start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=295 end-page=297 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Efficacy of Rituximab in High-risk Renal Transplant Recipients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although graft survival following renal transplantation (RTx) has improved, outcomes following highrisk RTx are variable. Preexisting antibodies, including donor-specific antibodies (DSA), play an important role in graft dysfunction and survival. We have designed a study to investigate the safety and efficacy of anti-CD20 monoclonal antibodies (rituximab) in high-risk RTx recipients. Major eligibility criteria include: 1) major and minor ABO blood group mismatch, 2) positive DSA. Thirty-five patients will receive 200 mg/body of rituximab. The primary endpoint is the incidence of B cell depletion. This study will clarify whether rituximab is efficacious in improving graft survival in high-risk RTx recipients. en-copyright= kn-copyright= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuiYosuke en-aut-sei=Mitsui en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiokaTakashi en-aut-sei=Yoshioka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AriyoshiYuichi en-aut-sei=Ariyoshi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitagawaMasashi en-aut-sei=Kitagawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanabeKatsuyuki en-aut-sei=Tanabe en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugiyamaHiroshi en-aut-sei=Sugiyama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=end-stage renal disease kn-keyword=end-stage renal disease en-keyword=immunosuppression kn-keyword=immunosuppression en-keyword=kidney transplantation kn-keyword=kidney transplantation END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=299 end-page=302 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants. en-copyright= kn-copyright= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UeharaShinya en-aut-sei=Uehara en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshiiAyano en-aut-sei=Ishii en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoMasumi en-aut-sei=Yamamoto en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsuhataRitsuko en-aut-sei=Mitsuhata en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Takamoto Atsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WatanabeToyohiko en-aut-sei=Watanabe en-aut-mei=Toyohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Kawasaki Hospital, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Center for innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=probiotics kn-keyword=probiotics en-keyword=lactobacilli kn-keyword=lactobacilli en-keyword=Lactobacillus crispatus kn-keyword=Lactobacillus crispatus en-keyword=urinary tract infection kn-keyword=urinary tract infection en-keyword=vaginal suppository kn-keyword=vaginal suppository END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=4 article-no= start-page=327 end-page=330 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study about the Efficacy of Metformin to Immune Function in Cancer Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=A study to evaluate the effect of metformin on the immune system was commenced in July 2014. Metformin is one of the most commonly prescribed drugs for type 2 diabetes, and previous studies have reported that metformin has an anti-tumor effect. The aim of this study is to evaluate the efficacy of metformin on the immune system in human cancer patients in vivo. The primary outcome parameter will be the rate change in the population of CD8+ T cells, which produce multiple cytokines. en-copyright= kn-copyright= en-aut-name=WatanabeMototsugu en-aut-sei=Watanabe en-aut-mei=Mototsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EikawaShingo en-aut-sei=Eikawa en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HinotsuShiro en-aut-sei=Hinotsu en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyoshiShinichiro en-aut-sei=Miyoshi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=metformin kn-keyword=metformin en-keyword=CD8+ T cells kn-keyword=CD8+ T cells en-keyword=cancer immunology kn-keyword=cancer immunology END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=80 end-page=84 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=201110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A phase II study of amrubicin and topotecan combination therapy in patients with relapsed or extensive-disease small-cell lung cancer: Okayama Lung Cancer Study Group Trial 0401 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Backgrounds: Chemotherapy is a mainstay in the treatment of extensive-disease small-cell lung cancer (ED-SCLC), although the survival benefit remains modest. We conducted a phase II trial of amrubicin (a topoisomerase II inhibitor) and topotecan (a topoisomerase I inhibitor) in chemotherapy-naïve and relapsed SCLC patients. Methods: Amrubicin (35 mg/m(2)) and topotecan (0.75 mg/m(2)) were administered on days 3-5 and 1-5, respectively. The objective response rate (ORR) was set as the primary endpoint, which was assessed separately in chemotherapy-naïve and relapsed cases. Results: Fifty-nine patients were enrolled (chemotherapy-naïve 31, relapsed 28). The ORRs were 74% and 43% in the chemotherapy-naïve and relapsed cases, respectively. Survival data were also promising, with a median progression-free survival time and median survival time of 5.3 and 14.9 months and 4.7 and 10.2 months in the chemotherapy-naïve and relapsed cases, respectively. Even refractory-relapsed cases responded to the treatment favorably (27% ORR). The primary toxicity was myelosuppression with grades 3 or 4 neutropenia in 97% of the patients, which led to grades 3 or 4 febrile neutropenia in 41% of the patients and two toxic deaths. Conclusion: This phase II study showed the favorable efficacy and moderate safety profiles of a topotecan and amrubicin two-drug combination especially in relapsed patients with ED-SCLC. en-copyright= kn-copyright= en-aut-name=NogamiNaoyuki en-aut-sei=Nogami en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChikamoriKenichi en-aut-sei=Chikamori en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShibayamaTakuo en-aut-sei=Shibayama en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KishinoDaizo en-aut-sei=Kishino en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HosokawaShinobu en-aut-sei=Hosokawa en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TamaokiAkihiko en-aut-sei=Tamaoki en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaritaShingo en-aut-sei=Harita en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=UeokaHiroshi en-aut-sei=Ueoka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShinkaiTetsu en-aut-sei=Shinkai en-aut-mei=Tetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Department of Respiratory Medicine, NHO Shikoku Cancer Center affil-num=2 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=3 en-affil= kn-affil=Department of Medicine, Chugoku Central Hospital affil-num=4 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=5 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=6 en-affil= kn-affil=Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center affil-num=7 en-affil= kn-affil=Department of Medicine, NHO Minami-Okayama Medical Center affil-num=8 en-affil= kn-affil=Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center affil-num=9 en-affil= kn-affil=Department of Respiratory Medicine, Okayama Red Cross Hospital affil-num=10 en-affil= kn-affil=Department of Respiratory Medicine, Okayama Institute of Health and Prevention affil-num=11 en-affil= kn-affil=Department of Medicine, Chugoku Central Hospital affil-num=12 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital affil-num=13 en-affil= kn-affil=Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center affil-num=14 en-affil= kn-affil=Department of Respiratory Medicine, NHO Shikoku Cancer Center affil-num=15 en-affil= kn-affil=Department of Respiratory Medicine, Okayama University Hospital en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Topotecan kn-keyword=Topotecan en-keyword=Amrubicin kn-keyword=Amrubicin en-keyword=Chemo-naive kn-keyword=Chemo-naive en-keyword=Sensitive relapse kn-keyword=Sensitive relapse en-keyword=Refractory relapse kn-keyword=Refractory relapse END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=11 article-no= start-page=2009 end-page=2018 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples.
Methods
Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction.
Results
ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes.
