Updated on 2025/06/06

写真a

 
NINOMIYA Kiichiro
 
Organization
Scheduled update Special-Appointment Assistant Professor
Position
Special-Appointment Assistant Professor
External link

Degree

  • 医学 ( 2018.6   岡山大学 )

  • Doctor of Philosophy ( 2018.6   Okayama University )

Research Interests

  • システマティックレビュー

  • 肺癌

  • 医学統計

  • ゲノム医療

Education

  • Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences    

    2014.4 - 2018.6

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    Country： Japan

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  • Okayama University   医学部   医学科

    2003.4 - 2009.3

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    Country： Japan

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Research History

  • Okayama University Hospital   Center for Comprehensive Genomic Medicine   Assisstant Professor

    2022.4

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    Country：Japan

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  • Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences   Department of Hematology, Oncology and Respiratory Medicine   Assistant Professor

    2021.4 - 2022.3

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    Country：Japan

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  • Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences   Department of Hematology, Oncology and Respiratory Medicine   Assistant Professor

    2018.4 - 2021.3

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    Country：Japan

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  • Okayama University Hospital   Department of Respiratory Medicine   Medical doctor

    2013.4 - 2014.12

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    Country：Japan

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  • Chugoku Central Hospital   Internal Medicine   Medical doctor

    2011.4 - 2013.3

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  • Chugoku Central Hospital   early Resident

    2009.4 - 2011.3

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    Country：Japan

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Committee Memberships

  •   高齢者がん診療ガイドライン作成委員会 運営委員  

    2021.4 - 2023.3   

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  • Japanese Society of Medical Oncology   Member of Cancer Immunotherapy Guidelines Committee  

    2021.2   

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    Committee type：Academic society

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  • 日本肺癌学会   中国・四国支部 評議員  

    2018.7   

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    Committee type：Academic society

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  • Japanese Lung Cancer Society   Guideline Committee Member of JLCS  

    2015.5   

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    Committee type：Academic society

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Papers

  • Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines. International journal

    Tatsuya Nishi, Ayako Morita, Naofumi Hara, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yosuke Togashi, Yoshinobu Maeda, Eiki Ichihara

    Lung cancer (Amsterdam, Netherlands)   201   108415 - 108415   2025.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective in treating ALK-rearranged non-small-cell lung cancer (NSCLC). However, at least 40% of patients develop acquired resistance during treatment. Adaptive or acquired resistance to ALK TKIs could be mediated through epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) signaling. Sixteen percent of acquired resistance cases are linked to bypass signaling. METHODS: In this study, we evaluated the effects of amivantamab, a bi-specific antibody targeting both EGFR and MET, on ALK-rearranged NSCLC cells. We investigated the effect of amivantamab on the ALK-rearranged NSCLC cell lines H3122, ABC-19, and ABC-11. RESULTS: Combining alectinib with amivantamab resulted in greater inhibition of cell growth inhibition in H3122 and ABC-19 cells compared to alectinib alone, but not in ABC-11 cells. EGFR TKI erlotinib showed similar efficacy in H3122 and ABC-19 cells, whereas MET TKI tepotinib was ineffective in both, suggesting that the efficacy of amivantamab is through EGFR inhibition. Unlike H3122 and ABC-19 cells, ABC-11 cells were resistant to EGFR/MET signaling inhibition. Interestingly, amivantamab enhanced alectinib efficacy against ABC-11 cells in the presence of peripheral blood mononuclear cells (PBMCs), despite showing no effect alone without PBMCs, suggesting action through non-signal inhibitory mechanisms. Finally, we treated alectinib-resistant cellswith alectinib, with or without amivantamab, and found that amivantamab restored the sensitivity of these cells to alectinib. CONCLUSION: The bi-specific antibody amivantamab, which targets EGFR and MET, enhanced the efficacy of alectinib through both signal and non-signal inhibitory mechanisms in ALK-rearranged NSCLC cells.

    DOI： 10.1016/j.lungcan.2025.108415

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  • High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells. International journal

    Hiroaki Matsuura, Takamasa Ishino, Toshifumi Ninomiya, Kiichiro Ninomiya, Kota Tachibana, Akiko Honobe-Tabuchi, Yoshinori Muto, Takashi Inozume, Youki Ueda, Kadoaki Ohashi, Yoshinobu Maeda, Joji Nagasaki, Yosuke Togashi

    Cancer science   2025.2

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    Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb.

    DOI： 10.1111/cas.70029

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  • A single-arm, phase II study of sotorasib plus carboplatin/pemetrexed in advanced non-squamous non-small cell lung cancer patients with KRAS G12C mutation (WJOG14821L, SCARLET). International journal

    Hiroaki Akamatsu, Shinya Sakata, Koichi Azuma, Hiroshige Yoshioka, Takehiro Uemura, Yuko Tsuchiya-Kawano, Seiya Esumi, Takashi Kurosaki, Yuki Sato, Tomohiro Sakamoto, Kiichiro Ninomiya, Ryo Toyozawa, Yasuto Yoneshima, Takehito Shukuya, Toshiyuki Kozuki, Kana Watanabe, Haruko Daga, Terufumi Kato, Toshiaki Takahashi, Mitsuo Osuga, Yasuhiro Koh, Satoshi Morita, Nobuyuki Yamamoto

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   2025.1

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    BACKGROUND: The efficacy and safety of sotorasib plus platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous non-small cell lung cancer (non-Sq NSCLC) were previously reported with limited follow-up period. METHOD: SCARLET was a single-arm phase II study of chemotherapy-naïve patients with KRAS G12C-mutated non-Sq NSCLC. Participants received sotorasib 960 mg daily plus four cycles of carboplatin (area under the curve, 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary endpoint was the overall response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and disease progression (jRCT2051210086). RESULTS: Thirty patients were enrolled between Oct 2021 and Jul 2022, with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI], 78.5-94.8%; 95% CI, 70.8-97.6%), median PFS was 6.6 months (95% CI, 5.3-16.7 months), and median OS was 20.6 months (95% CI, 8.1 months-not estimated). Among patients with programmed death ligand 1 expression levels ≥ 1% and < 1%, ORRs were 82.3 and 100% and median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 months, respectively). TP53 mutation and epidermal growth factor receptor (EGFR) and MET amplification were detected acquired resistances. CONCLUSION: In patients with KRAS G12C-mutated non-Sq NSCLC, sotorasib plus carboplatin/pemetrexed demonstrated favorable efficacy especially in PD-L1 <1%, with manageable toxicity.

    DOI： 10.1016/j.jtho.2025.01.006

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  • Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study. International journal

    Shigeru Tanzawa, Hiroshige Yoshioka, Toshihiro Misumi, Eisaku Miyauchi, Kiichiro Ninomiya, Yasunori Murata, Masafumi Takeshita, Fumihiko Kinoshita, Takatoshi Fujishita, Shunichi Sugawara, Yosuke Kawashima, Kazuki Hashimoto, Masahide Mori, Akihiko Miyanaga, Anna Hayashi, Hisashi Tanaka, Ryoichi Honda, Masafumi Nojiri, Yuki Sato, Akito Hata, Nobuhisa Ishikawa, Toshiyuki Kozuki, Takahisa Kawamura, Go Saito, Teppei Yamaguchi, Kazuhiro Asada, Satoshi Tetsumoto, Hiroshi Tanaka, Satoshi Watanabe, Yukihiro Umeda, Kakuhiro Yamaguchi, Kazuya Nishii, Kosuke Tsuruno, Yuki Misumi, Hiroshi Kuraishi, Ken Yoshihara, Akira Nakao, Akihito Kubo, Toshihiko Yokoyama, Kana Watanabe, Nobuhiko Seki

    Therapeutic advances in medical oncology   17   17588359251318850 - 17588359251318850   2025

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    BACKGROUND: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear. OBJECTIVE: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy. DESIGN: This was a sub-analysis of the retrospective multicenter NINJA study. METHODS: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations. RESULTS: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021). CONCLUSION: GCN as a second-line or later therapy may be tolerable regardless of the patient's baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival.

    DOI： 10.1177/17588359251318850

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  • Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study. International journal

    Fumihiko Kinoshita, Shigeru Tanzawa, Toshihiro Misumi, Hiroshige Yoshioka, Eisaku Miyauchi, Kiichiro Ninomiya, Yasunori Murata, Masafumi Takeshita, Masafumi Yamaguchi, Shunichi Sugawara, Yosuke Kawashima, Kazuki Hashimoto, Masahide Mori, Akihiko Miyanaga, Anna Hayashi, Hisashi Tanaka, Ryoichi Honda, Masafumi Nojiri, Yuki Sato, Ken Yamamoto, Ken Masuda, Toshiyuki Kozuki, Takahisa Kawamura, Takuji Suzuki, Teppei Yamaguchi, Kazuhiro Asada, Satoshi Tetsumoto, Hiroshi Tanaka, Satoshi Watanabe, Yukihiro Umeda, Kakuhiro Yamaguchi, Shoichi Kuyama, Kosuke Tsuruno, Yuki Misumi, Hiroshi Kuraishi, Ken Yoshihara, Akira Nakao, Akihito Kubo, Toshihiko Yokoyama, Kana Watanabe, Nobuhiko Seki

    Therapeutic advances in medical oncology   17   17588359241312503 - 17588359241312503   2025

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    BACKGROUND: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear. OBJECTIVES: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration. DESIGN: This was a sub-analysis of the retrospective multicenter NINJA study. METHODS: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders. RESULTS: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495). CONCLUSION: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days.

    DOI： 10.1177/17588359241312503

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  • A Prompt Diagnosis and Treatment of a Case of Nuclear Protein of the Testis Carcinoma Characterized by a Bronchial Lesion and High Serum Alpha-fetoprotein Level Following Genomic Testing.

    Hiroaki Matsuura, Go Makimoto, Naohiro Oda, Kiichiro Ninomiya, Hisao Higo, Masanori Fujii, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda

    Internal medicine (Tokyo, Japan)   63 ( 19 )   2655 - 2660   2024.10

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    Nuclear protein of the testis carcinoma (NUTC) is a rare and aggressive malignancy. We herein report a case of NUTC in the lung characterized by a bronchial lesion and elevated alpha-fetoprotein levels. A 35-year-old Japanese man presented to our institution with suspected advanced lung cancer based on a histological examination. Subsequently, next-generation sequencing (NGS) yielded a positive BRD4-NUTM1 fusion. In addition, positive NUT immunostaining of the lung biopsy specimen confirmed NUTC in the lungs. Systemic chemotherapy and radiotherapy showed a temporary response, with decreased serum alpha-fetoprotein levels. We highlight this case of a prompt diagnosis by NGS of NUTC in a young individual with a rapidly progressing tumor.

