Updated on 2025/06/09

Information

 

写真a

 
TAKADA KAZUKI
 
Organization
Kyushu University Hospital Department of Advanced Medicine and Innovative Technology Assistant Professor
School of Medicine Department of Medicine(Concurrent)
Kyushu University Hospital Department of Advanced Medicine and Innovative Technology(Concurrent)
Title
Assistant Professor

Research Areas

  • Life Science / Respiratory surgery

Degree

  • 医学博士 ( 2017.3 Kyushu University )

Research History

  • Kyushu University 先端医工学診療部 Assistant Professor 

    2025.4 - Present

  • 外科 部長 

    済生会福岡総合病院

    2021.4 - 2025.3

  • 呼吸器外科 部長 

    北九州市立医療センター

    2020.4 - 2021.3

  • Kyushu University 呼吸器外科(2) 医員 

    2018.4 - 2020.3

Education

  • Kyushu University   医学研究院   博士課程

    2013.4 - 2017.3

  • Kyushu University   医学部   医学科

    2004.4 - 2010.3

Research Interests・Research Keywords

  • Research theme: Clinical significance of PD-L1 expression and the search for biomarkers for immune checkpoint inhibitors in lung cancer

    Keyword: 肺癌

    Research period: 2014.4 - Present

Awards

  • 2024年度第17回日本呼吸器外科学会賞

    2024.5  

  • 令和5年度若手外科医のための臨床研究助成

    2024.4  

  • 第15回福岡県医学会賞 奨励賞

    2023.2  

  • 第52回福岡県すこやか健康事業団がん研究助成金奨励賞

    2018.1  

  • 第58回日本肺癌学会学術集会優秀ポスター賞

    2017.12  

  • 第21回九州肺癌カンファレンス研究奨励賞

    2016.7  

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Papers

  • ASO Visual Abstract: Significance of Tumor Microvasculature in the Tumor Microenvironment in Adenocarcinoma with <i>EGFR</i> Common Mutation

    Matsudo, K; Takada, K; Hashinokuchi, A; Nagano, T; Kinoshita, F; Akamine, T; Kohno, M; Takenaka, T; Shimokawa, M; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   32 ( 6 )   4207 - 4208   2025.6   ISSN:1068-9265 eISSN:1534-4681

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    Publisher:Annals of surgical oncology  

    DOI: 10.1245/s10434-025-17067-5

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  • CD155 expression and co-expression with PD-L1 are not associated with poor prognosis in patients with stage II and III lung adenocarcinoma undergoing surgical resection

    Matsudo, K; Takada, K; Hashinokuchi, A; Nagano, T; Kinoshita, F; Akamine, T; Kohno, M; Takenaka, T; Shimokawa, M; Oda, Y; Yoshizumi, T

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   2025.4   ISSN:1341-9625 eISSN:1437-7772

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    Language:English   Publisher:International Journal of Clinical Oncology  

    Background: CD155 has been identified as a ligand for T-cell immunoreceptor with Ig and ITIM domains. Herein, we investigated the relationship between the expressions of CD155 and programmed cell death-ligand 1 (PD-L1) and clinical outcomes in patients with surgically resected lung adenocarcinoma. Methods: This study included 426 patients diagnosed with pathological stage (pStage) I–III lung adenocarcinoma who underwent surgery at Kyushu University Hospital. The number of tumor cells expressing CD155 and PD-L1 was assessed by immunohistochemistry, and the clinical significance of CD155 expression and CD155/PD-L1 co-expression in prognosis was investigated. Results: Among the enrolled cohort, 320 (75.1%), 60 (14.1%), and 46 (10.8%) patients were diagnosed with pStage I, II, and III, respectively. Tissues from 112 patients (26.3%) were classified as having high CD155 expression. Co-expression of CD155 and PD-L1 was observed in 44 patients (10.3%). The High CD155 and CD155/PD-L1 co-expression groups had significantly poorer prognosis in pStage I–III lung adenocarcinoma. However, subgroup analysis revealed that the clinical significance of both CD155 expression and CD155/PD-L1 co-expression differed widely between patients with pStage I and II–III. Multivariate Cox proportional hazards regression analyses showed that high CD155 expression and CD155/PD-L1 co-expression were not independent poor prognostic factors in pStage II-III lung adenocarcinoma. Conclusion: Our findings suggest that neither CD155 expression or CD155/PD-L1 co-expression are associated with poor prognosis in pStage II-III lung adenocarcinoma.

    DOI: 10.1007/s10147-025-02771-9

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  • Prognostic impact of PD-L1 expression in surgically resected <i>EGFR</i>-mutant lung adenocarcinoma: A real-world database study in Japan (CReGYT-01 EGFR study)

    Nomura, K; Takada, K; Kinoshita, F; Muto, S; Matsubara, T; Kouki, Y; Katsumata, S; Hamada, A; Haratake, N; Fujino, K; Yoshikawa, M; Suzawa, K; Shien, K; Suda, K; Ohara, S; Fukuda, S; Suzuki, H; Okamoto, T; Hirai, F; Aokage, K; Shiono, S; Soh, J; Tsuboi, M; Shimokawa, M; Ohde, Y

    INTERNATIONAL JOURNAL OF CANCER   156 ( 7 )   1480 - 1491   2025.4   ISSN:0020-7136 eISSN:1097-0215

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    Language:English   Publisher:International Journal of Cancer  

    The expression of programmed cell death-ligand 1 (PD-L1) and mutation in epidermal growth factor receptor (EGFR) are biomarkers used for perioperative treatment of lung adenocarcinoma. However, the clinical significance of PD-L1 expression in surgically resected EGFR-mutant lung adenocarcinoma remains unclear. We conducted a real-world database of patients with surgically resected lung adenocarcinoma from 2015 to 2018 was constructed across 21 centers in Japan. The association among PD-L1 expression, EGFR mutations, and prognosis was evaluated. Among 847 patients, PD-L1 expression was negative (tumor proportion score [TPS] < 1%) in 429 (51%), weakly positive (TPS = 1%–49%) in 275 (32%), and strongly positive (TPS ≥50%) in 143 (17%) patients. EGFR mutations were detected in 331 (39%) patients. PD-L1 expression was associated with poor recurrence-free survival (RFS) (p <.001) in both EGFR-mutant and wild-type patients. However, in EGFR-mutant patients, PD-L1 expression was not associated with overall survival (OS) (p =.506). Multivariable analysis confirmed an association between PD-L1 expression and RFS but not OS. Furthermore, in EGFR-mutant patients treated with EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment post-relapse, PD-L1 expression was not associated with overall response rate (p =.714), disease control rate (p =.554), or progression-free survival (p =.660). In conclusion, PD-L1 expression predicted poor RFS-independent EGFR status but did not show any association with OS in EGFR-mutant patients. The efficacy of post-relapse EGFR-TKI treatment was independent of PD-L1 expression. The significance of PD-L1 expression in perioperative EGFR-TKI therapy should be evaluated.

