Development of AI for the drug therapy of hepatocellular carcinoma using medical image and immunogenomics

• Project/Area Number: 21K07184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kindai University
• Principal Investigator: Nishida Naoshi 近畿大学, 医学部, 教授 (60281755)
• Co-Investigator(Kenkyū-buntansha): 目加田 慶人 中京大学, 工学部, 教授 (00282377)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝細胞癌 / 薬物療法 / 人工知能 / 医用画像 / 腫瘍免疫微小環境 / 免疫チェックポイント阻害剤 / ドライバー変異 / 遺伝子変異 / 予測モデル / Radiomics / 分子標的薬 / バイオマーカー / 画像診断 / ニューラルネットワーク / 治療効果予測 / 化学療法 / 免疫微小環境

Outline of Research at the Start

肝癌に対する薬物療法においては有効なバイオマーカーがなく、治療薬は医師の経験に基づき選択されている。近年、医用画像を学習させた人工知能(AI)により、治療効果を予測する試みがなされている。一方、腫瘍の画像上の特徴は腫瘍形質を反映し、治療薬の効果は、腫瘍形質に関わる遺伝子変異や微小免疫環境の影響を受けると予想される。本研究では、進行肝癌の一次治療薬としてチロシンキナーゼ阻害剤や免疫チェックポイント阻害剤が使用された例において、医用画像情報に加え、遺伝子変異や免疫関連遺伝子発現情報を独自の手法でスコア化し、学習データとしてAIに与え、AIが症例に応じて最適な治療薬を見出し得るかを検討する。

Outline of Final Research Achievements

We developed an AI to predict the efficacy of immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC). 154 HCC tissues were used to classify tumors based on mutation, histopathology and imaging information. Using scores generated by CD8+ lymphocytes, PD-L1, and β-catenin activation, progression-free survival for PD-1 antibody treatment was successfully stratified in test cohort.Another model was also developed to predict disease control by lenvatinib using imaging information. Radiomics features were extracted from CT, and compared to the LightGBM model, the neural network (NN) model showed better performance with the average correct response rate was 0.58. To further improve accuracy, we used the mutual information as a measure of the relevance of features to create a better model with fewer features. As a result, the GLSZM (Gray Level Size Zone Matrix), a radiomics feature, was particularly useful for discrimination with better performance.

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌（以下肝癌）は本邦のがんの部位別死亡率で5位を占め、その治療法の確立は社会的に重要な問題である。現在、肝癌の1次治療薬として、チロシンキナーゼ阻害剤が2種、複合免疫療法が2種承認されている。しかし、これらの薬物療法においては有効なバイオマーカーがなく、治療薬は医師の経験に基づき選択されている。本研究成果は肝癌の治療における反応性を病理、遺伝子、画像から予測するのものであり、これにより、無駄な治療を避け、患者の生活の質を向上させることが期待できる。さらに治療前にその効果の予測ができれば、肝癌治療の個別化医療の実現に向けた一歩となり得る。

Research Products

• [Journal Article] Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumours (2024)
  • Author(s): Celsa Ciro、Cabibbo Giuseppe、Fulgenzi Claudia A.M.、SchNishida Naoshi、et al.
  • Journal Title: Journal of Hepatology Volume: 80 Issue: 3 Pages: 431-442
  • DOI: 10.1016/j.jhep.2023.10.040
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Safety and Efficacy of Lenvatinib in Very Old Patients with Unresectable Hepatocellular Carcinoma (2024)
  • Author(s): Camera Silvia、Rimini Margherita、Rossari Federico、Tada Toshifumi、Suda Goki、Cascinu Stefano、Casadei-Gardini Andrea
  • Journal Title: Targeted Oncology Volume: 19 Issue: 1 Pages: 29-39
  • DOI: 10.1007/s11523-023-01029-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma (2024)
  • Author(s): Balcar Lorenz、Scheiner Bernhard、Fulgenzi Claudia Angela Maria、D’Alessio Antonio、Pomej Katharina、Roig Marta Bofill、Meyer Elias Laurin、Che Jaekyung、Nishida Naoshi、Lee Pei-Chang、Wu Linda、Ang Celina、Krall Anja、Saeed Anwaar、Stefanini Bernardo、Naoshiu Nishida、et al.
  • Journal Title: JHEP Reports Volume: 6 Issue: 2 Pages: 100982-100982
  • DOI: 10.1016/j.jhepr.2023.100982
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of body mass index on the prognosis of unresectable HCC patients receiving first‐line Lenvatinib or atezolizumab plus bevacizumab (2024)
  • Author(s): Rimini Margherita、Stefanini Bernardo、Tada Toshifumi、Suda Goki、Shimose Shigeo、Kudo Masatoshi、Naoshi Nishida、et al.
  • Journal Title: Liver International Volume: － Issue: 5 Pages: 1108-1125
  • DOI: 10.1111/liv.15885
  • Peer Reviewed / Open Access
• [Journal Article] Role of the prognostic nutritional index in predicting survival in advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab. (2023)
  • Author(s): Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa Ramos J, Masi G, Yoo C, Lonardi S, Stefanini B, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Montes M, Vivaldi C, Solda C, Hiraoka A, Sho T, Niizeki T, Nishida N, et al.