    DOI： 10.2169/internalmedicine.2938-23

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  • MET遺伝子増幅を認め、カプマチニブが著効した原発不明癌の1例

    槇本 剛, 田中 孝明, 住井 遼平, 表 梨華, 二宮 貴一朗, 安藤 弥生, 前田 嘉信, 田端 雅弘

    日本癌治療学会学術集会抄録集   62回   ICCJ3 - 3   2024.10

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  • 小児・AYA世代がんのゲノム医療 小児・AYA世代の肉腫におけるゲノム医療の意義

    中田 英二, 遠西 大輔, 二宮 貴一朗, 冨田 秀太, 山本 英喜, 岡崎 哲也, 平沢 晃, 豊岡 伸一, 尾崎 敏文

    日本癌治療学会学術集会抄録集   62回   OSY16 - 2   2024.10

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    Language：Japanese   Publisher：(一社)日本癌治療学会  

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  • EGFR変異陽性非小細胞肺癌患者に対するアファチニブ±ベバシズマブ療法のバイオマーカー探索

    二宮 貴一朗, 坂井 和子, 大橋 圭明, 石川 暢久, 上月 稔幸, 久山 彰一, 金地 伸拓, 横山 俊秀, 二宮 崇, 堀田 勝幸, 西尾 和人, 木浦 勝行

    肺癌   64 ( 5 )   527 - 527   2024.10

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    Language：Japanese   Publisher：(NPO)日本肺癌学会  

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  • A Case of Single-lung Transplant in a Patient with Mycobacterium avium Pulmonary Disease Successfully Treated with Amikacin Liposome Inhalation Suspension.

    Taichi Ozeki, Hisao Higo, Hiroki Omori, Shunta Mori, Shin Tanaka, Go Makimoto, Kiichiro Ninomiya, Akihiko Taniguchi, Masanori Fujii, Kentaro Miyoshi, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Seiichiro Sugimoto, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Nobuaki Miyahara

    Internal medicine (Tokyo, Japan)   2024.9

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    A 55-year-old man presented to our hospital with idiopathic pulmonary fibrosis (IPF). He was registered with the Japan Organ Transplant Network the following year due to disease progression. Treatment with clarithromycin, ethambutol, and rifampicin for complications of Mycobacterium avium pulmonary disease was initiated, but sputum conversion could not be achieved. The administration of an amikacin liposome inhalation suspension (ALIS) resulted in sputum conversion, and single-lung transplantation was performed. ALIS therapy was continued after lung transplantation, and no M. avium disease was observed for 15 months. ALIS may cause M. avium pulmonary disease with additional indications for lung transplantation.

    DOI： 10.2169/internalmedicine.3854-24

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  • Response to Imatinib in a Patient With Gastric Adenocarcinoma With KIT Q556_K558 In-Frame Deletion: A Case Report. International journal

    Kiichiro Ninomiya, Daisuke Ennishi, Kunio Okamoto, Midori Ando, Satoko Nakamura, Shuta Tomida, Yoshiyuki Ayada, Go Makimoto, Eiki Ichihara, Natsuko Okita, Shinichi Toyooka, Yoshinobu Maeda, Masahiro Tabata

    JCO precision oncology   8   e2400228   2024.9

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    Imatinib may be a useful targeted agent for patients with advanced gastric adenocarcinoma who have KIT mutations.

    DOI： 10.1200/PO.24.00228

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  • 新たながん遺伝子パネル検査 TruSight Oncology 500(TSO500)の臨床的意義(Clinical relevance of novel comprehensive genomic profiling assay - TruSight Oncology 500(TSO500))

    遠西 大輔, 冨田 秀太, 松井 啓隆, 藤野 泰輝, 檜井 孝夫, 杉本 健樹, 川上 耕史, 松本 光史, 山本 弥寿子, 曳野 肇, 二宮 貴一朗, 山本 英喜, 柳井 広之, 平沢 晃, 豊岡 伸一, 豊岡 伸一

    日本癌学会総会記事   83回   P - 2114   2024.9

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  • 肉腫におけるゲノム医療の進歩 C-CATデータを用いた肉腫のゲノム解析

    中田 英二, 遠西 大輔, 二宮 貴一朗, 山本 英喜, 冨田 秀太, 国定 俊之, 藤原 智洋, 二川 摩周, 平沢 晃, 豊岡 伸一, 尾崎 敏文

    日本整形外科学会雑誌   98 ( 8 )   S1727 - S1727   2024.9

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  • Concomitant osimertinib and antituberculosis therapy in an elderly patient with EGFR-mutated lung cancer and pulmonary tuberculosis: A case report. International journal

    Hiroaki Matsuura, Hisao Higo, Tadahiro Kuribayashi, Akihiko Tamaoki, Takamasa Nakasuka, Mari Uno, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Nobuaki Miyahara, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Kadoaki Ohashi

    Thoracic cancer   15 ( 17 )   1390 - 1394   2024.6

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    The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well-established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89-year-old female, diagnosed with epidermal growth factor receptor (EGFR)-mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.

    DOI： 10.1111/1759-7714.15324

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  • 加速する骨・軟部腫瘍に対するゲノム医療: 現状と課題 肉腫におけるゲノム医療の現状と課題

    中田 英二, 遠西 大輔, 二宮 貴一朗, 山本 英喜, 冨田 秀太, 藤原 智洋, 国定 俊之, 平沢 晃, 豊岡 伸一, 尾崎 敏文

    日本整形外科学会雑誌   98 ( 6 )   S1457 - S1457   2024.6

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  • 加速する骨・軟部腫瘍に対するゲノム医療: 現状と課題 肉腫におけるゲノム医療の現状と課題

    中田 英二, 遠西 大輔, 二宮 貴一朗, 山本 英喜, 冨田 秀太, 藤原 智洋, 国定 俊之, 平沢 晃, 豊岡 伸一, 尾崎 敏文

    日本整形外科学会雑誌   98 ( 6 )   S1457 - S1457   2024.6

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  • 肝切除後の難治性気管支胆汁瘻に対してEndobronchial Watanabe Spigotの挿入が感染制御に有効であった1例

    宇野 真梨, 槇本 剛, 藤 智和, 大森 洋樹, 肥後 寿夫, 本倉 優美, 田中 孝明, 森 俊太, 大西 桐子, 二宮 貴一朗, 頼 冠名, 市原 英基, 田端 雅弘, 宮原 信明, 堀田 勝幸, 大橋 圭明

    気管支学   46 ( Suppl. )   S337 - S337   2024.5

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    Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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  • 肺癌における抗CTLA-4抗体が腫瘍浸潤制御性T細胞に与える影響の解明

    冨樫 庸介, 渡部 智文, 松浦 宏昌, 二宮 貴一朗

    日本呼吸器学会誌   13 ( 増刊 )   124 - 124   2024.3

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  • Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study. International journal

    Tadahiro Kuribayashi, Kadoaki Ohashi, Kazuya Nishii, Kiichiro Ninomiya, Yukari Tsubata, Nobuhisa Ishikawa, Masahiro Kodani, Nobuhiro Kanaji, Masahiro Yamasaki, Kazunori Fujitaka, Shoichi Kuyama, Nagio Takigawa, Nobukazu Fujimoto, Tetsuya Kubota, Masaaki Inoue, Keiichi Fujiwara, Shingo Harita, Ichiro Takata, Kenji Takada, Sachi Okawa, Katsuyuki Kiura, Katsuyuki Hotta

    Journal of cancer research and clinical oncology   150 ( 2 )   89 - 89   2024.2

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    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.

    DOI： 10.1007/s00432-024-05618-4

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  • Artemis: A Multicenter, Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of First-Line Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas. International journal

    Yusuke Okuma, Shogo Nomura, Jun Sakakibara-Konishi, Yoko Tsukita, Shuji Murakami, Yukio Hosomi, Yuichi Tambo, Yoshihito Kogure, Hiroshige Yoshioka, Motohiro Tamiya, Kiichiro Ninomiya, Eiji Iwama

    Clinical lung cancer   2024.2

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    BACKGROUND: Thymic carcinoma is a rare cancer with an aggressive clinical presentation and no organotypic symptoms. Despite using platinum-based chemotherapy as first-line treatment, the prognosis remains poor, necessitating a novel therapeutic strategy. METHODS: The artemis trial is a Phase II, single-arm, multicenter study designed to evaluate the efficacy and safety of carboplatin, paclitaxel, lenvatinib, and pembrolizumab as first-line chemotherapy for patients with advanced or recurrent thymic carcinoma. A total of 35 patients will be enrolled in this study and will receive induction therapy every 3 weeks for up to 4 cycles, followed by pembrolizumab every 3 weeks, and daily lenvatinib as maintenance therapy for up to 31 cycles (for 2 years). Lenvatinib will be continued until disease progression or unacceptable toxicity based on the discretion of the attending physician. CONCLUSION: The primary endpoint of the study is the objective response rate, with secondary endpoints including progression-free survival, overall survival, duration of response, disease control rate, and safety profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832827 Registered on April 27, 2023, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05832827. Japan Registry of Clinical Trials (jRCT), jRCT2031230114. Registered on May 22, 2023, https://jrct.niph.go.jp/latest-detail/jRCT2031230114.

    DOI： 10.1016/j.cllc.2024.02.002

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  • Protracted coronavirus disease 2019 after chimeric antigen receptor-T cell therapy successfully treated with sequential multidrug therapy. International journal

    Masahiro Yamashita, Hisao Higo, Nobuharu Fujii, Chiaki Matsumoto, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Nobuaki Miyahara

    Respiratory medicine case reports   51   102104 - 102104   2024

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    A 56-year-old woman who received CD19 chimeric antigen receptor-T cell therapy for refractory diffuse large B-cell lymphoma developed severe coronavirus disease 2019 (COVID-19) and was treated with nirmatrelvir/ritonavir in April 2022. However, she experienced persistent fatigue and cough and fever in June. Computed tomography revealed bilateral ground-glass opacities (GGO), and the patient was treated with corticosteroids for organizing pneumonia after COVID-19. Partial improvement was observed, but new GGO appeared despite corticosteroid therapy. Genome analysis of severe acute respiratory syndrome coronavirus 2 detected Omicron variant BA.1.1.2, which was prevalent at the time of initial infection. The patient was diagnosed with protracted COVID-19 and was treated with remdesivir, molnupiravir, nirmatrelvir/ritonavir, and tixagevimab/cilgavimab. These treatments appeared to contribute to the improvement of protracted COVID-19.

