工藤正俊業績
分子標的治療および免疫療法に関する開発研究

進行肝癌に対する分子標的薬は 2007 年に SHARP 試験および Asia Pacific 試験にてソラフェニブ
がプラセボに対して survival benefit があることが初めて証明され世界的には承認となった。日本においても 2009 年 5 月に同薬剤が承認となりそれ以降 10 年間唯一の肝癌に対する分子標的薬として使用されてきた。ソラフェニブに加えて薬剤選択肢を増やすためあるいはソラフェニブを超える薬剤開発のため 2007 年から 2016 年の間、肝細胞癌に対する一次治療薬の臨床試験、二次治療薬の臨床試験、TACE 併用試験、アジュバント試験などが約 20 試験以上と多数行われた。工藤正俊はこれらの殆どの臨床試験の Global Steering Committee もしくは Global PI として臨床試験を主導した。中でもポジ
ティブ試験となった RESORCE 試験(Regorafenib)、REFLECT 試験(Lenvatinib)、REACH-2 試験(Ramcirumab)などの Global Steering Committee Member (REFLECT 試験は Global PI)として臨床試験をポジティブに導き、現在日本において承認されている一次治療薬 (Lenvatinib)、二次治療薬(Regorafenib, Ramucirumab)の 3 剤の開発試験に貢献した。
また世界では認められているもう一つの二次治療薬である、Cabozaitinib の第 3 相 CELESTIAL 試
験の global 試験には日本全体としては参加できなかったが、ブリッジング Phase 2 として行われた日本の臨床試験の National PI として日本での治験を主導し、2020 年末に承認予定となっている。
これ以外にも、医師主導型臨床試験として肝動注化学療法とソラフェニブとの組み合わせがソラフ
ェニブを上回る効果を示すかどうか、すなわち肝動注がソラフェニブに上乗せ効果があるかどうかを検証する SILIUS 試験を国内の 33 施設と共同で行い、Lancet Gastroenterology and Hepatology (2019年)に発表した。この結果については Primary endpoint である肝動注化学療法の上乗せ効果こそ示せなかったものの、最終的なサブ解析も含め肝動注化学療法は両葉多発結節の BCLC B の肝細胞癌にはソラフェニブ以上の効果は無い事、及び VP4 などの Major Vascular Invasion に対して肝動注化学療法は明らかに効果がある事を前向き比較試験(RCT)において証明することができた。更には、TACE とSorafenib の併用の有効性を示す TACTICS 試験を TACE + Sorafenib 対 Sorafenib 群で前向き比較試験を行い、独自に設定した time to unTACEable progression を主体とした PFS において TACE 単独
よりも圧倒的に有意な差をもって PFS を延長させる事を示し Gut (2019)に発表した。これまでネガ
ティブな臨床試験が 5 本 (Sorafenib との併用では Post TACE 試験、SPACE 試験、TACE-2 試験の 3試験、及び Brivanib との併用の BRISK-TA 試験ならびに Orantinib との併用の ORIENTAL 試験)のいずれの試験も失敗した中で失敗した原因から学んで Trial Design を熟考することにより新たな trial
design で行った RCT で試験を成功に導いた。結果的に分子標的薬をできるだけ長く TACE と併用する事により TACE と TACE との間隔を短くし、肝予備能を維持することにより患者の Outcome を良好にすることを前向き比較試験にて世界で初めて証明した。ちなみに Post-TACE 試験(Eur J Cancer2011), BRISK-TA 試験(Hepatology 2014), ORIENTAL 試験(Lancet GH 2019)の全ての試験の global
PI を工藤正俊が勤め 1st author としてこれらの雑誌に発表した。工藤正俊はこれらの業績により日本肝臓学会織田賞(2018 年)ならびに SGH がん特別賞(2019 年)を受賞した。
また免疫療法に関してはニボルマブの CheckMate040 試験(Phase 1/2 試験)の cohort 1（単剤試験）、
Cohort 4 (Nivolumab +Ipilimumab=PD-1 Ab + CTLA-4 Ab), cohort 5 (Child-Pugh B)に関しても

Steering committee として参画し、さらに Phase 3 CheckMate459 試験にも参画しそれぞれ論文発表している（Lancet, Lancet Oncology, JAMA Oncology, J Hepatology など）。また Pembrolizumab の開発においても Phase 1/2 試験の KEYNOTE-224 試験や Phase 3 の KEYNOTE-240 試験に Global
Steering Committee Member として開発に参画した。また Pembrolizumab と Lenvatinib 併用のPhase 1b 試験にも参画しこれらの結果は Lancet, Lancet Oncology, J Clin Oncology などに共著者として掲載されている。2019 年に ESMO Asia で発表となった Atezolizumab + Bevacizumab の併用試
験にも Global Steering Committee として参加し試験を positive に導き肝細胞癌においては初の免疫療法として確立した（New Engl J Med 2020）。

(*: Corresponding author)

1.

Lencioni R, Marrero J, Venook A, Ye SL, Kudo M: Design and rationale for the
non-interventional Global Investigation of therapeutic DEcisions inhepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON)
study. Int J Clin Pract 64: 1034-1041, 2010. (IF=2.444)

2.

Kudo M＊: Current status of molecularly targeted therapy for hepatocellular
carcinoma: clinical practice. Int J Clin Oncol 15: 242-255, 2010. (IF=2.879)

3.

Kudo M＊, Ueshima K: Positioning of a molecular-targeted agent, Sorafenib, inthe treatment algorithm for hapatocellular carcinoma and implication of many
complete remission cases in Japan. Oncology 78: S154-166, 2010. (IF=2.642)

4.

Furuse J, Okusaka T, Kaneko S, Kudo M, Nakachi K, Ueno H, Yamashita T,
Ueshima K: Phase I/II study of the pharmacokinetics, safety, and efficacy of S1 in patients with advanced hepatocellular carcinoma. Cancer Sci 101: 26062611, 2010. (IF=4.966)

5.

Kudo K, Arao T, Tanaka K, Kaneda H, Matsumoto K, Tamura D, Aomatsu K,
Velasco M, Fujita Y, Saijo N, Kudo M, Nishio K: Antitumor activity of BIBF
1120, a triple angiokinase inhibitor, and use of VEGFR2+pTyr+ peripheral
blood leukocytes as a pharmacodynamic biomarker in vivo. Clin Cancer Res
17: 1373-1381, 2011. (IF=10.107)

6.

Hagiwara S, Kudo M＊, Ueshima K, Chung H, Yamaguchi M, Takita M, Haji S,
Kimura M, Arao T, Nishio K, Park AM, Munakata H: The cancer stem cellmarker CD133 is a predictor of the effectiveness of S1+pegylated interferon α2b therapy against advanced hepatocellular carcinoma. J Gastroenterol 46:
212-221, 2011. (IF=6.132)

7.

Kudo M＊: Molecular targeted therapy for hepatocellular carcinoma: bench to
bedside. Digest Dis 29: 273-277, 2011. (IF=2.493)

8.

Kudo M＊: Signaling pathway and molecular-targeted therapy forhepatocellular carcinoma. Digest Dis 29: 289-302, 2011. (IF=2.493)

9.

Kudo M＊: mTOR inhibitor for the treatment of hepatocellular carcinoma.
Digest Dis 29: 310-315, 2011. (IF=2.493)

10.

Kudo M＊: Future treatment option for hepatocellular carcinoma: a focus on
brivanib. Digest Dis 29: 316-320, 2011. (IF=2.493)

11.

Ueshima K, Kudo M＊, Takita M, Nagai T, Tatsumi C, Ueda T, Kitai S,
Ishikawa E, Yada N, Inoue T, Hagiwara S, Minami Y, Chung H, Sakurai T:
Des-γ-carboxyprothrombin may be a promising biomarker to determine thetherapeutic efficacy of Soraenib for hepatocellular carcinoma. Digest Dis 29:
321-325, 2011. (IF=2.493)

12.

Yoshida H, Shiratori Y, Kudo M, Shiina S, Mizuta T, Kojiro M, Yamamoto K,
Koike Y, Saito K, Koyanagi N, Kawabe T, Kawazoe S, Kobashi H, Kasugai H,
Osaki Y, Araki Y, Izumi N, Oka H, Tsuiji K, Toyota J, Seki T, Osawa T, Masaki
N, Ichinose M, Seike M, Ishikawa A, Ueno Y, Tagawa K, Kuromatsu R,
Sakisaka S, Ikeda H, Kuroda H, Hokuryu H, Yamashita T, Sakaida I,
Katamoto T, Kikuchi K, Nomoto M, Omata M: Effect of vitamin K2 on therecurrence of hepatocellular carcinoma. Hepatology 54: 532-540, 2011.
(IF=14.679)

13.

Kudo M＊, Imanaka K, Chiba N, Nakachi K, Tak WT, Takayama T, Yoon JH,
Hori T, Kumada H, Hayashi N, Kaneko S, Tsubouchi H, Suh DJ, Furuse J,
Okusaka T, Tanaka K, Matsui O, Wada M, Yamaguchi I, Ohya T, Meinhardt G,
Okita K: Phase III study of Sorafenib after transarterial chemoembolisation in
Japanese and Korean patients with unresectable hepatocellular carcinoma.
Eur J Cancer 47: 2117-2127, 2011. (IF=7.275)

14.