  • Journal Title: Oncology Volume: ー Issue: 5 Pages: 283-291
  • DOI: 10.1159/000528818
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors. (2023)
  • Author(s): Wu YL, van Hyfte G, Ozbek U, Reincke M, Gampa A, Mohamed YI, Nishida N, Wietharn B, Amara S, Lee PC, Scheiner B, Balcar L, Pinter M, Vogel A, Weinmann A, Saeed A, Pillai A, Rimassa L, Naqash AR, Muzaffar M, Huang YH, Kaseb AO, Kudo M, Pinato DJ, Ang C.
  • Journal Title: Frontiers in oncology Volume: 13 Pages: 128569-1128569
  • DOI: 10.3389/fonc.2023.1128569
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis? (2023)
  • Author(s): Rimini M, Persano M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Yoo C, Lonardi S, Piscaglia F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Montes M, Vivaldi C, Solda C, Hiraoka A, Sho T, Niizeki T, Nishida N, et al.
  • Journal Title: Targeted Oncology Volume: 18 Issue: 2 Pages: 221-233
  • DOI: 10.1007/s11523-023-00953-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients (2023)
  • Author(s): Rimini M, Persano M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Salani F, Lonardi S, Piscaglia F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Schirripa M, Montes M, Vivaldi C, Solda C, Hiraoka A, Sho T, Niizeki T, Nishida N, et al.
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: ー Issue: 10 Pages: 7565-7577
  • DOI: 10.1007/s00432-023-04678-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Advances in Immunotherapy for Hepatocellular Carcinoma. (2023)
  • Author(s): Hagiwara S, Nishida N, Kudo M.
  • Journal Title: Cancers Volume: 15 (7) Issue: 7 Pages: 2070-2070
  • DOI: 10.3390/cancers15072070
  • Peer Reviewed / Open Access
• [Journal Article] Impact of body mass index in patients receiving atezolizumab plus bevacizumab for hepatocellular carcinoma. (2023)
  • Author(s): Vithayathil M, D'Alessio A, Fulgenzi CAM, Nishida N, Schonlein M, von Felden J, Schulze K, Wege H, Saeed A, Wietharn B, Hildebrand H, Wu L, Ang C, Marron TU, Weinmann A, Galle PR, Bettinger D, Bengsch B, Vogel A, Balcar L, et al.
  • Journal Title: Hepatology international Volume: ー Issue: 4 Pages: 904-914
  • DOI: 10.1007/s12072-023-10491-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of β-Catenin Activation in the Tumor Immune Microenvironment and Immunotherapy of Hepatocellular Carcinoma (2023)
  • Author(s): Morita Masahiro、Nishida Naoshi、Aoki Tomoko、Chishina Hirokazu、Takita Masahiro、Ida Hiroshi、Hagiwara Satoru、Minami Yasunori、Ueshima Kazuomi、Kudo Masatoshi
  • Journal Title: Cancers Volume: 15 Issue: 8 Pages: 2311-2311
  • DOI: 10.3390/cancers15082311
  • Peer Reviewed / Open Access
• [Journal Article] Non-Inflamed Tumor Microenvironment and Methylation/Downregulation of Antigen-Presenting Machineries in Cholangiocarcinoma (2023)
  • Author(s): Nishida Naoshi、Aoki Tomoko、Morita Masahiro、Chishina Hirokazu、Takita Masahiro、Ida Hiroshi、Hagiwara Satoru、Minami Yasunori、Ueshima Kazuomi、Kudo Masatoshi
  • Journal Title: Cancers Volume: 15 Issue: 8 Pages: 2379-2379
  • DOI: 10.3390/cancers15082379
  • Peer Reviewed / Open Access
• [Journal Article] Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients (2023)
  • Author(s): Persano Mara、Rimini Margherita、Tada Toshifumi、Suda Goki、Shimose Shigeo、Kudo Masatoshi、Cheon Jaekyung、Masi Gianluca、Yoo Changhoon、Lonardi Sara、Tovoli Francesco、Kumada Takashi、Sakamoto Naoya、Tamburini Emiliano、Cabibbo Giuseppe、Foschi Francesco Giuseppe、Scartozzi Mario、Casadei-Gardini Andrea
  • Journal Title: European Journal of Cancer Volume: 189 Pages: 112933-112933
  • DOI: 10.1016/j.ejca.2023.05.021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Achievement of Complete Response and Drug-Free Status by Atezolizumab plus Bevacizumab Combined with or without Curative Conversion in Patients with Transarterial Chemoembolization-Unsuitable, Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Proof-Of-Concept Study (2023)
  • Author(s): Kudo Masatoshi、Aoki Tomoko、Ueshima Kazuomi、Naohsi Nishida、et al
  • Journal Title: Liver Cancer Volume: 12 Issue: 4 Pages: 321-338
  • DOI: 10.1159/000529574
  • Peer Reviewed / Open Access
• [Journal Article] The role of FGFR inhibitors in the treatment of intrahepatic cholangiocarcinoma: unveiling the future challenges in drug therapy (2023)
  • Author(s): Nishida Naoshi
  • Journal Title: Hepatobiliary Surgery and Nutrition Volume: 12 Issue: 5 Pages: 790-794
  • DOI: 10.21037/hbsn-23-411
  • Peer Reviewed
• [Journal Article] Genetic/Epigenetic Alteration and Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Transforming the Immune Microenvironment with Molecular-Targeted Agents (2023)
  • Author(s): Nishida Naoshi、Kudo Masatoshi
  • Journal Title: Liver Cancer Volume: － Issue: 2 Pages: 1-14
  • DOI: 10.1159/000534443
  • Peer Reviewed / Open Access
• [Journal Article] Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma (2023)
  • Author(s): Dharmapuri Sirish、Ozbek Umut、Jethra Hiren、Naoshi Nishida, et al.