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  • A Unique Case of Sarcoid-associated Myelopathy Accompanied by Lung Cancer.

    Koh Tadokoro, Yumi Nakada, Ryo Sasaki, Yumiko Nakano, Taijun Yunoki, Kotaro Shin, Masataka Taoka, Kiichiro Ninomiya, Emi Nomura, Mami Takemoto, Ryuta Morihara, Toru Yamashita

    Internal medicine (Tokyo, Japan)   62 ( 23 )   3531 - 3535   2023.12

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    The differential diagnosis of myelopathy in patients with malignancies may be challenging, as a spinal biopsy is not always applicable. A 66-year-old woman who had shown transient double vision and nausea developed spasticity and impaired deep sensation in both feet. Magnetic resonance imaging showed abnormal gadolinium enhancement of the brainstem, spinal meninges, and nerve root. Cerebrospinal fluid (CSF) revealed mild pleocytosis and elevated protein and decreased glucose levels, although CSF cytology was normal. Lung carcinoma was simultaneously detected, and noncaseating granuloma was detected from the hilar and axillary lymph nodes, so she was diagnosed with sarcoid-associated myelopathy. Her symptoms were kept stable by intravenous methylprednisolone, oral prednisolone, and methotrexate. This is the first case of sarcoid-associated myelopathy accompanied by lung cancer, suggesting the importance of clinical course, repetitive CSF cytology, and a biopsy of the lymph nodes to distinguish sarcoid-associated myelopathy from meningeal metastasis in patients with malignancies.

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  • 【肺癌に対する薬物治療の最前線】免疫療法耐性とVEGF阻害による克服

    大橋 圭明, 二宮 貴一朗, 栗林 忠弘

    医学のあゆみ   287 ( 7 )   487 - 491   2023.11

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  • CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. International journal

    Naofumi Hara, Eiki Ichihara, Hirohisa Kano, Chihiro Ando, Ayako Morita, Tatsuya Nishi, Sachi Okawa, Takamasa Nakasuka, Atsuko Hirabae, Masaya Abe, Noboru Asada, Kiichiro Ninomiya, Go Makimoto, Masanori Fujii, Toshio Kubo, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Translational lung cancer research   12 ( 10 )   2098 - 2112   2023.10

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    BACKGROUND: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance. METHODS: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC. RESULTS: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation. CONCLUSIONS: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.

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  • Necitumumabの皮膚障害と有効性の関連性 多施設共同後方視的観察(NINJA Study)からの新たな知見

    川嶋 庸介, 丹澤 盛, 村田 泰規, 藤下 卓才, 宮永 晃彦, 田中 寿志, 野尻 正文, 佐藤 悠城, 秦 明登, 益田 健, 上月 稔幸, 川村 卓久, 山口 哲平, 朝田 和博, 吉岡 弘鎮, 宮内 栄作, 二宮 貴一朗, 三角 俊裕, 関 順彦

    肺癌   63 ( 5 )   487 - 487   2023.10

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  • Severe Cytokine Release Syndrome and Immune Effector Cell-associated Neurotoxicity Syndrome in a Man Receiving Immune Checkpoint Inhibitors for Lung Cancer: A Case Report.

    Takaaki Tanaka, Masataka Taoka, Go Makimoto, Kiichiro Ninomiya, Hisao Higo, Masanori Fujii, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda

    Internal medicine (Tokyo, Japan)   2023.9

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    A 55-year-old man with stage IV lung adenocarcinoma was treated with cisplatin, pemetrexed, nivolumab, and ipilimumab. Approximately 100 days after treatment initiation, he became disoriented and presented to the emergency department with a high fever. Blood tests revealed liver and kidney dysfunctions. Subsequently, the patient developed generalized convulsions that required intensive care. He was clinically diagnosed with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Organ damage was gradually controlled with immunosuppressive drugs, including steroids, and the patient was discharged. Successful treatment is rare in patients with CRS, including ICANS, during immune checkpoint inhibitor treatment for solid tumors.

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  • Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer. International journal

    Chihiro Ando, Eiki Ichihara, Tatsuya Nishi, Ayako Morita, Naofumi Hara, Kenji Takada, Takamasa Nakasuka, Hiromi Watanabe, Hirohisa Kano, Kazuya Nishii, Go Makimoto, Takumi Kondo, Kiichiro Ninomiya, Masanori Fujii, Toshio Kubo, Kadoaki Ohashi, Ken-Ichi Matsuoka, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer science   2023.9

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    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.

    DOI： 10.1111/cas.15958

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  • Radiation-Induced Lung Injury With Lung Cancer Treated With the Combination Therapy of Nintedanib and Dexamethasone. International journal

    Junko Itano, Goro Kimura, Kiichiro Ninomiya, Yasushi Tanimoto

    Cureus   15 ( 9 )   e45678   2023.9

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    Radiation-induced lung injury (RILI) associated with lung cancer becomes refractory. Nintedanib is a multi-kinase inhibitor that suppresses the development of pulmonary fibrosis. Herein, we report a case of RILI with progressive pulmonary fibrosis after stereotactic body radiation therapy in a 70-year-old man with lung cancer. The patient responded well to the initial prednisolone therapy but became resistant during tapering. The combination therapy of nintedanib and dexamethasone resulted in a temporary improvement in RILI. Nintedanib is not a standard therapy for RILI, and further investigation is needed to evaluate the effects of nintedanib on RILI complicated by lung cancer.

    DOI： 10.7759/cureus.45678

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  • Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies. International journal

    Naoya Kemmotsu, Kiichiro Ninomiya, Kei Kunimasa, Takamasa Ishino, Joji Nagasaki, Yoshihiro Otani, Hiroyuki Michiue, Eiki Ichihara, Kadoaki Ohashi, Takako Inoue, Motohiro Tamiya, Kazuko Sakai, Youki Ueda, Hiromichi Dansako, Kazuto Nishio, Katsuyuki Kiura, Isao Date, Yosuke Togashi

    International journal of cancer   2023.8

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    Intracranial metastases are common in nonsmall-cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies compared with those treated without PD-1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade were suppressed. Accordingly, long-lived memory precursor effector T cells and antigen-specific T cells were increased by PD-1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD-1 blockade therapies, aggressive local therapies could be worthwhile.

    DOI： 10.1002/ijc.34700

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  • 肉腫診療におけるがん遺伝子パネルの有用性

    中田 英二, 藤原 智洋, 国定 俊之, 遠西 大輔, 山本 英喜, 二宮 貴一朗, 冨田 秀太, 二川 摩周, 平沢 晃, 豊岡 伸一, 尾崎 敏文

    日本整形外科学会雑誌   97 ( 8 )   S1894 - S1894   2023.8

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  • Continuation of osimertinib in EGFR-mutant non-small-cell lung cancer patients bearing CNS metastasis (EPONA study). International journal

    Yusuke Okuma, Shogo Nomura, Kiichiro Ninomiya, Hiroshi Gyotoku, Shuji Murakami, Yoshihito Kogure, Daijiro Harada, Kyoichi Okishio, Hiroaki Okamoto, Yasushi Goto

    Future oncology (London, England)   19 ( 22 )   1515 - 1521   2023.7

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    The patients harboring EGFR-mutated non-small-cell lung cancer, treated with EGFR tyrosine kinase inhibitor will lead to longer survival than those having non-small-cell lung cancer (NSCLC) patient who do not harbor EGFR mutations. This ongoing clinical trial is to investigate the secondary chemoprevention effect of osimertinib from CNS with platinum doublets chemotherapy in patients who had progressive disease outside of CNS lesions. The aim of this randomized, phase II trial is to evaluate platinum and pemetrexed chemotherapy followed by pemetrexed maintenance with or without continuation of osimertinib for secondary CNS prevention in patients with brain metastatic NSCLC with EGFR mutation, with other than CNS lesions, but no progressive disease in the CNS lesion after osimertinib. The primary end point is to assess progression-free survival by investigator assessment. The key secondary end points are overall survival, response rate, time to CNS controlling, time to whole-brain irradiation and safety. Clinical trial registration: Japan Registry of Clinical Trials (jRCT), Japan (jRCTs071200029).

    DOI： 10.2217/fon-2022-1128

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  • Significance of the comprehensive geriatric assessment in the administration of chemotherapy to older adults with cancer: Recommendations by the Japanese Geriatric Oncology Guideline Committee. International journal

    Kiichiro Ninomiya, Daisuke Inoue, Ken Sugimoto, Chie Tanaka, Keiko Murofushi, Toru Okuyama, Shigeaki Watanuki, Chiyo K Imamura, Daisuke Sakai, Naomi Sakurai, Kiyotaka Watanabe, Kazuo Tamura, Toshiaki Saeki, Hiroshi Ishiguro

    Journal of geriatric oncology   101485 - 101485   2023.4

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    INTRODUCTION: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved. MATERIALS AND METHODS: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions. DISCUSSION: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA.

    DOI： 10.1016/j.jgo.2023.101485

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  • [Ⅲ. The Role of Comprehensive Genomic Profiling in Sarcoma].

    Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Toshifumi Ozaki, Shinichi Toyooka, Daisuke Ennishi, Hideki Yamamoto, Kiichiro Ninomiya, Shuta Tomida, Akira Hirasawa, Mashu Futagawa, Masahiro Tabata

    Gan to kagaku ryoho. Cancer & chemotherapy   50 ( 3 )   314 - 320   2023.3

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  • Musculoskeletal Tumor 骨・軟部腫瘍 骨・軟部腫瘍におけるがん遺伝子プロファイリング検査 骨・軟部腫瘍診療におけるがん遺伝子パネルの役割

    中田 英二, 藤原 智洋, 国定 俊之, 尾崎 敏文, 豊岡 伸一, 遠西 大輔, 山本 英喜, 二宮 貴一朗, 冨田 秀太, 平沢 晃, 二川 摩周, 田端 雅弘

    癌と化学療法   50 ( 3 )   314 - 320   2023.3

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  • 原発性肺癌との鑑別を要しAFPが著明高値であったNUT Carcinomaの1例

    松浦 宏昌, 槇本 剛, 小田 尚廣, 大橋 圭明, 二宮 貴一朗, 藤井 昌学, 市原 英基, 堀田 勝幸, 田端 雅弘, 木浦 勝行

    気管支学   45 ( 2 )   148 - 148   2023.3

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  • PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer. International journal

    Takamasa Nakasuka, Kadoaki Ohashi, Kazuya Nishii, Atsuko Hirabae, Sachi Okawa, Nahoko Tomonobu, Kenji Takada, Chihiro Ando, Hiromi Watanabe, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Hiromi Kumon, Yoshinobu Maeda, Katsuyuki Kiura

    Lung cancer (Amsterdam, Netherlands)   178   1 - 10   2023.2

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    OBJECTIVES: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored. MATERIALS AND METHODS: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined. RESULTS: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity. CONCLUSION: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME.

