Annual Report 2021
Department of Hepatobiliary and Pancreatic Oncology
Masafumi Ikeda, Shuichi Mitsunaga, Hiroshi Imaoka, Mitsuhito Sasaki, Kazuo Watanabe, Taro Shibuki, Kei Okumura, Hiroki Eguchi, Kanae Inoue, Tomonao Taira, Sunsuke Imamura
Introduction
The Department of Hepatobiliary and Pancreatic Oncology is responsible for the diagnosis and treatment of patients with hepatic, biliary, and pancreatic cancers as well as interventional management by endoscopic or percutaneous procedures (Table 1). Our goal is to provide high-quality cancer treatment with adequate palliative care, and to develop novel and effective treatments and procedures through well-designed clinical trials and research.
Table 1. Number of cancer patients
The Team and What We Do
Our department is composed of five staff oncologists and six residents, with an average of 40 beds in the hospital. These doctors are divided into two teams and each team determines daily treatment plans for each admitted patient, and all doctors discuss overall treatment strategy for all admitted patients in our department once a week. The main treatment strategies for individual patients are discussed in weekly tumor board conferences attended by medical oncologists, surgeons, radiologists, radiation oncologists, and pharmacists. Furthermore, we are also responsible for endoscopic abdominal ultrasonographic examinations, endoscopic or percutaneous ultrasound-guided biopsies of abdominal masses, local ablative therapy for liver tumors, endoscopic or percutaneous biliary drainage, abscess drainage and stenting for obstructive jaundice, etc. (Table 2).
Research activities
Hepatocellular carcinoma (HCC)
Systemic therapy is one of the most important treatment modalities for advanced-stage hepatocellular carcinoma (HCC), and, in recent years, it has made rapid progress. At present, all six regimens, including atezolizumab plus bevacizumab, sorafenib, and lenvatinib as a first-line treatment, regorafenib, cabozantinib, and ramucirumab as a second or later line treatment, are available in clinical practice for HCC. Recently, it was also reported that the phase III trial of durvalumab plus tremelimumab achieved the primary endpoint, and this combination therapy will also be available in clinical practice. How to utilize these regimens is an important issue to be solved in daily practice in the future. Biliary tract cancer (BTC)
Biliary tract cancer (BTC)
Systemic therapy for BTC is given to perioperative adjuvant therapy and unresectable patients. As first-line systemic therapy, gemcitabine (Gem) plus cisplatin therapy (GC), Gem plus S-1 therapy (GS), and Gem plus cisplatin plus S-1 therapy (GCS) are established as standard treatments in Japan, and recently, GC plus durvalumab has been reported to have better survival benefit than GC. In addition, favorable results on efficacy with an IDH inhibitor for IDH1 mutations, FGFR inhibitors for FGFR2 fusion, and dabrafenib plus trametinib, a BRAF inhibitor plus MEK inhibitor for BRAF-V600E mutation and HER2 inhibitor for HER2 positive have been reported in the development of molecular-targeted agents based on genomic alterations, and among them, the FGFR inhibitor pemigatinib has been only reimbursed in Japan in 2021. Further development of combination therapy of cytotoxic agents, molecular targeted agents and immunotherapy are expected in first-line and second-line treatment for unresectable BTC. Neuroendocrine tumor (NET)
Neuroendocrine tumor (NET)
For unresectable NETs, drug therapy is performed, with a wide range of treatment options, such as a somatostatin analogue, everolimus, and streptozocin. Sunitinib is also used for NETs originating from the pancreas. Additionally, peptide receptor radionucleotide therapy (PRRT) was approved for NETs expressing somatostatin receptors in Japan in 2021. On the other hand, platinum-based chemotherapy is used for neuroendocrine carcinoma.