    DOI: 10.1002/ijc.35270

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  • Significance of Tumor Microvasculature in the Tumor Microenvironment in Adenocarcinoma with <i>EGFR</i> Common Mutations

    Matsudo, K; Takada, K; Hashinokuchi, A; Nagano, T; Kinoshita, F; Akamine, T; Kohno, M; Takenaka, T; Shimokawa, M; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   32 ( 4 )   3031 - 3039   2025.4   ISSN:1068-9265 eISSN:1534-4681

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    Background: Tumor microvasculature is an important component of the tumor microenvironment (TME), and it has been reported that tumor microvasculature induces TME to become immunosuppressive via vascular endothelial growth factor. However, the significance of this in adenocarcinoma with epidermal growth factor receptor (EGFR) common mutations has not been fully investigated. Methods: We analyzed 262 patients with adenocarcinoma harboring EGFR common mutations who underwent surgery at Kyushu University Hospital between 2006 and 2021. Microvessel density (MVD) was calculated by CD34 immunohistochemistry. Patients were categorized into high and low MVD status, which was compared with the clinicopathological characteristics. Results: A total of 136 (51.9%) patients had L858R mutation, and 126 (48.1%) had Exon 19 Del. Regarding MVD status; 133 patients (50.8%) were classified as high and 129 (49.2%) as low. Fisher’s exact test revealed a significant association of high MVD status with high CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.0187), low GZMB+ TILs (p = 0.0019), and high Foxp3+ TILs (p = 0.0003). On multivariate analysis, MVD status was significantly associated with Foxp3+ TILs and GZMB+ TILs. Fisher’s exact test also revealed that tumors with L858R mutation had a high MVD status (p = 0.0136) compared with tumors with deletions of exon 19 (Exon 19 Del), and multivariate analysis revealed that L858R mutation was significantly associated with high MVD status. Conclusions: In adenocarcinomas harboring EGFR common mutations, abundant tumor microvasculature might induce the TME to be immunosuppressive. Tumors with L858R mutation compared with Exon 19 Del might be more likely to form an immunosuppressive TME owing to the abundance of tumor microvasculature.

    DOI: 10.1245/s10434-024-16806-4

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  • Clinical significance of CD155 expression in surgically resected lung squamous cell carcinoma(タイトル和訳中)

    Nagano Taichi, Takada Kazuki, Hashinokuchi Asato, Matsudo Kyoto, Kinoshita Fumihiko, Akamine Takaki, Kohno Mikihiro, Shimokawa Mototsugu, Takenaka Tomoyoshi, Oda Yoshinao, Yoshizumi Tomoharu

    International Journal of Clinical Oncology   30 ( 1 )   62 - 71   2025.1   ISSN:1341-9625

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  • Clinical significance of CD155 expression in surgically resected lung squamous cell carcinoma

    Nagano, T; Takada, K; Hashinokuchi, A; Matsudo, K; Kinoshita, F; Akamine, T; Kohno, M; Shimokawa, M; Takenaka, T; Oda, Y; Yoshizumi, T

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   30 ( 1 )   62 - 71   2025.1   ISSN:1341-9625 eISSN:1437-7772

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    Background: Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated. Materials and methods: We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. Results: Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan–Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group. Conclusion: Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.

    DOI: 10.1007/s10147-024-02640-x

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  • ASO Visual Abstract: Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma

    Nagano, T; Takada, K; Narutomi, F; Kinoshita, F; Akamine, T; Kohno, M; Shimokawa, M; Takenaka, T; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   31 ( 13 )   8684 - 8685   2024.12   ISSN:1068-9265 eISSN:1534-4681

  • CD155 Expression in Early-Stage Lung Adenocarcinoma

    Matsudo, K; Takada, K; Kinoshita, F; Hashinokuchi, A; Nagano, T; Akamine, T; Kohno, M; Takenaka, T; Shimokawa, M; Oda, Y; Yoshizumi, T

    ANNALS OF THORACIC SURGERY   118 ( 6 )   1197 - 1205   2024.12   ISSN:0003-4975 eISSN:1552-6259

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    Background: Cluster of differentiation (CD) 155 is a transmembrane protein that belongs to the nectin-like molecule family, which is widely overexpressed in several types of cancer. However, the clinical significance of CD155 in pathologic stage I lung adenocarcinoma remains poorly understood. Methods: We analyzed 320 patients diagnosed with pathologic stage I lung adenocarcinoma who underwent surgical treatment at Kyushu University Hospital between 2006 and 2015. The number of tumor cells expressing CD155 was assessed by immunohistochemistry, and patients were categorized into high and low CD155 expression groups. We compared the clinical and pathologic characteristics and clinical outcomes between these groups. Results: Mutation status of the epidermal growth factor receptor gene (EGFR) was determined in 237 patients. A total of 106 patients (33.1%) had EGFR wild-type, and 131 patients (40.9%) had EGFR mutant-type. CD155 expression was classified as high in 77 patients (24.1%) and as low in 243 (75.9%) as low. Multivariate analysis identified pleural invasion and EGFR wild-type as independent predictors of high CD155 expression. The Kaplan-Meier plot demonstrated significantly poorer recurrence-free survival and overall survival in the high CD155 group compared with the low CD155 group. Multivariate analysis showed high CD155 expression was an independent poor prognostic factor for recurrence-free and overall survival. Subgroup analyses revealed that a prognostic difference related to CD155 expression was observed only in patients with EGFR wild-type but not in those with EGFR mutant-type. Conclusions: Our findings suggest that high expression of CD155 is associated with EGFR wild-type and could serve as a valuable prognostic marker in pathologic stage I lung adenocarcinoma, particularly in cases without EGFR mutation.