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  • 肺膿瘍を合併し急速な増大を認めたが,迅速に診断しテポチニブが奏効したMET陽性肺癌の1例

    目瀬 優衣, 槇本 剛, 藤井 昌学, 市原 英基, 大橋 圭明, 木浦 勝行, 久保 寿夫, 田端 雅弘, 二宮 貴一朗, 堀田 勝幸

    肺癌   63 ( 1 )   68 - 69   2023.2

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  • 肺膿瘍を合併し急速な増大を認めたが,迅速に診断しテポチニブが奏効したMET陽性肺癌の1例

    目瀬 優衣, 槇本 剛, 藤井 昌学, 市原 英基, 大橋 圭明, 木浦 勝行, 久保 寿夫, 田端 雅弘, 二宮 貴一朗, 堀田 勝幸

    肺癌   63 ( 1 )   68 - 69   2023.2

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  • Safety of anti-SARS-CoV-2 messenger RNA vaccine in lung cancer patients undergoing anticancer chemotherapy: A multicenter, prospective, observational, patient-reported outcome study. International journal

    Daijiro Harada, Tomoki Tamura, Kiichiro Ninomiya, Toshio Kubo, Shoichi Kuyama, Sayaka Tachibana, Koji Inoue, Kenichi Chikamori, Kenichiro Kudo, Nobuaki Ochi, Yoshinobu Maeda, Katsuyuki Kiura

    Thoracic cancer   14 ( 3 )   231 - 236   2023.1

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    BACKGROUND: COVID-19 incidence is high in patients with cancer. The fatality rate was high for the Delta variant, necessitating infection prevention by vaccination. This study evaluated the safety of a SARS-CoV-2 vaccine in patients with advanced lung cancer receiving anticancer therapy. METHODS: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer and planning SARS-CoV-2 vaccination. Early side effects within 7 days of vaccination were evaluated using patient-reported outcome (PRO) surveys. Chi-square test and multivariate logistic regression analyses were used. RESULTS: Post-vaccination PROs were collected from 406 patients (252 were males). The mean age was 72 years. Treatment at the time of initial vaccination included chemotherapy, immune checkpoint inhibitors (ICI), a combination of chemotherapy and ICI, targeted therapy including tyrosine kinase inhibitors, and others in 115, 93, 45, 147, and six cases, respectively. The vaccines administered were BNT162b2 and mRNA273 in 361 and three cases, respectively and unknown in 42 cases. A total of 16.1% of patients developed fever (38°C) after the second mRNA vaccination (95% confidence interval: 12.6%-20.1%). This rate is comparable to data previously reported in 120 patients and slightly higher than that of healthy participants of the BNT162b2 study. Patients receiving treatment with cytotoxic anticancer agents were more likely to have high fever. Multivariate analysis showed no correlation between fever frequency and patient background. No serious initial adverse events due to vaccination were observed. CONCLUSIONS: Anti-SARS-CoV-2 mRNA vaccination is safe; however, post-vaccination fever is more common in patients undergoing lung cancer treatment than in healthy individuals.

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  • osimertinibが誘導する抗腫瘍免疫はM2マクロファージの抑制により増強される

    大川 祥, 大橋 圭明, 西井 和也, 中須賀 崇匡, 平生 敦子, 高田 健二, 西村 淳, 栗林 忠弘, 安東 千裕, 西 達也, 森田 絢子, 槇本 剛, 二宮 貴一朗, 藤井 昌学, 市原 英基, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   62 ( 6 )   657 - 657   2022.11

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  • リアルワールドデータから本邦のNecitumumabの立ち位置を考える(NINJA study)

    丹澤 盛, 吉岡 弘鎮, 宮内 栄作, 二宮 貴一朗, 三角 俊裕, 関 順彦

    肺癌   62 ( 6 )   649 - 649   2022.11

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  • CD8陽性細胞抵抗性Egfr肺癌に対するSTING agonistによる抗腫瘍免疫の誘導

    西村 淳, 大橋 圭明, 栗林 忠弘, 森田 絢子, 西 達也, 大川 祥, 高田 健二, 安東 千裕, 中須賀 崇匡, 西井 和也, 平生 敦子, 二宮 貴一朗, 槇本 剛, 藤井 昌学, 市原 英基, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   62 ( 6 )   754 - 754   2022.11

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  • EGFR変異陽性肺癌に対するAd-SGE-REICと抗PD-1抗体併用による抗腫瘍免疫賦活効果

    中須賀 崇匡, 大橋 圭明, 西井 和也, 平生 敦子, 大川 祥, 高田 健二, 西村 淳, 栗林 忠弘, 安東 千裕, 西 達也, 森田 絢子, 槇本 剛, 二宮 貴一朗, 藤井 昌学, 市原 英基, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    肺癌   62 ( 6 )   715 - 715   2022.11

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  • EGFR阻害が誘導するEgfr肺癌に対する抗腫瘍免疫を逐次的VEGFR-2/PD-1阻害が増強する

    西井 和也, 大橋 圭明, 冨田 秀太, 中須賀 崇匡, 平生 敦子, 大川 祥, 西村 淳, 安東 千裕, 槇本 剛, 二宮 貴一朗, 加藤 有加, 久保 寿夫, 市原 英基, 堀田 勝幸, 田端 雅弘, 豊岡 伸一, 鵜殿 平一郎, 前田 嘉信, 木浦 勝行

    肺癌   62 ( 6 )   657 - 657   2022.11

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  • COVID-19 Vaccine-Associated Lymphadenopathy Mimicking Regrowth of Axillary Lymph Node Metastasis of Lung Adenocarcinoma.

    Taku Noumi, Hiromi Watanabe, Kiichiro Ninomiya, Kadoaki Ohashi, Eiki Ichihara, Toshio Kubo, Go Makimoto, Yuka Kato, Masanori Fujii, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Hotta, Katsuyuki Kiura

    Acta medica Okayama   76 ( 5 )   593 - 596   2022.10

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    We encountered a woman with re-enlarged axillary lymph nodes during a computed tomography (CT) scan for surveillance of lung adenocarcinoma with axillary lymph node metastasis at the initial diagnosis that had shrunk with standard chemotherapy. We first suspected cancer recurrence and considered a change in the chemotherapeutic regimen. However, after careful history taking regarding the timing of her Coronavirus Disease 2019 (COVID-19) vaccination, and subsequent careful, close follow-up, radiological shrinkage suggested a strictly benign cause. Especially in lung cancer with a medical history of axillary lymph node involvement, cliniciansshould be aware that vaccine-associated lymphadenopathy can mimic cancer recurrence and sometimesprompt serious misjudgment regarding a current treatment course and strategy.

    DOI： 10.18926/AMO/64041

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  • 活性型EGFRmt陽性進行非小細胞肺癌に対するアファチニブ±ベバシズマブの第II相試験

    二宮 貴一朗, 二宮 崇, 石川 暢久, 上月 稔幸, 久山 彰一, 金地 伸拓, 井上 孝司, 横山 俊秀, 八杉 昌幸, 柴山 卓夫, 青江 啓介, 藤高 一慶, 小谷 昌広, 尾瀬 功, 木浦 勝行

    日本癌治療学会学術集会抄録集   60回   O6 - 6   2022.10

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  • Fulminant Myocarditis for Non-small-cell Carcinoma of the Lung with Nivolumab and Ipilimumab Plus Chemotherapy: A Case Report.

    Tomoka Nishimura, Kiichiro Ninomiya, Mitsutaka Nakashima, Satoshi Akagi, Tadahiro Kuribayashi, Hisao Higo, Katsuyuki Hotta, Yoshinobu Maeda, Hiroshi Ito, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   62 ( 9 )   1319 - 1322   2022.9

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    A 59-year-old man with a high level of antinuclear antibody received nivolumab and ipilimumab plus chemotherapy for lung cancer. Two weeks after the second course, he was admitted with a fever and severe fatigue. 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 fulminant myocarditis as an irAE, and the further exploration of viable treatment strategies is required.

    DOI： 10.2169/internalmedicine.0505-22

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  • CD8+ T-cell responses are boosted by dual PD-1/VEGFR2 blockade after EGFR inhibition in Egfr-mutant lung cancer. International journal

    Kazuya Nishii, Kadoaki Ohashi, Shuta Tomida, Takamasa Nakasuka, Atsuko Hirabae, Sachi Okawa, Jun Nishimura, Hisao Higo, Hiromi Watanabe, Hirohisa Kano, Chihiro Ando, Go Makimoto, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Heiichiro Udono, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer immunology research   10 ( 9 )   1111 - 1126   2022.7

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    Epidermal growth factor receptor (EGFR) is the most frequently mutated driver oncogene in non-smoking-related, non-small-cell lung cancer (NSCLC). EGFR-mutant NSCLC has a non-inflamed tumor microenvironment (TME), with low infiltration by CD8+ T cells and, thus, immune checkpoint inhibitors, such as anti-programmed cell death-1 (anti-PD-1) have weak anti-tumor effects. Here, we showed that CD8+ T-cell responses were induced by an EGFR-tyrosine kinase inhibitor (TKI) in syngeneic Egfr-mutant NSCLC tumors, which was further pronounced by sequential dual blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2). However, simultaneous triple blockade had no such effect. PD-1/VEGFR2 dual blockade did not exert tumor-inhibitory effects without pre-treatment with the EGFR-TKI, suggesting that treatment schedule is crucial for efficacy of the dual blockade therapy. Pre-treatment with EGFR-TKI increased the CD8+ T-cell/regulatory T-cell (Treg) ratio, while also increasing expression of immunosuppressive chemokines and chemokine receptors, as well as increasing the number of M2-like macrophages, in the TME. Discontinuing EGFR-TKI treatment reversed the transient increase of immunosuppressive factors in the TME. The subsequent PD-1/VEGFR2 inhibition maintained increased numbers of infiltrating CD8+ T cells and CD11c+ dendritic cells. Depletion of CD8+ T cells in vivo abolished tumor growth inhibition by EGFR-TKI alone and the sequential triple therapy, suggesting that EGFR inhibition is a prerequisite for the induction of CD8+ T-cell responses. Our findings could aid in developing an alternative immunotherapy strategy in patients with cancers that have driver mutations and a non-inflamed TME.