Pancreatic cancer (PC)
For unresectable PC, Gem plus nab-paclitaxel and FOLFIRINOX for first-line chemotherapy, nano-liposomal irinotecan plus 5-fluorouracil / leucovorin for second-line chemotherapy, and olaparib as maintenance therapy for platinum-sensitive patients with germline BRCA mutations, have been approved in Japan. However, no significant progress was made this year. Precision medicine based on genome alterations has been actively performed and pembrolizumab for MSI-H and TMB-H and larotrectinib, and entrectinib for NTRK fusion are covered by insurance, but patients with these alterations are extremely rare. Recently, sotorasib and adagrasib for KRASG12C mutation, zenocutuzumab for NRG-1 fusion gene, tocilizumab aiming to release resistance to chemotherapy, etc. are of interest and being developed.
Clinical trials
Ninety clinical trials (sponsored: 46 trials, investigator-initiated: 43 trials) are ongoing, and 10 clinical trials (sponsored: 3 trials, investigator-initiated: 7 trials) are being planned for the upcoming year.
HCC
Lenvatinib plus pembrolizumab was a highly promising regimen, with high response rates, prolonged progression-free survival and overall survival reported in phase Ib trials. However, a phase III trial comparing lenvatinib plus pembrolizumab with lenvatinib plus placebo for unresectable hepatocellular carcinoma could not demonstrate their survival benefit. The development of new regimens is actively underway via triplet and quatro regimens as well as doublet regimens, such as combination therapy of VEGFR-targeted multi-kinase inhibitors or antibodies, and immune checkpoint inhibitors.
A prospective observational study, PRISM, was conducted with the aim of collecting real-world data in Japan and establishing real-world evidence, and recently, the planned sample size of 1000 patients was reached. Some clinical trials of new agents anti-Glypican3/CD3 bispecific antibody (ERY974) as the first-line therapy, and a phase I trial of lenvatinib plus beta-catenin modulator (E7386) as the second- or later-line therapy are underway.
BTC
The enrollments of some sponsored trials of GC plus immune checkpoint inhibitors, including durvalumab, bintrafusp alfa and pembrolizumab, as first-line chemotherapy have been completed. Among them, GC plus durvalumab demonstrated survival benefit, and will be reimbursed in Japan. The enrollments of some investigator-initiated trials of nivolumab plus lenvatinib, DS8201a for HER2 positive, and niraparib for BRCA mutation in patients with advanced BTCs refractory to Gem-based chemotherapy were terminated. For patients with occupational cholangiocarcinoma, a phase II trial of nivolumab was also ongoing as an investigator-initiated trial. Some sponsored trials of JPH203 for anti-cancer drug targeting L-type amino acid transporter 1, E7090 for FGFR2 fusion, LY3410738 for IDH1 mutation, etc. for second- or later-line advanced BTCs were underway.
PC
Some investigator-initiated trials of a phase II/III trial of neoadjuvant S-1 and concurrent radiotherapy vs. Gem plus nab-paclitaxel for borderline resectable PC (GABARNANCE), a phase III trial of concurrent S-1 and radiotherapy combined with nivolumab vs. S-1 and radiotherapy alone for locally advanced or borderline resectable PC (JCOG1908E), Gem plus nab-paclitaxel vs. modified FOLFIRINOX vs. S-IROX for metastatic PC (JCOG1611), as the first-line setting and a phase II trial of nano-liposomal-irinotecan plus S-1 for metastatic PC as the second-line setting were ongoing. Some sponsored trials of FOLFIRINOX or Gem plus nab-paclitaxel with molecular targeted agents or immune checkpoint inhibitors were initiated and in recruitment.
Neuroendocrine tumor
A phase III trial of everolimus plus lanreotide vs. everolimus (investigator-initiated trial) and a phase II trial of surufatinib (sponsored trial) are ongoing for gastroentero and pancreatic neuroendocrine tumor.
Others
Some investigator-initiated studies using circulating tumor DNA are ongoing for hepatobiliary & pancreatic cancer.
Education
For our residents, daily training is provided through group discussions on the daily practice of management of inpatients and outpatients. Also, they can learn about the indications, administration and management of the adverse events from loco-regional treatments to systemic chemotherapy for hepatic, biliary, and pancreatic cancer patients and the accompanying procedures to undertake diagnosis and interventional management, and provide outpatient care. In addition, they can give presentations on their research in domestic and overseas meetings and write papers in English under the instruction of staff physicians.