Conclusions
High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy. en-copyright= kn-copyright= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraTakehiro en-aut-sei=Matsubara en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KayataniHiroe en-aut-sei=Kayatani en-aut-mei=Hiroe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakataMinoru en-aut-sei=Takata en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Okayama University Hospital Biobank, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Hospital Biobank, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=18 en-affil=Okayama University Hospital Biobank, Okayama University Hospital kn-affil= affil-num=19 en-affil=Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Graduate School of Biostudies, Radiation Biology Center, Kyoto University kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=ALK G1202R kn-keyword=ALK G1202R en-keyword=Alectinib kn-keyword=Alectinib en-keyword=Amphiregulin kn-keyword=Amphiregulin en-keyword=MET kn-keyword=MET en-keyword=NSCLC kn-keyword=NSCLC END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue=6 article-no= start-page=823 end-page=828 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Re-administration of Osimertinib in Osimertinib-induced Interstitial Lung Disease with an Organizing Pneumonia Pattern: A Case Report and Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract= Osimertinib is the standard therapy for epidermal-growth-factor-receptor (EGFR)-mutant lung cancers. We herein report a case of osimertinib-induced interstitial lung disease (OsiILD) with an organizing pneumonia (OP) pattern and provide a literature-based review. Six months after osimertinib administration, a 75-year-old woman with right pleural carcinomatosis developed ILD with an OP pattern. After salvage chemotherapy, osimertinib with corticosteroid was successfully re-administered. A literature review suggested that 1) OsiILD with an OP pattern was rare but should be recognized, and 2) re-administration of osimertinib in OsiILD was successful in select patients. A criterion that determines whether a patient would benefit from re-administration is warranted. en-copyright= kn-copyright= en-aut-name=ItanoJunko en-aut-sei=Itano en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=osimertinib kn-keyword=osimertinib en-keyword=drug-induced ILD kn-keyword=drug-induced ILD en-keyword=reversed halo sign kn-keyword=reversed halo sign en-keyword=organizing pneumonia pattern kn-keyword=organizing pneumonia pattern en-keyword=re-administration kn-keyword=re-administration END start-ver=1.4 cd-journal=joma no-vol=111 cd-vols= no-issue=10 article-no= start-page=3739 end-page=3746 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status en-subtitle= kn-subtitle= en-abstract= kn-abstract=Most clinical trials of non-small-cell lung cancer (NSCLC) exclude patients with poor ECOG performance status (PS). Thus, the efficacy of immune checkpoint inhibitors (ICIs) in patients with poor PS remains unclear. Herein, we used data from a retrospective cohort to assess the potential clinical benefits of ICIs in NSCLC patients with poor PS. Data from NSCLC patients who received ICI monotherapy at 9 institutions between December 2015 and May 2018 were retrospectively analyzed. After excluding 4 patients who lacked PS data, a total of 527 ICI-treated patients, including 79 patients with PS 2 or higher, were used for our analyses. The progression-free survival (PFS) and overall survival (OS) of patients with PS 2 or higher were significantly shorter compared with those of PS 0-1 patients (median PFS, 4.1 vs 2.0 months;P < .001 and median OS, 17.4 vs 4.0 months;P < .001). Among NSCLC patients with programmed cell death protein-ligand 1 (PD-L1) expression of 50% or higher who were treated with pembrolizumab as first-line therapy, the median PFS times of patients with PS 2 and 0-1 were 7.3 and 8.1 months, respectively. There was no significant difference in PFS between patients with PS 2 and 0-1 (P = .321). Although poor PS was significantly associated with worse outcomes in NSCLC patients treated with ICIs, pembrolizumab as a first-line treatment in NSCLC patients expressing high levels of PD-L1 could provide a clinical benefit, even in patients with PS 2. en-copyright= kn-copyright= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KayataniHiroe en-aut-sei=Kayatani en-aut-mei=Hiroe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HosokawaShinobu en-aut-sei=Hosokawa en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KishinoDaizo en-aut-sei=Kishino en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeKazuhiko en-aut-sei=Watanabe en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Himeji Red Cross Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=9 en-affil=Department of General Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=non-small cell-lung cancer kn-keyword=non-small cell-lung cancer en-keyword=PD-L1 kn-keyword=PD-L1 en-keyword=pembrolizumab kn-keyword=pembrolizumab en-keyword=poor performance status kn-keyword=poor performance status END start-ver=1.4 cd-journal=joma no-vol=149 cd-vols= no-issue= article-no= start-page=46 end-page=52 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202011 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives
In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs).
Materials and methods
Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed.
Results
In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, −4.5; 99% CI: −9.04, −0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600‒1.026]; dyspnea 0.79 [0.625‒1.006]; chest pain 0.76 [0.575‒0.996]; fatigue 0.82 [0.653‒1.027]; appetite loss 0.70 [0.542‒0.899]), functioning, and global health status/QoL.
Conclusion
Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP. en-copyright= kn-copyright= en-aut-name=GoldmanJonathan W. en-aut-sei=Goldman en-aut-mei=Jonathan W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GarassinoMarina Chiara en-aut-sei=Garassino en-aut-mei=Marina Chiara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChenYuanbin en-aut-sei=Chen en-aut-mei=Yuanbin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ÖzgüroğluMustafa en-aut-sei=Özgüroğlu en-aut-mei=Mustafa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DvorkinMikhail en-aut-sei=Dvorkin en-aut-mei=Mikhail kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TrukhinDmytro en-aut-sei=Trukhin en-aut-mei=Dmytro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=StatsenkoGalina en-aut-sei=Statsenko en-aut-mei=Galina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=JiJun Ho en-aut-sei=Ji en-aut-mei=Jun Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HochmairMaximilian J. en-aut-sei=Hochmair en-aut-mei=Maximilian J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=VoitkoOleksandr en-aut-sei=Voitko en-aut-mei=Oleksandr kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HavelLibor en-aut-sei=Havel en-aut-mei=Libor kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=PoltoratskiyArtem en-aut-sei=Poltoratskiy en-aut-mei=Artem kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=LosonczyGyörgy en-aut-sei=Losonczy en-aut-mei=György kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ReinmuthNiels en-aut-sei=Reinmuth en-aut-mei=Niels kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=PatelNikunj en-aut-sei=Patel en-aut-mei=Nikunj kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=LaudPeter J. en-aut-sei=Laud en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShireNorah en-aut-sei=Shire en-aut-mei=Norah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=JiangHaiyi en-aut-sei=Jiang en-aut-mei=Haiyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Paz-AresLuis en-aut-sei=Paz-Ares en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=David Geffen School of Medicine at UCLA kn-affil= affil-num=2 en-affil=Fondazione IRCCS Istituto Nazionale dei Tumori kn-affil= affil-num=3 en-affil=Cancer & Hematology Centers of Western Michigan kn-affil= affil-num=4 en-affil=Istanbul University–Cerrahpaşa, Cerrahpaşa School of Medicine kn-affil= affil-num=5 en-affil=BHI of Omsk Region Clinical Oncology Dispensary kn-affil= affil-num=6 en-affil=Odessa National Medical University kn-affil= affil-num=7 en-affil=Omsk Regional Cancer Center, kn-affil= affil-num=8 en-affil=Okayama University Hospital kn-affil= affil-num=9 en-affil=Samsung Changwon Hospital, Sungkyunkwan University School of Medicine kn-affil= affil-num=10 en-affil=Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf kn-affil= affil-num=11 en-affil=Kyiv City Clinical Oncological Centre kn-affil= affil-num=12 en-affil=Thomayer Hospital, First Faculty of Medicine, Charles University kn-affil= affil-num=13 en-affil=Petrov Research Institute of Oncology kn-affil= affil-num=14 en-affil=Semmelweis University kn-affil= affil-num=15 