    DOI： 10.1158/2326-6066.CIR-21-0751

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  • 大量喀血に対して気管支動脈塞栓術と気管支充填術が奏効したALK陽性肺癌の1例

    藤岡 佑輔, 田岡 征高, 槇本 剛, 栗林 忠弘, 松浦 宏昌, 下西 惇, 二宮 貴一朗, 肥後 寿夫, 久保 寿夫, 大橋 圭明, 堀田 勝幸, 宮原 信明, 田端 雅弘, 木浦 勝行

    気管支学   44 ( Suppl. )   S307 - S307   2022.5

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  • がん遺伝子パネル検査を行った胸腺がん5例の検討

    久保 寿夫, 二宮 貴一朗, 槇本 剛, 加藤 有加, 藤井 昌学, 市原 英基, 大橋 圭明, 堀田 勝幸, 田端 雅弘, 前田 嘉信, 木浦 勝行

    日本呼吸器学会誌   11 ( 増刊 )   279 - 279   2022.4

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  • Identification of targetable kinases in idiopathic pulmonary fibrosis. International journal

    Hisao Higo, Kadoaki Ohashi, Shuta Tomida, Sachi Okawa, Hiromasa Yamamoto, Seiichiro Sugimoto, Satoru Senoo, Go Makimoto, Kiichiro Ninomiya, Takamasa Nakasuka, Kazuya Nishii, Akihiko Taniguchi, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Nobuaki Miyahara, Yoshinobu Maeda, Shinichi Toyooka, Katsuyuki Kiura

    Respiratory research   23 ( 1 )   20 - 20   2022.2

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    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.

    DOI： 10.1186/s12931-022-01940-y

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  • Short-term safety of an anti-severe acute respiratory syndrome coronavirus 2 messenger RNA vaccine for patients with advanced lung cancer treated with anticancer drugs: A multicenter, prospective, observational study. International journal

    Tomoki Tamura, Kiichiro Ninomiya, Toshio Kubo, Shoichi Kuyama, Sayaka Tachibana, Koji Inoue, Kenichi Chikamori, Kenichiro Kudo, Nobuaki Ochi, Daijiro Harada, Yoshinobu Maeda, Katsuyuki Kiura

    Thoracic cancer   13 ( 3 )   453 - 459   2022.2

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    BACKGROUND: Since 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become prevalent worldwide. In severe cases, the case fatality rate is high, and vaccine prevention is important. This study evaluated the safety of receiving SARS-CoV-2 vaccine in patients with advanced lung cancer receiving anticancer therapy. METHODS: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer who planned to receive SARS-CoV-2 vaccination. Early adverse events within 7 days of vaccine injection were evaluated using patient-reported surveys. The chi-square test and multivariate logistic regression analyses were used. RESULTS: Among 120 patients receiving lung cancer treatment, 73 were men; the mean age of the patients was 73.5 years. The treatments received for lung cancer at the time of the first vaccine injection were chemotherapy, ICIs, combined chemotherapy and ICIs, and targeted therapies, including tyrosine kinase inhibitors, in 30, 28, 17, and 45 patients, respectively. All patients received SARS-CoV-2 messenger RNA (mRNA) vaccine. After the second mRNA vaccine dose, 15.4% of patients had fever of 38°C (95% confidence interval: 9.34%-23.2%); this rate was slightly higher than that for healthy participants at the time of the BNT162b2 trial. Patients treated with cytotoxic anticancer drugs tended to have high fever. In the multivariate analyses, male sex was associated with higher fever frequencies. However, there were no serious early adverse events due to vaccination. CONCLUSIONS: Anti-SARS-CoV-2 mRNA vaccination tends to be safe, but fever following vaccination tends to be more common among patients undergoing lung cancer treatment than among healthy individuals.

    DOI： 10.1111/1759-7714.14281

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  • 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

    Masataka Taoka, Go Makimoto, Noriyuki Umakoshi, Kiichiro Ninomiya, Hisao Higo, Yuka Kato, Masanori Fujii, Toshio Kubo, Eiki Ichihara, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Respiratory Medicine Case Reports   38   101669 - 101669   2022

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    DOI： 10.1016/j.rmcr.2022.101669

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  • Successful and Prompt Treatment with Tepotinib for Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation Combined with Lung Abscess Formation: A Case Report. International journal

    Go Makimoto, Atsushi Shimonishi, Kadoaki Ohashi, Kiichiro Ninomiya, Hisao Higo, Yuka Kato, Masanori Fujii, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Case reports in oncology   15 ( 2 )   494 - 498   2022

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    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® Pan Lung Cancer polymerase chain reaction Panel (AmoyDx® 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® 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.

    DOI： 10.1159/000524326

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  • Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR-mutant lung cancer with HIF-1 alpha/TGF-alpha expression

    Kazuya Nishii, Kadoaki Ohashi, Hiromi Watanabe, Go Makimoto, Takamasa Nakasuka, Hisao Higo, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    ONCOLOGY LETTERS   22 ( 3 )   2021.9

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    DOI： 10.3892/ol.2021.12900

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  • Pulmonary Aspergilloma and Allergic Bronchopulmonary Aspergillosis Following the 2018 Heavy Rain Event in Western Japan: A Case Report.

    Eri Ando, Takamasa Nakasuka, Toshio Kubo, Akihiko Taniguchi, Kiichiro Ninomiya, Yuka Kato, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Katsuyuki Hotta, Masaomi Yamane, Nobuaki Miyahara, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   61 ( 3 )   379 - 383   2021.8

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    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.

    DOI： 10.2169/internalmedicine.7124-21

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  • SHP2 inhibition enhances the effects of tyrosine kinase inhibitors in preclinical models of treatment-naïve ALK-, ROS1-, or EGFR-altered non-small-cell lung cancer. International journal

    Hirohisa Kano, Eiki Ichihara, Hiromi Watanabe, Kazuya Nishii, Chihiro Ando, Takamasa Nakasuka, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Molecular cancer therapeutics   20 ( 9 )   1653 - 1662   2021.6

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    After molecular-targeted therapy, some cancer cells may remain that are resistant to therapies targeting oncogene alterations, such as those in the genes encoding the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) as well as c-ros oncogene 1 (ROS1). The mechanisms underlying this type of resistance are unknown. Here we report the potential role of Src homology 2 domain-containing phosphatase 2 (SHP2) in the residual cells of ALK/ROS1/EGFR-altered non-small-cell lung cancer (NSCLC). Molecular-targeted therapies failed to inhibit the ERK signaling pathway in the residual cells whereas the SHP2 inhibitor SHP099 abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo. Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising therapeutic strategy for oncogene-driven NSCLC.

    DOI： 10.1158/1535-7163.MCT-20-0965

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  • A novel osimertinib-resistant human lung adenocarcinoma cell line harbouring mutant EGFR and activated IGF1R. International journal

    Go Makimoto, Kiichiro Ninomiya, Toshio Kubo, Ryota Sunami, Yuka Kato, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Japanese journal of clinical oncology   51 ( 6 )   956 - 965   2021.5

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    OBJECTIVE: A third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is the standard treatment for patients with non-small cell lung cancer harbouring mutant EGFR. Unfortunately, these patients inevitably acquire resistance to EGFR-TKI therapies, including osimertinib. However, the mechanism associated with this resistance remains unclear. METHODS: A 63-year-old Japanese female with lung adenocarcinoma underwent right upper lobectomy (pT1bN2M0 pStage IIIA, EGFR Ex21 L858R). She manifested post-operative tumour recurrence with multiple lung metastases 8 months later and began gefitinib treatment. The lung lesions re-grew 15 months later, and EGFR T790M mutation was detected in the lung metastasis re-biopsy. She was administered osimertinib; however, it relapsed with pleural effusion 16 months later. We isolated cells from the osimertinib-resistant pleural effusion to establish a novel cell line, ABC-31. RESULTS: Although the EGFR L858R mutation was detected in ABC-31 cells, the T790M mutation was lost. ABC-31 cells were resistant to EGFR-TKIs, including osimertinib. Phospho-receptor tyrosine kinase array revealed activation of the insulin-like growth factor 1 receptor (IGF1R), whereas overexpression of the IGF1R ligand, IGF2, induced IGF1R activation in ABC-31 cells. Combination therapy using EGFR-TKIs and IGF1R inhibitor acted synergistically in vitro. She was re-administered osimertinib since EGFR-TKIs and IGF1R inhibitor combination therapy was impossible in clinical practice. This had a slight and short-lived effect. CONCLUSIONS: Taken together, we have successfully established a new osimertinib-resistant lung adenocarcinoma cell line with activated IGF1R. These ABC-31 cells will help develop novel therapeutic strategies for patients with lung adenocarcinoma resistant to specific treatment via IGF1R activation.

    DOI： 10.1093/jjco/hyab048

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  • VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers. International journal

    Hiromi Watanabe, Eiki Ichihara, Hiroe Kayatani, Go Makimoto, Kiichiro Ninomiya, Kazuya Nishii, Hisao Higo, Chihiro Ando, Sachi Okawa, Takamasa Nakasuka, Hirohisa Kano, Naofumi Hara, Atsuko Hirabae, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer science   112 ( 5 )   1853 - 1864   2021.5

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    DOI： 10.1111/cas.14801

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  • 非小細胞肺癌におけるOligometastatic diseaseの管理と治療

    二宮 貴一朗, 大熊 裕介, 海老 規之, 青景 圭樹, 大矢 由子, 阪本 智宏, 上月 稔幸, 野崎 要, 白井 克幸, 野中 哲生, 里内 美弥子, 石川 仁, 堀田 勝幸, 滝口 裕一

    肺癌   61 ( 2 )   95 - 99   2021.4

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  • Marginal Zone Lymphoma and Lung Adenocarcinoma with an EGFR Exon 19 E746-S752del Mutation in a Patient with IgG4-related Disease.

    Sachi Okawa, Kammei Rai, Nobuharu Fujii, Yuka Gion, Kiichiro Ninomiya, Yuka Kato, Akihiko Taniguchi, Toshio Kubo, Ichihara Eiki, Kadoaki Ohashi, Nobuaki Miyahara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   60 ( 17 )   2831 - 2837   2021.3

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    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.

