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Background The purpose of this study is to investigate the clinical characteristics and the efficacy of the cytotoxic chemotherapy in the first and second line setting in EML4-ALK positive NSCLC with advanced stage. Methods EML4-ALK fusion was screened with RT-PCR and immunohistochemistry. When positive results were obtained with either method, gene rearrangement of ALK was confirmed with fluorescent in-situ hybridization. Clinical features and the efficacy of chemotherapy were evaluated retrospectively. Results We evaluated 20 EML4-ALK positive patients with advanced stage. Seventeen (85%) of 20 had stage IV disease. Nine cases were male, and 11 were female. The mean ages were 46.3 years (range26-79). Most of their CT findings demonstrated mass or nodule in primary sites, while 2 cases showed air-space consolidation. In patients with stage IV the most common sites of metastasis at the first onset were bone (47.0%), followed by pleura (35.2%), liver (29.4%), and lung (23.5%). In 13 cases of which were evaluable in the first line setting, 7 (53.8%) had a partial response (PR), 4 (30.8%) had stable disease (SD), and 2 (15.4%) had progressive disease (PD). Among 10 evaluable cases in the second line setting, 2 (20%) had a PR, 5 (50%) had SD, and 3 had PD (30%). Two patients who had a PR were both treated by oral ALK inhibitor (crizotinib). One case had no response to crizotinib. Within the 7 patients who were treated by cytotoxic agents, none had marked clinical response. Five patients (71.4%) had SD, 2 patients had PD (28.6%) on single cytotoxic drug. Conclusions Our study suggests that the EML4-ALK positive patients may show relatively favorable response to cytotoxic drug in the first line setting, but low response in the second line setting. These data could be helpful for further clinical trials including EML4-ALK patients. Disclosure T. Mitsudomi: Dr. Mitsudomi has received lecture fees from AstraZeneca and Chugai, and he is a member of advisory boards of Pfizer and Boehringer-Ingelheim. All other authors have declared no conflicts of interest.

Aim: The purpose of this study is to better identify imaging characteristics on computed tomography (CT) in patients with non-small-cell lung carcinoma (NSCLC) with known epidermal growth factor receptor (EGFR) mutations, KRAS mutations, and anaplastic lymphoma kinase (ALK) gene rearrangements. Methods: Two hundred fifty-seven patients with a diagnosis of NSCLC and EGFR mutations, KRAS mutations or ALK gene rearrangements were assessed. We retrospectively analyzed the CT characteristics of each cohort. Results: We evaluated 257 patients with NSCLC. One hundred fifty-three patients (59.5%) had EGFR mutations, 54 patients (21.0%) had KRAS mutations, and 50 (19.5%) had ALK gene rearrangements. All mutations were mutually exclusive. Most patients had stage III or IV disease. One hundred twenty-one cases were male, and 136 were female. The mean age was 62.1 years (range29-89). Patients with EGFR mutations tend to have ground grass opacity (GGO), air bronchograms, and lung metastases (p Conclusions: These findings may help to make a proper diagnosis in the current era of molecular targeted therapies. Disclosure: All authors have declared no conflicts of interest.

Background ALK-fluorescence in situ hybridization (FISH) testing in all EGFR/KRAS-negative adenocarcinomas remains time- and cost-consuming and not suitable for a large-scale screening, in contrast to immunohistochemistry (IHC) for ALK protein expression. However, there appeared some IHC positive but FISH negative cases for ALK in lung cancer. Methods and case report A 69-year-old man who had received a right lower lobectomy for lung adenocarcinoma (pT1N0M0), recurred with brain metastasis 3 years later and treated with gamma-knife therapy, was referred to our hospital. CT showed a right hilar mass and enlarged mediastinal lymph nodes. An endoscopically visible tumor protruding into the lumen of the right upper lobe was biopsied. Histopathology revealed CD56+ and synaptophysin-positive neuroendocrine carcinoma. ALK protein expression was positive by IHC but ALK rearrangement was negative by FISH using a dual-color break-apart probe. Interestingly, positive immunostainigs of ALK, CD56 and synaptophysin were observed in primary lung adenocarcinoma but no ALK rearrangement was shown by FISH. The patient received chemotherapy with carboplatin and pemetrexed. After local progeression, he was treated with carboplatin and etoposide. Conclusions A case of lung adenocarcinoma with neuroendocrine differentiation exhibiting discordance between IHC and FISH for ALK was presented. Although FISH is a gold-standard reference, sensitivity and specificity of IHC for ALK protein or the relationship between IHC and FISH for ALK should be further investigated in a large number of patients.