en-affil=Asklepios Lung Clinic kn-affil= affil-num=16 en-affil=AstraZeneca kn-affil= affil-num=17 en-affil=Statistical Services Unit, University of Sheffield kn-affil= affil-num=18 en-affil=AstraZeneca kn-affil= affil-num=19 en-affil=AstraZeneca kn-affil= affil-num=20 en-affil=Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc kn-affil= en-keyword=Small-cell lung cancer kn-keyword=Small-cell lung cancer en-keyword=Durvalumab kn-keyword=Durvalumab en-keyword=Platinum-etoposide kn-keyword=Platinum-etoposide en-keyword=CASPIAN kn-keyword=CASPIAN en-keyword=Patient-reported outcomes kn-keyword=Patient-reported outcomes en-keyword=Health-related quality of life kn-keyword=Health-related quality of life END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=6 article-no= start-page=393 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction en-subtitle= kn-subtitle= en-abstract= kn-abstract=The detection of certain oncogenic driver mutations, including those of epidermal growth factor receptor (EGFR), is essential for determining treatment strategies for advanced non‑small cell lung cancer (NSCLC). The current study assessed the feasibility of testing exhaled breath condensate (EBC) for EGFR mutations by droplet digital PCR (ddPCR). Samples were collected from 12 patients with NSCLC harboring EGFR mutations that were admitted to Okayama University Hospital between June 1, 2014 and December 31, 2017. A total of 21 EBC samples were collected using the RTube™ method and EGFR mutations (L858R, exon 19 deletions or T790M) were assessed through ddPCR analysis (EBC‑ddPCR). A total of 3 healthy volunteer samples were also tested to determine a threshold value for each mutation. Various patient characteristics were determined, including sex (3 males and 9 females), age (range 54‑81 years; median, 66 years), smoking history (10 had never smoked; 2 were former smokers), histology (12 patients exhibited adenocarcinoma), clinical stage (9 patients were stage IV; 3 exhibited post‑operative recurrence) and EGFR mutation type (4 had L858R; 8 had exon 19 deletions; 8 had T790M). EBC‑ddPCR demonstrated positive droplets in 8 of the 12 patients. The sensitivity and specificity of each mutation was as follows: 27.3 and 80.0% for EGFR L858R, 30.0 and 90.9% for EGFR Ex19del, and 22.2 and 100% for EGFR T790M. EBC‑ddPCR analysis of EGFR mutations exhibited modest sensitivity and acceptable specificity. EBC‑ddPCR is a minimally invasive and replicable procedure and may be a complementary method for EGFR testing in patients where blood or tissue sampling proves difficult. en-copyright= kn-copyright= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraTakehiro en-aut-sei=Matsubara en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Okayama University Hospital Biobank kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Okayama University Hospital Biobank kn-affil= affil-num=17 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=epidermal growth factor receptor mutations kn-keyword=epidermal growth factor receptor mutations en-keyword=droplet digital PCR kn-keyword=droplet digital PCR en-keyword=exhaled breath condensate kn-keyword=exhaled breath condensate en-keyword=EGFR-TKIs kn-keyword=EGFR-TKIs END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page=725 end-page=731 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel prospective umbrella-type lung cancer registry study for clarifying clinical practice patterns: CS-Lung-003 study protocol en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction
Conventional cancer registries are suitable for simple surveillance of cancer patients, including disease frequency and distribution, demographics, and prognosis; however, the collected data are inadequate to clarify comprehensively diverse clinical questions in daily practice.
Methods
We constructed an umbrella‐type lung cancer patient registry (CS‐Lung‐003) integrating multiple related prospective observational studies (linked studies) that reflect clinical questions about lung cancer treatment. The primary endpoint of this registry is to clarify daily clinical practice patterns in lung cancer treatment; a key inclusion criterion is pathologically diagnosed lung cancer. Under this registry, indispensable clinical items are detected in advance across all active linked studies and gathered prospectively and systematically to avoid excessive or insufficient data collection. Researchers are to input information mutually, irrespective of the relevance to each researcher's own study. Linked studies under the umbrella of the CS‐Lung‐003 registry will be updated annually with newly raised clinical questions; some linked studies will be newly created, while others will be deleted after the completion of the analysis. Enrollment began in July 2017.
Discussion
We successfully launched the umbrella‐type CS‐Lung‐003 registry. Under this single registry, researchers collaborate on patient registration and data provision for their own and other studies. Thus, the registry will produce results for multiple domains of study, providing answers to questions about lung cancer treatment raised by other researchers. Through such analysis of each linked study, this registry will contribute to the comprehensive elucidation of actual daily practice patterns in lung cancer treatment.
Key points
CS‐Lung‐003 registry directly integrates multiple linked studies created under the umbrella of this cancer registry to solve various clinical questions regarding daily practice patterns of lung cancer treatment. en-copyright= kn-copyright= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObataHideto en-aut-sei=Obata en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaYutaka en-aut-sei=Ueda en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamasakiMasahiro en-aut-sei=Yamasaki en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoritakaTomonori en-aut-sei=Moritaka en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AwayaYoshikazu en-aut-sei=Awaya en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoKeisuke en-aut-sei=Sugimoto en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShibayamaTakuo en-aut-sei=Shibayama en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KubotaTetsuya en-aut-sei=Kubota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KodaniMasahiro en-aut-sei=Kodani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KishinoDaizo en-aut-sei=Kishino en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IshikawaNobuhisa en-aut-sei=Ishikawa en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TsubataYukari en-aut-sei=Tsubata en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IshiiTomoya en-aut-sei=Ishii en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FujitakaKazunori en-aut-sei=Fujitaka en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Shimonoseki City Hospital kn-affil= affil-num=3 en-affil=Yamaguchi-ken Saiseikai Shimonoseki General Hospital kn-affil= affil-num=4 en-affil=Kagawa Prefectural Central Hospital kn-affil= affil-num=5 en-affil=National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=6 en-affil=Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital kn-affil= affil-num=7 en-affil=Ehime Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Miyoshi Central Hospital kn-affil= affil-num=9 en-affil=Japanese Red Cross Kobe Hospital kn-affil= affil-num=10 en-affil=Chugoku Central Hospital kn-affil= affil-num=11 en-affil=National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=12 en-affil=KKR Takamatsu Hospital kn-affil= affil-num=13 en-affil=National Hospital Organization Okayama Medical Center kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine and Allergology, Kochi Medical School, Kochi University kn-affil= affil-num=15 en-affil=Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University kn-affil= affil-num=16 en-affil=Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=17 en-affil=Okayama Rosai Hospital kn-affil= affil-num=18 en-affil=Hiroshima Prefectural Hospital kn-affil= affil-num=19 en-affil=Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=20 en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine kn-affil= affil-num=21 en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=22 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=23 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Database kn-keyword=Database en-keyword=observational study kn-keyword=observational study en-keyword=real world data kn-keyword=real world data en-keyword=surveillance kn-keyword=surveillance en-keyword=treatment kn-keyword=treatment END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=5 article-no= start-page=643 end-page=649 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC.
Methods
Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest.
Results
Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred.