  • Journal Title: World Journal of Gastrointestinal Oncology Volume: 15 Issue: 11 Pages: 1900-1912
  • DOI: 10.4251/wjgo.v15.i11.1900
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] <scp>α‐FAtE</scp>: A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma (2023)
  • Author(s): Rossari Federico、Tada Toshifumi、Suda Goki、Shimose Shigeo、Kudo Masatoshi、Naoshi Nishida, et al.
  • Journal Title: International Journal of Cancer Volume: 154 Issue: 6 Pages: 1043-1056
  • DOI: 10.1002/ijc.34799
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Incidence of Hyper Progressive Disease in Combination Immunotherapy and Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Monotherapy for Unresectable Hepatocellular Carcinoma (2023)
  • Author(s): Aoki Tomoko、Kudo Masatoshi、Ueshima Kazuomi、Morita Masahiro、Chishina Hirokazu、Takita Masahiro、Hagiwara Satoru、Ida Hiroshi、Minami Yasunori、Tsurusaki Masakatsu、Nishida Naoshi
  • Journal Title: Liver Cancer Volume: 13 Issue: 1 Pages: 56-69
  • DOI: 10.1159/000531024
  • Peer Reviewed / Open Access
• [Journal Article] Successful initial tofacitinib treatment for acute severe ulcerative colitis with steroid resistance: a case series. (2023)
  • Author(s): Komeda Y, Kono M, Kashida H, Tribonias G, Masaki S, Takada R, Nagai T, Hagiwara S, Nishida N, Takenaka M, Honjo H, Matsui S, Tsuji N, Kudo M.
  • Journal Title: Annals of gastroenterology Volume: 35 (1) Pages: 97-102
  • DOI: 10.20524/aog.2022.0768
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Artificial intelligence models for the diagnosis and management of liver diseases. (2023)
  • Author(s): Nishida N, Kudo, M
  • Journal Title: Ultrasonography Volume: 42(1) Issue: 1 Pages: 10-19
  • DOI: 10.14366/usg.22110
  • Peer Reviewed / Open Access
• [Journal Article] Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. (2022)
  • Author(s): Casadei-Gardini A, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Rimassa L, Presa J, Masi G, Yoo C, Lonardi S, Tovoli F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Montes M, Vivaldi C, Solda C, Piscaglia F, Hiraoka A, Nishida N, et al.
  • Journal Title: European journal of cancer Volume: 180 Pages: 9-20
  • DOI: 10.1016/j.ejca.2022.11.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study. (2022)
  • Author(s): Talbot T, D'Alessio A, Pinter M, Balcar L, Scheiner B, Marron TU, Jun T, Dharmapuri S, Ang C, Saeed A, Hildebrand H, Muzaffar M, Fulgenzi CAM, Amara S, Naqash AR, Gampa A, Pillai A, Wang Y, Khan U, Lee PC, Huang YH, Bengsch B, Bettinger D, Mohamed YI, Kaseb A, Pressiani T, Nishida N, Kudo M, et al.
  • Journal Title: Liver international Volume: 43(3) Issue: 3 Pages: 695-707
  • DOI: 10.1111/liv.15502
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study. (2022)
  • Author(s): Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Rimassa L, Presa J, Masi G, Yoo C, Lonardi S, Tovoli F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Kawaguchi T, Montes M, Vivaldi C, Solda C, Piscaglia F, Hiraoka A, Sho T, Nishida N, et al.
  • Journal Title: Journal of cancer research and clinical oncology Volume: ー Issue: 9 Pages: 5591-5602
  • DOI: 10.1007/s00432-022-04512-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab. (2022)
  • Author(s): Wu YL, Fulgenzi CAM, D'Alessio A, Cheon J, Nishida N, Saeed A, Wietharn B, Cammarota A, Pressiani T, Personeni N, Pinter M, Scheiner B, Balcar L, Huang YH, Phen S, Naqash AR, Vivaldi C, Salani F, Masi G, Bettinger D, Vogel A, Schonlein M, von Felden J, Schulze K, Wege H, Galle PR, Kudo M, et al
  • Journal Title: Cancers Volume: 14(23) Issue: 23 Pages: 5834-5834
  • DOI: 10.3390/cancers14235834
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study (2022)
  • Author(s): Fulgenzi CAM, Cheon J, D'Alessio A, Nishida N, Ang C, Marron TU, Wu L, Saeed A, Wietharn B, Cammarota A, Pressiani T, Personeni N, Pinter M, Scheiner B, Balcar L, Napolitano A, Huang YH, Phen S, Naqash AR, Vivaldi C, Salani F, Masi G, Bettinger D, Vogel A, Schonlein M, von Felden J, Schulze K, Kudo M, et al.