    DOI: 10.1016/j.athoracsur.2024.05.042

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  • ASO Author Reflections: Relationship Between SIRPα Expression on Tumor-Associated Macrophages and Tumor Microenvironment in Lung Squamous Cell Carcinoma

    Nagano, T; Takada, K; Takenaka, T; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   31 ( 10 )   6725 - 6726   2024.10   ISSN:1068-9265 eISSN:1534-4681

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    DOI: 10.1245/s10434-024-15839-z

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  • Prognostic Analysis of Completely Resected Lung Adenocarcinoma with Uncommon EGFR Mutations: CReGYT-01 EGFR Study

    Hayasaka, K; Haratake, N; Notsuda, H; Katsumata, S; Hamada, A; Nomura, K; Fujino, K; Yoshikawa, M; Suzawa, K; Shien, K; Suda, K; Ohara, S; Fukuda, S; Kinoshita, I; Takamori, S; Muto, S; Takanashi, Y; Mizuno, K; Kawase, A; Hayakawa, T; Sekihara, K; Toda, M; Matsuo, S; Takegahara, K; Hashimoto, M; Nakahashi, K; Endo, M; Ozawa, H; Fujikawa, R; Tomioka, Y; Namba, K; Matsubara, T; Suzuki, J; Watanabe, H; Takada, K; Hoshino, H; Toyoda, T; Koki, Y; Shiono, S; Shimokawa, M; Soh, J; Ohde, Y; Okada, Y

    JOURNAL OF THORACIC ONCOLOGY   19 ( 10 )   S232 - S233   2024.10   ISSN:1556-0864 eISSN:1556-1380

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  • Clinicopathological Analysis of Each EGFR Status in Surgically Resected Lung Adenocarcinoma: A RealWorld Study (CReGYT-01 EGFR)

    Hoshino, H; Katsumata, S; Hamada, A; Haratake, N; Nomura, K; Fujino, K; Yoshikawa, M; Suzawa, K; Shien, K; Suda, K; Ohara, S; Fukuda, S; Kinoshita, I; Hayasaka, K; Notsuda, H; Takamori, S; Muto, S; Takanashi, Y; Mizuno, K; Kawase, A; Hayakawa, T; Sekihara, K; Toda, M; Matsuo, S; Takegahara, K; Hashimoto, M; Nakahashi, K; Endo, M; Ozawa, H; Fujikawa, R; Tomioka, Y; Namba, K; Matsubara, T; Suzuki, J; Watanabe, H; Takada, K; Toyoda, T; Nakasone, S; Kawasaki, H; Shimokawa, M; Kouki, Y; Shiono, S; Soh, J; Ohde, Y

    JOURNAL OF THORACIC ONCOLOGY   19 ( 10 )   S499 - S499   2024.10   ISSN:1556-0864 eISSN:1556-1380

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  • Clinical Relevance of PD-L1 Expression Levels in Surgically Resected EGFR-Mutant Lung Adenocarcinoma Patients (CReGYT-01 Study)

    Kinoshita, F; Nomura, K; Takada, K; Muto, S; Matsubara, T; Kouki, Y; Katsumata, S; Hamada, A; Haratake, N; Fujino, K; Yoshikawa, M; Suzawa, K; Shien, K; Suda, K; Ohara, S; Fukuda, S; Suzuki, H; Okamoto, T; Hirai, F; Aokage, K; Shiono, S; Soh, J; Tsuboi, M; Shimokawa, M; Ohde, Y; Takenaka, T; Yoshizumi, T

    JOURNAL OF THORACIC ONCOLOGY   19 ( 10 )   S233 - S233   2024.10   ISSN:1556-0864 eISSN:1556-1380

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  • Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma

    Nagano, T; Takada, K; Narutomi, F; Kinoshita, F; Akamine, T; Kohno, M; Shimokawa, M; Takenaka, T; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   31 ( 9 )   6309 - 6319   2024.9   ISSN:1068-9265 eISSN:1534-4681

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    Language:English   Publisher:Annals of Surgical Oncology  

    Background: Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression. Patients and Methods: Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry. Results: There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ. Conclusion: Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.

    DOI: 10.1245/s10434-024-15649-3

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  • Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study

    Katsumata, S; Shimokawa, M; Hamada, A; Haratake, N; Nomura, K; Fujino, K; Yoshikawa, M; Suzawa, K; Shien, K; Suda, K; Ohara, S; Fukuda, S; Kinoshita, F; Hayasaka, K; Notsuda, H; Takamori, S; Muto, S; Takanashi, Y; Mizuno, K; Kawase, A; Hayakawa, T; Sekihara, K; Matsuo, S; Takegahara, K; Hashimoto, M; Nakahashi, K; Endo, M; Ozawa, H; Fujikawa, R; Tomioka, Y; Namba, K; Matsubara, T; Suzuki, J; Watanabe, H; Toda, M; Takada, K; Hoshino, H; Kaiho, T; Toyoda, T; Kouki, Y; Shiono, S; Soh, J; Ohde, Y

    EUROPEAN JOURNAL OF CANCER   201   113951   2024.4   ISSN:0959-8049 eISSN:1879-0852

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    Objectives: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. Methods: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. Results: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2–3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. Conclusion: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

    DOI: 10.1016/j.ejca.2024.113951

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  • 'MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC' (vol 19, pg 434, 2024)

    Haratake, N; Ozawa, H; Morimoto, Y; Yamashita, N; Daimon, T; Bhattacharya, A; Wang, KY; Nakashoji, A; Isozaki, H; Shimokawa, M; Kikutake, C; Suyama, M; Hashinokuchi, A; Takada, K; Takenaka, T; Yoshizumi, T; Mitsudomi, T; Hata, AN; Kufe, D