Conclusions
Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events. en-copyright= kn-copyright= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IsozakiHideko en-aut-sei=Isozaki en-aut-mei=Hideko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BesshoAkihiro en-aut-sei=Bessho en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosokawaShinobu en-aut-sei=Hosokawa en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakataIchiro en-aut-sei=Takata en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=Okayama Lung Cancer Study Group en-aut-sei=Okayama Lung Cancer Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=2 en-affil=Department of Clinical Pharmaceutics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Kurashiki Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Kurashiki Central Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=9 en-affil= kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil= kn-affil= en-keyword=Alectinib kn-keyword=Alectinib en-keyword=anaplastic lymphoma kinase kn-keyword=anaplastic lymphoma kinase en-keyword=crizotinib kn-keyword=crizotinib en-keyword=drug therapy kn-keyword=drug therapy en-keyword=non-small cell lung carcinoma kn-keyword=non-small cell lung carcinoma END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=1 article-no= start-page=100107 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations en-subtitle= kn-subtitle= en-abstract= kn-abstract=Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients. en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraokaShunsuke en-aut-sei=Teraoka en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZenkeYoshitaka en-aut-sei=Zenke en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KenmotsuHirotsugu en-aut-sei=Kenmotsu en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYukiko en-aut-sei=Nakamura en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkumaYusuke en-aut-sei=Okuma en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamiyaAkihiro en-aut-sei=Tamiya en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NosakiKaname en-aut-sei=Nosaki en-aut-mei=Kaname kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriseMasahiro en-aut-sei=Morise en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AokageKeiju en-aut-sei=Aokage en-aut-mei=Keiju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OyaYuko en-aut-sei=Oya en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakamotoTomohiro en-aut-sei=Sakamoto en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TanakaKentaro en-aut-sei=Tanaka en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaHisashi en-aut-sei=Tanaka en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TanizakiJunko en-aut-sei=Tanizaki en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MiuraSatoru en-aut-sei=Miura en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MizutaniHideaki en-aut-sei=Mizutani en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MiyauchiEisaku en-aut-sei=Miyauchi en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamaguchiOu en-aut-sei=Yamaguchi en-aut-mei=Ou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=EbiNoriyuki en-aut-sei=Ebi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=GotoYasushi en-aut-sei=Goto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SasakiTakaaki en-aut-sei=Sasaki en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=DagaHaruko en-aut-sei=Daga en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=YamanakaTakeharu en-aut-sei=Yamanaka en-aut-mei=Takeharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=AmanoShinsuke en-aut-sei=Amano en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HasegawaKazuo en-aut-sei=Hasegawa en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ImamuraChiyo K. en-aut-sei=Imamura en-aut-mei=Chiyo K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SuzukiKenichi en-aut-sei=Suzuki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=NakajimaKazuko en-aut-sei=Nakajima en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NishimotoHitomi en-aut-sei=Nishimoto en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=OizumiSatoshi en-aut-sei=Oizumi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HidaToyoaki en-aut-sei=Hida en-aut-mei=Toyoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=TakiguchiYuichi en-aut-sei=Takiguchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=4 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=8 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital East kn-affil= affil-num=11 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=12 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=13 en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University kn-affil= affil-num=14 en-affil=Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Medical Oncology, Kishiwada City Hospital kn-affil= affil-num=17 en-affil=Department of Internal Medicine, Niigata Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Tohoku University Hospital kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center kn-affil= affil-num=21 en-affil=Department of Respiratory Oncology, Iizuka Hospital kn-affil= affil-num=22 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=23 en-affil=Respiratory Center, Asahikawa Medical University kn-affil= affil-num=24 en-affil=Department of Medical Oncology, Osaka City General Hospital kn-affil= affil-num=25 en-affil=Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine Kyoto University kn-affil= affil-num=26 en-affil=Department of Biostatistics, Yokohama City University School of Medicine kn-affil= affil-num=27 en-affil=Japan Federation of Cancer Patient Groups kn-affil= affil-num=28 en-affil=Japan Lung Cancer Alliance kn-affil= affil-num=29 en-affil=Advanced Cancer Translational Research Institute, Showa University kn-affil= affil-num=30 en-affil=Division of Applied Pharmaceutical Education and Research, Hoshi University kn-affil= affil-num=31 en-affil=Department of Nursing and The Division of Stem Cell Transplantation, Shizuoka Cancer Center kn-affil= affil-num=32 en-affil=Department of Nursing, Okayama University Hospital kn-affil= affil-num=33 en-affil=Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=34 en-affil=Department of Thoracic Oncology, Aichi Cancer Center Hospital kn-affil= affil-num=35 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=36 en-affil=Department of Medical Oncology, Chiba University Hospital kn-affil= en-keyword=Non–small cell lung cancer kn-keyword=Non–small cell lung cancer en-keyword=Epidermal growth factor receptor kn-keyword=Epidermal growth factor receptor en-keyword=Systematic review kn-keyword=Systematic review en-keyword=Guidelines kn-keyword=Guidelines END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC. en-copyright= kn-copyright= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KayataniHiroe en-aut-sei=Kayatani en-aut-mei=Hiroe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=20 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=7 article-no= start-page=393 end-page=396 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Evaluation of the Safety and Feasibility of Adenosine-assisted Clipping Surgery for Unruptured Cerebral Aneurysms: Study Protocol en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effectiveness of adenosine-induced flow arrest in surgical clipping for the cerebral aneurysms with difficulties in temporary clip placement to the proximal main trunk has been reported. This is the first clinical trial to evaluate the safety and feasibility of adenosine-assisted clipping surgery for unruptured cerebral aneurysms (UCAs) in Japan. The inclusion criteria are as follows: patients over 20 years old, patients who agree to be enrolled in this study after providing informed consent, patients who undergo clipping surgery for UCA in our institute, and patients in whom the surgeons (T.H. or I.D.) judge that decompression of the aneurysm is effective. The primary endpoint is a modified Rankin Scale (mRS) score 30 days after surgery. We plan to enroll 10 patients in this study. The original protocol of adenosine administration was established in this trial. Herein, we present the study protocol. en-copyright= kn-copyright= en-aut-name=HishikawaTomohito en-aut-sei=Hishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MuraiSatoshi en-aut-sei=Murai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiKazuhiko en-aut-sei=Nishi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EbisudaniYuki en-aut-sei=Ebisudani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoYu en-aut-sei=Sato en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugiuKenji en-aut-sei=Sugiu en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShimizuKazuyoshi en-aut-sei=Shimizu en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiMotomu en-aut-sei=Kobayashi en-aut-mei=Motomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakagawaKoji en-aut-sei=Nakagawa en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Kimura-OnoAya en-aut-sei=Kimura-Ono en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=adenosine kn-keyword=adenosine en-keyword=clipping kn-keyword=clipping en-keyword=unruptured cerebral aneurysm kn-keyword=unruptured cerebral aneurysm END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=3 article-no= start-page=639 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202177 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR‑mutant lung cancer with HIF‑1α/TGF‑α expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with lung cancer harboring