Llovet JM, Paradis V, Kudo M, Zucman-Rossi J: Tissue biomarkers as
predictors of outcome and selection of transplant candidates with
hepatocellular carcinoma. Liver Transplant 17: S67-71, 2011. (IF=4.570)

15.

Kudo M＊: Hepatocellular carcinoma in 2011 and beyond: From thepathogenesis to molecular targeted therapy. Oncology 81: 1-10, 2011.
(IF=2.642)

16.

Sakurai T, Kudo M: Signaling pathways governing tumor angiogenesis.
Oncology 81: 24-29, 2011. (IF=2.642)

17.

Sakurai T, Kudo M, Itoh K, Ryu U, Higashitsuji H, Fujita J: Adriamycin
enhances proteasome-mediated generation of the proapoptotic processed form

of MAGE-A4 in hepatoma cells. Oncology 81: 30-35, 2011. (IF=2.642)
18.

Kudo M＊: Adjuvant therapy after curative treatment for hepatocellular
carcinoma. Oncology 81: 50-55, 2011. (IF=2.642)

19.

Inuzuka T, Nishikawa H, Sekikawa A, Takeda H, Henmi S, Sakamoto A, Saito
S, Kita R, Kimura T, Osaki Y, Kudo M: Complete response of advanced
hepatocellular carcinoma with multiple lung metastases treated withSorafenib: A case report. Oncology 81: 152-157, 2011. (IF=2.642)

20.

Han KH, Kudo M, Ye SL, Choi JY, Poon RTP, Seong J, Park JW, Ichida T,
Chung JW, Chow P, Cheng AL: Asian consensus workshop report: Expert
consensus guideline for the management of intermediate and advanced
hepatocellular carcinoma in Asia. Oncology 81: 158-164, 2011. (IF=2.642)

21.

Suzuki H, Murata K, Gotoh T, Kusano M, Okano H, Oyamada T, Yasuda Y,
Imamura M, Kudo M, Mizokami M, Sakamoto A: Phenotype-dependent
production of des-γ-carboxy prothrombin in hepatocellular carcinoma. J
Gastroenterol 46: 1219-1229, 2011. (IF=6.132)

22.

Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A, Abecassis
M, Balabaud C, Barritt GJ, Belghiti J, Bhoori S, Bossuyt P, Breitenstein S,
Broelsch C, Bruix J, Burra P, Burroughs A, Busuttil R,Charlton M, Cherqui D,
Colombo ML, d’Albuquerque C, D’Alessandro A, de Santibanez EJ, Dufour F,
Durand F, Dutkowski P, Duvoux C, El-Serag H, Fan ST, Finn RS, Fisher R,
Forner A, Freeman R, Fung J, Geier A, Germani G, Gores G, Gouw AS, Grant
D, Greig P, Gurusamy K, Hanto D, Heaton N, Heim M, Hemming A, Hippen B,
Hisham A, Hubscher S, Ichida T, Kahn D, Kew M, Kita Y, Kiuchi T, Klintmalm
GB, Kneteman N, Kojiro M, Kudo M, Langer B, Lee JM, Lee SG, Lencioni R,
Lerut J, Lesurtel M, Livraghi T, Llovet JM, Lo CM, Lodge P, MacCaughan G,
Madoff D, Majno P, Marcellin P, Marrero J, Mazzaferro V, Mergental H, Merle
P, Miksad R, Mornex F, Mullhaupt B, Olthoff K, Paradis V, Perrier A,
Pestalozzi B, Pomfret E, Poon R, Porte R, Greig P, Prasad KR, Raptis D,
Roskams T, Rossi M, Samuel D, Schlitt H, Schwartz M, Sexton Dobby AM,
Shaked A, Sherman M, Siegler M, Suh KS, Todo S, Toso C, Trevisani F, Trotter
JJ, Veldecasas GJ, Vauthey N, Vilgrain V, Villamil F, Vonlanthen R, Wald C,
Weber A, Wiesner R, Wright L, Yao F, Zheng SS, Zucman-Rossi J:
Recommendations for liver transplantation for hepatocellular carcinoma: aninternational consensus conference report. Lancet Oncol 13: e11-22, 2012.
(IF=33.752)

23.

Lencioni R, Kudo M, Ye SL, Bronowicki JP, Chen XP, Dagher L, Furuse J,
Geschwind JF, Guevara LL, Papandreou C, Sanyal AJ, Takayama T, Yoon SK,

Nakajima K, Cihon F, Heldner S, Marrero JA: First interim analysis of the
GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular
carcinoma and Of its treatment with sorafeNib) non-interventional study. Int J
Clin Pract 66:675-683, 2012.(IF=2.444)
24.

Hagiwara S, Kudo M, Nagai T, Inoue T, Ueshima K, Nishida N, Watanabe T,
Sakurai T: Activation of JNK and high expression level of CD133 predict a poor
response to Sorafenib in hepatocellular carcinoma. Brit J Cancer 106:19972003, 2012. (IF=5.791)

25.

Kudo M＊: Why does every hepatocellular carcinoma clinical trial using
molecular targeted agents fail? Liver Cancer 1(2):59-60, 2012. (IF=9.720)

26.

Kudo M＊: Treatment of advanced hepatocellular carcinoma with emphasis on
hepatic arterial infusion chemotherapy and molecular targeted therapy. Liver
Cancer 1(2):62-70, 2012. (IF=9.720)

27.

Nishida N, Kudo M, Nagasaka T, Ikai I, Goel A: Characteristic patterns ofaltered DNA methylation predict emergence of human hepatocellular
carcinoma. Hepatology 56:994-1003, 2012. (IF=14.679)

28.

Kudo M＊: Signaling pathway/molecular targets and new targeted agents
under development in hepatocellular carcinoma. World J Gastroenterol
18:6005-6017, 2012. (IF=3.665)

29.

Kudo M＊: Targeted therapy for Liver Cancer: updated review in 2012. Curr
Cancer Drug Tar 12:1062-1072, 2012. (IF=2.912)

30.

Kaneko S, Furuse J, Kudo M, Ikeda K, Honda M, Nakamoto Y, Onchi M,
Shiota G, Yokosuka O, Sakaida I, Takehara T, Ueno Y, Hiroishi K, Nishiguchi
S, Moriwaki H, Yamamoto K, Sata M, Obi S, Miyayama S, Imai Y: Guidelineon the use of new anticancer drugs for the treatment of hepatocellular
carcinoma 2010 update. Hepatol Res 42:523-542, 2012. (IF=3.165)

31.

Minata M, Harada K, Kudo M, Ikai I, Nishida N: The prognostic value ofvascular endothelial growth factor in hepatocellular carcinoma for predicting
metastasis after curative resection. Oncology 84:75-81, 2013. (IF=2.642)

32.

Nishida N, Arizumi T, Takita M, Nagai T, Kitai S, Yada N, Hagiwara S, Inoue
T, Minami Y, Ueshima K, Sakurai T, Ida H, Kudo M: Quantification of tumor
DNA in serum and vascular invasion of human hepatocellular carcinoma.
Oncology 84:82-87, 2013. (IF=2.642)

33.

Minata M, Kudo M, Harada K, Ikai I, Nishida N: Expression of E-cadherin andvascular endothelial growth factor in noncancerous liver is associated withrecurrence of hepatocellular carcinoma after curative resection. Oncology
84:88-92, 2013. (IF=2.642)
34.

Nishida N, Kudo M: Recent advancements in comprehensive genetic analyses
for human hepatocellular carcinoma. Oncology 84:93-97, 2013. (IF=2.642)

35.

Sakurai T, Kudo M, Umemura A, He G, Elsharkawy AM, Seki E, Karin M: p38
α inhibits liver fibrogenesis and consequent hepatocarcinogenesis by curtailingaccumulation of reactive oxygen species. Cancer Res 73:215-224, 2013.
(IF=9.727)

36.

Arao T, Ueshima K, Matsumoto K, Nagai T, Kimura H, Hagiwara S,
Sakurai T, Haji S, Kanazawa K, Hidaka H, Iso Y, Kubota K, Shimada M,
Utsunomiya T, Hirooka M, Hiasa Y, Toyoki Y, Hakamada K, Yasui K,
Kumada T, Toyoda H, Sato S, Hisai H, Kuzuya T, Tsuchiya K, Izumi N, Arii S,
Nishio K, Kudo M: FGF3/FGF4 amplification and multiple lung matastases in
responders to sorafenib in hepatocellular carcinoma. Hepatology 57:1407-1415,
2013. (IF=14.679)

37.

Inaba Y, Kanai F, Aramaki T, Yamamoto T, Tanaka T, Yamakado K, Kaneko S,
Kudo M, Imanaka K, Kora S, Nishida N, Kawai N, Seki H, Matsui O, Arioka
H, Arai Y: A randomized phase II study of TSU-68 in patients with
hepatocellular carcinoma treated by transarterial chemoembolization. Eur J
Cancer 49:2832-2840, 2013. (IF=7.275)

38.

Sakurai T, Kudo M*: Molecular link between liver fibrosis and hepatocellular
carcinoma. Liver Cancer 2(3-4):365-366, 2013. (IF=9.720)

39.

Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu
J, Poggi G, Omata M, Lowenthal SP, Lanzalone S, Yang L, Lechuga MJ,
Raymond E, for the SUN1170 HCC Study Group: Sunitinib versus sorafenib in
advanced hepatocellular cancer: results of a randomized phase III trial. J Clin
Oncol 10;31:4067-4075, 2013. (IF=32.956)

40.

Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, Hsu CH, Hu TH,
Heo J, Xu J, Lu L, Chao Y, Boucher E, Han KH, Paik SW, Avina JR, Kudo M,
Yan L, Sobhonslidsuk A, Komov D, Decaens T, Tak WY, Jeng LB, Liu D,
Ezzeddine R, Walters I, Cheng AL: Brivanib versus Sorafenib as first-line
therapy in patients with unresectable, advanced hepatocellular carcinoma:
results from the randomized Phase III BRISK-FL study. J Clin Oncol 31:35173524, 2013. (IF=32.956)

41.

Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, Kang YK,Assenat E, Lim HY, Boige V, Mathurin P, Fartoux L, Lin DY, Bruix J, Poon RT,
Sherman M, Blanc, JF, Finn RS, Tak WY, Chao Y, Ezzeddine R, Liu D, Walters
I, Park JW: Brivanib in patients with advanced hepatocellular carcinoma who
were intolerant to sorafenib or for whom sorafenib faied: results from therandomized phase III BRISK-PS study. J Clin Oncol 31:3509-3516, 2013.
(IF=32.956)
42.

Lencioni R, Kudo M, Ye SL, Bronowicki JP, Chen XP, Dagher L, FuruseJ,
Geschwind JF, de Guevara LL, Papandreou C, Takayama T, Yoon SK,
Nakajima K, Lehr R, Heldner S, Sanyal AJ: GIDEON (Global Investigation oftherapeutic DEcisions in hepatocellular carcinoma and Of its treatment withsorafeNib): second interim analysis. Int J Clin Pract 68:609-617, 2014.
(IF=2.444)

43.

Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RTP, Blanc JF,
Vogel A, Chen CL, Dorval E, Radosavljevic MPR, Santoro A, Daniele B, Furuse
J, Jappe A, Perraud K, Anak O, Sellami DB, Chen LT: Effect of everolimus on
survival in advanced hepatocellular carcinoma after failure of sorafenib: The
EVOLVE-1 randomized clinical trial. J Am Med Assoc (JAMA) 312:57-67, 2014.
(IF=45.450)

44.

Kudo M*: Biomarkers and personalized sorafenib therapy. Liver Cancer 3:399404, 2014. (IF=9.720)

45.

Kudo M*: Emerging strategies for the management of hepatocellular
carcinoma. Digest Dis 32:655-657, 2014. (IF=2.493)

46.

Arizumi T, Ueshima K, Chishina H, Kono M, Takita M, Kitai S, Inoue T, Yada
N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M*: Duration of stabledisease is associated with overall survival in patients with advanced
hepatocellular carcinoma treated with sorafenib. Digest Dis 32:705-710, 2014.
(IF=2.493)

47.

Arizumi T, Ueshima K, Chishina H, Kono M, Takita M, Kitai S, Inoue T, Yada
N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M*: Decreased bloodflow after sorafenib administration is an imaging biomarker to predict overall
survival in patients with advanced hepatocellular carcinoma. Digest Dis
32:733-739, 2014. (IF=2.493)

48.

Kudo M*, Han G, Finn RS, Poon RTP, Blanc JF, Yan L, Yang J, Lu L, Tak WY,
Yu X, Lee JH, Lin SM, Wu C, Tanwandee T, Shao G, Walters IB, Cruz CD,
Poulart V, Wang JH: Brivanib as adjuvant therapy to transarterial
chemoembolization in patients with hepatocellular carcinoma: a randomized

phase III trial. Hepatology 60:1697-1707, 2014. (IF=14.679)
49.

Arizumi T, Ueshima K, Takeda H, Osaki Y, Takita M, Inoue T, Kitai S, Yada N,
Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M*: Comparison ofsystems for assessment of post-therapeutic response to sorafenib forhepatocellular carcinoma. J Gastroenterol 49:1578-1587, 2014. (IF=6.132)

50.

Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, Kudo M, Kang YK,Chen PJ, Toh HC, Gorbunova V, Eskens FA, Qian J, McKee MD, Ricker JL,
Carlson DM, Nowiem SE: Linifanib versus sorafenib in patients with advanced
hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol
33:172-179, 2015. (IF=32.956)

51.

Okita K, Izumi N, Ikeda K, Osaki Y, Numata K, Ikeda M, Kokudo N, Imanaka
K, Nishiguchi S, Kondo S, Nishigaki Y, Shiomi S, Ueshima K, Isoda N, Karino
Y, Kudo M, Tanaka K, Kaneko S, Moriwaki H, Makuuchi M, Okusaka T,
Hayashi N, Ohashi Y, Kumada H, and Peretinoin Study Group: Survey ofsurvival among patients with hepatitis C virus-related hepatocellular
carcinoma treated with peretinoin, an acyclic retinoid, after the completion of arandomized placebo-controlled trial. J Gastroenterol 50:667-674, 2015.
(IF=6.132)

52.

Okita K, Izumi N, Matsui O, Tanaka K, Kaneko S, Moriwaki H, Ikeda K,
Osaki Y, Numata K, Nakachi K, Kokudo N, Imanaka K, Nishiguchi S,
Okusaka T, Nishigaki Y, Shiomi S, Kudo M, Ido K, Karino Y, Hayashi N,
Ohashi Y, Makuuchi M, Kumada H, Peretinoin Study Group: Peretinoin after
curative therapy of hepatitits C-related hepatocellular carcinoma: arandomized double-blind placebo-controlled study. J Gastroenterol 50:191-202,2015. (IF=6.132)

53.

Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Chung HC,
Baron AD, Pfiffer TE, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I,
Chang SC, Abada PB, Yang L, Schwartz JD, Kudo M, REACH Trail
Investigators: Ramucirumab versus placebo as second-line treatment inpatients with advanced hepatocellular carcinoma following first-line therapy
with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3
trial. Lancet Oncol 16:859-870, 2015. (IF= 33.752)

54.

Sheen IS, Izumi N, Austin T, Wang Q, Greenberg J, Shiratori S, Beckman RA,
Kudo M and the investigators’study group: Safety and efficacy of tigatuzumab
plus sorafenib as first-line therapy in subjects with advanced hepatocellular
carcinoma: a phase 2 randomized study. J Hepatol 63:896-904, 2015.
(IF=20.582)

55.

Arizumi T, Ueshima K, Iwanishi M, Chishina H, Kono M, Takita M, Kitai S,
Inoue T, Yada N, Hagiwara S, Ida H, Minami Y, Sakurai T, Nishida N, Kitano
M, Kudo M*: Real-life clinical practice with sorafenib in advanced
hepatocellular carcinoma: a single-center experience second analysis. Digest
Dis 33:728-734, 2015. (IF=2.493)

56.

Kudo M*, Arizumi T, Ueshima K, Sakurai T, Kitano M, Nishida N:
Subclassification of BCLC stage hepatocellular carcinoma and treatment
strategies: Proposal of modified Bolondi subclassification (Kinki Criteria).
Digest Dis 33:751-758, 2015. (IF=2.493)

57.

Arizumi T, Ueshima K, Iwanishi M, Minami T, Chishina H, Kono M, Takita M,
Kitai S, Inoue T, Yada N, Hagiwara S, Ida H, Minami Y, Sakurai T, Kitano M,
Nishida N, Kudo M*: Validation of a modified substaging system (Kinki
Criteria) for patients with intermediate-stage hepatocellular carcinoma.
Oncology 89:47-52, 2015. (IF=2.642)

58.

Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon
RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS,
Makuuchi M, Souza F, Le Berre MA, Meinhardt G, Llovet JM: Adjuvant
sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a
phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol
16:1344-1354, 2015. (IF=33.752)

59.

Ueshima K, Kudo M*, Tanaka M, Kumada T, Chung H, Hagiwara S, Inoue T,
Yada N, Kitai S: Phase I/II study of sorafenib in combination with hepatic
arterial infusion chemotherapy using low-dose cisplatin and 5-fluorouracil.
Liver Cancer 4:263-273, 2015. (IF=9.720)

60.

Kudo M*: Molecular targeted therapy for hepatocellular carcinoma: where are
we now? Liver Cancer 4:1-7, 2015. (IF=9.720)

61.

Arizumi T, Ueshima K, Minami T, Kono M, Chishina H, Takita M, Kitai S,
Inoue T, Yada N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M*:
Effectiveness of sorafenib in patients with transcatheter arterial
chemoembolization (TACE) refractory and intermediate-stage hepatocellular
carcinoma. Liver Cancer 4:253-262, 2015. (IF=9.720)

62.

Kang YK, Yau T, Park JW, Lim HY, Lee TY, Obi S, Chan SL, Qin SK, Kim RD,
Casey M, Chen C, Bhattacharyya H, Williams JA, Valota O, Chakrabarti D,
Kudo M: Randomized phase II study of axitinib versus placebo plus best
supportive care in second-line treatment of advanced hepatocellular
carcinoma. Ann Oncol 26:2457-2463, 2015. (IF=18.274)

63.

Kudo M*: Heterogeneity and subclassification of Barcelona Clinic Liver Cancer
Stage B. Liver Cancer 5:91-96, 2016. (IF=9.720)

64.