    DOI： 10.2169/internalmedicine.6470-20

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  • A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401. International journal

    Kiichiro Ninomiya, Toshihide Yokoyama, Katsuyuki Hotta, Isao Oze, Kuniaki Katsui, Tae Hata, Hiroshige Yoshioka, Akihiro Bessho, Shinobu Hosokawa, Shoichi Kuyama, Kenichiro Kudo, Toshiyuki Kozuki, Daijiro Harada, Masayuki Yasugi, Toshi Murakami, Masamoto Nakanishi, Nagio Takigawa, Yoshinobu Maeda, Katsuyuki Kiura

    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer   29 ( 9 )   5237 - 5244   2021.3

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    DOI： 10.1007/s00520-021-06092-1

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  • Comparison of bronchoscopy and computed tomography-guided needle biopsy for re-biopsy in non-small cell lung cancer patients. International journal

    Hirohisa Kano, Toshio Kubo, Kiichiro Ninomiya, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Katsuyuki Hotta, Masahiro Tabata, Takao Hiraki, Susumu Kanazawa, Yoshinobu Maeda, Katsuyuki Kiura

    Respiratory investigation   59 ( 2 )   240 - 246   2021.3

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    DOI： 10.1016/j.resinv.2020.12.001

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  • Randomized study comparing mannitol with furosemide for the prevention of cisplatin-induced renal toxicity in non-small cell lung cancer: The OLCSG1406 trial. International journal

    Go Makimoto, Katsuyuki Hotta, Isao Oze, Kiichiro Ninomiya, Masamoto Nakanishi, Naofumi Hara, Hirohisa Kano, Hiromi Watanabe, Yusuke Hata, Kazuya Nishii, Takamasa Nakasuka, Junko Itano, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Eiki Ichihara, Daisuke Minami, Akiko Sato, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Asia-Pacific journal of clinical oncology   17 ( 1 )   101 - 108   2021.2

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    DOI： 10.1111/ajco.13423

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  • Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations. International journal

    Kiichiro Ninomiya, Shunsuke Teraoka, Yoshitaka Zenke, Hirotsugu Kenmotsu, Yukiko Nakamura, Yusuke Okuma, Akihiro Tamiya, Kaname Nosaki, Masahiro Morise, Keiju Aokage, Yuko Oya, Toshiyuki Kozuki, Tomohiro Sakamoto, Kentaro Tanaka, Hisashi Tanaka, Junko Tanizaki, Satoru Miura, Hideaki Mizutani, Eisaku Miyauchi, Ou Yamaguchi, Noriyuki Ebi, Yasushi Goto, Takaaki Sasaki, Haruko Daga, Satoshi Morita, Takeharu Yamanaka, Shinsuke Amano, Kazuo Hasegawa, Chiyo K Imamura, Kenichi Suzuki, Kazuko Nakajima, Hitomi Nishimoto, Satoshi Oizumi, Toyoaki Hida, Katsuyuki Hotta, Yuichi Takiguchi

    JTO clinical and research reports   2 ( 1 )   100107 - 100107   2021.1

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    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.

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  • Immune checkpoint inhibitor efficacy and safety in older non-small cell lung cancer patients. International journal

    Toshio Kubo, Hiromi Watanabe, Kiichiro Ninomiya, Kenichiro Kudo, Daisuke Minami, Etsuko Murakami, Nobuaki Ochi, Takashi Ninomiya, Daijiro Harada, Masayuki Yasugi, Eiki Ichihara, Kadoaki Ohashi, Kammei Rai, Keiichi Fujiwara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Japanese journal of clinical oncology   50 ( 12 )   1447 - 1453   2020.12

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    DOI： 10.1093/jjco/hyaa152

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  • Impact of HER2 expression on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS study subset analysis. International journal

    Kadoaki Ohashi, Kiichiro Ninomiya, Hiroshige Yoshioka, Akihiro Bessho, Takuo Shibayama, Keisuke Aoe, Nobuhisa Ishikawa, Toshiyuki Kozuki, Haruyuki Kawai, Shoichi Kuyama, Seigo Miyoshi, Kazunori Fujitaka, Hideto Obata, Yukari Tsubata, Yoshikazu Awaya, Masaaki Inoue, Koji Inoue, Naokatsu Horita, Hiroyuki Yanai, Katsuyuki Hotta, Katsuyuki Kiura

    Lung cancer (Amsterdam, Netherlands)   150   83 - 89   2020.12

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    DOI： 10.1016/j.lungcan.2020.09.024

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  • Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction. International journal

    Kazuya Nishii, Kadoaki Ohashi, Tomoki Tamura, Kiichiro Ninomiya, Takehiro Matsubara, Satoru Senoo, Hirohisa Kano, Hiromi Watanabe, Naohiro Oda, Go Makimoto, Hisao Higo, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Hiromasa Yamamoto, Shuta Tomida, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Katsuyuki Kiura

    Oncology letters   20 ( 6 )   393 - 393   2020.12

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    DOI： 10.3892/ol.2020.12256

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  • Beneficial effect of erlotinib and trastuzumab emtansine combination in lung tumors harboring EGFR mutations. International journal

    Hiroe Kayatani, Kadoaki Ohashi, Kiichiro Ninomiya, Go Makimoto, Kazuya Nishii, Hisao Higo, Hiromi Watanabe, Hirohisa Kano, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Biochemical and biophysical research communications   532 ( 3 )   341 - 346   2020.11

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    DOI： 10.1016/j.bbrc.2020.07.055

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  • Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status. International journal

    Hirohisa Kano, Eiki Ichihara, Daijiro Harada, Koji Inoue, Hiroe Kayatani, Shinobu Hosokawa, Daizo Kishino, Kazuhiko Watanabe, Nobuaki Ochi, Naohiro Oda, Naofumi Hara, Kiichiro Ninomiya, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer science   111 ( 10 )   3739 - 3746   2020.10

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    DOI： 10.1111/cas.14590

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  • Pilot evaluation of a HER2 testing in non-small-cell lung cancer. International journal

    Katsuyuki Hotta, Hiroyuki Yanai, Kadoaki Ohashi, Kiichiro Ninomiya, Hiromi Nakashima, Hiroe Kayatani, Minoru Takata, Katsuyuki Kiura

    Journal of clinical pathology   73 ( 6 )   353 - 357   2020.6

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    DOI： 10.1136/jclinpath-2019-206204

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  • Patients' preferences and perceptions of lung cancer treatment decision making: results from Okayama lung cancer study group trial 1406. International journal

    Go Makimoto, Katsuyuki Hotta, Isao Oze, Kiichiro Ninomiya, Masamoto Nakanishi, Naofumi Hara, Hirohisa Kano, Hiromi Watanabe, Yusuke Hata, Kazuya Nishii, Takamasa Nakasuka, Junko Itano, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Eiki Ichihara, Daisuke Minami, Akiko Sato, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Acta oncologica (Stockholm, Sweden)   59 ( 3 )   324 - 328   2020.3

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  • Influence of age on the efficacy of immune checkpoint inhibitors in advanced cancers: a systematic review and meta-analysis. International journal

    Kiichiro Ninomiya, Isao Oze, Yuka Kato, Toshio Kubo, Eiki Ichihara, Kammei Rai, Kadoaki Ohashi, Toshiyuki Kozuki, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Katsuyuki Hotta

    Acta oncologica (Stockholm, Sweden)   59 ( 3 )   249 - 256   2020.3

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    DOI： 10.1080/0284186X.2019.1695062

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  • Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden. International journal

    Go Makimoto, Kadoaki Ohashi, Shuta Tomida, Kazuya Nishii, Takehiro Matsubara, Hiroe Kayatani, Hisao Higo, Kiichiro Ninomiya, Akiko Sato, Hiromi Watanabe, Hirohisa Kano, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Minoru Takata, Yoshinobu Maeda, Katsuyuki Kiura

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   14 ( 11 )   2009 - 2018   2019.11

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    DOI： 10.1016/j.jtho.2019.07.017

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  • EGFR-TKI acquired resistance in lung cancers harboring EGFR mutations in immunocompetent C57BL/6J mice. International journal

    Hisao Higo, Kadoaki Ohashi, Go Makimoto, Kazuya Nishii, Kenichiro Kudo, Hiroe Kayatani, Hiromi Watanabe, Hirohisa Kano, Kiichiro Ninomiya, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

    Lung cancer (Amsterdam, Netherlands)   136   86 - 93   2019.10

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    DOI： 10.1016/j.lungcan.2019.08.019

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  • Programmed cell death-ligand 1 expression and efficacy of cisplatin-based chemotherapy in lung cancer: A sub-analysis of data from the two Okayama Lung Cancer Study Group prospective feasibility studies. International journal

    Kazuya Nishii, Katsuyuki Hotta, Kiichiro Ninomiya, Yuka Kato, Eiki Ichihara, Kadoaki Ohashi, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Respiratory investigation   57 ( 5 )   460 - 465   2019.9

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    DOI： 10.1016/j.resinv.2019.04.004

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  • The effect and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer. International journal

    Hiromi Watanabe, Toshio Kubo, Kiichiro Ninomiya, Kenichiro Kudo, Daisuke Minami, Etsuko Murakami, Nobuaki Ochi, Takashi Ninomiya, Daijiro Harada, Masayuki Yasugi, Eiki Ichihara, Kadoaki Ohashi, Keiichi Fujiwara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Japanese journal of clinical oncology   49 ( 8 )   762 - 765   2019.8

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    DOI： 10.1093/jjco/hyz066

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  • A Prospective Cohort Study to Define the Clinical Features and Outcome of Lung Cancers Harboring HER2 Aberration in Japan (HER2-CS STUDY). International journal

    Kiichiro Ninomiya, Tae Hata, Hiroshige Yoshioka, Kadoaki Ohashi, Akihiro Bessho, Shinobu Hosokawa, Nobuhisa Ishikawa, Masahiro Yamasaki, Takuo Shibayama, Keisuke Aoe, Toshiyuki Kozuki, Shingo Harita, Yutaka Ueda, Toshi Murakami, Nobukazu Fujimoto, Hiroyuki Yanai, Shinichi Toyooka, Minoru Takata, Katsuyuki Hotta, Katsuyuki Kiura

    Chest   156 ( 2 )   357 - 366   2019.8

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    DOI： 10.1016/j.chest.2019.01.011

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  • The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV.

    Hiroaki Akamatsu, Kiichiro Ninomiya, Hirotsugu Kenmotsu, Masahiro Morise, Haruko Daga, Yasushi Goto, Toshiyuki Kozuki, Satoru Miura, Takaaki Sasaki, Akihiro Tamiya, Shunsuke Teraoka, Yukari Tsubata, Hiroshige Yoshioka, Yoshihiro Hattori, Chiyo K Imamura, Yuki Katsuya, Reiko Matsui, Yuji Minegishi, Hidenori Mizugaki, Kaname Nosaki, Yusuke Okuma, Setsuko Sakamoto, Takashi Sone, Kentaro Tanaka, Shigeki Umemura, Takeharu Yamanaka, Shinsuke Amano, Kazuo Hasegawa, Satoshi Morita, Kazuko Nakajima, Makoto Maemondo, Takashi Seto, Nobuyuki Yamamoto

    International journal of clinical oncology   24 ( 7 )   731 - 770   2019.7

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    DOI： 10.1007/s10147-019-01431-z

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  • Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer. International journal

    Eiki Ichihara, Katsuyuki Hotta, Kiichiro Ninomiya, Toshio Kubo, Kadoaki Ohashi, Kammei Rai, Hisaaki Tanaka, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Lung cancer (Amsterdam, Netherlands)   132   54 - 58   2019.6

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    DOI： 10.1016/j.lungcan.2019.02.021

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  • Recent treatment strategy for advanced squamous cell carcinoma of the lung in Japan.

