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: 西田 直生志 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: Granted (Fiscal Year 2022)
• 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 / 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 / Radiomics / 治療効果予測 / 人工知能 / 化学療法 / 医用画像 / 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 Annual Research Achievements

本研究では、肝癌治療前の画像情報と遺伝子変異、腫瘍免疫環境を情報として肝癌薬物療法の効果を予測する人工知能(AI)を開発することを目的としている。2年目の課題として、治療前画像情報から治療効果を予測するAIに、遺伝子変異情報、腫瘍免疫情報を加えて学習させるための基礎的検討を行った。154例の肝癌組織にて、免疫チェックポイント分子の発現を免疫染色にて検討した。また、deep sequenceによる癌関連遺伝子変異、およびmRNA発現より肝癌をTMEの面から分類し、TCGAから得た377例の肝癌のexome, transcriptomeデータにて結果を確認した。加えて、肝癌症例でPD-1抗体を投与された34例の治療前生検を用い、TMEとPD-1抗体治療効果との関連を解析した。さらに画像所見よりTMEを反映する特徴を抽出した。PD-L1陽性肝癌はCD8+リンパ球(TIL)が有意に多く、PI3K-Akt経路に活性型変異を持つ傾向にあった(p = 0.0206)、TILには複数の抑制型受容体が発現していた。一方、b-カテニン経路の活性型変異を持つ肝癌はPD-L1陰性 (p = 0.0302)。TCGAコホートにおいても、同様の関連を示した。腫瘍の b-カテニン経路活性化, CD8+ TIL量, PD-L1発現にて抗PD-1抗体の無増悪生存期間を層別化できた(p < 0.0001)。造影MRIによる肝細胞相でのrelative enhance ratio (RER)はPD-1抗体治療の有効性と関連した。すなわち"immune hot-type"では、TILには複数の抑制型受容体が発現し、PI3K-Akt変異例が多い。"immune clod-type"ではb-カテニン経路活性型変異を持つ。TMEや腫瘍画像所見の解析より、抗PD-1抗体有効例を推定可能であった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

2年目に課題として、肝癌化学療法の効果を予測する人工知能開発のため、肝癌標本を用い、遺伝子変異の網羅的解析、transcriptome解析と免疫染色による肝癌の腫瘍免疫環境の分類を行った。また、腫瘍免疫環境を反映する遺伝子変異プロファイルの特徴、特にimmune cold phenotypeとb-カテニン経路活性化変異の関連を見出し、さらにb-カテニン経路活性化を持つ肝癌の画像的特徴を明らかにした。これは腫瘍のPD-1抗体治療への反応性と関連した。すなわち、画像的特徴と遺伝子変異プロファイル、transcriptome解析と免疫染色に基づく腫瘍免疫環境による人口知能の学習は、肝癌薬物療法の効果を推定する有効な情報であることを明らかにしたため、2年目の目標はおおよそ達成できたと考える。

Strategy for Future Research Activity

2年目の成果で明らかにした、次世代シークエンサーによるゲノム変異、免疫関連遺伝子のトランスクリプトーム解析の結果を学習データに加え、人工知能の再学習を行う。教師データとして、腫瘍の反応性に加え、治療開始後の腫瘍進行までの期間（Time To Progression: TTP)を付与する。画像に加え、genomics/immunogenomicsの情報を学習したAIモデルにより、症例毎に、最適治療を提示させ、治療計画の個人適応（オーダーメイド医療）を目指した人工知能モデルを検討する。さらに、肝癌で肝細胞癌に次いで多い肝内胆管細胞癌の画像情報、次世代シークエンサーによるゲノム変異、免疫関連遺伝子のトランスクリプトーム解析を行い、治療計画の個人適応を目的とした人工知能開発の可能性を探る。

Research Products

• [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] 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] 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 / 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 (2) Issue: 2 Pages: 221-233
  • DOI: 10.1007/s11523-023-00953-x
  • Peer Reviewed / Int'l Joint Research
• [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] 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] 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] 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] 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] 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] 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