Geschwind JF, Kudo M, Marrero JA, Venook AP, Chen XP, Bronowicki JP,
Dagher L, Furuse J, de Guevara LL, Papandreou C, Sanyal AJ, Takayama T,
Ye SL, Yoon SK, Nakajima K, Lehr R, Heldner S, Lencioni R: TACE treatment
in patients with sorafenib-treated unresectable hepatocellular carcinoma inclinical practice: final analysis of GIDEON (Global Investigation of therapeutic
DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib).
Radiology 279:630-640, 2016. (IF=7.931)

65.

Abou-Alfa GK, Puig O, Daniele B, Kudo M, Merle P, Park JW, Ross P, Peron
JM, Ebert O, Chan S, Poon TP, Colombo M, Okusaka T, Ryoo BY, Minguez B,
Tanaka T, Ohtomo T, Ukrainskyi S, Boisserie F, Rutman O, Chen YC, Xu C,
Shochat E, Jukofsky L, Reis B, Chen G, Di Laurenzio L, Lee R, Yen CJ:
Randomized Phase II placebo controlled study of codrituzumab in previously
treated patients with advanced hepatocellular carcinoma. J Hepatol 65:289295, 2016. (IF=20.582)

66.

Kudo M*, Lencioni R, Marrero JA, Venook AP, Bronowicki JP, Chen XP, Dagher
L, Furuse J, Geschwind JFH, Ladron de Guevara L, Papandreou C, Sanyal AJ,
Takayama T, Yoon SK, Nakajima K, Lehr R, Heldner S, Ye SL: Regional
differences in sorafenib-treated patients with hepatocellular carcinoma:
GIDEON observational study. Liver Int 36:1196-1205, 2016. (IF=5.175)

67.

Kudo M*: Recent trends in the management of hepatocellular carcinoma withspecial emphasis on treatment with regorafenib and immune checkpoint
inhibitors. Digest Dis 34:714-730, 2016. (IF=2.493)

68.

Arizumi T, Ueshima K, Iwanishi M, Minami T, Chishina H, Kono M, Takita M,
Kitai S, Inoue T, Yada N, Hagiwara S, Minami Y, Ida H, Sakurai T, Kitano M,
Nishida N, Kudo M*: Validation of Kinki criteria, a modified substaging
system, in patients with intermediate stage hepatocellular carcinoma. Digest
Dis 34:671-678, 2016. (IF=2.493)

69.

Ramaswami R, Pinato DJ, Kubota K, Ishizuka M, Arizumi T, Kudo M, Jang
JW, Kim YW, Pirisi M, Allara E, Sharma R: Prognostic sub-classification ofintermediate-stage hepatocellular carcinoma: a multicenter cohort study withpropensity score analysis. Med Oncol 33:114-121, 2016. (IF=2.834)

70.

Ikeda M, Shimizu S, Sato T, Morimoto M, Kojima Y, Inaba Y, Hagihara A,
Kudo M, Nakamori S, Kaneko S, Sugimoto R, Tahara T, Ohmura T, Yasui K,
Sato K, Ishii H, Furuse J, Okusaka T: Sorafenib plus hepatic arterial infusion

chemotherapy with cisplatin versus sorafenib for advanced hepatocellular
carcinoma: Randomized phase II trial. Ann Oncol 27: 2090-2096, 2016.
(IF=18.274)
71.

Kudo M*: Regorafenib as second-line systemic therapy may change thetreatment strategy and management paradigm for hepatocellular carcinoma.
Liver Cancer 5:235-244, 2016. (IF=9.720)

72.

Kudo M*, Ikeda M, Takayama T, Numata K, Izumi N, Furuse J, Okusaka T,
Kadoya M, Yamashita S, Ito Y, Kokudo N: Safety and efficacy of sorafenib inJapanese patients with hepatocellular carcinoma in clinical practice: asubgroup analysis of GIDEON. J Gastroenterol 51:1150-1160, 2016. (IF=6.132)

73.

Marrero JA, Kudo M, Venook AP, Ye SL, Bronowicki JP, Chen XP, Dagher L,
Furuse J, Geschwind JH, de Guevara LL, Papandreou C, Takayama T, Sanyal
AJ, Yoon SK, Nakajima K, Lehr R, Heldner S, Lencioni R: Observational
registry of sorafenib use in clinical practice across Child-Pugh subgroups: the
GIDEON study. J Hepatol 65:1140-1147, 2016. (IF=20.582)

74.

Pinato DJ, Arizumi T, Jang JW, Allara E, Suppiah P, Smirne C, Tait P, Pai M,
Grossi G, Kim YW, Pirisi M, Kudo M, Sharma R: Combined sequential use of
HAP and ART scores to predict survival outcome and treatment failure
following chemoembolization in hepatocellular carcinoma: a multi-centercomparative study. Oncotarget 7:44705-44718, 2016. (IF=5.168)

75.

Park JO, Ryoo BY, Yen CJ, Kudo M, Yang L, Abada PB, Cheng R, Orlando M,
Zhu AX, Okusaka T: Second-line ramucirumab therapy for advanced
hepatocellular carcinoma (REACH): an East Asian and non-East Asian
subgroup analysis. Oncotarget 7:75482-75491, 2016. (IF=5.168)

76.

Kudo M*: Immune checkpoint blockade in hepatocellular carcinoma: 2017
update. Liver Cancer 6:1-12, 2017. (IF=9.720)

77.

Kudo M*: Molecular targeted agents for hepatocellular carcinoma: current
status and future perspectives. Liver Cancer 6:101-112, 2017. (IF=9.720)

78.

Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka
O, Rosmorduc O, Breder V, Gerolami, Masi G, Ross P, Song T, Bronowicki JP,
Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA,
Baumhauer A, Meinhardt G, Han G, on behalf of the RESORCE Investigators:
Regorafenib for patients with hepatocellular carcinoma who progressed on
sorafenib treatment (RESORCE): a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet 389:56-66, 2017. (IF=60.392)

79.

Kudo M*: Immune checkpoint inhibitors in hepatocellular carcinoma: basics
and ongoing clinical trials. Oncology 92:50-62, 2017. (IF=2.642)

80.

Kudo M*: A new era of systemic therapy for hepatocellular carcinoma withregorafenib and lenvatinib. Liver Cancer 6:177-184, 2017. (IF=9.720)

81.

Kudo M*: Albumin-Bilirubin grade and hepatocellular carcinoma treatment
algorithm. Liver Cancer 6:185-188, 2017. (IF=9.720)

82.

Pinato DJ, Yen C, Bettinger D, Ramaswami R, Arizumi T, Ward C, Pirisi M,
Burlone ME, Thimme R, Kudo M, Sharma R: The albumin-bilirubin grade
improves hepatic reserve estimation post-sorafenib failure: implications for
drug development. Aliment Pharm Ther 45:714-722, 2017. (IF=7.515)

83.

Pinato DJ, Sharma R, Allara E, Yen C, Arizumi T, Kubota K, Bettinger D, Jang
JW, Smirne C, Kim YW, Kudo M, Howell J, Ramaswami R, Burlone ME,
Guerra V, Thimme R, Ishizuka M, Stebbing J, Pirisi M, Carr BI: The ALBI
grade provides objective hepatic reserve estimation across each BCLC stage ofhepatocellular carcinoma. J Hepatol 66:338-346, 2017. (IF=20.582)

84.

Hiraoka A, Kumada T, Kudo M, Hirooka M, Tsuji K, Itobayashi E, Kariyama
K, Ishikawa T, Tajiri K, Ochi H, Tada T, Toyoda H, Nouso K, Kawasaki H,
Hiasa Y, Michitaka K on behalf of the Real-Life Practice Experts for HCC(RELPEC) Study Group and HCC 48 Group: Albumin-bilirubin (ALBI) grade
as part of the evidence-based clinical practice guideline for HCC of the Japan
Society of Hepatology: a comparison with the liver damage and Child-Pughclassifications. Liver Cancer 6:204-215, 2017. (IF=9.720)

85.

Kudo M*, Moriguchi M, Numata K, Hidaka H, Tanaka H, Ikeda M, Kawazoe S,
Ohkawa S, Sato Y, Kaneko S, Furuse J, Takeuchi M, Fang X, Date Y, Takeuchi
M, Okusaka T: S-1 versus placebo in patients with sorafenib-refractoryadvanced hepatocellular carcinoma (S-CUBE): a randomised, double-blind,multicentre, phase 3 trial. Lancet Gastroenterol Hepatol 2:407-417, 2017.
(IF=14.789)

86.

Ikeda K, Kudo M, Kawazoe S, Osaki Y, Ikeda M, Okusaka T, Tamai T, Suzuki
T, Hisai T, Hayato S, Okita K, Kumada H: Phase 2 Study of Lenvatinib inpatients with advanced hepatocellular carcinoma. J Gastroenterol 52:512-519,
2017. (IF=6.132)

87.

Kudo M*, Hatano E, Ohkawa S, Fujii H, Masumoto A, Furuse J, Wada Y, Ishii
H, Obi S, Kaneko S, Kawazoe S, Yokosuka O, Ikeda M, Ukai K, Morita S, Tsuji
A, Kudo T, Shimada M, Osaki Y, Tateishi R, Sugiyama G, Abada PB, Yang L,
Okusaka T, Zhu AX: Ramucirumab as second-line treatment in patients with

advanced hepatocellular carcinoma: Japanese subgroup analysis of the
REACH trial. J Gastroenterol 52:494-503, 2017. (IF=6.132)
88.