    JOURNAL OF THORACIC ONCOLOGY   20 ( 3 )   399 - 399   2024.3   ISSN:1556-0864 eISSN:1556-1380

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  • MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC

    Haratake, N; Ozawa, H; Morimoto, Y; Yamashita, N; Daimon, T; Bhattacharya, A; Wang, KY; Nakashoji, A; Isozaki, H; Shimokawa, M; Kikutake, C; Suyama, M; Hashinokuchi, A; Takada, K; Takenaka, T; Yoshizumi, T; Mitsudomi, T; Hata, AN; Kufe, D

    JOURNAL OF THORACIC ONCOLOGY   19 ( 3 )   434 - 450   2024.3   ISSN:1556-0864 eISSN:1556-1380

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    Language:English   Publisher:Journal of Thoracic Oncology  

    Introduction: Osimertinib is an irreversible EGFR tyrosine kinase inhibitor approved for the first-line treatment of patients with metastatic NSCLC harboring EGFR exon 19 deletions or L858R mutations. Patients treated with osimertinib invariably develop acquired resistance by mechanisms involving additional EGFR mutations, MET amplification, and other pathways. There is no known involvement of the oncogenic MUC1-C protein in acquired osimertinib resistance. Methods: H1975/EGFR (L858R/T790M) and patient-derived NSCLC cells with acquired osimertinib resistance were investigated for MUC1-C dependence in studies of EGFR pathway activation, clonogenicity, and self-renewal capacity. Results: We reveal that MUC1-C is up-regulated in H1975 osimertinib drug-tolerant persister cells and is necessary for activation of the EGFR pathway. H1975 cells selected for stable osimertinib resistance (H1975-OR) and MGH700-2D cells isolated from a patient with acquired osimertinib resistance are found to be dependent on MUC1-C for induction of (1) phospho (p)-EGFR, p-ERK, and p-AKT, (2) EMT, and (3) the resistant phenotype. We report that MUC1-C is also required for p-EGFR, p-ERK, and p-AKT activation and self-renewal capacity in acquired osimertinib-resistant (1) MET-amplified MGH170-1D #2 cells and (2) MGH121 Res#2/EGFR (T790M/C797S) cells. Importantly, targeting MUC1-C in these diverse models reverses osimertinib resistance. In support of these results, high MUC1 mRNA and MUC1-C protein expression is associated with a poor prognosis for patients with EGFR-mutant NSCLCs. Conclusions: Our findings reveal that MUC1-C is a common effector of osimertinib resistance and is a potential target for the treatment of osimertinib-resistant NSCLCs.

    DOI: 10.1016/j.jtho.2023.10.017

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  • Treatment-related adverse events of combination chemoimmunotherapy versus chemotherapy alone in first-line treatment for non-small cell lung cancer: a systematic review and meta-analysis of randomized clinical trials

    Takada, K; Takamori, S; Mizuki, F; Miura, N; Shikada, Y; Shimokawa, M

    JOURNAL OF THORACIC DISEASE   16 ( 1 )   430 - 438   2024.1   ISSN:2072-1439 eISSN:2077-6624

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    Language:English   Publisher:Journal of Thoracic Disease  

    Background: Numerous meta-analyses have examined immunotherapy-induced adverse events (AEs) in non-small cell lung cancer (NSCLC). However, there is limited research comparing AEs from combination chemoimmunotherapy versus chemotherapy alone in the first-line NSCLC treatment, particularly regarding specific toxic symptoms and hematological toxicities associated with the addition of immune checkpoint inhibitors (ICIs). Methods: We conducted a meta-analysis of randomized clinical trials (RCTs) comparing ICIs + non-ICIs versus non-ICIs alone as first-line therapy in NSCLC, sourced from PubMed and Scopus databases. Our objective was to assess treatment-related AEs in both regimens, focusing on identifying the more prevalent toxic symptoms and hematological toxicities with ICI treatment. We calculated the relative risks (RRs) and 95% confidence intervals (CIs), and estimated the pooled RRs and 95% CIs using common- or random-effects models. Results: Our analysis included 10 trials with 6,008 patients. Combination chemoimmunotherapy significantly increased the risk of grade 3 or higher treatment-related AEs, treatment discontinuation, and deaths due to treatment-related AEs. Moreover, patients receiving combination chemoimmunotherapy had a significantly higher risk of certain toxic symptoms (all-grade: vomiting, diarrhea, and constipation; high-grade: fatigue and diarrhea) and pneumonitis (both all-grade and high-grade). Conclusions: These findings offer crucial insights into the toxicity profile of combination chemoimmunotherapy, serving as a valuable resource for clinicians managing lung cancer care.

    DOI: 10.21037/jtd-23-1532

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  • ASO Visual Abstract: Granzyme B (GZMB)-Positive Tumor-Infiltrating Lymphocytes in Lung Adenocarcinoma: Significance as a Prognostic Factor and Association With Immunosuppressive Proteins

    Kinoshita, F; Takada, K; Wakasu, S; Saito, S; Hashinokuchi, A; Matsudo, K; Nagano, T; Akamine, T; Kohno, M; Takenaka, T; Shimokawa, M; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   30 ( 13 )   8290 - 8291   2023.12   ISSN:1068-9265 eISSN:1534-4681

  • Granzyme B (GZMB)-Positive Tumor-Infiltrating Lymphocytes in Lung Adenocarcinoma: Significance as a Prognostic Factor and Association with Immunosuppressive Proteins

    Kinoshita, F; Takada, K; Wakasu, S; Saito, S; Hashinokuchi, A; Matsudo, K; Nagano, T; Akamine, T; Kohno, M; Takenaka, T; Shimokawa, M; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   30 ( 12 )   7579 - 7589   2023.11   ISSN:1068-9265 eISSN:1534-4681

