Identification of resistant clone for the chemotherapy of hepatocellular carcinoma using cell free DNA

• Project/Area Number: 21K07950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kindai University
• Principal Investigator: Kudo Masatoshi 近畿大学, 医学部, 教授 (10298953)
• Co-Investigator(Kenkyū-buntansha): 西田 直生志 近畿大学, 医学部, 教授 (60281755)
• 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: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肝細胞癌 / 免疫チェックポイント阻害剤 / アジュバント療法 / 腫瘍免疫微小環境 / cell-free DNA / ドライバー変異 / アジュバント / ctDNA / 再発 / 遺伝子変異 / セルフリーDNA / 腫瘍微小免疫環境 / 無再発生存期間 / 化学療法 / cell free DNA / ゲノム診断

Outline of Research at the Start

肝細胞癌（肝癌）薬物療法の進歩により、顕著な抗腫瘍反応が認められる例が増えている。しかし、腫瘍の縮小後に再増悪する例も多い。これらは、腫瘍細胞のゲノム変化による耐性変異獲得の結果と予想できる。そこで、腫瘍由来と考えられる血中のcell free DNA（cfDNA）の遺伝子変化を、同一例で経時的に解析し、癌関連遺伝子変異の分子系統樹を作成することにより、薬物療法への反応時から増悪時への移行期に生じるゲノム変化を同定して薬剤耐性クローンのゲノムの特徴を解析する。

Outline of Final Research Achievements

We investigated the association between the circulating tumor DNA (ctDNA) in postoperative plasma and recurrence in 32 patients who received adjuvant immune checkpoint inhibitors (ICIs) after radical hepatocellular carcinoma (HCC) surgery. A valiant of 10 copies/ml or more was considered as ctDNA positive. Tumor immune microenvironment (TIME) was classified by examining immune-related molecules and β-catenin-associated molecules. Patients were classified into 2 groups (β-catenin pathway activated and inactivated), and TIME-hot/exhausted and cold/Treg types). Postoperative recurrence-free survival (RFS) on ICI was significantly longer in the β-catenin pathway inactivation group and in the hot/exhausted TIME group. The median RFS for ctDNA-positive cases was 26.2 months and NR for ctDNA-negative cases, with a trend toward shorter RFS in ctDNA-positive cases . The cases with copy number variation on the β-catenin-related loci showed significantly shorter RFS under ICI treatment.

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤(ICI)は肝癌治療の重要な薬剤であるが、腫瘍免疫微小環境(TIME)が効果に影響する。TIMEの解析には腫瘍組織が必要であり、生検は侵襲的でリスクを伴う。一方、循環血液中の腫瘍由来DNA（ctDNA）は非侵襲的、かつ繰り返し採取可能である。近年、β-catenin 経路の活性化はnon-inflamed型のTIMEの誘因になることが報告されたが、本研究ではβ-catenin 経路異常をctDNAから検出でき、ICIの治療効果予測に応用できる可能性を示した。また、ICI治療中のctDNAは癌細胞残存の指標となることを示した。この成果は肝癌の治療戦略に意義がある。