Howell J, Pinato DJ, Ramaswami R, Bettinger D, Arizumi T, Ferrari C, Yen C,
Gibbin A, Burlone ME, Guaschino G, Sellers L, Black J, Pirisi M, Kudo M,
Thimme R, Park JW, Sharma R: On-target sorafenib toxicity predicts improved
survival in hepatocellular carcinoma: a multi-centre, prospective study.
Aliment Pharm Ther 45:1146-1155, 2017. (IF=7.515)

89.

Ikeda M, Shimizu S, Sato T, Morimoto M, Kojima Y, Inaba Y, Hagihara A,
Kudo M, Nakamori S, Kaneko S, Sugimoto R, Tahara T, Ohmura T, Yasui K,
Sato K, Ishii H, Furuse J, Okusaka T: Reply to the Letter to the editor'Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus
Sorafenib for advanced hepatocellular carcinoma: randomized phase II trial' by
Fornaro et al. Ann Oncol 28:903-904, 2017. (IF=18.274)

90.

Lencioni R, Montal R, Torres F, Park JW, Decaens T, Raoul JL, Kudo M, Chang
C, Rios J, Boige V, Assenat E, Kang YK, Lim HY, Walters I, Llovet JM:
Objective response by mRECIST as a predictor and potential surrogate endpoint of overall survival in advanced HCC. J Hepatol 66:1166-1172, 2017.
(IF=20.582)

91.

Pinato DJ, Ramaswami R, Arizumi T, Ferrari C, Gibbin A, Burlone M,
Guaschino G, Tonuitto P, Black J, Sellers L, Kudo M, Pirisi M, Sharma R:
Integration of the cancer-related inflammatory response as a stratifying
biomarker of survival in hepatocellular carcinoma treated with sorafenib.
Oncotarget 8:36161-36170, 2017. (IF=5.168)

92.

El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo
SP, Trojan J, Welling TH, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J,
dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I: Nivolumab inpatients with advanced hepatocellular carcinoma (CheckMate040): an openlabel, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet
389:2492-2502, 2017. (IF=60.392)

93.

Banno E, Togashi Y, de Velasco MA, Mizukami T, Nakamura Y, Terashima M,
Sakai K, Fujita Y, Kamata K, Kitano M, Kudo M, Nishio K: Clinicalsignificance of Akt2 in advanced pancreatic cancer treated with erlotinib. Int J
Oncol 50:2049-2058, 2017. (IF=3.899)

94.

Arizumi T, Ueshima K, Iwanishi M, Minami T, Chishina H, Kono M, Takita M,
Yada N, Hagiwara S, Minami Y, Ida H, Komeda Y, Takenaka M, Sakurai T,
Watanabe T, Nishida N, Kudo M*: The overall survival of patients with

hepatocellular carcinoma correlates with the newly defined time to progression
after transarterial chemoembolization. Liver Cancer 6:227-235, 2017.
(IF=9.720)
95.

Chau I, Peck-Radosavljevic M, Borg C, Malfertheiner P, Seitz JF, Park JO,
Ryoo BY, Yen CJ, Kudo M, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron
AD, Okusaka T, Bowman L, Cui ZL, Girvan AC, Abada PB, Yang L, Zhu AX:
Ramucirumab as second-line treatment in patients with advanced
hepatocellular carcinoma following first-line therapy with sorafenib: patientfocused outcome results from the randomised phase III REACH study. Eur J
Cancer 81:17-25, 2017. (IF=7.275)

96.

Kudo M*: New Era in the Treatment of Chronic Liver Diseases and Liver
Cancer: State-of-the Art Progress in 2017. Digest Dis 35:493-497, 2017.
(IF=2.493)

97.

Hagiwara S, Minami Y, Ida H, Ueshima K, Kamata K, Minaga K, Komeda Y,
Takenaka M, Sakurai T, Watanabe T, Nishida N, Kudo M*: Impact of Tumor
Factors on survival in Patients with Hepatocellular Carcinoma classified basedon Kinki Criteria Stage B2. Digest Dis 35:583-588, 2017. (IF=2.493)

98.

Arizumi T, Minami T, Chishina H, Kono M, Takita M, Yada N, Hagiwara S,
Minami Y, Ida H, Ueshima K, Kamata K, Minaga K, Komeda Y, Takenaka M,
Sakurai T, Watanabe T, Nishida N, Kudo M*: Time to transcatheter arterial
chemoembolization refractoriness in patients with hepatocellular carcinoma in
Kinki criteria stages B1 and B2. Digest Dis 35:589-597, 2017. (IF=2.493)

99.

Hiraoka A, Kumada T, Kudo M, Hirooka M, Koizumi Y, Hiasa Y, Tajiri K,
Toyoda H, Tada T, Ochi H, Joko K, Shimada N, Deguchi A, Ishikawa T, Imai M,
Tsuji K, Michitaka K: Hepatic function during repeated TACE procedures andprognosis after introducing sorafenib in patients with unresectable
hepatocellular carcinoma: multicenter analysis. Digest Dis 35:602-610, 2017.
(IF=2.493)

100. Ueshima K, Nishida N, Kudo M*: Sorafenib-regorafenib sequential therapy inadvanced hepatocellular carcinoma: a single-institute experience. Digest Dis
35:611-617, 2017. (IF=2.493)
101. Nishida N, Kudo M: Role of immune checkpoint blockade in the treatment forhuman hepatocellular carcinoma. Digest Dis 35:618-622, 2017. (IF=2.493)
102. Kudo M*: Lenvatinib in advanced hepatocellular carcinoma. Liver Cancer
6:253-263, 2017. (IF=9.720)

103. Hiraoka A, Michitaka K, Kumada T, Izumi N, Kadoya M, Kokudo N, Kubo S,
Matsuyama Y, Nakashima O, Sakamoto M, Takayama T, Kokudo T,
Kashiwabara K, Kudo M, the Liver Cancer Study Group of Japan: Validationand potential of albumin-bilirubin grade and prognostication in a nationwide
survey of 46,681 hepatocellular carcinoma patients in japan: the need for amore detailed evaluation of hepatic function. Liver Cancer 6: 325-336, 2017.
(IF=9.720)
104. Sakurai T, Yada N, Hagiwara S, Arizumi T, Minaga K, Kamata K, Takenaka
M, Minami Y, Watanabe T, Nishida N, Kudo M: Gankyrin induces STAT3
activation in tumor microenvironment and sorafenib resistance inhepatocellular carcinoma. Cancer Sci 108:1996-2003, 2017. (IF=4.966)
105. Sakurai T, Yada N, Hagiwara S, Arizumi T, Minaga K, Kamata K, Takenaka
M, Minami Y, Watanabe T, Nishida N, Kudo M: Gankyrin induces STAT3
activation in tumor microenvironment and sorafenib resistance inhepatocellular carcinoma. Cancer Sci 108:1996-2003, 2017. (IF=4.966)
106. Ogawa C, Morita M, Omura A, Noda T, Kubo A, Matsunaka T, Tamaki H,
Shibatoge M, Tsutsui A, Senoh T, Nagano T, Takaguchi K, Tani J, Morishita A,
Yoneyama H, Masaki T, Moriya A, Ando M, Deguchi A, Kokudo Y, Minami Y,
Ueshima K, Sakurai T, Nishida N, Kudo M*: Hand-foot syndrome and postprogression treatment are the good predictors of better survival in advanced
hepatocellular carcinoma treated with sorafenib: a multicenter study. Oncology
93:113-119, 2017. (IF=2.642)
107. Kudo M*, Arizumi T: Transarterial Chemoembolization in Combination with
Molecular Targeted Agent: Lessons from Negative Trials (Post-TACE, BRISKTA, SPACE, ORIENTAL, and TACE-2). Oncology 93:127-134, 2017. (IF=2.642)
108. Kudo M*: Systemic Therapy for Hepatocellular Carcinoma: 2017 Update.
Oncology 93:135-146, 2017. (IF=2.642)
109. Kudo M*: Immuno-Oncology in hepatocellular carcinoma: 2017 update.
Oncology 93:147-159, 2017. (IF=2.642)
110. Nishida N, Kudo M: Oncogenic signal and tumor microenvironment inhepatocellular carcinoma. Oncology 93:160-164, 2017. (IF=2.642)
111. Yen C, Sharma R, Rimassa L, Arizumi T, Bettinger D, Choo HY, Pressiani T,
Burlone ME, Pirisi M, Giordano L, Abdulrahman A, Kudo M, Thimme R, Park
JW, Pinato DJ: Treatment stage migration maximizes survival outcomes inpatients with hepatocellular carcinoma treated with sorafenib: anobservational study. Liver Cancer 6:313-324, 2017. (IF=9.720)