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    Background: Granzyme B (GZMB) is a serine protease produced by cytotoxic lymphocytes that reflects the activity of anti-tumor immune responses in tumor-infiltrating lymphocytes (TILs); however, the prognostic significance of GZMB+ TILs in lung adenocarcinoma is poorly understood. Methods: We analyzed 273 patients with pathological stage (pStage) I–IIIA lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We evaluated GZMB+ TIL counts by immunohistochemistry. We set the cut-off values at 12 cells/0.04 mm2 for GZMB+ TILs and divided the patients into GZMB-High (n = 171) and GZMB-Low (n = 102) groups. Then, we compared the clinicopathological characteristics of the two groups and clinical outcomes. Programmed cell death ligand-1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression in tumor cells was also evaluated, and combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 were performed. Results: GZMB-Low was significantly associated with pStage II–III, PD-L1 positivity, and IDO1 positivity. Disease-free survival (DFS) and overall survival (OS) in the GZMB-Low group were significantly worse than in the GZMB-High group. In multivariable analysis, GZMB-Low was an independent prognostic factor for both DFS and OS. Furthermore, combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 showed that GZMB-Low with high expression of these immunosuppressive proteins had the worst prognosis. Conclusions: We analyzed GZMB+ TIL counts in lung adenocarcinoma and elucidated its prognostic significance and association with PD-L1 and IDO1. GZMB+ TIL counts might reflect the patient’s immunity against cancer cells and could be a useful prognostic marker of lung adenocarcinoma.

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  • Real-World Data of Completely Resected Lung Adenocarcinoma Harboring Common EGFR Mutation in Japan (CReGYT-01 EGFR study)

    Katsumata, S; Hamada, A; Haratake, N; Takamori, S; Takanashi, Y; Hayasaka, K; Nomura, K; Toda, M; Kaiho, T; Hoshino, H; Ozawa, H; Matsuo, S; Suzuki, J; Nakahashi, K; Fujino, K; Takegahara, K; Kinoshita, I; Takada, K; Yoshikawa, M; Tomioka, Y; Koki, Y; Shimokawa, M; Soh, J; Shiono, S; Ohde, Y

    JOURNAL OF THORACIC ONCOLOGY   18 ( 11 )   S267 - S268   2023.11   ISSN:1556-0864 eISSN:1556-1380

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  • Impact of Neoadjuvant Immune Checkpoint Inhibitors on Surgery and Perioperative Complications in Patients With Non-small-cell Lung Cancer: A Systematic Review

    Takada, K; Takamori, S; Brunetti, L; Crucitti, P; Cortellini, A

    CLINICAL LUNG CANCER   24 ( 7 )   581 - +   2023.11   ISSN:1525-7304 eISSN:1938-0690

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    Several clinical trials are currently underway to evaluate immune checkpoint inhibitors (ICIs) as neoadjuvant treatment for patients with early-stage non–small-cell lung cancer (NSCLC), and their use in clinical practice is expected to increase in the future. Therefore, a proper assessment of surgical outcomes and perioperative complications after neoadjuvant ICIs is essential to establish recommendations and guidelines. We performed a systematic literature review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), searching the PubMed and Scopus databases from the January 1, 2017, to the July 27, 2023, to identify potentially relevant published trials of neoadjuvant ICIs in patients with reseactable NSCLC with available information on surgical outcomes and perioperative complications. A total of 18 studies were included in the review. The rates of surgery cancellation ranged from 0% to 45.8%. Importantly, adverse events (AEs) were the least reported underlying cause, while disease progression caused from 0% to 75% of cancellations. Surgery delays ranged from 0% to 31.3% with AEs as the most frequently reported underlying cause. However, 6 out of 13 trials (46.2%) reported no surgery delays. Conversion rates from minimally invasive to open chest surgery were available for 7 trials and ranged from 0% to 53.8%. Thirty-day mortality rates ranged from 0% to 5.4%, with 11 out of 16 trials reporting 0%. A few reports described perioperative complications in detail. Considering the limited evidence available, we can preliminarily confirm that preoperative ICIs are safe and well tolerated even from the surgical perspective. Additional details on intraoperative findings from prospective controlled trials are needed to establish and disseminate guidelines and recommendations for thoracic surgeons.

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  • Impact of the pretreatment prognostic nutritional index on the survival after first-line immunotherapy in non-small-cell lung cancer patients

    Oku, Y; Toyokawa, G; Wakasu, S; Kinoshita, F; Takamori, S; Watanabe, K; Haratake, N; Nagano, T; Kosai, K; Takada, K; Fujimoto, A; Higashijima, K; Shiraishi, Y; Tanaka, K; Takeoka, H; Okamoto, M; Yamashita, T; Shimokawa, M; Shoji, F; Yamazaki, K; Okamoto, T; Seto, T; Ueda, H; Takeo, S; Nakashima, N; Okamoto, I; Takenaka, T; Yoshizumi, T

    CANCER MEDICINE   12 ( 13 )   14327 - 14336   2023.7   ISSN:2045-7634

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    Background: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. Materials and Methods: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. Results: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51–0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32–0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). Conclusion: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.

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  • Comments on "Lymphocyte-to-monocyte ratio is an independent prognostic factor in surgically treated small cell lung cancer: An international multicenter analysis"

    Takada, K; Takamori, S

    LUNG CANCER   175   154 - 155   2023.1   ISSN:0169-5002 eISSN:1872-8332

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    DOI: 10.1016/j.lungcan.2022.07.001

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  • Comments on 'Biomarkers of systemic inflammation predict survival with first-line immune checkpoint inhibitors in non-small-cell lung cancer'

    Takada, K; Takamori, S

    ESMO OPEN   7 ( 6 )   2022.12   eISSN:2059-7029

  • Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade

    Takada, K; Buti, S; Bersanelli, M; Shimokawa, M; Takamori, S; Matsubara, T; Takenaka, T; Okamoto, T; Hamatake, M; Tsuchiya-Kawano, Y; Otsubo, K; Nakanishi, Y; Okamoto, I; Pinato, DJ; Cortellini, A; Yoshizumi, T