  • Journal Title: European journal of cancer Volume: 175 Pages: 204-213
  • DOI: 10.1016/j.ejca.2022.08.024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. (2022)
  • Author(s): Vithayathil M, D'Alessio A, Fulgenzi CAM, Nishida N, Schonlein M, von Felden J, Schulze K, Wege H, Saeed A, Wietharn B, Hildebrand H, Wu L, Ang C, Marron TU, Weinmann A, Galle PR, Bettinger D, Bengsch B, Vogel A, Balcar L, Scheiner B, Lee PC, Huang YH, Amara S, Muzaffar M, Naqash AR, Cammarota A, Kudo M, et al.
  • Journal Title: Liver international Volume: 42(11) Issue: 11 Pages: 2538-2547
  • DOI: 10.1111/liv.15405
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic Factors for Overall Survival in Patients with HCV-Related HCC Undergoing Molecular Targeted Therapies: Beyond a Sustained Virological Response. (2022)
  • Author(s): Minami Y, Aoki T, Chishina H, Takita M, Hagiwara S, Ida H, Ueshima K, Nishida N, Kudo M.
  • Journal Title: Cancers Volume: 14(19) Issue: 19 Pages: 4850-4850
  • DOI: 10.3390/cancers14194850
  • Peer Reviewed / Open Access
• [Journal Article] Progression from early to advanced stage of immune-related cholangitis. (2022)
  • Author(s): Hagiwara S, Yoshida T, Nishida N, Ida H, Ueshima K, Minami Y, Takita M, Aoki T, Morita M, Cishina H, Komeda Y, Yoshida A, Hayashi H, Nakagawa K, Kudo M.
  • Journal Title: Hepatology research Volume: 52(10) Issue: 10 Pages: 888-892
  • DOI: 10.1111/hepr.13817
  • Peer Reviewed
• [Journal Article] Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study. (2022)
  • Author(s): Antonio D'Alessio, Claudia Angela Maria Fulgenzi, Naoshi Nishida, Martin Schnlein, Johann von Felden, Kornelius Schulze, Henning Wege, Vincent E Gaillard, Anwaar Saeed, et al.
  • Journal Title: Hepatology Volume: Online ahead of print Issue: 4 Pages: 1000-1012
  • DOI: 10.1002/hep.32468
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Validation of the easy-to-use lenvatinib prognostic index to predict prognosis in advanced hepatocellular carcinoma patients treated with lenvatinib. (2022)
  • Author(s): Rimini M, Kang W, Burgio V, Persano M, Aoki T, Shimose S, Tada T, Kumada T, Sho T, Lai E, Celsa C, Campani C, Tonnini M, Tamburini E, Hiraoka A, Takaguchi K, Nishida N, Iwamoto H, Itobayashi E, Tsuji K, Sakamoto N, Ishikawa T, Toyoda H, Kudo M, et al.
  • Journal Title: Hepatology research Volume: 52(12) Issue: 12 Pages: 1050-1059
  • DOI: 10.1111/hepr.13824
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC (2022)
  • Author(s): Sharma R, Pillai A, Marron TU, Fessas P, Saeed A, Jun T, Dharmapuri S, Szafron D, Naqash AR, Gampa A, Wang Y, Khan U, Muzaffar M, Lee CJ, Lee PC, Bulumulle A, Paul S, Bettinger D, Hildebrand H, Yehia M, Pressiani T, Kaseb A, Huang YH, Ang C, Kudo M, Nishida N, Personeni N, Rimassa L, Pinato DJ.
  • Journal Title: Hepatology communications Volume: 6(7) Issue: 7 Pages: 1776-1785
  • DOI: 10.1002/hep4.1927
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, propensity score-matched study. (2022)
  • Author(s): Marinelli B, Kim E, D'Alessio A, Cedillo M, Sinha I, Debnath N, Kudo M, Nishida N, Saeed A, Hildebrand H, Kaseb AO, Abugabal YI, Pillai A, Huang YH, Khan U, Muzaffar M, Naqash AR, Patel R, Fischman A, Bishay V, Bettinger D, Sung M, Ang C, Schwartz M, Pinato DJ, Marron T.
  • Journal Title: Journal for immunotherapy of cancer Volume: 10(6) Issue: 6 Pages: e004205-e004205
  • DOI: 10.1136/jitc-2021-004205
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] .Value of artificial intelligence with novel tumor tracking technology in the diagnosis of gastric submucosal tumors by contrast-enhanced harmonic endoscopic ultrasonography. (2022)
  • Author(s): Tanaka H, Kamata K, Ishihara R, Handa H, Otsuka Y, Yoshida A, Yoshikawa T, Ishikawa R, Okamoto A, Yamazaki T, Nakai A, Omoto S, Minaga K, Yamao K, Takenaka M, Watanabe T, Nishida N, Kudo M.
