[Well Differentiated Liposarcoma of a Lung:Report of a Case].

A 61-year-old woman was referred for further evaluation of an intracystic nodule in her left upper lung. Computed tomography( CT) showed a 15 mm nodule in a pulmonary cyst adjacent to aortic arch and mediastinum. Fluorodeoxyglucose-positron emission tomography (FDG-PET)-CT showed little uptake of FDG in the lesion. No abnormality was found in the bronchoscopy findings. On imaging findings, the possibility of pulmonary aspergilloma was considered, but the serological findings were inconsistent, and surgical resection of the lesion was performed for both diagnosis and treatment. The final pathohistological diagnosis was well differentiated liposarcoma. No adjuvant therapy was performed and the patient has been well without recurrence for 2 years after the surgery. We report a rare case of well differentiated liposarcoma of a lung mimicking pulmonary aspergilloma.

[Endobronchial Hamartoma Treated with Bronchoscopic Microwave Tissue Coagulation and Electrosurgical Snaring:Report of a Case].

A 35-year-old man had chronic cough and was treated as asthma at local doctor. Since the symptoms was not improved, chest computed tomography( CT) was performed and an approximately 5 mm nodule with calcification was found in the left main bronchi. He was referred to our hospital for treatment. Bronchoscopic examination revealed a polypoid lesion in the membranous part of the left main bronchus. Since transbronchial biopsy revealed no malignant findings, bronchoscopic resection using microwave tissue coagulation and electrosurgical snaring was performed safely under the general anesthesia. The tumor was histologically diagnosed as endobronchial hamartoma.

Most Important Things and Associated Factors With Prioritizing Daily Life in Patients With Advanced Lung Cancer.

PURPOSE: Patients' values and priorities in their lives should be appreciated from an early phase of incurable diseases such as advanced cancer. However, studies examining these characteristics have been lacking. This study attempted to determine what patients with advanced lung cancer valued most, once they had been diagnosed, and any associated factors. METHODS: Patients with newly diagnosed advanced lung cancer (N = 248) were enrolled in a questionnaire survey conducted at 16 hospitals in Japan. Their priorities were assessed using a free-text response to the question what is the most important thing to you now? at the time of diagnosis and 3 months after diagnosis. The free-text responses were classified into 10 categories for quantification. The clinical characteristics associated with the category describing daily life were further examined. RESULTS: Free-text comments were obtained from 103 (44.0%) and 66 (42.6%) patients at the time of diagnosis and at 3 months, respectively. The most frequent categories were family (at diagnosis: 50.5%; at 3 months: 50.0%) and daily life (at diagnosis: 33.0%; at 3 months: 36.4%), followed by health (at diagnosis: 32.0%; at 3 months: 27.3%) at both time points. The patients mentioning daily life, the issues related to how to spend daily life, showed significantly higher total scores and functional well-being subscale scores on the Functional Assessment of Cancer Therapy-Lung scale at both time points and lower depression scores at diagnosis and lower anxiety scores at 3 months on the Hospital Anxiety and Depression Scale. CONCLUSION: Family and daily life were highly valued by patients with advanced lung cancer at diagnosis. A better quality of life and better mood were associated with mentioning daily life, which should be taken into account in care planning to maintain patients' involvement in daily life even with incurable diseases.

Long-term Survival of a Patient with Small Cell Lung Cancer Secreting ADH and ACTH Simultaneously, Following the Prolonged Use of Amrubicin.

Paraneoplastic syndromes are frequently observed in lung cancer, especially in small cell lung cancer (SCLC). Although there have been many reports on paraneoplastic syndromes, few reports have been published on SCLC that simultaneously produces antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH), and these reports described the prognosis of such cases as extremely poor. We herein present a rare case of a Japanese woman with SCLC accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Cushing's syndrome. The survival of the patient was prolonged by the long-term administration of amrubicin.

Erlotinib as second- or third-line treatment in elderly patients with advanced non-small cell lung cancer: Keio Lung Oncology Group Study 001 (KLOG001).