    EUROPEAN JOURNAL OF CANCER   172   199 - 208   2022.9   ISSN:0959-8049 eISSN:1879-0852

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    Background: We previously validated in European patients with NSCLC treated with programmed death-1 (PD-1) checkpoint inhibitors the cumulative detrimental effect of concomitant medications. Materials and methods: We evaluated the prognostic ability of a “drug score” computed on the basis of baseline corticosteroids, proton pump inhibitors, and antibiotics, in an independent cohort of Japanese patients with advanced NSCLC treated with PD-1 monotherapy. Subsequently, we assessed the impact of baseline probiotics on the score's diagnostic ability and their interaction with antibiotics in influencing survival. Results: Among the 293 eligible patients, good (19.5 months), intermediate (13.4 months), and poor (3.7 months) risk groups displayed a significantly different overall survival (OS) (log-rank test for trend: p = 0.016), but with a limited diagnostic ability (C-index: 0.57, 95%CI: 0.53–0.61), while no significant impact on progression-free survival (PFS) was reported (log-rank test for trend: p = 0.080; C-index: 0.55, 95%CI: 0.52–0.58). Considering the impact of the probiotics∗antibiotics interaction (p-value 0.0510) on OS, we implemented the drug score by assigning 0 points to concomitant antibiotics and probiotics. With the adapted drug score good, intermediate, and poor risk patients achieved a median OS of 19.6 months, 13.1 months, and 3.7 months, respectively, with a similar diagnostic ability (log-rank test for trend: p = 0.006; C-index: 0.58, 95%CI: 0.54–0.61). However, the diagnostic ability for PFS of the adapted score was improved (log-rank test for trend: p = 0.034; C-index: 0.62, 95%CI: 0.54–0.69). Conclusions: Although we failed to validate the drug score in this independent Japanese cohort, we showed that probiotics may have an antibiotic-dependent impact on its prognostic value. Further investigation looking at the effect of concomitant medications and probiotics across cohorts of different ethnicities is warranted.

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  • Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials

    Takada, K; Shimokawa, M; Mizuki, F; Takamori, S; Takenaka, T; Miura, N; Shikada, Y; Yoshizumi, T

    EUROPEAN JOURNAL OF MEDICAL RESEARCH   27 ( 1 )   157   2022.8   ISSN:0949-2321 eISSN:2047-783X

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    Introduction: Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy. Methods: We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models. Results: We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72–0.87) for males and 0.69 (0.54–0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55–0.66) for males and 0.56 (0.44–0.70) for females. Conclusions: In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients.

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  • Relationship between consolidation tumor ratio and tumor-infiltrating lymphocytes in small-sized lung adenocarcinoma

    Ono, Y; Tagawa, T; Kinoshita, F; Haratake, N; Takada, K; Kohno, M; Takenaka, T; Kamitani, T; Shimokawa, M; Oda, Y; Mori, M; Yoshizumi, T

    THORACIC CANCER   13 ( 15 )   2134 - 2141   2022.8   ISSN:1759-7706 eISSN:1759-7714

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    Background: Consolidation tumor ratio (CTR) is associated with cancer progression and histological invasiveness in lung adenocarcinoma (LAD). However, little is known about the association between CTR and immune-related factors, including tumor-infiltrating lymphocytes (TILs) density or tumor expression of programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) in small-sized LAD. Methods: This study included 258 patients with LAD (<3 cm) who underwent surgery. Patients were assigned to four groups: CTR = 0; 0 < CTR <0.5; 0.5 ≤ CTR <1 (ground-glass opacity [GGO] group); and CTR = 1 (pure-solid group). CD4+, CD8+, and FoxP3+ TIL density and PD-L1 and IDO1 tumor expression were assessed by immunohistochemistry. Results: Among the GGO group, CD8+ and FoxP3+ TIL density increased significantly with increasing CTR (p < 0.001 and p < 0.001, respectively). Moreover, PD-L1 and IDO1 expression was significantly higher in the pure-solid group than in the GGO group (p < 0.001 and p < 0.001, respectively). Conclusions: CTR was correlated with the abundance of CD8+ and FoxP3+ TILs in the GGO group. PD-L1 and IDO1 positivity rates were significantly higher in the pure-solid group than in the GGO group. Increased CTR may be correlated with immunosuppressive condition.

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  • A propensity score-matched analysis of the impact of statin therapy on the outcomes of patients with non-small-cell lung cancer receiving anti-PD-1 monotherapy: a multicenter retrospective study

    Takada, K; Shimokawa, M; Takamori, S; Shimamatsu, S; Hirai, F; Tagawa, T; Okamoto, T; Hamatake, M; Tsuchiya-Kawano, Y; Otsubo, K; Inoue, K; Yoneshima, Y; Tanaka, K; Okamoto, I; Nakanishi, Y; Mori, M

    BMC CANCER   22 ( 1 )   503   2022.5   eISSN:1471-2407

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    Background: Many studies have recently reported the association of concomitant medications with the response and survival in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy. However, the clinical impact of statin therapy on the outcome of cancer immunotherapy in patients with NSCLC is poorly understood. Methods: In our database, we retrospectively identified and enrolled 390 patients with advanced or recurrent NSCLC who were treated with anti-programmed cell death-1 (PD-1) monotherapy in clinical practice between January 2016 and December 2019 at 3 medical centers in Japan to examine the clinical impact of statin therapy on the survival of patients with NSCLC receiving anti-PD-1 monotherapy. A propensity score-matched analysis was conducted to minimize the bias arising from the patients’ backgrounds. Results: The Kaplan–Meier curves of the propensity score-matched cohort showed that the overall survival (OS), but not the progression-free survival (PFS), was significantly longer in patients receiving statin therapy. However, a Cox regression analysis in the propensity score-matched cohort revealed that statin therapy was not an independent favorable prognostic factor, although it tended to be correlated with a favorable outcome. Conclusions: Statin therapy may be a combination tool for cancer immunotherapy in patients with NSCLC. These findings should be validated in further prospective studies with larger sample sizes.