Future Prospects
The number of patients with HCC in Japan is on the decline, and the number of patients with BTC has plateaued. However, the incidence rate in these cancers remains high compared to other countries, and the efficacy of standard treatments for them is limited. The development of new agents is urgently needed in Japan. Therefore, we actively participate in drug development from the early phases, lead domestic clinical trials, and also plan international clinical trials in collaboration with overseas investigators. It is also necessary to develop biomarker research and endoscopic management alongside cancer treatment.
List of papers published in 2021
Journal
1. Yamada I, Morizane C, Okusaka T, Mizusawa J, Kataoka T, Ueno M, Ikeda M, Okano N, Todaka A, Shimizu S, Mizuno N, Sekimoto M, Tobimatsu K, Yamaguchi H, Nishina T, Shirakawa H, Kojima Y, Oono T, Kawamoto Y, Furukawa M, Iwai T, Sudo K, Okamura K, Yamashita T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J. The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: an exploratory analysis of JCOG1113. Scientific reports, 12:987, 2022
2. Azemoto N, Ueno M, Yanagimoto H, Mizuno N, Kawamoto Y, Maruki Y, Watanabe K, Suzuki R, Kaneko J, Hisada Y, Sato H, Kobayashi S, Miyata H, Furukawa M, Mizukami T, Miwa H, Ohno Y, Tsuji K, Tsujimoto A, Nagano H, Okuyama H, Asagi A, Okano N, Ishii H, Morizane C, Ikeda M, Furuse J. Endoscopic duodenal stent placement versus gastrojejunostomy for unresectable pancreatic cancer patients with duodenal stenosis before introduction of initial chemotherapy (GASPACHO study): a multicenter retrospective study. Japanese journal of clinical oncology, 52:134-142, 2022
3. Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. Journal of hepatology, 76:862-873, 2022
4. Yachida S, Totoki Y, Noë M, Nakatani Y, Horie M, Kawasaki K, Nakamura H, Saito-Adachi M, Suzuki M, Takai E, Hama N, Higuchi R, Hirono S, Shiba S, Kato M, Furukawa E, Arai Y, Rokutan H, Hashimoto T, Mitsunaga S, Kanda M, Tanaka H, Takata S, Shimomura A, Oshima M, Hackeng WM, Okumura T, Okano K, Yamamoto M, Yamaue H, Morizane C, Arihiro K, Furukawa T, Sato T, Kiyono T, Brosens LAA, Wood LD, Hruban RH, Shibata T. Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System. Cancer discovery, 12:692-711, 2022
5. Nakajima H, Harano K, Nakai T, Kusuhara S, Nakao T, Funasaka C, Kondoh C, Matsubara N, Naito Y, Hosono A, Mitsunaga S, Ishii G, Mukohara T. Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer. Breast, 61:136-144, 2022
6. Shibuki T, Mizuta T, Shimokawa M, Koga F, Ueda Y, Nakazawa J, Komori A, Otsu S, Arima S, Fukahori M, Makiyama A, Taguchi H, Honda T, Mitsugi K, Nio K, Ide Y, Ureshino N, Shirakawa T, Otsuka T. Prognostic nomogram for patients with unresectable pancreatic cancer treated with gemcitabine plus nab-paclitaxel or FOLFIRINOX: A post-hoc analysis of a multicenter retrospective study in Japan (NAPOLEON study). BMC Cancer. 2:19, 2022
7. Koga F, Kawaguchi Y, Shimokawa M, Murayama K, Nakashita S, Oza N, Ureshino N, Takahashi H, Ueda Y, Nakazawa J, Komori A, Otsu S, Arima S, Fukahori M, Makiyama A, Taguchi H, Honda T, Shibuki T, Nio K, Ide Y, Mizuta T, Shirakawa T, Otsuka T, Mitsugi K. Gemcitabine plus nab-paclitaxel in older patients with metastatic pancreatic cancer: A post-hoc analysis of the real-world data of a multicenter study (the NAPOLEON study). J Geriatr Oncol, 13:82-87, 2022
