro, Bussolengo Filiberto Dalmasso, Torino Peter Dalquen, Basel Peter Davies, Liverpool Fernando De Benedetto, Chieti Francesco de Blasio, Arco Felice Marc Decramer, Leuven P.N. Richard Dekhuijzen, Nijmegen Jose Pablo Diaz Jimenez, Barcelona Robert Dinwiddie, London Peter Dorow, Berlin Keith Dorrington, Oxford Roberto Duranti, Firenze Michael Dusmet, London J. Eckmayr, Wels B. Emmerich, Munchen Armin Ernst, Boston, Mass. Santiago Ewig, Bonn H. Fabel, Hannover A. Fairfax, Stafford Franco Falcone, Bologna Rudolf Ferlinz, Bad Gastein Jean-William Fitting, Lausanne Pierre Fournel, St. Etienne Lutz Freitag, Hemer Dimitris Georgopoulos, Heraklion Vassilis Georgoulias, Heraklion Helen Giamarelou, Marousi, Athens Simon Godfrey, Jerusalem A. Greening, Edinburgh Paul Haber, Wien Dean Handley, Marlborough, Mass. Patricia L. Haslam, London W. Heindl, Wien Arthur Helbling, Bern Bill Hesselmar, West Perth Richard Hodder, Ottawa J.C. Hogg, Vancouver Rudolf Maria Huber, Munchen Gerard Huchon, Paris David W. Hudgel, Detroit, Mich. Stasia Jastrzembski, Newark, N.J. Amal Jubran, Maywood, Ill. Frank Kanniess, Grosshansdorf Jack Kastelik, Cottingham, East Yorkshire Philipp Kaufmann, Zurich Roland Keller, Aarau Frank Kelly, London Paul Kemp, Leeds Ok Hwa Kim, Kyonggi-do Carl M. Kirsch, San Jose, Calif. Nikolaus Konietzko, Essen D. Kohler, Schmallenberg-Grafschaft Richard Kraemer, Bern Claus Kroegel, Jena Friedrich Kummer, Wien Boris Lams, London Irene Lang, Wien Didier Lardinois, Zurich R. Lazor, Geneve Ph. Leuenberger, Lausanne Brian Lipworth, Dundee H. Lode, Berlin Stelios Loukides, Athens Maurizio Luisetti, Pavia Piero Maestrelli, Padova H. Magnussen, Grosshansdorf Katerina Malagari, Papagou, Athens Carlo Manca, Parma Milan Marel, Praha Charles-Hugo Marquette, Lille C. Marriott, London Praveen N. Mathur, Indianapolis, Ind. Heinrich Matthys, Freiburg/Br. Harald Mauch, Berlin Thomas Meisl, Wien Giovanni Migliori, Tradale M. Miniati, Pisa Anna Maria Moretti, Bari A.H. Morice, Cottingham Gianna Moscato, Pavia Michael Rolf Mueller, Wien

7333 Background: The purpose of this study was to determine maximum tolerated dose (MTD) of a combination of GEM plus CBDCA administration on a biweekly schedule for inoperable NSCLC, and to assess...

7237 Background: The purpose of this study was to determine maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of a combination of gemcitabine plus carboplatin administration in a bi...