Research Products

• [Journal Article] Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024)
  • Author(s): Llovet Josep M.、Pinyol Roser、Yarchoan Mark、Singal Amit G.、Marron Thomas U.、Schwartz Myron、Pikarsky Eli、Kudo Masatoshi、Finn Richard S.
  • Journal Title: Nature Reviews Clinical Oncology Volume: 21 Issue: 4 Pages: 294-311
  • DOI: 10.1038/s41571-024-00868-0
  • Peer Reviewed / Int'l Joint Research
• [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] Objective Response to Systemic Therapy Is a Strong Predictor of Overall Survival in Patients with Unresectable Hepatocellular Carcinoma (2023)
  • Author(s): Kudo Masatoshi
  • Journal Title: Liver Cancer Volume: 13 Issue: 1 Pages: 1-5
  • DOI: 10.1159/000535516
  • Peer Reviewed / Open Access
• [Journal Article] Atezolizumab in Combination with Bevacizumab for the Management of Patients with Hepatocellular Carcinoma in the First-Line Setting: Systematic Literature Review and Meta-Analysis (2023)
  • Author(s): Vogel Arndt、Finn Richard S.、Kudo Masatoshi, et al.
  • Journal Title: Liver Cancer Volume: 12 Issue: 6 Pages: 510-520
  • DOI: 10.1159/000533166
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Current Therapeutic Strategies for Hepatocellular Carcinoma in Japan (2023)
  • Author(s): Kudo Masatoshi
  • Journal Title: Liver Cancer Volume: 12 Issue: 6 Pages: 497-509
  • DOI: 10.1159/000534304
  • Peer Reviewed / Open Access
• [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] <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] Development and clinical validation of a novel algorithmic score (GAAD) for detecting HCC in prospective cohort studies (2023)
  • Author(s): Piratvisuth Teerha、Hou Jinlin、Tanwandee Tawesak、Berg Thomas、Vogel Arndt、Trojan Jorg、De Toni Enrico N.、Kudo Masatoshi、et al.
  • Journal Title: Hepatology Communications Volume: 7 Issue: 11
  • DOI: 10.1097/hc9.0000000000000317
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial (2023)
  • Author(s): Qin Shukui、Chen Minshan、Cheng Ann-Lii、Kaseb Ahmed O、Kudo Masatoshi、et al.
  • Journal Title: The Lancet Volume: 402 Issue: 10415 Pages: 1835-1847
  • DOI: 10.1016/s0140-6736(23)01796-8
  • Peer Reviewed / Int'l Joint Research
• [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 / 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] 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] Clinical implication of immune checkpoint inhibitor on the chronic hepatitis B virus infection (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, Hayashi H, Nakagawa K, Kudo M.
  • Journal Title: Hepatology Research Volume: 52 (9) Issue: 9 Pages: 754-761
  • DOI: 10.1111/hepr.13798
  • Peer Reviewed
• [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] 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] 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
• [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] 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] 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] 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] 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] 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] 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] 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] 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
• [Presentation] Atezolizumab plus Bevacisumab versus lenvatinib for BCLC-B stage patients with hepatocellular carcinoma : a large real life worldwide population (2024)
  • Author(s): Vitiello F, Rimini M, Persano M, Tada T, Shimose S, Kudo M, et al.
  • Organizer: EASL Liver Cancer Summit
  • Int'l Joint Research
• [Presentation] Lenvatinib (L) versus sorafenib (S) second-line therapy in hepatocellular carcinoma (HCC) patients progressed to atezolizumab plus bevacizumab (AB) (2024)
  • Author(s): Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, et al.
  • Organizer: EASL Liver Cancer Summit
  • Int'l Joint Research
• [Presentation] Intermediate Stage肝細胞癌の治療戦略-ABC conversion therapy- (2024)
  • Author(s): 工藤正俊
  • Organizer: 第27回日本肝がん分子標的治療研究会
  • Invited
• [Presentation] 複合免疫療法時代における最適な治療戦略を考える (2023)
  • Author(s): 工藤正俊
  • Organizer: Gunma HCC Expert Meeting
  • Invited
• [Presentation] Effectiveness of lenvatinib in patients with unresectable hepatocellular carcinoma: A multicenter observational study in Japan (2023)
  • Author(s): Izumi N, Kudo M, et al.
  • Organizer: ESMO-Asia
  • Int'l Joint Research / 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: AI研究の実装化に向けた課題
• [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 消化肝癌における免疫療法の実際
• [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 進行肝癌薬物療法の課題と展望
• [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] 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: 治療起因性肝障害のマネジメント-DILI・HBV再活性化・irAE・IRIS
• [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: 肝がんのマネジメント-発がん予防・内科治療・外科治療・再発予防
• [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: ビッグデータやAI、IoT による新たな肝癌診療モデルの構築
• [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 肝癌におけるPrecision Oncology
• [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; 肝癌免疫療法の治療向上を目指して
• [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 肝疾患の遺伝子解析による病態解明と臨床展開
• [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 消化器癌における免疫治療と分子標的治療の基礎研究と臨床
• [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, Masatoshi Kudo
  • Organizer: ASCO Gastrointestinal Cancers Symposium (ASCO-GI) 2022
• [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, et al.
  • Organizer: ASCO Gastrointestinal Cancers Symposium (ASCO-GI)
• [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] US-US overlay fusion ガイドを用いたラジオ波焼灼術の最前線 (2021)
  • Author(s): 南 康範, 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8
• [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微小免疫環境と癌関連分変異との関連 (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] 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: 消化器病学会週間 JDDW 2021
• [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
• [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