    Satoru Senoo, Kiichiro Ninomiya, Katsuyuki Hotta, Katsuyuki Kiura

    International journal of clinical oncology   24 ( 5 )   461 - 467   2019.5

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    DOI： 10.1007/s10147-019-01424-y

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  • Significance of re-biopsy of histological tumor samples in advanced non-small-cell lung cancer in clinical practice.

    Katsuyuki Hotta, Kiichiro Ninomiya, Eiki Ichihara, Katsuyuki Kiura

    International journal of clinical oncology   24 ( 1 )   41 - 45   2019.1

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    DOI： 10.1007/s10147-018-1344-x

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  • A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation: Okayama Lung Cancer Study Group trial 1403. International journal

    Naohiro Oda, Kastuyuki Hotta, Kiichiro Ninomiya, Daisuke Minami, Eiki Ichihara, Toshi Murakami, Toshihide Yokoyama, Hirohisa Ichikawa, Kenichi Chikamori, Nagio Takigawa, Nobuaki Ochi, Shingo Harita, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer chemotherapy and pharmacology   82 ( 6 )   1031 - 1038   2018.12

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    DOI： 10.1007/s00280-018-3694-5

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  • Combined effect of cabozantinib and gefitinib in crizotinib-resistant lung tumors harboring ROS1 fusions. International journal

    Yuka Kato, Kiichiro Ninomiya, Kadoaki Ohashi, Shuta Tomida, Go Makimoto, Hiromi Watanabe, Kenichiro Kudo, Shingo Matsumoto, Shigeki Umemura, Koichi Goto, Eiki Ichihara, Takashi Ninomiya, Toshio Kubo, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Katsuyuki Kiura

    Cancer science   109 ( 10 )   3149 - 3158   2018.10

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    DOI： 10.1111/cas.13752

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  • Pembrolizumab for the first-line treatment of non-small cell lung cancer. International journal

    Kiichiro Ninomiya, Katsuyuki Hotta

    Expert opinion on biological therapy   18 ( 10 )   1015 - 1021   2018.10

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    DOI： 10.1080/14712598.2018.1522300

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  • Osimertinib Depletes EGFR T790M in the Spinal Fluid of Patients with Carcinomatous Meningitis of Lung Adenocarcinoma Harboring De Novo EGFR T790M. International journal

    Satoru Senoo, Kadoaki Ohashi, Kazuya Nishii, Naofumi Hara, Hirohisa Kano, Kiichiro Ninomiya, Yoshinobu Maeda, Katsuyuki Kiura

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   13 ( 8 )   e140-e142 - E142   2018.8

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  • Clinical significance of repeat rebiopsy in detecting the EGFR T790M secondary mutation in patients with non-small cell lung cancer. International journal

    Eiki Ichihara, Katsuyuki Hotta, Toshio Kubo, Tsukasa Higashionna, Kiichiro Ninomiya, Kadoaki Ohashi, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Oncotarget   9 ( 50 )   29525 - 29531   2018.6

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    Background: Osimertinib is an essential drug to treat non-small-cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) T790M mutation, and rebiopsy is necessary to detect this mutation. However, the significance of repeat rebiopsy in NSCLC patients whose first rebiopsy was T790M-negative remains unclear. We used a retrospective cohort to clarify this issue. Methods: We reviewed the medical records of patients with NSCLC harboring EGFR mutations who underwent EGFR tyrosine kinase inhibitor (TKI) treatment at Okayama University Hospital between January 2015 and January 2017. Results: Of 102 patients with EGFR-mutant NSCLC, 55 underwent rebiopsy after acquired resistance to prior EGFR TKIs. Pre-existing activating EGFR mutations were found in all 55 rebiopsied samples. Of the 55 samples, 25 were T790M-positive (45%). Among the remaining 30 patients (T790M-negative on the first rebiopsy), 21 underwent additional rebiopsies following interval therapy. Of the 21 patients, 11 were T790M-positive on the second rebiopsy and 1 on the third. We also evaluated the efficacy of osimertinib in patients who needed a repeat rebiopsy to detect the T790M mutation. Osimertinib showed good activity with an objective response rate of 50%. Conclusions: Repeat rebiopsy increases the ability to detect a secondary mutation (T790M) in EGFR.

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  • Randomized Phase II Study Comparing Mannitol with Furosemide for the Prevention of Renal Toxicity Induced by Cisplatin-based Chemotherapy with Short-term Low-volume Hydration in Advanced Non-small Cell Lung Cancer: The OLCSG1406 Study Protocol.

    Go Makimoto, Eiki Ichihara, Katsuyuki Hotta, Kiichiro Ninomiya, Isao Oze, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Acta medica Okayama   72 ( 3 )   319 - 323   2018.6

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    DOI： 10.18926/AMO/56080

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  • A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non-Small Cell Lung Cancer. International journal

    Katsuyuki Hotta, Keisuke Aoe, Toshiyuki Kozuki, Kadoaki Ohashi, Kiichiro Ninomiya, Eiki Ichihara, Toshio Kubo, Takashi Ninomiya, Kenichi Chikamori, Daijiro Harada, Naoyuki Nogami, Taizo Hirata, Shiro Hinotsu, Shinichi Toyooka, Katsuyuki Kiura

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   13 ( 2 )   273 - 279   2018.2

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    DOI： 10.1016/j.jtho.2017.10.032

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  • MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib. International journal

    Kiichiro Ninomiya, Kadoaki Ohashi, Go Makimoto, Shuta Tomida, Hisao Higo, Hiroe Kayatani, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

    Scientific reports   8 ( 1 )   1955 - 1955   2018.1

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    DOI： 10.1038/s41598-018-20326-z

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  • Potential influence of interleukin-6 on the therapeutic effect of gefitinib in patients with advanced non-small cell lung cancer harbouring EGFR mutations. International journal

    Tomoki Tamura, Yuka Kato, Kadoaki Ohashi, Kiichiro Ninomiya, Go Makimoto, Hiroko Gotoda, Toshio Kubo, Eiki Ichihara, Takehiro Tanaka, Koichi Ichimura, Yoshinobu Maeda, Katsuyuki Hotta, Katsuyuki Kiura

    Biochemical and biophysical research communications   495 ( 1 )   360 - 367   2018.1

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    DOI： 10.1016/j.bbrc.2017.10.175

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  • Congestive Heart Failure During Osimertinib Treatment for Epidermal Growth Factor Receptor (EGFR)-mutant Non-small Cell Lung Cancer (NSCLC).

    Hiromi Watanabe, Eiki Ichihara, Hirohisa Kano, Kiichiro Ninomiya, Mitsune Tanimoto, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   56 ( 16 )   2195 - 2197   2017.8

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    DOI： 10.2169/internalmedicine.8344-16

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  • Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403. International journal

    Naohiro Oda, Eiki Ichihara, Katsuyuki Hotta, Kiichiro Ninomiya, Takashi Ninomiya, Toshio Kubo, Daisuke Minami, Toshi Murakami, Toshihide Yokoyama, Daijiro Harada, Shoichi Kuyama, Hirohisa Ichikawa, Koji Inoue, Daizo Kishino, Masaaki Inoue, Nagio Takigawa, Takuo Shibayama, Shingo Harita, Mitsune Tanimoto, Katsuyuki Kiura

    Clinical lung cancer   18 ( 2 )   241 - 244   2017.3

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    DOI： 10.1016/j.cllc.2016.07.003

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  • Three-Arm Randomized Trial of Sodium Alginate for Preventing Radiation-Induced Esophagitis in Locally Advanced Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy: The OLCSG1401 Study Protocol. International journal

    Kiichiro Ninomiya, Eiki Ichihara, Katsuyuki Hotta, Naoyuki Sone, Toshi Murakami, Daijiro Harada, Isao Oze, Toshio Kubo, Hisaaki Tanaka, Shoichi Kuyama, Daizo Kishino, Akihiro Bessho, Shingo Harita, Kuniaki Katsui, Mitsune Tanimoto, Katsuyuki Kiura

    Clinical lung cancer   18 ( 2 )   245 - 249   2017.3

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    DOI： 10.1016/j.cllc.2016.08.001

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  • A suspected case of rocuronium-sugammadex complex-induced anaphylactic shock after cesarean section.

    Masakazu Yamaoka, Miki Deguchi, Kiichiro Ninomiya, Toshiaki Kurasako, Mutsuko Matsumoto

    Journal of anesthesia   31 ( 1 )   148 - 151   2017.2

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    DOI： 10.1007/s00540-016-2280-4

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  • Trastuzumab Emtansine in HER2+ Recurrent Metastatic Non-Small-Cell Lung Cancer: Study Protocol. International journal

    Kadoaki Ohashi, Katsuyuki Hotta, Taizo Hirata, Keisuke Aoe, Toshiyuki Kozuki, Kiichiro Ninomiya, Hiroe Kayatani, Hiroyuki Yanai, Shinichi Toyooka, Shiro Hinotsu, Minoru Takata, Katsuyuki Kiura

    Clinical lung cancer   18 ( 1 )   92 - 95   2017.1

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    DOI： 10.1016/j.cllc.2016.06.014

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  • Pneumocystis Pneumonia Concomitant with Ectopic ACTH Syndrome Caused by a Large Cell Neuroendocrine Carcinoma of the Thymus.