EGFR T790M; however, acquired resistance is inevitable due to genetic and epigenetic changes in cancer cells. In addition, a recent randomized clinical trial revealed that the combination of osimertinib and bevacizumab failed to exhibit superior progression‑free survival compared with osimertinib alone. The present study aimed to investigate the effect of triple therapy with osimertinib, bevacizumab and cetuximab in xenograft tumors with different initial tumor volumes (conventional model, 200 mm3 and large model, 500 mm3). The results demonstrated that osimertinib significantly inhibited tumor growth in both the conventional and large models; however, maximum tumor regression was attenuated in the large model in which hypoxia‑inducible factor‑1α (HIF‑1α) and transforming growth factor‑α (TGF‑α) expression levels increased. Although the combination of osimertinib and bevacizumab exerted a greater inhibitory effect on tumor growth compared with osimertinib in the conventional model, the effect of this combination therapy was attenuated in the large model. TGF‑α attenuated sensitivity to osimertinib in vitro; however, this negative effect was counteracted by the combination of osimertinib and cetuximab, but not osimertinib and bevacizumab. In the large xenograft tumor model, the triple therapy induced the greatest inhibitory effect on tumor growth compared with osimertinib alone and its combination with bevacizumab. Clinical trials of the triple therapy are required for patients with lung cancer with EGFR mutations and HIF‑1α/TGF‑α. en-copyright= kn-copyright= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=epidermal growth factor receptor kn-keyword=epidermal growth factor receptor en-keyword=osimertinib kn-keyword=osimertinib en-keyword=bevacizumab kn-keyword=bevacizumab en-keyword=cetuximab kn-keyword=cetuximab en-keyword=hypoxia‑inducible factor‑1α kn-keyword=hypoxia‑inducible factor‑1α en-keyword=transforming growth factor‑α kn-keyword=transforming growth factor‑α END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=17 article-no= start-page=2831 end-page=2837 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Marginal Zone Lymphoma and Lung Adenocarcinoma with an EGFR Exon 19 E746-S752del Mutation in a Patient with IgG4-related Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 68-year-old man presented with a solid mass at the left renal pelvis and ureter with multiple systemic lymphadenopathies and a mass with a cavity in the right lower lobe of the lung. While a transbronchial lung biopsy revealed no malignancy, a biopsy of the renal pelvis showed marginal zone lymphoma with polyclonal IgG4-positive cells. The serum IgG4 level and presence of a bilateral orbital mass suggested Mikulicz disease. The lesions shrank following the administration of steroids. A rebiopsy confirmed lung adenocarcinoma, and its background showed IgG4-positive cells a year later. IgG4-related diseases require careful follow-up because they can be complicated by malignancy. en-copyright= kn-copyright= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GionYuka en-aut-sei=Gion en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=EGFR kn-keyword=EGFR en-keyword=IgG4-related disease kn-keyword=IgG4-related disease en-keyword=marginal zone lymphoma kn-keyword=marginal zone lymphoma en-keyword=osimertinib kn-keyword=osimertinib END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=4 article-no= start-page=100191 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting.
Patients and methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m(2) each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%.
Results: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade >= 3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade >= 3 or treatment-related death did not occur.
Conclusions: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed. en-copyright= kn-copyright= en-aut-name=HottaK. en-aut-sei=Hotta en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaekiS. en-aut-sei=Saeki en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamaguchiM. en-aut-sei=Yamaguchi en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaradaD. en-aut-sei=Harada en-aut-mei=D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BesshoA. en-aut-sei=Bessho en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaK. en-aut-sei=Tanaka en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=InoueK. en-aut-sei=Inoue en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=GembaK. en-aut-sei=Gemba en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShiojiriM. en-aut-sei=Shiojiri en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoY. en-aut-sei=Kato en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NinomiyaT. en-aut-sei=Ninomiya en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuboT. en-aut-sei=Kubo en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KishimotoJ. en-aut-sei=Kishimoto en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShioyamaY. en-aut-sei=Shioyama en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KatsuiK. en-aut-sei=Katsui en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SasakiJ. en-aut-sei=Sasaki en-aut-mei=J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraK. en-aut-sei=Kiura en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SugioK. en-aut-sei=Sugio en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Kumamoto University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=4 en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Kyushu University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kitakyushu Municipal Medical Center kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical and Translational Research, Kyushu University Hospital kn-affil= affil-num=14 en-affil=Clinical Radiology, Radiology Informatics and Network, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=15 en-affil=Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Thoracic and Breast Surgery, Oita University kn-affil= en-keyword=non-small-cell lung cancer kn-keyword=non-small-cell lung cancer en-keyword=locally advanced setting kn-keyword=locally advanced setting en-keyword=chemoradiation kn-keyword=chemoradiation en-keyword=epidermal growth factor receptor kn-keyword=epidermal growth factor receptor END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset en-subtitle= kn-subtitle= en-abstract= kn-abstract=This prespecified subanalysis of the global, randomized controlled phase Ill KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFRIALK alterations and a PD-L1 tumor proportion score of 50% or greater. en-copyright= kn-copyright= en-aut-name=SatouchiMiyako en-aut-sei=Satouchi en-aut-mei=Miyako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NosakiKaname en-aut-sei=Nosaki en-aut-mei=Kaname kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakagawaKazuhiko en-aut-sei=Nakagawa en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AoeKeisuke en-aut-sei=Aoe en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurataTakayasu en-aut-sei=Kurata en-aut-mei=Takayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SekineAkimasa en-aut-sei=Sekine en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriikeAtsushi en-aut-sei=Horiike en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FukuharaTatsuro en-aut-sei=Fukuhara en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugawaraShunichi en-aut-sei=Sugawara en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmemuraShigeki en-aut-sei=Umemura en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakaHideo en-aut-sei=Saka en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakaiHiroshi en-aut-sei=Sakai en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KishiKazuma en-aut-sei=Kishi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatakamiNobuyuki en-aut-sei=Katakami en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HidaToyoaki en-aut-sei=Hida en-aut-mei=Toyoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkamotoHiroaki en-aut-sei=Okamoto en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtagiShinji en-aut-sei=Atagi en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OhiraTatsuo en-aut-sei=Ohira en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HanShi Rong en-aut-sei=Han en-aut-mei=Shi Rong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NoguchiKazuo en-aut-sei=Noguchi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=EbianaVictoria en-aut-sei=Ebiana en-aut-mei=Victoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, Hyogo Cancer Center kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=3 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=4 en-affil=Department of Medical Oncology, Faculty of Medicine, Kindai University kn-affil= affil-num=5 en-affil=Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center kn-affil= affil-num=8 en-affil=Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=9 en-affil=Miyagi Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=11 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine and Medical Oncology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=13 en-affil=Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=14 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=15 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital kn-affil= affil-num=17 en-affil=Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital kn-affil= affil-num=18 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Oncology, Aichi Cancer Center kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=22 