112. Kawakami H, Tanizaki J, Tanaka K, Haratani K, Hayashi H, Takeda M,
Kamata K, Takenaka M, Kimura M, Chikugo T, Sato T, Kudo M, Ito A,
Nakagawa K: Imaging and clinicopathological features of nivolumab-related
cholangitis in patients with non-small cell lung cancer. Invest New Drugs
35:529-536, 2017. (IF=3.525)
113. Zhu AX, Baron AD, Malfertheiner P, Kudo M, Kawazoe S, Pezet D, Weissinger
F, Brandi G, Barone CA, Okusaka T, Wada Y, Park JO, Ryoo BY, Cho JY,
Chung HC, Li CP, Yen CJ, Lee KD, Yang L, Abada PB, Chang SC, Chau I:
Ramucirumab as second-line treatment in patients with advanced
hepatocellular carcinoma: Analysis of REACH trial results by Child-Pughscore. JAMA Oncol 3:235-243, 2017. (IF=24.799)
114. Harding JJ, Watanabe T, El-Dika I, Nishida N, Abou-Alfa GK, Kudo M: 2.5“Gastrointestinal Malignancies”; 2.5.3 Hepatocellular carcinoma. In “ESMO
Handbook of Immuno-Oncology”, Haanen J, Lugowska I, Garassino MC,
Califano R, ed., 2018, pp191-202. (IF=0.000)
115. Kudo M*, Cheng AL, Park JW, Park JH, Liang PC, Hidaka H, Izumi N, Heo J,
Lee YJ, Sheen IS, Chiu CF, Arioka H, Morita S, Arai Y: Orantinib versus
placebo combined with transcatheter arterial chemoembolisation in patientswith unresectable hepatocellular carcinoma (ORIENTAL): a randomised,double-blind, placebo-controlled, multicentre, phase 3 study. Lancet
Gastroenterol Hepatol 3:37-46, 2018. (IF=14.789)
116. Kudo M*: Lenvatinib may drastically change the treatment landscape of
hepatocellular carcinoma. Liver Cancer 7:1-19, 2018. (IF=9.720)
117. Kudo M*: Combination cancer immunotherapy in hepatocellular carcinoma.
Liver Cancer 7:20-27, 2018. (IF=9.720)
118. Kudo M*, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW,
Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C,
Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL: Lenvatinib versus
sorafenib in first-line treatment of patients with unresectable hepatocellular
carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391:1163-1173,
2018. (IF=60.392)
119. Kudo M*, Kang YK, Park JW, Qin S, Inaba Y, Assenat E, Umeyama Y, Lechuga
MJ, Valota O, Fujii Y, Martini JF, Williams JA, Obi S: Regional differences in
efficacy, safety and biomarkers for second-line axitinib in patients withadvanced hepatocellular carcinoma: from a randomized phase II study. Liver
Cancer, 7:148-164, 2018. (IF=9.720)

120. Kudo M*, Ueshima K, Yokosuka O, Ogasawara S, Obi S, Izumi N, Aikata H,
Nagano H, Hatano E, Sasaki Y, Hino K, Kumada T, Yamamoto K, Imai Y,
Iwadou S, Ogawa C, Okusaka T, Kanai F, Akazawa K, Yoshimura KI, Johnson
P, Arai Y; SILIUS study group: Sorafenib plus low-dose cisplatin andfluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone inpatients with advanced hepatocellular carcinoma (SILIUS): a randomised,
open label, phase 3 trial. Lancet Gastroenterol Hepatol 3:424-432, 2018.
(IF=14.789)
121. Raoul JL, Kudo M, Finn RS, Edeline J, Reig M, Galle PR: Systemic therapy forintermediate and advanced hepatocellular carcinoma: Sorafenib and beyond.
Cancer Treat Rev 68:16-24, 2018. (IF=8.885)
122. Kudo M*: Cabozantinib as a second-line agent in advanced hepatocellular
carcinoma. Liver Cancer 7:123-133, 2018. (IF=9.720)
123. Chau I, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Kudo M,
Pfiffer T, Hatano E, Chung HC, Kopeckova K, Phelip JM, Brandi G, Ohkawa S,
Li CP, Okusaka T, Hsu Y, Abada PB, Zhu AX: Alpha-fetoprotein kinetics inpatients with hepatocellular carcinoma receiving ramucirumab or placebo: ananalysis of the phase 3 REACH study. Brit J Cancer 119:19-26, 2018.
(IF=5.791)
124. Yen CJ, Muro K, Kim TW, Kudo M, Shih JY, Lee KW, Chao Y, Kim SW,
Yamazaki K, Sohn J, Cheng R, Zhang Y, Binder P, Mi G, Orlando M, Chung
HC: Ramucirumab safety in East Asian patients: A meta-analysis of six global,
randomized, double-blind, placebo-controlled, phase III clinical trials. J Glob
Oncol 4:1-12,2018. (IF=0.000)
125. Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C,
Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele
B, Webber AL, Ebbinghaus, SW, Ma J, Siegel AB, Cheng AL, Kudo M, for the
KEYNOTE-224 investigators: Pembrolizumab in patients with advanced
hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a
non-randomised, open-label phase 2 trial. Lancet Oncol 19:940-952, 2018.
(IF=33.752)
126. Nishida N, Kudo M: Immune checkpoint blockade for the treatment of humanhepatocellular carcinoma. Hepatol Res 48:622-634, 2018. (IF=3.165)
127. Kudo M*: Proposal of primary endpoints for TACE combination trials withsystemic therapy: Lessons learned from 5 negative trials and the positive
TACTICS trial. Liver Cancer 7:225-234, 2018. (IF=9.720)

128. Kudo M*: Extremely high objective response rate of Lenvatinib: Its clinicalrelevance and changing the treatment paradigm in hepatocellular carcinoma.
Liver Cancer 7:215-224, 2018. (IF=9.720)
129. Kudo M*: Ramucirumab as second-line systemic therapy in hepatocellular
carcinoma. Liver Cancer 7:305-311, 2018. (IF=9.720)
130. Kudo M*: Systemic therapy for hepatocellular carcinoma: Latest advances.
Cancers 10, 2018 (doi: 10.3390/cancers10110412). (IF=6.162)
131. Kato R, Hayashi H, Sano K, Handa K, Kumode T, Ueda H, Okuno T,
Kawakami H, Matsumura I, Kudo M, Nakagawa K: Nivolumab-induced
hemophilia A presenting as gastric ulcer bleeding in a patient with non-small
cell lung cancer. J Thorac Oncol 13:e239-e241, 2018. (IF=13.357)
132. Chau I, Peck-Radosavljevic M, Borg C, Malfertheiner P, Seitz JF, Park JO,
Ryoo BY, Yen CJ, Kudo M, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron
AD, Okusaka T, Bowman L, Cui ZL, Girvan AC, Abada PB, Yang L, Zhu AX:
Corrigendum to “Ramucirumab as second-line treatment in patients withadvanced hepatocellular carcinoma following first-line therapy with sorafenib:
Patient-focused outcome results from the randomised phase III REACH
study”. Eur J Cancer 100:135-136, 2018. (IF=7.275)
133. Tak WY, Ryoo BY, Lim HY, Kim DY, Okusaka T, Ikeda M, Hidaka H, Yeon JE,
Mizukoshi E, Morimoto M, Lee MA, Yasui K, Kawaguchi Y, Heo J, Morita S,
Kim TY, Furuse J, Katayama K, Aramaki T, Hara R, Kimura T, Nakamura O,
Kudo M: Phase I/II study of first-line combination therapy with sorafenib plus
resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy foradvanced hepatocellular carcinoma in east Asian patients. Invest New Drugs
36:1072-1084, 2018. (IF=3.525)
134. Nishida N, Nishimura T, Kaido T, Minaga K, Yamao K, Kamata K, Takenaka
M, Ida H, Hagiwara S, Minami Y, Sakurai T, Watanabe T, Kudo M: Molecularscoring of hepatocellular carcinoma for predicting metastatic recurrence andrequirements of systemic chemotherapy. Cancers 10: E367, 2018 (doi:10.3390/cancers10100367). (IF=6.162)
135. Kudo M*: Cabozantinib for advanced hepatocellular carcinoma. Hepatobil
Surg Nutr 8:153-156, 2019. (IF=5.296)
136. Zhu AX, Kang YK, Yen CJ, Finn RS, Galle P, Llovet JM, Assenat E, Brandi G,
Pracht M, Lim HY, Rau KM, Motomura K, Ohno I, Merle P, Daniele B, Shin
DB, Gerken G, Borg C, Hiriart JB, Okusaka T, Morimoto M, Hsu Y, Abada PB,
Kudo M: Ramucirumab after sorafenib in patients with advancedhepatocellular carcinoma and increased alpha-fetoprotein concentrations(REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Oncol 20:282-296, 2019. (IF=33.752)
137. Escudier B, Worden F, Kudo M: Sorafenib: Key lessons from over 10 years ofexperience. Expert Rev Anticancer Ther 19:177-189, 2019. (IF=3.573)
138. Kudo M*: Combination cancer immunotherapy with molecular targeted
agents/anti-CTLA-4 antibody for hepatocellular carcinoma. Liver Cancer 8:111, 2019. (IF=9.720)
139. Kudo M*: Targeted and immune therapies for hepatocellular carcinoma:predictions for 2019 and beyond. World J Gastroenterol 25:789-807, 2019.
(IF=3.665)
140. Hidaka H, Izumi N, Aramaki T, Ikeda M, Inaba Y, Imanaka K, Okusaka T,
Kanazawa S, Kaneko S, Kora S, Saito H, Furuse J, Matsui O, Yamashita T,
Yokosuka O, Morita S, Arioka H, Kudo M, Arai Y: Subgroup analysis of efficacy
and safety of orantinib in combination with TACE in Japanese HCC patientsin a randomized phase III trial (ORIENTAL). Med Oncol 36:52, 2019.
(IF=2.834)
141. Hiraoka A, Kumada T, Tsuji K, Takaguchi K, Itobayashi E, Kariyama K, Ochi
H, Tajiri K, Hirooka M, Shimada N, Ishikawa T, Tachi Y, Tada T, Toyoda H,
Nouso K, Joko K, Hirasa Y, Michitaka K, Kudo M, on behalf of the RELPEC
Study Group of HCC 48 Group: Validation of modified ALBI grade for moredetailed assessment of hepatic function in hepatocellular carcinoma patients: A
multicenter analysis. Liver Cancer 8:121-129, 2019. (IF=9.720)
142. Kudo M*: Objective response by mRECIST is an independent prognostic factorof overall survival in systemic therapy for hepatocellular carcinoma. Liver
Cancer 8:73-77, 2019. (IF=9.720)
143. Kono M, Sakurai T, Okamoto K, Masaki S, Nagai T, Komeda Y, Kamata K,
Minaga K, Yamao K, Takenaka M, Watanabe T, Nishida N, Kudo M: Efficacy
and safety of chemotherapy following anti-PD-1 antibody therapy for gastriccancer: a case of sclerosing cholangitis. Intern Med 58:1263-1266, 2019.
(IF=1.005)
144. Takeda H, Nishijima N, Nasu A, Komekado H, Kita R, Kimura T, Osaki Y,
Kudo M: Long-term antitumor effect of lenvatinib on unresectable
hepatocellular carcinoma with portal vein invasion. Hepatol Res 49:594-599,
2019. (IF=3.165)