  • Journal Title: Journal of gastroenterology and hepatology Volume: 37(5) Issue: 5 Pages: 841-846
  • DOI: 10.1111/jgh.15780
  • Peer Reviewed
• [Journal Article] Role of phlebotomy in the treatment of liver damage related to erythropoietic porphyria. (2022)
  • Author(s): Hagiwara S, Nishida N, Ida H, Ueshima K, Minami Y, Takita M, Aoki T, Morita M, Chishina H, Komeda Y, Yoshida A, Park AM, Sato M, Kawada A, Nakano H, Nakagawa H, Kudo M.
  • Journal Title: Scientific reports Volume: 12(1) Issue: 1 Pages: 6100-6100
  • DOI: 10.1038/s41598-022-10089-z
  • Peer Reviewed / Open Access
• [Journal Article] Artificial intelligence (AI) models for the ultrasonographic?diagnosis of liver tumors and comparison of diagnostic accuracies between AI and human experts (2022)
  • Author(s): Nishida Naoshi、Yamakawa Makoto、Shiina Tsuyoshi、Mekada Yoshito、Nishida Mutsumi、Sakamoto Naoya、Nishimura Takashi、Iijima Hiroko、Hirai Toshiko、Takahashi Ken、Sato Masaya、Tateishi Ryosuke、Ogawa Masahiro、Mori Hideaki、Kitano Masayuki、Toyoda Hidenori、Ogawa Chikara、Kudo Masatoshi、JSUM A. I. investigators
  • Journal Title: Journal of Gastroenterology Volume: 57 Issue: 4 Pages: 309-321
  • DOI: 10.1007/s00535-022-01849-9
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma (2022)
  • Author(s): Tomoko Aoki, Naoshi Nishida, Masatoshi Kudo
  • Journal Title: Cancers Volume: 14 Issue: 2 Pages: 444-444
  • DOI: 10.3390/cancers14020444
  • Peer Reviewed / Open Access
• [Journal Article] Current Perspectives on the Immunosuppressive Niche and Role of Fibrosis in Hepatocellular Carcinoma and the Development of Antitumor Immunity. (2022)
  • Author(s): Tomoko Aoki, Naoshi Nishida, Masatoshi Kudo
  • Journal Title: The journal of histochemistry and cytochemistry Volume: 70 Issue: 1 Pages: 53-81
  • DOI: 10.1369/00221554211056853
  • Peer Reviewed / Open Access
• [Journal Article] The Systemic Inflammatory Response Identifies Patients with Adverse Clinical Outcome from Immunotherapy in Hepatocellular Carcinoma. (2021)
  • Author(s): Ambreen Muhammed, Claudia Angela Maria Fulgenzi, Sirish Dharmapuri, Matthias Pinter, Lorenz Balcar, Bernhard Scheiner, Thomas U Marron, Tomi Jun,, Naoshi Nishida, et al.
  • Journal Title: Cancers Volume: 14 Issue: 1 Pages: 186-186
  • DOI: 10.3390/cancers14010186
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Objective Response Predicts Survival in Advanced Hepatocellular Carcinoma treated with Systemic Therapies. (2021)
  • Author(s): Masatoshi Kudo, Robert Montal, Richard S Finn, Florian Castet, Kazuomi Ueshima, Naoshi Nishida, Philipp K Haber, Youyou Hu, Yasutaka Chiba, Myron Schwartz, Tim Meyer, Riccardo Lencioni, Josep M Llovet
  • Journal Title: Clinical cancer research Volume: Online ahead of print Issue: 16 Pages: 3443-3451
  • DOI: 10.1158/1078-0432.ccr-21-3135
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease. (2021)
  • Author(s): Satoru Hagiwara, Naoshi Nishida, Kazuomi Ueshima, Yasunori Minami, Yoriaki Komeda, Tomoko Aoki, Masahiro Takita, Masahiro Morita, Hirokazu Chishina, Akihiro Yoshida, Hiroshi Ida, Masatoshi Kudo
  • Journal Title: Cells Volume: 10 Issue: 11 Pages: 3257-3257
  • DOI: 10.3390/cells10113257
  • Peer Reviewed / Open Access
• [Journal Article] Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma. (2021)
  • Author(s): Petros Fessas, Muntaha Naeem, Matthias Pinter, Thomas U Marron, David Szafron, Lorenz Balcar, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, Naoshi Nishida, et al
  • Journal Title: Liver Cancer Volume: 10 Issue: 6 Pages: 583-592
  • DOI: 10.1159/000519108
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Higher enhancement intrahepatic nodules on the Hepatobiliary Phase of Gd-EOB-DTPA-enhanced MRI as a Poor Responsive Marker of Anti-PD-1 / PD-L1 Monotherapy for Unresectable Hepatocellular Carcinoma. (2021)
  • Author(s): Aoki T, Nishida N, Ueshima K, Morita M, Chishina H, Takita M, Hagiwara S, Ida H, Minami Y, Yamada A, Sofue K, Tsurusaki M, Kudo M.