    DOI: 10.1186/s12885-022-09385-8

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  • The clinical impact of concomitant medication use on the outcome of postoperative recurrent non-small-cell lung cancer in patients receiving immune checkpoint inhibitors

    Takada, K; Shimokawa, M; Takamori, S; Shimamatsu, S; Hirai, F; Ono, Y; Tagawa, T; Okamoto, T; Hamatake, M; Okamoto, I; Mori, M

    PLOS ONE   17 ( 2 )   2022.2   ISSN:1932-6203

  • Assessment of the albumin-bilirubin grade as a prognostic factor in patients with non-small-cell lung cancer receiving anti-PD-1-based therapy

    Takada, K; Takamori, S; Shimokawa, M; Toyokawa, G; Shimamatsu, S; Hirai, F; Tagawa, T; Okamoto, T; Hamatake, M; Tsuchiya-Kawano, Y; Otsubo, K; Inoue, K; Yoneshima, Y; Tanaka, K; Okamoto, ; Nakanishi, Y; Mori, M

    ESMO OPEN   7 ( 1 )   100348   2022.2   eISSN:2059-7029

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    Introduction: The albumin-bilirubin (ALBI) grade is a novel indicator of the liver function. Some studies showed that the ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. The association between the ALBI grade and outcomes in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy, however, is poorly understood. Methods: We retrospectively enrolled 452 patients with advanced or recurrent NSCLC who received anti-programmed cell death protein 1 (PD-1)-based therapy between 2016 and 2019 at three medical centers in Japan. The ALBI score was calculated from albumin and bilirubin measured at the time of treatment initiation and was stratified into three categories, ALBI grade 1-3, with reference to previous reports. We examined the clinical impact of the ALBI grade on the outcomes of NSCLC patients receiving anti-PD-1-based therapy using Kaplan–Meier survival curve analysis with log-rank test and Cox proportional hazards regression analysis. Results: The classifications of the 452 patients were as follows: grade 1, n = 158 (35.0%); grade 2, n = 271 (60.0%); and grade 3, n = 23 (5.0%). Kaplan–Meier survival curve analysis showed that the ALBI grade was significantly associated with progression-free survival and overall survival. Moreover, Cox regression analysis revealed that the ALBI grade was an independent prognostic factor for progression-free survival and overall survival. Conclusion: The ALBI grade was an independent prognostic factor for survival in patients with advanced or recurrent NSCLC who receive anti-PD-1-based therapy. These findings should be validated in a prospective study with a larger sample size.

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  • The clinical impact of concomitant medication use on the outcome of postoperative recurrent non-small-cell lung cancer in patients receiving immune checkpoint inhibitors

    Takada K., Shimokawa M., Takamori S., Shimamatsu S., Hirai F., Ono Y., Tagawa T., Okamoto T., Hamatake M., Okamoto I., Mori M.

    PLoS ONE   17 ( 2 February )   e0263247   2022.2

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    A recent study suggested that proton pump inhibitor (PPI) use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs) was associated with poor clinical outcomes. However, the clinical impact of PPI use on the outcome of patients receiving ICIs for postoperative recurrent NSCLC is unknown. The outcomes of 95 patients with postoperative recurrence of NSCLC receiving ICIs at 3 medical centers in Japan were analyzed. We conducted adjusted Kaplan–Meier survival analyses with the log-rank test, a Cox proportional hazards regression analysis, and a logistic regression analysis using inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients’ backgrounds. The IPTW-adjusted Kaplan–Meier curves revealed that the progression-free survival (PFS), but not the overall survival (OS), was significantly longer in patients who did not receive PPIs than in those who did receive them. The IPTW-adjusted Cox regression analysis revealed that PPI use was an independent poor prognostic factor for the PFS and OS. Furthermore, in the IPTW-adjusted logistic regression analysis, PPI non-use was an independent predictor of disease control. In this multicenter and retrospective study, PPI use was associated with poor clinical outcomes in patients with postoperative recurrence of NSCLC who were receiving ICIs. PPIs should not be prescribed indiscriminately to patients with postoperative recurrence of NSCLC who intend to receive ICIs. These findings should be validated in a future prospective study.

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  • 肺・食道を含む3つの癌が同時発症した局所進行膵癌患者に対してコンバージョン手術が奏効した症例 症例報告(A case of successful conversion surgery for locally advanced pancreatic cancer with synchronous triple cancer of the lung and esophagus: a case report)

    Mita Junya, Iguchi Tomohiro, Iseda Norifumi, Takada Kazuki, Hirose Kosuke, Miura Naoko, Honboh Takuya, Emi Yasunori, Akashi Tetsuro, Kato Seiya, Sadanaga Noriaki, Matsuura Hiroshi

    Surgical Case Reports   8   1 of 6 - 6 of 6   2022.1

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    症例は59歳男性で、心窩部痛、食欲不振、体重減少のため当院へ入院した。CT検査と上部消化管内視鏡検査の結果、膵、肺、食道に癌が発生していることが判明した。膵癌は局所進行性で、肺と食道の癌はどちらかといえば非進行性であった。膵癌に対し、ゲムシタビンとnab-パクリタキセルの併用による強化化学療法を6コース施行したところ、腫瘍サイズは著明に縮小し、認められていた大動脈または腹腔動脈への浸潤像は観察されなくなった。その間、肺と食道の癌には大きな変化は認められなかった。それから膵癌(ypT3N0cM0、yp病期IIA)の根治的切除術(脾臓合併膵尾部切除術と左腎摘出術)を行ったが、術中、胃に粘膜下腫瘍を発見したため胃部分切除術も施行した。術後の病理検査では完全切除達成が確認された。次いで早期食道癌(pT1a[M]-LPM)に対し内視鏡的粘膜下層剥離術を、早期肺癌(pT2aN0M0、p病期IB)に対し胸腔鏡下で右上葉切除術と右下葉部分切除術を順次施行した。膵癌手術から8ヵ月後の時点で再発の徴候はみられず、QOLは良好であった。

  • Combination Antiemetic Therapy for Chemotherapy-Induced Nausea and Vomiting in Patients with NSCLC Receiving Carboplatin-Based Chemotherapy

    Shimokawa, M; Haratake, N; Takada, K; Toyokawa, G; Takamori, S; Mizuki, F; Takenaka, T; Hayashi, T

