Updated on 2024/11/20

Information

 

写真a

 
MATSUBARA TAICHI
 
Organization
Kyushu University Hospital Chest Surgery (2) Assistant Professor
Title
Assistant Professor

Papers

  • ASO Author Reflections: Impact of Glutathione Peroxidase 2 (GPX2) in Lung Adenocarcinoma

    Hashinokuchi, A; Matsubara, T; Takenaka, T; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   31 ( 8 )   5092 - 5093   2024.8   ISSN:1068-9265 eISSN:1534-4681

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    Language:English   Publisher:Annals of Surgical Oncology  

    DOI: 10.1245/s10434-024-15177-0

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  • ASO Visual Abstract: Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma

    Hashinokuchi, A; Matsubara, T; Ono, Y; Shunichi, S; Matsudo, K; Nagano, T; Kinoshita, F; Akamine, T; Kohno, M; Takenaka, T; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   31 ( 8 )   5098 - 5098   2024.8   ISSN:1068-9265 eISSN:1534-4681

  • Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma

    Hashinokuchi, A; Matsubara, T; Ono, Y; Shunichi, S; Matsudo, K; Nagano, T; Kinoshita, F; Akamine, T; Kohno, M; Takenaka, T; Oda, Y; Yoshizumi, T

    ANNALS OF SURGICAL ONCOLOGY   31 ( 7 )   4822 - 4829   2024.7   ISSN:1068-9265 eISSN:1534-4681

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    Language:English   Publisher:Annals of Surgical Oncology  

    Background: Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified. Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance. Results: qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS. Conclusions: GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

    DOI: 10.1245/s10434-024-15116-z

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  • Phase II Trial of Adjuvant Atezolizumab Therapy in Elderly Patients with Completely Resected Stage II/III Non-Small Cell Lung Cancer: RELIANCE Trial

    Matsubara, T; Yamaguchi, M; Shimokawa, M; Okamoto, I

    CLINICAL LUNG CANCER   25 ( 3 )   280 - 283   2024.5   ISSN:1525-7304 eISSN:1938-0690

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    Language:English   Publisher:Clinical Lung Cancer  

    Introduction: Atezolizumab following platinum chemotherapy and complete pulmonary resection has become the new standard of adjuvant care for patients with stage II-III non-small cell lung cancer (NSCLC) expressing programmed death-ligand 1 (PD-L1). However, the efficacy and safety of postoperative adjuvant therapy and subsequent atezolizumab in patients aged 75 and older have not been established. Methods: Patients with completely resected stage II–III NSCLC aged 75 and older will be prospectively registered in this single-arm phase II study. The enrolled patients will receive cisplatin plus vinorelbine (CDDP + VNR) followed by atezolizumab for up to 12 months. PD-L1 expression in at least 1% of cells will be confirmed by immunohistochemical staining. We plan to enroll 33 patients over 1 year at 25 institutions in Japan. The primary endpoint is the completion rate of adjuvant treatment (CDDP + VNR initiation to atezolizumab completion). Conclusion: The present study represents the first prospective trial of the tolerability of postoperative adjuvant therapy with immune checkpoint inhibitors in elderly individuals. The results of this trial might help promote postoperative adjuvant immunotherapy in the future for the elderly.

    DOI: 10.1016/j.cllc.2024.01.009

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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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    Language:English   Publisher:European Journal of Cancer  

    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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  • Biomarker Testing in Patients with Unresectable Advanced or Recurrent Non-Small Cell Lung Cancer

    Sakamoto T., Matsubara T., Takahama T., Yokoyama T., Nakamura A., Tokito T., Okamoto T., Akamatsu H., Oki M., Sato Y., Tobino K., Ikeda S., Mori M., Mimura C., Maeno K., Miura S., Harada T., Nishimura K., Hiraoka M., Kenmotsu H., Fujimoto J., Shimokawa M., Yamamoto N., Nakagawa K.

    JAMA Network Open   6 ( 12 )   2023.12

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    Publisher:JAMA Network Open  