145. Kudo M*: Pembrolizumab for the treatment of hepatocellular carcinoma. Liver
Cancer 8:143-154, 2019. (IF=9.720)
146. Qin S, Finn RS, Kudo M, Meyer T, Vogel A, Ducreux M, Macarulla TM,
Tomasello G, Boisserie F, Hou J, Li X, Song J, Zhu AX: Rationale 301 study:
Tislelizumab versus sorafenib as first-line treatment for unresectable
hepatocellular carcinoma. Future Oncol 15:1811-1822, 2019. (IF=2.660)
147. Kobayashi M, Kudo M, Izumi N, Kaneko S, Azuma M, Copher R, Meier G, Pan
J, Ishii M, Ikeda S: Cost-effectiveness analysis of lenvatinib treatment forpatients with unresectable hepatocellular carcinoma (uHCC) compared withsorafenib in Japan. J Gastroenterol 54:558-570, 2019. (IF=6.132)
148. Nishida N, Kudo M: Liver damage related to immune checkpoint inhibitor.
Hepatol Int 13:248-252, 2019. (IF=5.102)
149. Zhu AX, Finn RS, Galle PR, Llovet JM, Kudo M: Ramucirumab in advanced
hepatocellular carcinoma in REACH-2: the true value of alpha-fetoprotein.
Lancet Oncol 20:e191, 2019. doi: 10.1016/S1470-2045(19)30165-2, PMID:
30942178 (IF=33.752)
150. Kudo M*: Immuno-Oncology therapy for hepatocellular carcinoma: Current
status and ongoing trials. Liver Cancer 8:221-238, 2019. (IF=9.720)
151. Kudo M*, Ueshima K, Chan S, Minami T, Chishina H, Aoki T, Takita M,
Hagiwara S, Minami Y, Ida H, Takenaka M, Sakurai T, Watanabe T, Morita M,
Ogawa C, Wada Y, Ikeda M, Ishii H, Izumi N, Nishida N: Lenvatinib as an
initial treatment in patients with intermediate-stage hepatocellular carcinoma
beyond up-to-seven criteria and Child-Pugh A liver function: A proof-of-concept
study. Cancers 11, 2019, doi: 10.3390/cancers11081084. (IF=6.162)
152. Ueshima K, Nishida N, Hagiwara S, Aoki T, Minami T, Chishina H, Takita M,
Minami Y, Ida H, Takenaka M, Sakurai T, Watanabe T, Morita M, Ogawa C,
Hiraoka A, Johnson P, Kudo M*: Impact of baseline ALBI grade on theoutcomes of hepatocellular carcinoma patients treated with lenvatinib: A
multicenter study. Cancers 11, 2019, doi: 10.3390/cancers11070952. (IF=6.162)
153. Evans TRJ, Kudo M, Finn RS, Han KH, Cheng AL, Ikeda M, Kraljevic S, Ren
M, Dutcus CE, Piscaglia F, Sung MW: Urine protein: creatinine ratio vs 24hour urine protein for proteinuria management: Analysis from the phase 3
REFLECT study of lenvatinib vs sorafenib in hepatocellular carcinoma. Brit J
Cancer 121:218-221, 2019. (IF=5.791)
154. Minami Y, Kudo M*: Adjuvant therapy after radical surgery for hepatocellularcarcinoma: still an unmet need? Hepatobil Surg Nutr (HBSN) 8:414-416, 2019.
(IF=5.296)
155. Bettinger D, Pinato DJ, Schultheiss M, Sharma R, Rimassa L, Pressiani T,
Burlone ME, Pirisi M, Kudo M, Park JW, Buettner N, Neumann-Haefelin C,
Boettler T, Abbasi-Senger N, Alheit H, Baus W, Blanck O, Gerum S,
Guckenberger M, Habermehl D, Ostheimer C, Riesterer O, Tamihardja J,
Grosu AL, Thimme R, Brunner TB, Gkika E: Stereotactic body radiation
therapy as an alternative treatment for patients with hepatocellular
carcinoma compared to sorafenib: A propensity score analysis. Liver Cancer
8:281-294, 2019. (IF=9.720)
156. Kudo M*, Ueshima K, Chiba Y, Ogasawara S, Obi S, Izumi N, Aikata H,
Nagano H, Hatano E, Sasaki Y, Hino K, Kumada T, Yamamoto K, Imai Y,
Iwadou S, Ogawa C, Okusaka T, Kanai F, Arai Y: Objective response by
mRECIST is an independent prognostic factor for overall survival in
hepatocellular carcinoma treated with sorafenib in the SILIUS trial. Liver
Cancer 8:505-519, 2019. (IF=9.720)
157. Kudo M*: Scientific rationale for combination immunotherapy ofhepatocellular carcinoma with anti-PD-1/PD-L1 and anti-CTLA-4 antibodies.
Liver Cancer 8:413-426, 2019. (IF=9.720)
158. Kudo M*: A new treatment option for intermediate-stage hepatocellular
carcinoma with high tumor burden: Initial lenvatinib therapy with subsequent
selective TACE. Liver Cancer 8:299-311, 2019. (IF=9.720)
159. Hiraoka A, Kumada T, Michitaka K, Kudo M: Newly proposed ALBI grade and
ALBI-T score as tools for assessment of hepatic function and prognosis in
hepatocellular carcinoma patients. Liver Cancer 8:312-325, 2019. (IF=9.720)
160. Yau T, Hsu C, Kim TY, Choo SP, Kang YK, Hou MM, Numata K, Yeo W, Chopra
A, Ikeda M, Kuromatsu R, Moriguchi M, Chao Y, Zhao H, Anderson J, Dela
Cruz C, Kudo M: Nivolumab in advanced hepatocellular carcinoma: sorafenibexperienced asian cohort analysis. J Hepatol 71:543-552, 2019. (IF=20.582)
161. Hiraoka A, Kumada T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T,
Takaguchi K, Kariyama K, Itobayashi E, Tajiri K, Shimada N, Shibata H, Ochi
H, Tada T, Toyoda H, Nouso K, Tsutsui A, Nagano T, Itokawa N, Hayama K,
Imai M, Joko K, Tanaka H, Tamai T, Koizumi Y, Hiasa Y, Michitaka K, Kudo
M, Real-life Practice Experts for HCC (RELPEC) Study Group: Important
clinical factors in sequential therapy including lenvatinib against unresectable
hepatocellular carcinoma. Oncology 97:277-285, 2019. (IF=2.642)