    CANCER MANAGEMENT AND RESEARCH   14   2673 - 2680   2022   ISSN:1179-1322

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    Purpose: The incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in patients with non-small cell lung cancer (NSCLC) receiving carboplatin (CBDCA)-based chemotherapy (CBDCA + pemetrexed or paclitaxel) has not been clearly described. Therefore, we attempted to evaluate whether delayed CINV could be controlled using a combination of three antiemetics and identify individual risk factors. Methods: We pooled data from two prospective observational studies, namely a nationwide survey of CINV and a prospective, observational study in Japan, to assess whether delayed CINV could be controlled using a combination of three antiemetics and identified individual risk factors via inverse probability treatment-weighted analysis. Results: In total, 240 patients were evaluable in this study (median age, 66 years; male, 173; female, 67). The three-antiemetic regimen controlled delayed nausea (31.6% vs 47.3%) and vomiting (5.1% vs 23.1%) better than two antiemetics. Younger age (<70 years; odds ratio [OR] = 2.233), motion sickness (OR = 3.472), drinking habits (OR = 1.972), receipt of the CBDCA + pemetrexed regimen (OR = 2.041), and the use of two antiemetics (OR = 1.926) were risk factors for delayed nausea. Female sex (OR = 3.372), drinking habits (OR = 2.272), receipt of the CBDCA+ pemetrexed regimen (OR = 2.314), and the use of two antiemetics (OR = 6.830) were risk factors for delayed vomiting. Conclusion: Female sex, younger age, and receipt of the CBDCA + pemetrexed regimen increased the risk of CINV. Therefore, we recommend additional supportive antiemetics treatment for these patients.

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Presentations

  • 非小細胞肺癌におけるPD-L1発現の臨床的意義と免疫チェックポイント阻害薬治療における予後予測因子の探索 Invited

    高田和樹

    第41回日本呼吸器外科学会学術集会  2024.6 

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    Event date: 2024.5 - 2024.6

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  • 切除可能非小細胞肺癌に対する術前免疫療法の安全性に関する系統的レビュー

    高田和樹

    第64回日本肺癌学会学術集会  2023.11 

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    Event date: 2023.11

    Language:Japanese   Presentation type:Poster presentation  

  • 非小細胞肺癌患者における術前免疫チェックポイント阻害薬の安全性に関する系統的レビュー

    高田和樹

    第40回日本呼吸器外科学会学術集会  2023.7 

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  • 未治療非小細胞肺癌患者における複合癌免疫療法治療効果と性別-RCTのメタアナリシス-

    高田和樹

    第63回日本肺癌学会学術集会  2022.12 

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    Event date: 2022.12

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  • A Meta-Analysis for Treatment-Related Adverse Events of Combination Chemoimmunotherapy vs Chemotherapy in First-Line Treatment for NSCLC International conference

    Kazuki Takada

    IASLC 2022 Asia Conference on Lung Cancer  2022.10 

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    Event date: 2022.10

    Language:English   Presentation type:Poster presentation  

  • 非小細胞肺癌手術症例における残歯数と臨床病理学的因子および予後との関連

    高田和樹

    第39回日本呼吸器外科学会学術集会  2022.5 

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  • 若手臨床医が行うリアルワールドデータを用いた後ろ向き観察研究 Invited

    高田和樹

    第62回日本肺癌学会九州支部学術集会  2022.2 

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    Event date: 2022.2

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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MISC

Professional Memberships

  • 日本外科学会

  • 日本呼吸器外科学会

  • 日本胸部外科学会

  • 日本内視鏡外科学会

  • 日本肺癌学会

  • 日本癌学会

  • 日本癌治療学会

  • 日本臨床腫瘍学会

  • 日本呼吸器学会

  • 日本緩和医療学会

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Research Projects

  • 免疫チェックポイント阻害薬と整腸剤を併用した新規複合療法の開発

    Grant number:24K19436  2024.4 - 2027.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    高田 和樹

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    Grant type:Scientific research funding

    本研究は、非小細胞肺癌における免疫チェックポイント阻害薬(ICI)への酪酸菌製剤およびビフィズス菌製剤上乗せ効果を検証し、ICIと整腸剤を併用した新規複合療法開発に向けた基礎的検討を行うものである。
    ICIに加えて、酪酸菌製剤単独、ビフィズス菌製剤単独、もしくはその両製剤をルイス肺癌モデルマウスに投与し、以下の相違を検討する。①腫瘍径の推移、体重の推移、生存期間 ②血液、腫瘍、脾臓における免疫細胞の種類と割合 ③便中に含まれる短鎖脂肪酸の種類と割合 ④短鎖脂肪酸と生存期間との関係 また、非小細胞肺癌術後再発患者における便中に含まれる短鎖脂肪酸とICI治療効果、予後との関連を調べる。

    CiNii Research

  • Novel Combination Immunotherapy for Non-Small Cell Lung Cancer Targeting Poliovirus Receptor

    Grant number:19K16837  2019.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    TAKADA Kazuki

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    Grant type:Scientific research funding

    In 264 squamous cell carcinoma of the lung, high CD155 expression was associated with poor prognosis in both recurrence-free survival (RFS) and overall survival (OS) (p=0.0164, p=0.0023). In 363 lung adenocarcinoma of the lung, high CD155 expression was associated with poor prognosis for RFS (p=0.0188) and no significant difference for OS (p=0.0531). In EGFR mutant patients, there was no prognostic difference by CD155 expression, but in EGFR wild-type patients, high CD155 expression was associated with poor prognosis (RFS p=0.0253, OS p=0.0225).
    In squamous cell carcinoma of the lung and EGFR wild-type lung adenocarcinoma, high CD155 expression was associated with poor prognosis, suggesting that CD155 expression may be involved in tumor cell growth.

    CiNii Research

Educational Activities

  • 医学部生に対する臨床医学実習の基本事項に関して、実際に患者に接しながら指導している。特に外科、呼吸器外科分野において、担当している。

Class subject

  • 医工学入門

    2025.4 - Present  

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Surgical Clinical Medicine / Respiratory Surgery

Clinician qualification

  • Specialist

    Japan Surgical Society(JSS)

  • Specialist

    The Japanese Association for Chest Surgery

  • Specialist

    The Japanese Respiratory Society

  • Certifying physician

    日本がん治療認定医機構

  • Certifying physician

    肺がんCT検診認定機構

Year of medical license acquisition

  • 2011

Notable Clinical Activities

  • JCOGやWJOGなどの臨床試験グループに参加し、肺癌に対する手術に関する臨床試験に数多く参加・登録している。