  • Journal Title: Liver cancer Volume: 10 Issue: 6 Pages: 615-628
  • DOI: 10.1159/000518048
  • Peer Reviewed / Open Access
• [Journal Article] Improved Tumor Response to Lenvatinib Re-Treatment after Failure of Immune Checkpoint Inhibitors in a Patient with Advanced Hepatocellular Carcinoma. (2021)
  • Author(s): Satoru Hagiwara, Naoshi Nishida, Masatoshi Kudo
  • Journal Title: Liver cancer Volume: 10 Issue: 5 Pages: 535-538
  • DOI: 10.1159/000516692
  • Peer Reviewed / Open Access
• [Journal Article] Role of Oncogenic Pathways on the Cancer Immunosuppressive Microenvironment and Its Clinical Implications in Hepatocellular Carcinoma. (2021)
  • Author(s): Naoshi Nishida
  • Journal Title: Cancers Volume: 13 Issue: 15 Pages: 3666-3666
  • DOI: 10.3390/cancers13153666
  • Peer Reviewed / Open Access
• [Journal Article] Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody. (2021)
  • Author(s): Masahiro Morita, Naoshi Nishida, Kazuko Sakai, Tomoko Aoki, Hirokazu Chishina, Masahiro Takita, Hiroshi Ida, Satoru Hagiwara, Yasunori Minami, Kazuomi Ueshima, Kazuto Nishio, Yukari Kobayashi, Kazuhiro Kakimi, Masatoshi Kudo
  • Journal Title: Liver cancer Volume: 10 Issue: 4 Pages: 380-393
  • DOI: 10.1159/000516899
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease (2021)
  • Author(s): Satoru Hagiwara, Tomohiro Watanabe, Masatoshi Kudo, Kosuke Minaga, Yoriaki Komeda, Ken Kamata, Masatomo Kimura, Hidetoshi Hayashi, Kazuhiko Nakagawa, Kazuomi Ueshima, Yasunori Minami, Tomoko Aoki, Masahiro Takita, Masahiro Morita, Hirokazu Cishina, Hiroshi Ida, Ah-Mee Park, Naoshi Nishida
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 9242-9242
  • DOI: 10.1038/s41598-021-88824-1
  • Peer Reviewed / Open Access
• [Journal Article] Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma. (2021)
  • Author(s): Tomi Jun, Umut Ozbek, Sirish Dharmapuri, Camille Hardy-Abeloos, Huili Zhu, Jung-Yi Lin, Nicola Personeni, Tiziana Pressiani, Naoshi Nishida, et al.
  • Journal Title: Therapeutic advances in medical oncology Volume: 13
  • DOI: 10.1177/17588359211010937
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolic disease as a risk of hepatocellular carcinoma. (2021)
  • Author(s): Naoshi Nishida
  • Journal Title: Clinical and molecular hepatology Volume: 27 Issue: 1 Pages: 87-90
  • DOI: 10.3350/cmh.2020.0302
  • Peer Reviewed / Open Access
• [Journal Article] Serum Levels of α-Fetoprotein Increased More Than 10 Years Before Detection of Hepatocellular Carcinoma. (2021)
  • Author(s): David M Hughes, Sarah Berhane, C A Emily de Groot, Hidenori Toyoda, Toshifumi Tada, Takashi Kumada, Shinji Satomura, Naoshi Nishida, et al.
  • Journal Title: Clinical gastroenterology and hepatology Volume: 19 Issue: 1 Pages: 162-170
  • DOI: 10.1016/j.cgh.2020.04.084
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Wnt/β-catenin変異を有するヒト肝細胞癌における免疫微小環境の不均一性に関する検討 (2023)
  • Author(s): 青木智子, 西田直生志, 紅林泰、 他
  • Organizer: 第59回日本肝癌研究会 シンポジウム1 肝癌腫瘍微小環境
• [Presentation] 肝内胆管癌におけるゲノム・エピゲノム変化と腫瘍免疫微小環境 (2023)
  • Author(s): 西田 直生志, 青木 智子, 盛田 真弘, 他
  • Organizer: 第59回肝癌研究会 シンポジウム2: 肝内胆管癌薬物療法の進歩
• [Presentation] Non-inflamed typeの胆管癌における 抗原提示分子のメチル化と発現低下 (2023)
  • Author(s): 西田直生志, 工藤正俊
  • Organizer: 第45回日本肝臓学会西部会：ワークショップ3 予後改善に向けた胆管癌の集学的治療 2023年12月8日
• [Presentation] 切除不能HCCに対するABC conversion療法とclinical CRの現状 (2023)
  • Author(s): 青木智子, 西田直生志, 工藤正俊
  • Organizer: 第45回日本肝臓学会西部会: ワークショップ1 肝がん局所療法の多様性とその到達点