en-affil=Department of Surgery, Tokyo Medical University kn-affil= affil-num=23 en-affil=MSD K.K. kn-affil= affil-num=24 en-affil=MSD K.K. kn-affil= affil-num=25 en-affil=Merck & Co., Inc. kn-affil= affil-num=26 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=Japan kn-keyword=Japan en-keyword=non-small-cell lung carcinoma kn-keyword=non-small-cell lung carcinoma en-keyword=PD-L1 protein kn-keyword=PD-L1 protein en-keyword=pembrolizumab kn-keyword=pembrolizumab en-keyword=treatment outcome kn-keyword=treatment outcome END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=20 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of targetable kinases in idiopathic pulmonary fibrosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Methods Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). Results Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. Conclusions We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF. en-copyright= kn-copyright= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Idiopathic pulmonary fibrosis kn-keyword=Idiopathic pulmonary fibrosis en-keyword=RNA sequencing kn-keyword=RNA sequencing en-keyword=Molecular therapeutic target kn-keyword=Molecular therapeutic target en-keyword=Personalized therapy kn-keyword=Personalized therapy END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=3 article-no= start-page=379 end-page=383 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary Aspergilloma and Allergic Bronchopulmonary Aspergillosis Following the 2018 Heavy Rain Event in Western Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 16-year-old boy with asthma participated in recovery volunteer work following the 2018 heavy rains in Japan. One month later, he experienced chest pain and dyspnea. Chest computed tomography revealed a cavity with a fungal ball, and Aspergillus fumigatus was detected in his bronchoalveolar lavage fluid. He was treated with voriconazole, but new consolidations appeared rapidly. He also experienced allergic bronchopulmonary aspergillosis. After prednisolone prescription, the consolidations improved; however, his asthma worsened. He underwent partial lung resection to avoid allergens, and his symptoms improved. We must recognize cases of infection after a disaster, especially in patients with chronic respiratory diseases. en-copyright= kn-copyright= en-aut-name=AndoEri en-aut-sei=Ando en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=2 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=pulmonary aspergilloma kn-keyword=pulmonary aspergilloma en-keyword=allergic bronchopulmonary aspergillosis kn-keyword=allergic bronchopulmonary aspergillosis en-keyword=disaster kn-keyword=disaster END start-ver=1.4 cd-journal=joma no-vol=111 cd-vols= no-issue=12 article-no= start-page=4480 end-page=4489 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset en-subtitle= kn-subtitle= en-abstract= kn-abstract=This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD‐L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression‐free survival was 41.4 (95% confidence interval [CI], 4.2‐42.5) months with pembrolizumab and 4.1 (95% CI, 2.8‐8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11‐0.65]; one‐sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9‒NR) and 21.5 (95% CI, 5.2‐35.0) months, respectively (HR, 0.39 [95% CI, 0.17‐0.91]; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 pembrolizumab‐treated patients (52%) and four chemotherapy‐treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738. en-copyright= kn-copyright= en-aut-name=SatouchiMiyako en-aut-sei=Satouchi en-aut-mei=Miyako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NosakiKaname en-aut-sei=Nosaki en-aut-mei=Kaname kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakagawaKazuhiko en-aut-sei=Nakagawa en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AoeKeisuke en-aut-sei=Aoe en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurataTakayasu en-aut-sei=Kurata en-aut-mei=Takayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SekineAkimasa en-aut-sei=Sekine en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriikeAtsushi en-aut-sei=Horiike en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FukuharaTatsuro en-aut-sei=Fukuhara en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugawaraShunichi en-aut-sei=Sugawara en-aut-mei=Shunichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UmemuraShigeki en-aut-sei=Umemura en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SakaHideo en-aut-sei=Saka en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamamotoNobuyuki en-aut-sei=Yamamoto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakaiHiroshi en-aut-sei=Sakai en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KishiKazuma en-aut-sei=Kishi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KatakamiNobuyuki en-aut-sei=Katakami en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HidaToyoaki en-aut-sei=Hida en-aut-mei=Toyoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkamotoHiroaki en-aut-sei=Okamoto en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtagiShinji en-aut-sei=Atagi en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OhiraTatsuo en-aut-sei=Ohira en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HanShi Rong en-aut-sei=Han en-aut-mei=Shi Rong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NoguchiKazuo en-aut-sei=Noguchi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=EbianaVictoria en-aut-sei=Ebiana en-aut-mei=Victoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, Hyogo Cancer Center kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center kn-affil= affil-num=3 en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=4 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, Kansai Medical University kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center kn-affil= affil-num=8 en-affil=Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Miyagi Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital kn-affil= affil-num=11 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine and Medical Oncology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=13 en-affil=Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=14 en-affil=Internal Medicine III, Wakayama Medical University kn-affil= affil-num=15 en-affil=Department of Thoracic Oncology, Saitama Cancer Center kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, Respiratory Center, Totanomon Hospital kn-affil= affil-num=17 en-affil=Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital kn-affil= affil-num=18 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Oncology, Aichi Cancer Center kn-affil= affil-num=20 en-affil=Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=22 en-affil=Department of Surgery, Tokyo Medical University kn-affil= affil-num=23 en-affil=MSD, K.K. kn-affil= affil-num=24 en-affil=MSD, K.K. kn-affil= affil-num=25 en-affil=Merck & Co., Inc. kn-affil= affil-num=26 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=Japan kn-keyword=Japan en-keyword=non-small-cell lung carcinoma kn-keyword=non-small-cell lung carcinoma en-keyword=PD-L1 protein kn-keyword=PD-L1 protein en-keyword=pembrolizumab kn-keyword=pembrolizumab en-keyword=treatment outcome kn-keyword=treatment outcome END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=494 end-page=498 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=2022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful and Prompt Treatment with Tepotinib for Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation Combined with Lung Abscess Formation: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tepotinib, the novel MET-tyrosine kinase inhibitor, shows an antitumor effect for patients with non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping mutation. In January 2022, the AmoyDx (R) Pan Lung Cancer polymerase chain reaction Panel (AmoyDx (R) panel), which had a shorter turnaround time than the conventional test, was launched in Japan as a tepotinib companion test. We report a patient with an advanced MET-mutant NSCLC promptly diagnosed using the AmoyDx (R) panel and successfully treated with tepotinib. Although the patient's performance status (PS) worsened due to the rapid tumor progression and lung abscess formation, the tumor shrank immediately after tepotinib treatment with marked PS improvement. en-copyright= kn-copyright= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimonishiAtsushi en-aut-sei=Shimonishi en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=MET kn-keyword=MET en-keyword=Tepotinib kn-keyword=Tepotinib en-keyword=Non-small-cell lung cancer kn-keyword=Non-small-cell lung cancer END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=24 article-no= start-page=6184 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Effect of Pleural Effusion on Prognosis in Patients with Non-Small Cell Lung Cancer Undergoing Immunochemotherapy: A Retrospective Observational Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary Minimal data exists on pleural effusion (PE) for non-small cell lung cancer (NSCLC) patients undergoing combined ICI and chemotherapy. We retrospectively investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival and overall survival than those without PE. In addition, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. In conclusion, PE was associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group-Immune Chemotherapy Database (OLCSG-ICD) between December 2018 and December 