8. Ueno M, Morizane C, Okusaka T, Mizusawa J, Kataoka T, Ikeda M, Ozaka M, Okano N, Sugimori K, Todaka A, Shimizu S, Mizuno N, Yamamoto T, Sano K, Tobimatsu K, Katanuma A, Miyamoto A, Yamaguchi H, Nishina T, Shirakawa H, Kojima Y, Oono T, Kawamoto Y, Furukawa M, Iwai T, Sudo K, Miyakawa H, Yamashita T, Yasuda I, Takahashi H, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J. Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113. Scientific reports, 11:12885, 2021
9. Kobayashi S, Ueno M, Ogawa G, Fukutomi A, Ikeda M, Okusaka T, Sato T, Ito Y, Kadota T, Ioka T, Sugimori K, Sata N, Nakamori S, Shimizu K, Mizuno N, Ishii H, Furuse J. Impact of Renal Function on S-1 + Radiotherapy for Locally Advanced Pancreatic Cancer: An Integrated Analysis of Data From 2 Clinical Trials. Pancreas, 50:965-971, 2021
10. Hijioka S, Morizane C, Ikeda M, Ishii H, Okusaka T, Furuse J. Current status of medical treatment for gastroenteropancreatic neuroendocrine neoplasms and future perspectives. Japanese journal of clinical oncology, 51:1185-1196, 2021
11. Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, Qin S, Tai DW, Lim HY, Yau T, Yong WP, Cheng AL, Gasbarrini A, Damian S, Bruix J, Borad M, Bendell J, Kim TY, Standifer N, He P, Makowsky M, Negro A, Kudo M, Abou-Alfa GK. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 39:2991-3001, 2021
12. Sasaki M, Ueno H, Mitsunaga S, Ohba A, Hosoi H, Kobayashi S, Ueno M, Terazawa T, Goto M, Inoue D, Namiki S, Sakamoto Y, Kondo S, Morizane C, Ikeda M, Okusaka T. A phase II study of FOLFIRINOX with primary prophylactic pegfilgrastim for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. International journal of clinical oncology, 26:2065-2072, 2021
13. Ito T, Masui T, Komoto I, Doi R, Osamura RY, Sakurai A, Ikeda M, Takano K, Igarashi H, Shimatsu A, Nakamura K, Nakamoto Y, Hijioka S, Morita K, Ishikawa Y, Ohike N, Kasajima A, Kushima R, Kojima M, Sasano H, Hirano S, Mizuno N, Aoki T, Aoki T, Ohtsuka T, Okumura T, Kimura Y, Kudo A, Konishi T, Matsumoto I, Kobayashi N, Fujimori N, Honma Y, Morizane C, Uchino S, Horiuchi K, Yamasaki M, Matsubayashi J, Sato Y, Sekiguchi M, Abe S, Okusaka T, Kida M, Kimura W, Tanaka M, Majima Y, Jensen RT, Hirata K, Imamura M, Uemoto S. JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis. Journal of gastroenterology, 56:1033-1044, 2021
14. Naito Y, Kuboki Y, Ikeda M, Harano K, Matsubara N, Toyoizumi S, Mori Y, Hori N, Nagasawa T, Kogawa T. Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study. Investigational new drugs, 39:1568-1576, 2021
15. Chida K, Kawazoe A, Kawazu M, Suzuki T, Nakamura Y, Nakatsura T, Kuwata T, Ueno T, Kuboki Y, Kotani D, Kojima T, Taniguchi H, Mano H, Ikeda M, Shitara K, Endo I, Yoshino T. A Low Tumor Mutational Burden and PTEN Mutations Are Predictors of a Negative Response to PD-1 Blockade in MSI-H/dMMR Gastrointestinal Tumors. Clinical cancer research: an official journal of the American Association for Cancer Research, 27:3714-3724, 2021