• [Presentation] 人工知能とAI超音波の社会実装 (2023)
  • Author(s): 西田 直生志
  • Organizer: 私立医科大学臨床検査技師会学術研修会 特別講演
  • Invited
• [Presentation] 肝内胆管癌とFGFR2遺伝子異常に関する最新の話題 - 免疫微小環境の観点から - (2023)
  • Author(s): 西田 直生志
  • Organizer: 第44回日本肝臓学会東部会 スポンサードセミナー
  • Invited
• [Presentation] 超音波診断支援AIの開発と実装化に向けた課題 (2022)
  • Author(s): 西田 直生志
  • Organizer: JDDW 2022 統合プログラム6 基調講演
  • Invited
• [Presentation] 腹部超音波動画からの肝腫瘍検出AIプログラムの開発 (2022)
  • Author(s): 目加田 慶人, 西田直 生志, 工藤 正俊
  • Organizer: JDDW2022 統合プログラム6
• [Presentation] 肝細胞癌の微小環境と再発予防における免疫チェックポイント阻害剤の効果 (2022)
  • Author(s): 西田 直生志, 上嶋 一臣, 工藤 正俊
  • Organizer: JDDW2022 統合プログラム5
• [Presentation] 切除不能肝細胞癌におけるhyper progressive diseaseの頻度と有効な後治療 (2022)
  • Author(s): 青木 智子, 西田 直生志, 工藤 正俊
  • Organizer: JDDW2022 ワークショップ8
• [Presentation] B-mode超音波検査による肝腫瘤診断を支援する人工知能の開発 (2022)
  • Author(s): 西田 直生志
  • Organizer: 第16回肝癌治療ナビゲーション研究会: シンポジウム2
  • Invited
• [Presentation] Selection of Anti-PD-1 Antibody Effective Group Using Tumor Immunological Microenvironment (2022)
  • Author(s): Masahiro Morita, Naoshi Nishida, Masatoshi Kudo
  • Organizer: The Asian Pacific Association for the Study of the Liver [APASL] 2022, Workshop 15
  • Int'l Joint Research / Invited
• [Presentation] Role of Medical AI for the Management of Liver Disease in the Era of Viral Elimination;Development of AI-aided US Diagnosis for Focal Liver Lesions (2022)
  • Author(s): Naoshi Nishida
  • Organizer: The Asian Pacific Association for the Study of the Liver [APASL] Oncology 2022, Luncheon Seminar 2
  • Int'l Joint Research / Invited
• [Presentation] Examination of NASH -related Liver Carcinogenesis from Non -developed Fibrosis (2022)
  • Author(s): Satoru Hagiwara, Naoshi Nishida, Masatoshi Kudo
  • Organizer: The Asian Pacific Association for the Study of the Liver [APASL] Oncology 2022, Workshop 9
  • Int'l Joint Research / Invited
• [Presentation] 免疫チェックポイント阻害剤投与に伴うirAE肝障害、HBV再活性化についての検討 (2022)
  • Author(s): 萩原 智, 西田 直生志, 工藤 正俊
  • Organizer: 第58回日本肝臓学会総会 パネルディスカッション6
• [Presentation] Phase 2根治後NIVOLVE試験における奏功症例と特徴 (2022)
  • Author(s): 青木 智子, 西田 直生志, 工藤 正俊
  • Organizer: 第58回肝臓学会総会 シンポジウム2
• [Presentation] 人工知能(AI)によるB-mode超音波検査の 肝腫瘍鑑別支援と肝癌診療への展開 (2022)
  • Author(s): 西田 直生志, 工藤 正俊
  • Organizer: 第58回肝癌研究会 シンポジウム5
• [Presentation] 複合免疫療法時代におけるイメージングバイオマーカーとしてのEOB-MRIの役割 (2022)
  • Author(s): 青木智子, 西田直生志, 上嶋一臣, 盛田真弘, 千品寛和, 田北雅弘, 南康範, 依田広, 祖父江慶太郎, 鶴崎正勝, 工藤正俊
  • Organizer: 第58回日本肝癌研究会; パネルディスカッション8
• [Presentation] 複合免疫療法時代におけるhyper progressive disease (HPD) (2022)
  • Author(s): 青木智子, 西田直生志, 上嶋一臣, 盛田真弘, 千品寛和, 田北雅弘, 南康範, 萩原智, 依田広, 鶴崎正勝, 工藤正俊
  • Organizer: 第58回日本肝癌研究会 パネルディスカッション5
• [Presentation] Development of the AI model for diagnosis of liver tumor using B-mode ultrasonography (2022)
  • Author(s): Naoshi Nishida
  • Organizer: The 53th Annual Conference of the Korean Society of Ultrasound In Medicine, Hot Issue 1
  • Int'l Joint Research / Invited
• [Presentation] 肝疾患の遺伝子異常による病態解明と臨床展開 (2022)
  • Author(s): 萩原 智, 西田 直生志, 工藤 正俊
  • Organizer: 第108回日本消化器病学会総会 ワークショップ10
• [Presentation] 肝細胞癌における腫瘍微小免疫環境と免疫チェックポイント阻害剤の効果 (2022)
  • Author(s): 西田 直生志, 上嶋 一臣, 工藤 正俊
  • Organizer: 第108回日本消化器病学会総会 シンポジウム5
• [Presentation] Treatment for intermediate-stage HCC beyond up-to-seven criteria (2022)
  • Author(s): Naoshi Nishida
  • Organizer: The 31 Conference of the Asian Pacific Association for the Study of the Liver Disease (APASL) 2022: Meet-the-Experts 11