2020; the OLCSG-ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient's programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. en-copyright= kn-copyright= en-aut-name=NishimuraTomoka en-aut-sei=Nishimura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoKen en-aut-sei=Sato en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KishinoDaizo en-aut-sei=Kishino en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=pleural effusion kn-keyword=pleural effusion en-keyword=non-small cell carcinoma kn-keyword=non-small cell carcinoma en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=9 article-no= start-page=1319 end-page=1322 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fulminant Myocarditis for Non-small-cell Carcinoma of the Lung with Nivolumab and Ipilimumab Plus Chemotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 59-year-old man with a high level of antinuclear antibody received nivolumab and ipilimumab plus che-motherapy for lung cancer. Two weeks after the second course, he was admitted with a fever and severe fa-tigue. Laboratory studies showed elevated markers of myocardial damage, and a myocardial biopsy showed inflammatory cell infiltration, damaged myocardial fibers. Myocarditis was diagnosed as an immune-related adverse event (irAE), and high-dose corticosteroids were initiated. However, his cardiac function rapidly worsened, and he died on the fifth day after admission. There is no established treatment strategy for fulmi-nant myocarditis as an irAE, and the further exploration of viable treatment strategies is required. en-copyright= kn-copyright= en-aut-name=NishimuraTomoka en-aut-sei=Nishimura en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaMitsutaka en-aut-sei=Nakashima en-aut-mei=Mitsutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=myocarditis kn-keyword=myocarditis en-keyword=nivolumab plus ipilimumab kn-keyword=nivolumab plus ipilimumab en-keyword=irAE kn-keyword=irAE en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=83 cd-vols= no-issue=1 article-no= start-page=30 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: STAT3 plays a vital role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment and is reported to be a critical mediator of the oncogenic effects of EGFR mutations. STAT3 activation is mediated through JAK family kinases. We investigated the effect of the JAK1/2 inhibitor AZD1480 on lung tumors induced by an activating EGFR mutation. Materials and methods: Three EGFR tyrosine kinase inhibitor-resistant cell lines (RPC-9, PC-9/Van-R and PC-9/ER3) established from PC-9 harboring an EGFR exon19 deletion mutation were used. Growth inhibition was measured using an MIT assay. Effects of AZD1480 were also evaluated in the xenograft model and in the EGFR transgenic mice model. Protein expressions were assessed by immunoblotting and immunohistochemistry. Group differences were compared using Student's t-test. To evaluate the efficacy of AZD1480 on survival, AZD1480 or vehicle was administered orally from 7 weeks of age of the transgenic mice. Overall survival curves were calculated using the Kaplan-Meier method. Results: The sensitivities of resistant and parent cells to AZD1480 were similar in vitro. AZD1480 (30 or 50 mg/kg/day, per os) reduced angiogenesis and revealed significant tumor regression in a mouse xenograft model: Subsequently, the transgenic mice were treated with AZD1480 (30 mg/kg/day) or vehicle alone. The numbers of lung tumors (long axis exceeding 1 mm) in the AZD1480-treated group and control group were 0.37 +/- 0.18 and 2.25 +/- 0.53 (p <0.001), respectively. AZD1480 treatment suppressed pSTAT3, pJAK1, pJAK2 and angiogenesis. The median survival time in the AZD1480-treated group (217 days) was significantly greater than that in the control group (106 days) (log-rank test, p <0.0001). Conclusion: AZD1480 may be effective against lung tumors driven by an activating EGER mutation. en-copyright= kn-copyright= en-aut-name=MurakamiToshi en-aut-sei=Murakami en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YasugiMasaaki en-aut-sei=Yasugi en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HondaYoshihiro en-aut-sei=Honda en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=2 en-affil= kn-affil=Kawasaki Med Univ, Dept Gen Internal Med 4 affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=4 en-affil= kn-affil=Kawasaki Med Univ, Dept Gen Internal Med 4 affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=11 en-affil= kn-affil=Okayama Univ Hosp, Dept Allergy & Resp Med en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Oncogene addiction kn-keyword=Oncogene addiction en-keyword=EGFR kn-keyword=EGFR en-keyword=JAK2 kn-keyword=JAK2 en-keyword=STAT3 kn-keyword=STAT3 en-keyword=Transgenic mice kn-keyword=Transgenic mice END start-ver=1.4 cd-journal=joma no-vol=322 cd-vols= no-issue=1 article-no= start-page=168 end-page=177 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140310 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Src mediates ERK reactivation in gefitinib resistance in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=To study epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms, we established a novel gefitinib-resistant lung cancer cell line derived from an EGFR-mutant non-small cell lung cancer cell line (PC-9) pretreated with 4-(methylnitrosamino)1-(3-pyridy1)-1-butanone (designated PC9-GR). We found that gefitinib substantially suppressed the EGFR signaling pathway, whereas ERK was reactivated after several hours in PC9-GR but not in PC-9. The combination of gefitinib with ERK inhibition (by U0126) restored gefitinib susceptibility in PC9-GR, but PI3K-Akt inhibition with LY294002 did not. Although the levels of phosphorylated Src were up-regulated simultaneously with ERK reactivation, neither ERK suppression using U0126 nor an ERK-specific siRNA induced Src phosphorylation. Furthermore, dual inhibition of EGFR and Src restored gefitinib sensitivity in PC9-GR in vitro and in vivo. In conclusion, our results indicate that Src-mediated ERK reactivation may play a role in a novel gefitinib resistance mechanism, and that the combined use of gefitinib with a Src inhibitor may be a potent strategy to overcome this resistance. en-copyright= kn-copyright= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaDaijiro en-aut-sei=Harada en-aut-mei=Daijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasugiMasayuki en-aut-sei=Yasugi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=2 en-affil= kn-affil=Kawasaki Hosp, Kawasaki Med Sch, Dept Gen Internal Med 4 affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med affil-num=9 en-affil= kn-affil=Okayama Univ Hosp, Dept Resp Med en-keyword=EGFR kn-keyword=EGFR en-keyword=Src kn-keyword=Src en-keyword=ERK kn-keyword=ERK en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Gefitinib kn-keyword=Gefitinib en-keyword=Resistance kn-keyword=Resistance END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=2 article-no= start-page=127 end-page=132 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A prospective cohort study to define the clinical and pathological features of lung cancers harboring HER2 gene aberrations (the HER2-CS Study) and a phase II study of trastuzumab emtansine (recombinant) in patients with HER2-positive non-small cell lung cancer who recurred, progressed after standard chemotherapy, or were primarily refractory to standard chemotherapy kn-title=HER2異常等の低頻度の分子異常を有する非小細胞肺癌の臨床病理学的特徴を明らかにするための前向き観察研究(HER2-CS Study)と標準化学療法後再発・増悪または標準化学療法不応性のHER2陽性非小細胞肺癌患者を対象としたトラスツズマブエムタンシン(遺伝子組換え)の第2相試験 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name=木浦勝行 kn-aut-sei=木浦 kn-aut-mei=勝行 aut-affil-num=1 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name=堀田勝幸 kn-aut-sei=堀田 kn-aut-mei=勝幸 aut-affil-num=2 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name=佐藤晃子 kn-aut-sei=佐藤 kn-aut-mei=晃子 aut-affil-num=3 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name=大橋圭明 kn-aut-sei=大橋 kn-aut-mei=圭明 aut-affil-num=4 ORCID= en-aut-name=NinomiyaTakashi en-aut-sei=Ninomiya en-aut-mei=Takashi kn-aut-name=二宮崇 kn-aut-sei=二宮 kn-aut-mei=崇 aut-affil-num=5 ORCID= en-aut-name=MinnamiDaisuke en-aut-sei=Minnami en-aut-mei=Daisuke kn-aut-name=南大輔 kn-aut-sei=南 kn-aut-mei=大輔 aut-affil-num=6 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name=田端雅弘 kn-aut-sei=田端 kn-aut-mei=雅弘 aut-affil-num=7 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name=久保寿夫 kn-aut-sei=久保 kn-aut-mei=寿夫 aut-affil-num=8 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name=加藤有加 kn-aut-sei=加藤 kn-aut-mei=有加 aut-affil-num=9 ORCID= en-aut-name=HirataTaizo en-aut-sei=Hirata en-aut-mei=Taizo kn-aut-name=平田泰三 kn-aut-sei=平田 kn-aut-mei=泰三 aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=岡山大学病院 affil-num=2 en-affil= kn-affil=岡山大学病院 affil-num=3 en-affil= kn-affil=岡山大学病院 affil-num=4 en-affil= kn-affil=岡山大学病院 affil-num=5 en-affil= kn-affil=岡山大学病院 affil-num=6 en-affil= kn-affil=岡山大学病院 affil-num=7 en-affil= kn-affil=岡山大学病院 affil-num=8 en-affil= kn-affil=岡山大学病院 affil-num=9 en-affil= kn-affil=岡山大学病院 affil-num=10 en-affil= kn-affil=岡山大学病院 en-keyword=臨床研究中核病院 kn-keyword=臨床研究中核病院 en-keyword=国立研究開発法人日本医療研究開発機構 kn-keyword=国立研究開発法人日本医療研究開発機構 en-keyword=文部科学省橋渡し研究加速ネットワークプログラム kn-keyword=文部科学省橋渡し研究加速ネットワークプログラム en-keyword=HER2-CS study kn-keyword=HER2-CS study en-keyword=trastuzumab emtansine kn-keyword=trastuzumab emtansine END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=5 article-no= start-page=e0285273 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC.