16. Naitoh I, Kamisawa T, Tanaka A, Nakazawa T, Kubota K, Takikawa H, Unno M, Masamune A, Kawa S, Nakamura S, Okazaki K. Clinical characteristics of immunoglobulin IgG4-related sclerosing cholangitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 53:1308-1314, 2021
17. Suzuki H, Mitsunaga S, Ikeda M, Aoyama T, Yoshizawa K, Yoshimatsu H, Kawai N, Masuda M, Miura T, Ochiai A. Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer. Cancers, 13:2021
18. Furuse J, Ueno M, Ikeda M. Systemic therapy for hepatocellular carcinoma: current status and future perspectives. Japanese journal of clinical oncology, 51:1363-1371, 2021
19. Imaoka H, Sasaki M, Hashimoto Y, Watanabe K, Miyazawa S, Shibuki T, Mitsunaga S, Ikeda M. Impact of Endoscopic Ultrasound-Guided Tissue Acquisition on Decision-Making in Precision Medicine for Pancreatic Cancer: Beyond Diagnosis. Diagnostics (Basel, Switzerland), 11:2021
20. Kudo M, Finn RS, Morimoto M, Rau KM, Ikeda M, Yen CJ, Galle PR, Llovet JM, Daniele B, Lim HY, McIlwain DW, Yoshikawa R, Nakamura K, Liang K, Wang C, Abada P, Widau RC, Zhu AX. Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2). Liver cancer, 10:451-460, 2021
21. Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. The Lancet. Oncology, 22:991-1001, 2021
22. Kudo M, Ikeda M, Galle PR, Yamashita T, Finn RS, Liang K, Wang C, Sakaguchi S, Abada P, Widau RC, Zhu AX. Ramucirumab in patients with advanced hepatocellular carcinoma and elevated α-fetoprotein: Outcomes by treatment-emergent ascites. Hepatology research: the official journal of the Japan Society of Hepatology, 51:715-721, 2021
23. Maruki Y, Morizane C, Arai Y, Ikeda M, Ueno M, Ioka T, Naganuma A, Furukawa M, Mizuno N, Uwagawa T, Takahara N, Kanai M, Asagi A, Shimizu S, Miyamoto A, Yukisawa S, Kadokura M, Kojima Y, Furuse J, Nakajima TE, Sudo K, Kobayashi N, Hama N, Yamanaka T, Shibata T, Okusaka T. Correction to: Molecular detection and clinicopathological characteristics of advanced/recurrent biliary tract carcinomas harboring the FGFR2 rearrangements: a prospective observational study (PRELUDE Study). Journal of gastroenterology, 56:297, 2021
24. Ueno M, Morizane C, Furukawa M, Sakai D, Komatsu Y, Nakai Y, Tsuda M, Ozaka M, Mizuno N, Muto M, Fukutomi A, Ikeda M, Tsuji A, Katanuma A, Moriwaki T, Kajiwara T, Ishii H, Negoro Y, Shimizu S, Nemoto N, Kobayashi S, Makino K, Furuse J. A randomized, double-blind, phase II study of oral histone deacetylase inhibitor resminostat plus S-1 versus placebo plus S-1 in biliary tract cancers previously treated with gemcitabine plus platinum-based chemotherapy. Cancer medicine, 10:2088-2099, 2021
25. Finn RS, Kudo M, Cheng AL, Wyrwicz L, Ngan RKC, Blanc JF, Baron AD, Vogel A, Ikeda M, Piscaglia F, Han KH, Qin S, Minoshima Y, Kanekiyo M, Ren M, Dairiki R, Tamai T, Dutcus CE, Ikezawa H, Funahashi Y, Evans TRJ. Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase III REFLECT Study. Clinical cancer research: an official journal of the American Association for Cancer Research, 27:4848-4858, 2021
26. Wick A, Bähr O, Schuler M, Rohrberg K, Chawla SP, Janku F, Schiff D, Heinemann V, Narita Y, Lenz HJ, Ikeda M, Ando Y, Wick W, Steinbach JP, Burger MC, Wenger K, Lassen U, Sankhala KK, Roggia C, Genvresse I, Munhoz C, Rentzsch C, Reschke S, Langer S, Wagner M, Kaulfuss S, Cai C, Lagkadinou E, Jeffers M, Peña C, Tabatabai G. Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors. Clinical cancer research: an official journal of the American Association for Cancer Research, 27:2723-2733, 2021