  • Int'l Joint Research / Invited
• [Presentation] Treatment for intermediate-stage HCC beyond up-to-seven criteria (2022)
  • Author(s): Naoshi Nishida
  • Organizer: The 31 Conference of the Asian Pacific Association for the Study of the Liver Disease (APASL)
  • Int'l Joint Research / Invited
• [Presentation] Final Results of Adjuvant Nivolumab for Hepatocellular Carcinoma (HCC) after Surgical Resection (SR) or Radiofrequency Ablation (RFA) (NIVOLVE): A Phase 2 Prospective Multicenter Single Arm Trial and Exploratory Biomarker Analysis. (2022)
  • Author(s): Masatoshi Kudo, Kazuomi Ueshima, Shin Nakahira, Naoshi Nishida, Hiroshi Ida, Yasunori Minami, Takuya Nakai, Hiroshi Wada, Shoji Kubo, Kazuyoshi Ohkawa, Asahiro Morishita, Takeo Nomi, Koji Ishida, Shogo Kobayashi, Makoto Umeda, Masakatsu Tsurusaki, Yasutaka Chiba, Kenichi Yoshimura, Kazuko Sakai, Kazuto, Nishio
  • Organizer: ASCO Gastrointestinal Cancers Symposium (ASCO-GI) 2022
  • Int'l Joint Research
• [Presentation] Outcomes of beta blockers (BB) in hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) (2022)
  • Author(s): Linda Wu, Umut Ozbek, Grace Van Hyfte, Pei-Chang Lee, Marlene Reincke, Anuhya Gampa, Yehia Mohamed, Naoshi Nishida, Brooke Wietharn, Suneetha Amara, Lorenz Balcar, Matthias Pinter, A, dt Vogel, Arndt Weinmann, Anwaar Saeed, Lorenza Rimassa, Rafeh Naqash, Mahvish Muzaffar, David Pinato, Celina Ang
  • Organizer: ASCO Gastrointestinal Cancers Symposium (ASCO-GI) 2022
  • Int'l Joint Research
• [Presentation] 肝細胞癌におけるWnt/βカテニン経路活性化と腫瘍免疫環境 (2021)
  • Author(s): 盛田真弘, 西田直生志, 工藤正俊
  • Organizer: 日本消化器週間 JDDW2021 シンポジウム8
• [Presentation] 免疫チェックポイント阻害剤による肝障害の臨床的、病理学的検討 (2021)
  • Author(s): 萩原智, 西田直生志, 工藤正俊
  • Organizer: 日本消化器病週間 JDDW 2021 ワークショップ3
• [Presentation] Gd-EOB-DTPA-enhanced MRI肝細胞相で高信号の肝細胞癌は PD-1/PD-L1療法への一次耐性を反映し効果不良である (2021)
  • Author(s): 青木 智子, 西田 直生志, 上嶋 一臣, 盛田 真弘, 千品 寛和, 田北 雅弘, 南 康範, 萩原 智, 依田 広, 祖父江 慶太郎, 鶴崎 正勝, 工藤 正俊
  • Organizer: 日本消化器病週間 JDDW 2021
• [Presentation] Role of alteration of oncogenic pathways on the immunological microenvironment of hepatocellular carcinoma and its clinical implications (2021)
  • Author(s): Naoshi Nishida
  • Organizer: JSH International Liver Conference 2021
  • Int'l Joint Research / Invited
• [Presentation] 肝細胞癌における腫瘍微小免疫環境と癌関連分子変異との関連 (2021)
  • Author(s): 西田 直生志, 盛田 真弘, 工藤 正俊
  • Organizer: 第58回日本消化器免疫学会総会 シンポジウム2
  • Invited
• [Presentation] 機械学習を用いた進行肝癌に対するチロシンキナーゼ阻害剤の効果予測の試み (2021)
  • Author(s): 池田 裕亮, 目加田 慶人, 西田 直生志
  • Organizer: 第57回日本肝臓学会総会 ワークショップ11
• [Presentation] Gd-EOB-DTPA-enhanced MRI肝細胞相はPD-1/PD-L1抗体単独療法の非侵襲的なバイオマーカーである (2021)
  • Author(s): 青木 智子, 西田 直生志, 工藤 正俊
  • Organizer: 第57回日本肝臓学会総会 ワークショップ9
• [Presentation] 肝細胞癌における腫瘍免疫環境と抗PD-1抗体有効群の選別 (2021)
  • Author(s): 盛田 真弘, 西田 直生志, 工藤 正俊
  • Organizer: 第57回日本肝臓学会総会 シンポジウム1
• [Presentation] Genetic and Molecular / Immune Profiling Analyses of Hepatocellular carcinoma (2021)
  • Author(s): Naoshi Nishida
  • Organizer: The Liver Week 2021, LCSGJ-KLCA Joint Symposium
  • Int'l Joint Research / Invited
• [Book] Immunotherapy in Hepatocellular Carcinoma (2023)
  • Author(s): Naoshi Nishida, Masatoshi Kudo
  • Total Pages: 267
  • Publisher: MDPI Books
  • ISBN: 9783036566917
• [Book] 医療AIとディープラーニングシリーズ 超音波画像AI診断 (2021)
  • Author(s): 藤田 広志、椎名 毅、工藤 正俊
  • Total Pages: 198
  • Publisher: オーム社
  • ISBN: 9784274225765
• [Remarks] Reserach Map
  • URL: https://researchmap.jp/naoshinishida