    Importance: Biomarker testing for driver mutations is essential for selecting appropriate non-small cell lung cancer (NSCLC) treatment but is insufficient. Objective: To investigate the status of biomarker testing and drug therapy for NSCLC in Japan for identifying problems in treatment. Design, Setting, and Participants: The REVEAL cohort study included retrospective data collection and prospective follow-up from 29 institutions across Japan. Of 1500 patients diagnosed with advanced or recurrent NSCLC between January 1 and March 18, 2021, 1479 were eligible. Cases recognized at the wrong clinical stage (n = 12), diagnosed outside the study period (n = 6), not treated according to eligibility criteria before recurrence (n = 2), and with deficient consent acquisition procedure (n = 1) were excluded. Main Outcomes and Measures: The primary end point was the biomarker testing status. Treatment-related factors were examined. Results: Among the 1479 patients included in the analysis, the median age was 72 (range, 30-95) years; 1013 (68.5%) were men; 1161 (78.5%) had an Eastern Cooperative Oncology Group performance status 0 or 1; 1097 (74.2%) were current or past smokers; and 947 (64.0%) had adenocarcinoma. Biomarker status was confirmed in 1273 patients (86.1%). Multigene testing was performed in 705 cases (47.7%); single-gene testing, in 847 (57.3%); and both, in 279 (18.9%). Biomarker testing was performed for EGFR in 1245 cases (84.2%); ALK, in 1165 (78.8%); ROS1, in 1077 (72.8%); BRAF, in 803 (54.3%); and MET, in 805 (54.4%). Positivity rates among 898 adenocarcinoma cases included 305 (34.0%) for EGFR, 29 (3.2%) for ALK, 19 (2.1%) for ROS1, 11 (1.2%) for BRAF, and 14 (1.6%) for MET. Positivity rates among 375 nonadenocarcinoma cases were 14 (3.7%) for EGFR, 6 (1.6%) for ALK, 1 (0.3%) for ROS1, 3 (0.8%) for BRAF, and 8 (2.1%) for MET. Poor physical status, squamous cell carcinoma, and other comorbidities were associated with hampered multigene testing. Targeted therapy was received as first-line treatment by 263 of 278 cases (94.6%) positive for EGFR, 25 of 32 (78.1%) positive for ALK, 15 of 24 (62.5%) positive for ROS1, 9 of 12 (75.0%) positive for BRAF, and 12 of 19 (63.2%) positive for MET. Median overall survival of patients with positive findings for driver gene alteration and who received targeted therapy was 24.3 (95% CI, not reported) months; with positive findings for driver gene alteration and who did not receive targeted therapy, 15.2 (95% CI, 7.7 to not reported) months; and with negative findings for driver gene alteration, 11.0 (95% CI, 10.0-12.5) months. Multigene testing for nonadenocarcinomas and adenocarcinomas accounted for 705 (47.7%) of all NSCLC cases. Conclusions and Relevance: These findings suggest that multigene testing has not been sufficiently implemented in Japan and should be considered prospectively, even in nonadenocarcinomas, to avoid missing rare driver gene alterations..

    DOI: 10.1001/jamanetworkopen.2023.47700

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  • Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification

    Okada, N; Fukunaga, M; Miura, K; Nemoto, K; Matsumoto, J; Hashimoto, N; Kiyota, M; Morita, K; Koshiyama, D; Ohi, K; Takahashi, T; Koeda, M; Yamamori, H; Fujimoto, M; Yasuda, Y; Hasegawa, N; Narita, H; Yokoyama, S; Mishima, R; Kawashima, T; Kobayashi, Y; Sasabayashi, D; Harada, K; Yamamoto, M; Hirano, Y; Itahashi, T; Nakataki, M; Hashimoto, RI; Tha, KK; Koike, S; Matsubara, T; Okada, G; van Erp, TGM; Jahanshad, N; Yoshimura, R; Abe, O; Onitsuka, T; Watanabe, Y; Matsuo, K; Yamasue, H; Okamoto, Y; Suzuki, M; Turner, JA; Thompson, PM; Ozaki, N; Kasai, K; Hashimoto, R

    MOLECULAR PSYCHIATRY   28 ( 12 )   5206 - 5216   2023.12   ISSN:1359-4184 eISSN:1476-5578

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    Language:English   Publisher:Molecular Psychiatry  

    Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2–3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

    DOI: 10.1038/s41380-023-02141-9

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  • A project to investigate the actual status of biomarker testing in unresectable advanced or recurrent non-small cell lung cancer: WJOG15421 L (REVEAL)

    Kawashima, Y; Sakamoto, T; Matsubara, T; Takahama, T; Sakata, S; Tadashi, M; Yoshino, I; Nagata, K; Hata, A; Sugio, K; Takenaka, T; Okada, M; Nishimura, K; Hiraoka, M; Kenmotsu, H; Hujimoto, J; Shimokawa, M; University, WM; Nakagawa, K

    ANNALS OF ONCOLOGY   34   S1416 - S1416   2023.11   ISSN:0923-7534 eISSN:1569-8041

  • 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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    Language:English   Publisher:European Journal of Cancer  

    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.

    DOI: 10.1016/j.ejca.2022.06.002

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