    Naohiro Oda, Nobuaki Miyahara, Masahiro Tabata, Daisuke Minami, Kiichiro Ninomiya, Arihiko Kanehiro, Motoshi Komatsubara, Kenichi Inagaki, Mitsune Tanimoto, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   56 ( 5 )   551 - 555   2017

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    DOI： 10.2169/internalmedicine.56.7655

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  • Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non-Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405). International journal

    Hideko Isozaki, Katsuyuki Hotta, Eiki Ichihara, Nagio Takigawa, Kadoaki Ohashi, Toshio Kubo, Takashi Ninomiya, Kiichiro Ninomiya, Naohiro Oda, Hiroshige Yoshioka, Hirohisa Ichikawa, Masaaki Inoue, Ichiro Takata, Takuo Shibayama, Shoichi Kuyama, Keisuke Sugimoto, Daijiro Harada, Shingo Harita, Toshiaki Sendo, Mitsune Tanimoto, Katsuyuki Kiura

    Clinical lung cancer   17 ( 6 )   602 - 605   2016.11

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    DOI： 10.1016/j.cllc.2016.05.005

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  • Potential influence of being overweight on the development of hepatic dysfunction in Japanese patients with EGFR-mutated non-small cell lung cancer undergoing gefitinib monotherapy: the Okayama Lung Cancer Study Group experience. International journal

    Naohiro Oda, Katsuyuki Hotta, Hiroshige Yoshioka, Kenichiro Kudo, Eiki Ichihara, Yuka Kato, Kiichiro Ninomiya, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Akiko Sato, Nagio Takigawa, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    Cancer chemotherapy and pharmacology   78 ( 5 )   941 - 947   2016.11

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    DOI： 10.1007/s00280-016-3146-z

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  • A phase II study of topotecan and cisplatin with sequential thoracic radiotherapy in elderly patients with small-cell lung cancer: Okayama Lung Cancer Study Group 0102. International journal

    Toshio Kubo, Keiichi Fujiwara, Katsuyuki Hotta, Toshiaki Okada, Shoichi Kuyama, Shingo Harita, Takashi Ninomiya, Haruhito Kamei, Shinobu Hosokawa, Akihiro Bessho, Tadashi Maeda, Toshiyuki Kozuki, Nobukazu Fujimoto, Kiichiro Ninomiya, Mitsuhiro Takemoto, Susumu Kanazawa, Nagio Takigawa, Masahiro Tabata, Mitsune Tanimoto, Hiroshi Ueoka, Katsuyuki Kiura

    Cancer chemotherapy and pharmacology   78 ( 4 )   769 - 74   2016.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s00280-016-3135-2

    Web of Science

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  • Short-term low-volume hydration in cisplatin-based chemotherapy for patients with lung cancer: the second prospective feasibility study in the Okayama Lung Cancer Study Group Trial 1201.

    Kiichiro Ninomiya, Katsuyuki Hotta, Akiko Hisamoto-Sato, Eiki Ichihara, Hiroko Gotoda, Daisuke Morichika, Tomoki Tamura, Hiroe Kayatani, Daisuke Minami, Toshio Kubo, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

    International journal of clinical oncology   21 ( 1 )   81 - 7   2016.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s10147-015-0860-1

    Web of Science

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  • Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy; hoping for it as a public domain. International journal

    Katsuyuki Hotta, Kiichiro Ninomiya, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura

    Japanese journal of clinical oncology   45 ( 6 )   603 - 4   2015.6

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  • A Case of Advanced Gastric Cancer with Multiple Bone Metastases and Disseminated Intravascular Coagulation Successfully Treated by Combination Chemotherapy of S-1 plus Docetaxel

    二宮貴一朗, 万波智彦, 妹尾賢, 鈴木優子, 田村朋季, 木村耕介, 久保寿夫, 増成太郎, 岡田俊明, 木口亨, 瀬崎伸夫, 張田信吾, 中田安成, 園部宏

    癌と化学療法   39 ( 11 )   1719 - 22   2012

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    Language：Japanese  

    Advanced gastric cancer (AGC) accompanied by disseminated intravascular coagulation(DIC)has a poor prognosis, and has no established therapy. Here, we report a case of a 69-year-old woman referred to our hospital due to severe anemia and thrombocytopenia. Esophagogastroduodenoscopy demonstrated an AGC in the cardiac part of the stomach, which was histologically diagnosed as poorly-differentiated adenocarcinoma. Bone scintigraphy showed multiple metastases to the bone marrow. Her diagnosis was DIC resulting from AGC, with multiple bone metastases. She underwent chemotherapy with the following regimen: 60mg/m2 docetaxel(DOC)infusion on day 1 and daily oral administration of 100 mg/m2 S-1 for two weeks every three weeks. DIC subsided rapidly after initiation of the therapy and resolved in 12 days. She was discharged from the hospital 56 days after admission and survived 303 days. To our knowledge, this is the first case of AGC reported in the Japanese and English literature to obtain long-term survival in this setting. Combined chemotherapy of S-1 plus DOC may play an important role in the treatment of AGC developing DIC.

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Books

  • Respiratory Syndrome, 3rd Edition V

    （ Role： Contributor ,  NTRK fusion positive lung cancer）

    Nippon Rinsho  2021.12 

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  • 新臨床腫瘍学 : がん薬物療法専門医のために

    日本臨床腫瘍学会（ Role： Contributor ,  非小細胞肺がん）

    南江堂  2021.5  （ ISBN:9784524227396 ）

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    Total pages：xix, 757p   Language：Japanese

    CiNii Books

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  • 肺癌診療ガイドライン : 悪性胸膜中皮腫・胸腺腫瘍含む

    日本肺癌学会（ Role： Joint author）

    金原出版  2021.1  （ ISBN:9784307204194 ）

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    Total pages：43, 451p   Language：Japanese

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  • 肺がん化学療法副作用マネジメント

    倉田, 宝保, 吉岡, 弘鎮, 金田, 俊彦（ Role： Contributor ,  肺扁平上皮癌）

    メジカルビュー社  2019.7  （ ISBN:9784758318051 ）

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    Total pages：395p   Language：Japanese

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  • 肺癌診療ガイドライン : 悪性胸膜中皮腫・胸腺腫瘍含む

    日本肺癌学会（ Role： Joint author）

    金原出版  2018.12  （ ISBN:9784307203913 ）

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    Total pages：24, 394p   Language：Japanese

    CiNii Books

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  • 新臨床腫瘍学(改訂第5版): がん薬物療法専門医のために

    日本臨床腫瘍学会（ Role： Contributor ,  非小細胞肺がん）

    南江堂  2018.7  （ ISBN:4524237887 ）

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    Total pages：840   Language：Japanese

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    ASIN

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  • 肺癌診療ガイドライン : IV期非小細胞肺癌薬物療法

    日本肺癌学会（ Role： Joint author）

    金原出版  2017.12  （ ISBN:9784307203746 ）

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    Total pages：8, 63p   Language：Japanese

    CiNii Books

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  • 肺癌診療Q&A : 一つ上を行く診療の実践

    弦間, 昭彦（ Role： Contributor ,  術前化学療法）

    中外医学社  2017.10  （ ISBN:9784498131002 ）

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    Total pages：vii, 521p   Language：Japanese

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  • EBMの手法による肺癌診療ガイドライン : 悪性胸膜中皮腫・胸腺腫瘍含む

    日本肺癌学会（ Role： Joint author）

    金原出版  2016.12  （ ISBN:9784307203654 ）

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    Total pages：18, 333p   Language：Japanese

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MISC

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Research Projects

  • 腫瘍浸潤リンパ球に基づくがん免疫療法（抗CTLA-4抗体）のバイオマーカー開発

    Grant number：22K15607  2022.04 - 2024.03

    日本学術振興会  科学研究費助成事業  若手研究

    二宮 貴一朗

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

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  • Geriatric Oncology Gudeline-Establishing and Spreading (GOGGLES) Study

    Grant number：21EA1004  2021.04 - 2023.03

    Ministry of Health, Labour and Welfare  厚生労働科学研究費補助金 疾病・障害対策研究分野 がん対策推進総合研究  高齢者がん診療ガイドライン策定とその普及のための研究

    佐伯 俊昭, 石黒 洋, 小寺 泰弘, 唐澤 久美子, 渡邊 清高, 松田 晋哉, 二宮 貴一朗, 吉田 好雄, 石川 敏昭, 吉田 陽一郎

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  • Development of innovative HER2-targeted therapy in HER2-mutant lung cancer

    Grant number：19K16865  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

    二宮 貴一朗

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    本研究の目的は、HER2遺伝子変異肺がんに対して治療効果予測となる因子を臨床研究の残余ヒト検体を用いて見出し、基礎研究でその因子の影響及び新規治療法の効果を検証することにより、HER2遺伝子変異肺がんに対するHER2標的治療法のさらなる効果向上を目指すことである。
    目的を達成するため、まずHER2遺伝子変異陽性肺がんに特異的な何らかの因子を見出す解析を行うことを計画している。1,126例の肺がん検体が保存されているデータベース（UMIN000017003）から、まずHER2遺伝子変異のみを抽出し、その残余検体および保存DNAの質を確認した。そのうち、解析に足る13検体を抽出した。
    DNA検体はFFPE検体からの抽出検体であることに加え、保存から長期間が立っていたことから断片化が進んでおり質が低下していたため、次世代シークエンサーでの解析に足る質の担保のためFFPE抽出用のライブラリー作製を別途依頼し作成を進めている。
    今後、NovaSeqを用いた全エクソーム解析を行いその解析を行うことで、HER2遺伝子変異陽性肺がんの特徴を見出すことを予定している。
    また、その結果から新しい治療法の開発についてin vitro、in vivoでの検討を行う予定である。

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  • Potential influence of interleukin-6 on the therapeutic effect of gefitinib in patients with advanced non-small cell lung cancer harbouring EGFR mutations

    Grant number：26430163  2014.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Hotta Katsuyuki, Kato Yuka, Tamura Tomoki, Ninomiya Kiichiro, Ohashi Kadoaki

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    Grant amount：\5070000 （ Direct expense: \3900000 、 Indirect expense：\1170000 ）

    In our study, in 52 patients with EGFR-mutat lung cancer who received gefitinib, EGFR tyrosine kinase inhibitor (TKI), the high IL-6 expression group, accouting for 46%, tended to have poor progression-free survival as compared with the low expression group. In pre-clinical studies using cell lines, the efficacy of EGFR tyrosine kinase inhibitor was related to IL-6 expression level. Thus, EGFR-TKI treatment alone seems insufficient in the high IL-6 expression group, and further treatment strategy should be developed.

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Class subject in charge

  • Respiratory Medicine （2024academic year） special  - その他

  • Oncology （2024academic year） special  - その他

  • Internal Medicine (2)(Core Clinical Practice) （2024academic year） special  - その他

  • Respiratory Medicine （2023academic year） special  - その他

  • Oncology （2023academic year） special  - その他

  • Internal Medicine (2)(Core Clinical Practice) （2023academic year） special  - その他

  • Internal Medicine (2)(Core Clinical Practice) （2022academic year） special  - その他

  • Internal Medicine (2)(Core Clinical Practice) （2021academic year） special  - その他

  • Internal Medicine (2)(Core Clinical Practice) （2020academic year） special  - その他

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