27. Imaoka H, Ikeda M, Maehara K, Umemoto K, Ozaka M, Kobayashi S, Terashima T, Inoue H, Sakaguchi C, Tsuji K, Shioji K, Okamura K, Tsujimoto A, Nakamura I, Shirakawa H, Furukawa M, Ueno M, Morizane C, Furuse J. Risk stratification and prognostic factors in patients with unresectable undifferentiated carcinoma of the pancreas. Pancreatology: official journal of the International Association of Pancreatology (IAP)... [et al.], 21:738-745, 2021
28. Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S, Toyoda H, Imai Y, Hiraoka A, Ikeda M, Izumi N, Moriguchi M, Ogasawara S, Minami Y, Ueshima K, Murakami T, Miyayama S, Nakashima O, Yano H, Sakamoto M, Hatano E, Shimada M, Kokudo N, Mochida S, Takehara T. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver cancer, 10:181-223, 2021
29. Okano N, Furuse J, Ueno M, Morizane C, Yamanaka T, Ojima H, Ozaka M, Sasaki M, Takahara N, Nakai Y, Kobayashi S, Morimoto M, Hosoi H, Maeno S, Nagashima F, Ikeda M, Okusaka T. Multicenter Phase II Trial of Axitinib Monotherapy for Gemcitabine-Based Chemotherapy Refractory Advanced Biliary Tract Cancer (AX-BC Study). The oncologist, 26:97-e201, 2021
30. Ito T, Masui T, Ikeda M, Kobayashi N, Komoto I, Hosono M, Uemoto S. Statements for peptide receptor radionuclide therapy from JNETS. Japanese J Gastroenterol Res., 2:1070-1071, 2021
31. Hashimoto Y, Kumahara K, Ueda Y, Tahara M. Cholangioscopic finding of severe hemorrhagic cholangitis associated with immune-related adverse events. Gastrointestinal endoscopy, 94:859-860, 2021
32. Ikeda M, Okusaka T, Ohno I, Mitsunaga S, Kondo S, Ueno H, Morizane C, Gemmoto K, Suna H, Ushida Y, Furuse J. Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma. Immunotherapy, 13:371-385, 2021
33. Ishii T, Suzuki A, Kuwata T, Hisamitsu S, Hashimoto H, Ohara Y, Yanagihara K, Mitsunaga S, Yoshino T, Kinoshita T, Ochiai A, Shitara K, Ishii G. Drug-exposed cancer-associated fibroblasts facilitate gastric cancer cell progression following chemotherapy. Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 24:810-822, 2021
34. Otsuka T, Shirakawa T, Shimokawa M, Koga F, Kawaguchi Y, Ueda Y, Nakazawa J, Komori A, Otsu S, Arima S, Fukahori M, Okabe Y, Makiyama A, Taguchi H, Honda T, Shibuki T, Nio K, Ide Y, Mizuta T, Mitsugi K, Ureshino N. A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study. Int J Clin Oncol, 26:941-950, 2021
35. Taguchi H, Otsuka T, Shimokawa M, Arima S, Hashimoto S, Ido A, Koga F, Ueda Y, Nakazawa J, Komori A, Otsu S, Fukahori M, Makiyama A, Honda T, Shibuki T, Mizuta T, Mitsugi K, Nio K, Ide Y, Ureshino N, Shirakawa T. Gemcitabine Plus Nanoparticle Albumin-bound Paclitaxel Versus FOLFIRINOX for Recurrent Pancreatic Cancer After Resection. Anticancer Res, 41:3573-3582, 2021
36. Tatematsu N, Naito T, Okayama T, Tsuji T, Iwamura A, Tanuma A, Mitsunaga S, Miura S, Omae K, Mori K, Takayama K. Development of home-based resistance training for older patients with advanced cancer: The exercise component of the nutrition and exercise treatment for advanced cancer program. J Geriatr Oncol, 12:952-955, 2021