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Naoko Katsurada,1 Motoko Tachihara,1 Yukihisa Hatakeyama,1 Kiyoko Koyama,1 Masako Yumura,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Daisuke Hazama,1 Shuntaro Tokunaga,1 Daisuke Tamura,1 Kyosuke Nakata,1 Masatsugu Yamamoto,1 Hiroshi Kamiryo,1 Kazuyuki Kobayashi,1 Yugo Tanaka,2 Yoshimasa Maniwa,2 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; 2Division of General Theocratic Surgery, Kobe University Graduate School of Medicine, Kobe, JapanCorrespondence: Motoko TachiharaDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanTel +81-78-382-5660Fax +81-78-382-5661Email mt0318@med.kobe-u.ac.jpPurpose: Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors > 4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC.Patients and Methods: Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0– 1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit.Results: Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥ 75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4– 83.7). Two-year RFS was 56.8% (95% CI, 29.7– 76.9).Conclusion: The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.Keywords: nab-paclitaxel, carboplatin, adjuvant chemotherapy, non-small cell cancer

Motoko Tachihara,1 Tatsunori Kiriu,1 Akito Hata,2 Yukihisa Hatakeyama,3 Kyosuke Nakata,1 Tatsuya Nagano,1 Masatsugu Yamamoto,1 Kazuyuki Kobayashi,1 Hisashi Ohnishi,3 Nobuyuki Katakami,2 Yoshihiro Nishimura11Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan; 2Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo 650-0047, Japan; 3Department of Respiratory Medicine, Akashi Medical Center, Akashi, Hyogo 674-0063, JapanBackground: Nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) significantly improved overall survival in patients with metastatic pancreatic adenocarcinoma. Anti-tumor synergy between GEM and nab-PTX was recently demonstrated in a mouse model. We planned to assess the efficacy and safety of the combination of nab-PTX + GEM in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.Methods: Patients with advanced NSCLC with progressive disease after platinum-based chemotherapy, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and adequate kidney, liver and bone marrow function were eligible. Treatment consisted of nab-PTX (100 mg/m2) + GEM (1000 mg/m2) on days 1 and 8 of each 3-week cycle until progression disease or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).Results: Of the 28 patients enrolled, all were evaluable for response and toxicity. The median age was 68 years (range 47–79), and 23 were male and 5 female. The histologic subtypes were: adenocarcinoma in 19 patients, and squamous cell carcinoma in 9 patients. Seventeen patients had ECOG PS 1 and 11 patients had PS 0. Twenty-four patients were second line and 4 patients were third line. The median number of cycles administered was 4 (range 1–10). The overall response rate was 17.9%. The disease control rate was 67.9%. The median progression-free survival was 3.1 months (95% confidence interval [CI] =1.6–4.1). Adverse events were generally tolerable except grade 3 interstitial pneumonia with in 4 patients (14.3%).Conclusion: The efficacy of nab-PTX in combination with GEM in advanced second or third-line NSCLC patients was limited and the frequent occurrence of interstitial pneumonia was unacceptable.Keywords: nab-paclitaxel, gemcitabine, non-small-cell lung cancer

Toshinaga Tsuji,1 Ken Nakata,2 Jeffrey Vietri,3 Dena H Jaffe41Medical Affairs Department, Shionogi & Co., Ltd, Osaka, Japan; 2Medicine for Sports and Performing Arts, Osaka University, Suita, Japan; 3Health Outcomes Practice, Health Division, Kantar, 4 Ariel Sharon Street, Horsham, PA, USA; 4Health Outcomes Practice, Health Division, Kantar, Tel Aviv, IsraelObjectives: In Japan, osteoarthritis (OA) is a leading source of pain and disability; depressive disorders may limit patients’ ability to cope with OA. This study examined the incremental effect of depression on the relationship between OA and health-related outcomes.Methods: Data from the 2014 Japan National Health and Wellness Survey (N=30,000) were collected on demographics, OA characteristics, and health characteristics of patients with OA. Depression symptoms were measured, and outcomes included health-related quality of life (HRQoL), work productivity and activity impairment, and health care resource utilization. Generalized linear regression models controlling for confounders were used to predict health-related outcomes.Results: Of 565 respondents with OA, 63 (11%) had symptoms of moderate or severe depression. In adjusted models, HRQoL remained lower among respondents with than without depression (p

Mariko Kojima,1 Tatsuya Nagano,1 Kyosuke Nakata,1 Shigeo Hara,2 Naoko Katsurada,1 Masatsugu Yamamoto,1 Motoko Tachihara,1 Hiroshi Kamiryo,1 Kazuyuki Kobayashi,1 Takeshi Usui,3 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan; 2Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan; 3Department of Medical Genetics, Shizuoka General Hospital, Shizuoka City, Shizuoka, Japan Abstract: Hypoparathyroidism with sensorineural deafness and renal dysplasia (HDR) syndrome is an autosomal dominant condition caused by mutations of the gene encoding the dual zinc-finger transcription factor, GATA3. A previous study identified some patients with GATA3 gene variants and breast cancer, suggesting that GATA3 variants may contribute to tumorigenesis in estrogen receptor 1-positive breast tumors; however, these patients did not have HDR syndrome. A 32-year-old nonsmoking Japanese woman was histologically diagnosed with lung squamous cell carcinoma associated with HDR syndrome and a c.C952T>C (p.C318R) germline mutation in GATA3. This is the first report describing cancer in a patient with HDR syndrome. Our data indicates that GATA3 mutations may be a potential therapeutic target for lung cancer. Keywords: lung cancer, GATA3, missense variant, hypoparathyroidism, sensorineural deafness, renal dysplasia

The capacitance–voltage (C – V) and conductance–voltage (G – V) characteristics of GaN metal–insulator–semiconductor (MIS) structures have a frequency dependence due to the capture and emission of electrons by the high density of the interface states. However, the details of how an interface state affects C – V and G – V characteristics is still not well understood. In this paper, we report a numerical modeling method that can simulate the frequency dependent C – V and G – V characteristics of GaN MIS structures. [ABSTRACT FROM AUTHOR]