162. Yau T, Hsu C, Kim TY, Choo SP, Kang YK, Hou MM, Numata K, Yeo W, Chopra
A, Ikeda M, Kuromatsu R, Moriguchi M, Chao Y, Zhao H, Anderson J, Dela
Cruz C, Kudo M: Corrigendum to “Nivolumab in advanced hepatocellular
carcinoma: sorafenib-experienced asian cohort analysis (J Hepatol 71:543-552,
2019)”. J Hepatol 71:1278, 2019. (IF=20.582)
163. Hiraoka A, Kumada T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T,
Takaguchi K, Kariyama K, Itobayashi E, Tajiri K, Shimada N, Shibata H, Ochi
H, Tada T, Toyoda H, Nouso K, Tsutsui A, Nagano T, Itokawa N, Hayama K,
Imai M, Joko K, Koizumi Y, Hiasa Y, Michitaka K, Kudo M, on behalf of theReal-life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group(hepatocellular carcinoma experts from 48 clinics in Japan): Prognostic factor
of lenvatinib for unresectable hepatocellular carcinoma in real-world
conditions-multicenter anlysis. Cancer Med 8:3719-3728, 2019. (IF=3.491)
164. Evans TRJ, Kudo M, Finn RS, Han KH, Cheng AL, Ikeda M, Kraljevic S, Ren
M, Dutcus CE, Piscaglia F, Sung MW: Correction: Urine protein: creatinine
ratio vs 24-hour urine protein for proteinuria management: Analysis from thephase 3 REFLECT study of lenvatinib vs sorafenib in hepatocellular
carcinoma. Brit J Cancer 121:625, 2019. (IF=5.791)
165. Cheng AL, Hsu C, Chan SL, Choo SP, Kudo M: Challenges of combination
therapy with immune checkpoint inhibitors for hepatocellular carcinoma. J
Hepatol 72:307-319, 2020. (IF=20.582)
166. Alsina A, Kudo M, Vogel A, Cheng AL, Tak WY, Ryoo BY, Evans TRJ, López
López C, Daniele B, Misir S, Ren M, Izumi N, Qin S, Finn RS: Effects ofsubsequent systemic anticancer medication following first-line lenvatinib: A
post hoc responder analysis from the phase 3 REFLECT study in unresectable
hepatocellular carcinoma. Liver Cancer 9:93-104, 2020. (IF=9.720)
167. Hiraoka A, Kumada T, Fukunishi S, Atsukawa M, Hirooka M, Tsuji K,
Ishikawa T, Takaguchi K, Kariyama K, Itobayashi E, Tajiri K, Shimada N,
Shibata H, Ochi H, Tada T, Toyoda H, Yokohama K, Nouso K, Tsutsui A,
Nagano T, Itokawa N, Hayama K, Arai T, Imai M, Joko K, Koizumi Y, Hiasa Y,
Michitaka K, Kudo M, on behalf of the Real-Life Practice Experts for HCC(RELPEC) study group and HCC 48 Group: Post-progression treatment
eligibility of unresectable hepatocellular carcinoma patients treated withlenvatinib. Liver Cancer 9:73-83, 2020. (IF=9.720)
168. Cucchetti A, Zhong J, Berhane S, Toyoda H, Shi K, Tada T, Chong CCN, Xiang
BD, Li LQ, Lai PBS, Ercolani G, Mazzaferro V, Kudo M, Cescon M, Pinna AD,
Kumada T, Johnson PJ: The chances of hepatic resection curing hepatocellularcarcinoma. J Hepatol 72:711-717, 2020. (IF=20.582)
169. Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline
J, Chao Y, Ogasawara S, Yao T, Garrido M, Chan SL, Knox J, Daniele B,
Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL, for the KEYNOTE-240
investigators: Pembrolizumab as second-line therapy in patients withadvanced hepatocellular carcinoma in KEYNOTE-240: a randomized, doubleblind, phase 3 trial. J Clin Oncol 38:193-202, 2020. (IF=32.956)
170. Yamashita T, Kudo M, Ikeda K, Izumi N, Tateishi R, Ikeda M, Aikata H,
Kawaguchi Y, Wada Y, Numata K, Inaba Y, Kuromatsu R, Kobayashi M,
Okusaka T, Tamai T, Kitamura C, Saito K, Haruna K, Okita K, Kumada H:
REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib tosorafenib for the treatment of unresectable hepatocellular carcinoma: ananalysis of Japanese subset. J Gastroenterol 55:113-122, 2020. (IF=6.132)
171. Kudo M*: Scientific rationale for combined immunotherapy with PD-1/PD-L1
antibodies and VEGF inhibitors in advanced hepatocellular carcinoma.
Cancers 12: E1089, 2020, doi:10.3390/cancers12051089. (IF=6.162)
172. Hiraoka A, Kumada T, Tada T, Fukunishi S, Atsukawa M, Hirooka A, Tsuji K,
Ishikawa T, Takaguchi K, Kariyama K, Itobayashi E, Tajiri K, Shimada N,
Shibata H, Ochi H, Kawata K, Toyoda H, Ohama H, Tsutsui A, Itokawa N,
Hayama K, Arai T, Imai M, Nakamura S, Michitaka K, Hiasa Y, Kudo M, RealLife Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group:
Nutritional index as prognostic indicator in patients receiving lenvatinib
treatment for unresectable hepatocellular carcinoma. Oncology 98:295-302,
2020. (IF=2.642)
173. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V,
Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C,
Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL: Atezolizumab plus bevacizumab
in unresectable hepatocellular carcinoma. New Engl J Med 382:1894-1905,
2020. (IF=74.699)
174. Kudo M*: A new era in systemic therapy for hepatocellular carcinoma:
Atezolizumab plus bevacizumab combination therapy. Liver Cancer 9:119-137,
2020. (IF=9.720)
175. Hack SP, Spahn J, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Yopp A,
Chow P, Qin S: IMbrave050: a phase III trial of atezolizumab plus
bevacizumab in high-risk hepatocellular carcinoma after curative resection or
ablation. Future Oncol 16:975-989, 2020. (IF=2.660)

176. Nishida N, Kudo M: Immune phenotype and immune checkpoint inhibitors forthe treatment of human hepatocellular carcinoma. Cancers 12:E1274, 2020.
doi: 10.3390/cancers12051274. (IF=6.162)
177. Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig
C, Dussault I, Ikeda M: Phase 1 study of bintrafusp alfa, a bifunctional fusion
protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract
cancer. J Immunother Cancer 8:e000564, 2020. (IF=9.913)
178. Kudo M, Okusaka T, Motomura K, Ohno I, Morimoto M, Seo S, Wada Y, Sato S,
Yamashita T, Furukawa M, Aramaki T, Nadano S, Ohkawa K, Fujii H, Kudo T,
Furuse J, Takai H, Homma G, Yoshikawa R, Zhu AX: Ramucirumab after priorsorafenib in patients with advanced hepatocellular carcinoma and elevatedalpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial. J
Gastroenterol 55:627-639, 2020. (IF=6.132)
179. Kudo M*, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H, Izumi N,
Yamasaki T, Nojiri S, Hino K, Tsumura H, Kuzuya T, Isoda N, Yasui K, Aino H,
Ido A, Kawabe N, Nakao K, Wada Y, Yokosuka O, Yoshimura K, Okusaka T,
Furuse J, Kokudo N, Okita K, Johnson P, Arai Y, on behalf of the TACTICS
study group: Randomised, multicentre prospective trial of transarterial
chemoembolization (TACE) plus sorafenib as compared with TACE alone inpatients with hepatocellular carcinoma: TACTICS trial. Gut, 2020(Epub aheadof print). (IF=19.819)
180. Sakurai T, Nishida N, Kudo M: Promising anticancer therapy: combination of
immune checkpoint inhibitors and molecular-targeted agents. Hepatobil Surg
Nutr, 2020 (Epub ahead of print). (IF=5.296)
181. Nishida N, Sakai K, Morita M, Aoki T, Takita M, Hagiwara S, Komeda Y,
Takenaka M, Minami Y, Ida H, Ueshima K, Nishio K, Kudo M: Association
between genetic and immunological background of hepatocellular carcinoma
and expression of programmed cell death-1. Liver Cancer, 2020 (Epub ahead ofprint). (IF=9.720)
182. Kudo M, Galle PR, Llovet JM, Finn R, Vogel A, Motomura K, Assenat E, Merle
P, Brandi G, Daniele B, Okusaka T, Tomasek J, Borg C, Dadduzio V, Morimoto
M, Pracht M, Jen MH, Ubreva ND, Widau R, Shinozaki K, Yoshikawa R, Zhu
AX: Ramucirumab in elderly patients with hepatocellular carcinoma andelevated alpha-fetoprotein after sorafenib in REACH and REACH-2. Liver Int,
2020 (Epub ahead of print). (IF=5.175)
183. Yen CJ, Kudo M, Lim HY, Hsu CH, Vogel A, Brandi G, Cheng R, Nitu IS,

Abada P, Hsu Y, Zhu AX, Kang YK: Efficacy and safety of ramucirumab in
Asian and non-Asian patients with advanced hepatocellular carcinoma andelevated alpha-fetoprotein: pooled individual data analysis of two randomized
studies. Liver Cancer, 2020 (Epub ahead of print). (IF=9.720)
184. Kudo M*: A new era of systemic therapy for intermediate and advanced stage
hepatocellular carcinoma. Hepatobil Surg Nutr, 2020 (Epub ahead of print).
(IF=5.296)
185. Kudo M*: Better efficacy of ramucirumab in Japanese patients than in the
global population with unresectable hepatocellular carcinoma. Liver Cancer,
2020 (Epub ahead of print). (IF=9.720)
186. Llovet JM, Villanueva A, Marrero JA, Schwartz M, Meyer T, Galle P, Lencioni
R, Greten TF, Kudo M, Mandrekar SJ, Zhu AX, Finn RS, Roberts LR, for Panelof AASLD experts on Trial Design in HCC: Trial design and endpoints inhepatocellular carcinoma: AASLD consensus conference. Hepatology, 2020
(Epub ahead of print). (IF=14.679)
187. Kudo M*, Morimoto M, Moriguchi M, Izumi N, Takayama T, Yoshiji H, Hino K,
Oikawa T, Chiba T, Motomura K, Kato J, Yasuchika K, Ido A, Sato T, Ikawa Y,
Ueshima K, Ikeda M, Okusaka T, Tamura K, Furuse J: A randomized, doubleblind, placebo-controlled, phase III study of tivantinib in Japanese patientswith MET-high hepatocellular carcinoma. Cancer Sci, 2020 (Epub ahead ofprint). (IF=4.966)
188. Kudo M*: Recent advances in systemic therapy for hepatocellular carcinoma inan aging society: 2020 update. Liver Cancer, 2020 (Epub ahead of print).
(IF=9.720)