The aim of this study was to assess the efficacy and safety of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as second- or third-line treatment for elderly Japanese patients with non-small-cell lung cancer (NSCLC). The patients eligible for this phase II trial were aged ≥70 years, had stage III/IV or recurrent NSCLC, and had previously received 1 or 2 chemotherapy regimens that did not include EGFR-TKIs. The patients received erlotinib at a dose of 150 mg/day. The primary endpoint was overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. A total of 38 patients with a median age of 76 years were enrolled. The majority of the patients were men (66%), had an Eastern Cooperative Oncology Group performance status of 1 (58%), stage IV disease (66%) and adenocarcinoma (74%). Of the 35 patients, 13 (34%) had tumors with EGFR mutations. The ORR was 26.3% (95% confidence interval: 12.1-40.5%) and the disease control rate was 47.4%. The median PFS was 3.7 months and the median OS was 17.3 months. The grade 3 adverse events observed included rash (13%), diarrhea (5%), interstitial pneumonitis (5%), anorexia (3%) and gastrointestinal bleeding (3%). Grade 4 or 5 adverse events were not observed. The median OS did not differ significantly between patients aged <75 years (14.9 months) and those aged ≥75 years (19.0 months; P=0.226). Therefore, erlotinib was found to be effective and well-tolerated in elderly patients with previously treated NSCLC.

Overcoming EGFR Bypass Signal-Induced Acquired Resistance to ALK Tyrosine Kinase Inhibitors in ALK-Translocated Lung Cancer.

Activation of the EGFR pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib and alectinib. Ceritinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the ALK gene rearrangement. However, the precise mechanism underlying acquired resistance to ceritinib is not well-defined. This study set out to clarify the mechanism in ALK-translocated lung cancer and to find the preclinical rationale overcoming EGFR pathway-induced acquired resistance to ALK-TKIs. To this end, ceritinib-resistant cells (H3122-CER) were established from the H3122 NSCLC cell line harboring the ALK gene rearrangement via long-term exposure to ceritinib. H3122-CER cells acquired resistance to ceritinib through EGFR bypass pathway activation. Furthermore, H3122 cells that became resistant to ceritinib or alectinib through EGFR pathway activation showed cross-resistance to other ALK-TKIs. Ceritinib and afatinib combination treatment partially restored the sensitivity to ceritinib. IMPLICATIONS: This study proposes a preclinical rationale to use ALK-TKIs and afatinib combination therapy for ALK-translocated lung cancers that have acquired resistance to ALK-TKIs through EGFR pathway activation. Mol Cancer Res; 15(1); 106-14. ©2016 AACR.

Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells.

Alectinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the EML4-ALK gene rearrangement. The precise mechanism of acquired resistance to alectinib is not well defined. The purpose of this study was to clarify the mechanism of acquired resistance to alectinib in ALK-translocated lung cancer cells. We established alectinib-resistant cells (H3122-AR) from the H3122 NSCLC cell line, harboring the EML4-ALK gene rearrangement, by long-term exposure to alectinib. The mechanism of acquired resistance to alectinib in H3122-AR cells was evaluated by phospho-receptor tyrosine kinase (phospho-RTK) array screening and Western blotting. No mutation of the ALK-TK domain was found. Phospho-RTK array analysis revealed that the phosphorylation level of EGFR was increased in H3122-AR cells compared with H3122. Expression of TGFα, one of the EGFR ligands, was significantly increased and knockdown of TGFα restored the sensitivity to alectinib in H3122-AR cells. We found combination therapy targeting ALK and EGFR with alectinib and afatinib showed efficacy both in vitro and in a mouse xenograft model. We propose a preclinical rationale to use the combination therapy with alectinib and afatinib in NSCLC that acquired resistance to alectinib by the activation of EGFR bypass signaling.

In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer.

EGFR mutated lung cancer accounts for a significant subgroup of non-small-cell lung cancer (NSCLC). Over the last decade, multiple EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been developed to target mutated EGFR. However, there is little information regarding mutation specific potency of EGFR-TKIs against various types of EGFR mutations. The purpose of this study is to establish an in vitro model to determine the "therapeutic window" of EGFR-TKIs against various types of EGFR mutations, including EGFR exon 20 insertion mutations. The potency of 1st (erlotinib), 2nd (afatinib) and 3rd (osimertinib and rociletinib) generation EGFR-TKIs was compared in vitro for human lung cancer cell lines and Ba/F3 cells, which exogenously express mutated or wild type EGFR. An in vitro model of mutation specificity was created by calculating the ratio of IC50 values between mutated and wild type EGFR. The in vitro model identified a wide therapeutic window of afatinib for exon 19 deletions and L858R and of osimertinib and rociletinib for T790M positive mutations. The results obtained with our models matched well with previously reported preclinical and clinical data. Interestingly, for EGFR exon 20 insertion mutations, most of which are known to be resistant to 1st and 2nd generation EGFR-TKIS, osimertinib was potent and presented a wide therapeutic window. To our knowledge, this is the first report that has identified the therapeutic window of osimertinib for EGFR exon 20 insertion mutations. In conclusion, this model will provide a preclinical rationale for proper selection of EGFR-TKIs against clinically-relevant EGFR mutations.