Methods
Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.

Results
We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11).

Conclusion
Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. en-copyright= kn-copyright= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkumuraNorihito en-aut-sei=Okumura en-aut-mei=Norihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiHiroyuki en-aut-sei=Suzuki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataMasao en-aut-sei=Nakata en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiya en-aut-sei=Fujiwara en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GembaKenichi en-aut-sei=Gemba en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SanoIsao en-aut-sei=Sano en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujinagaTakuji en-aut-sei=Fujinaga en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaMasafumi en-aut-sei=Kataoka en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TerazakiYasuhiro en-aut-sei=Terazaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataokaKazuhiko en-aut-sei=Kataoka en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KosakaShinji en-aut-sei=Kosaka en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamashitaMotohiro en-aut-sei=Yamashita en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InokawaHidetoshi en-aut-sei=Inokawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NakamuraHiroshige en-aut-sei=Nakamura en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaYoshinori en-aut-sei=Yamashita en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshiokaHiroshige en-aut-sei=Yoshioka en-aut-mei=Hiroshige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MoritaSatoshi en-aut-sei=Morita en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MatsuoKeitaro en-aut-sei=Matsuo en-aut-mei=Keitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=SakamotoJunichi en-aut-sei=Sakamoto en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=DateHiroshi en-aut-sei=Date en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Chest Surgery, Fukushima Medical University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Kawasaki Medical School Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Chugoku Central Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center kn-affil= affil-num=10 en-affil=Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory S0urgery, Saga-Ken Medical Centre Koseikan kn-affil= affil-num=12 en-affil=Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=14 en-affil=Department of Thoracic Surgery, Shimane Prefectural Central Hospital kn-affil= affil-num=15 en-affil=Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=16 en-affil=Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center kn-affil= affil-num=17 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=18 en-affil=Division of General Thoracic Surgery, Tottori University Hospital kn-affil= affil-num=19 en-affil=Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center kn-affil= affil-num=20 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital kn-affil= affil-num=22 en-affil=Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine kn-affil= affil-num=23 en-affil=Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute kn-affil= affil-num=24 en-affil=Tokai Central Hospital kn-affil= affil-num=25 en-affil=Department of Thoracic Surgery, Kyoto University Hospital kn-affil= affil-num=26 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue= article-no= start-page=101669 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=2022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Massive hemoptysis in a post-operative patient with recurrent lung cancer successfully treated by the combination therapy of Endobronchial Watanabe Spigot and bronchial artery embolization en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 76-year-old woman who was treated with lorlatinib for postoperative recurrent anaplastic lymphoma kinase-positive lung adenocarcinoma visited our hospital with massive hemoptysis. Chest computed tomography showed massive bleeding from the right upper lobe; however, the cause of bleeding was unclear. After bronchial artery embolization (BAE), bronchial occlusion was performed using an Endobronchial Watanabe Spigot (EWS) that was easily placed because BAE had reduced the bleeding volume. Treatment with BAE alone was inadequate; however, additional therapy with EWS after BAE successfully controlled the massive hemoptysis, especially in this patient who underwent lobectomy to prevent respiratory dysfunction. en-copyright= kn-copyright= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Hemoptysis kn-keyword=Hemoptysis en-keyword=Bronchial artery embolization kn-keyword=Bronchial artery embolization en-keyword=Endoscopic bronchial occlusion kn-keyword=Endoscopic bronchial occlusion en-keyword=Endobronchial Watanabe Spigot kn-keyword=Endobronchial Watanabe Spigot END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue=11 article-no= start-page=4343 end-page=4354 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings. en-copyright= kn-copyright= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakadaKenji en-aut-sei=Takada en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeHiromi en-aut-sei=Watanabe en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine kn-affil= affil-num=21 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=alectinib kn-keyword=alectinib en-keyword=ALK kn-keyword=ALK en-keyword=gilteritinib kn-keyword=gilteritinib en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=TKI kn-keyword=TKI END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=2 article-no= start-page=89 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC.
Methods We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003).
Results A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046).
Conclusion ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.
en-copyright= kn-copyright= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsubataYukari en-aut-sei=Tsubata en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaNobuhisa en-aut-sei=Ishikawa en-aut-mei=Nobuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KodaniMasahiro en-aut-sei=Kodani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanajiNobuhiro en-aut-sei=Kanaji en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiMasahiro en-aut-sei=Yamasaki en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujitakaKazunori en-aut-sei=Fujitaka en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuyamaShoichi en-aut-sei=Kuyama en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KubotaTetsuya en-aut-sei=Kubota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraKeiichi en-aut-sei=Fujiwara en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HaritaShingo en-aut-sei=Harita en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TakataIchiro en-aut-sei=Takata en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TakadaKenji en-aut-sei=Takada en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Faculty of Medicine, Shimane University kn-affil= affil-num=6 en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital kn-affil= affil-num=7 en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=8 en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology, and Respiratory Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital kn-affil= affil-num=10 en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=12 en-affil=Department of Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine and Allergology, Kochi University Hospital kn-affil= affil-num=15 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=16 en-affil=Department of Respiratory Medicine, NHO Okayama Medical Center kn-affil= affil-num=17 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=18 en-affil=Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=EGFR kn-keyword=EGFR en-keyword=EGFR-TKI kn-keyword=EGFR-TKI en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors en-keyword=Performance status kn-keyword=Performance status END