664 results on '"Masafumi Ikeda"'
Search Results
2. Phase I study of the safety and clinical activity of the interleukin-8 inhibitor AMY109 combined with atezolizumab in patients with advanced solid cancers
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Yasutoshi Kuboki, Masafumi Ikeda, Shigehisa Kitano, Takafumi Koyama, Noboru Yamamoto, Yuki Yamaguchi, Yuki Nakagawa, Takaaki Ishida, Hidenori Mizugaki, Takatsugu Narikiyo, Ryoko Takubo, Chika Ogami, and Mayuko Sekiya
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Immunosuppressive conditions within the tumor microenvironment (TME) can allow tumors to evade the immune system, including by hampering programmed death ligand 1 (PD-L1) inhibitor activity. Interleukin (IL)-8 contributes to immunosuppression and fibrosis in the TME. AMY109, a humanized anti-IL-8 monoclonal antibody, reduced fibrosis and decreased immunosuppressive cells in tumor tissue in animals. Combining AMY109 with atezolizumab (anti-PD-L1 antibody) may enhance its antitumor effects by making the TME more favorable to PD-L1 inhibition.Methods This multicenter, open-label, dose-escalation study evaluated the safety, pharmacokinetics, and clinical activity of AMY109 plus atezolizumab in patients with previously treated advanced solid tumors and Eastern Cooperative Oncology Group performance status 0 or 1. Patients received AMY109 (2–45 mg/kg) plus atezolizumab (1200 mg) intravenously every 3 weeks in part 1, and AMY109 (15–45 mg/kg) plus atezolizumab (1200 mg) in part 2. Primary endpoints were the dose-limiting toxicity (DLT), safety, and pharmacokinetics of AMY109 and atezolizumab in Part 1, and safety and antitumor activity per investigator-assessed Response Evaluation Criteria in Solid Tumors 1.1 in part 2. Exploratory analyses of peripheral and tumor biomarker were conducted.Results Overall, 38 patients (18 in part 1 and 20 in part 2) were enrolled. Part 1 showed no DLTs and a dose-proportional increase in AMY109 exposure over 2–45 mg/kg, with no apparent change in mean atezolizumab serum concentrations across AMY109 dosing. Plasma IL-8 concentration accumulation was seen in all dose cohorts after AMY109 initiation. Grade 1–3 treatment-related adverse events (AEs) occurred in 21 of 38 patients (55%). Treatment-related serious AEs occurred in two patients (5%). No AEs led to treatment withdrawal. Partial responses (PRs) occurred in 2 of 38 patients; the confirmed objective response rate was 5%. These patients had uterocervical and pancreatic cancer, respectively, and had been treated for >500 days at the cut-off date: one had received 45 mg/kg of AMY109 throughout, and the other received 30 mg/kg of AMY109 until cycle 5, then 45 mg/kg thereafter.Conclusions With no DLTs, AMY109 plus atezolizumab was well tolerated in patients with advanced solid tumors, with no new safety signals. AMY109 showed a dose-proportional increase in exposure. The PRs in two patients were durable.
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- 2024
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3. Reply to the letter regarding ‘Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 Study’
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Masatoshi Kudo, Kaoru Tsuchiya, Tatsuya Yamashita, Hironori Koga, Yuki Nakagawa, and Masafumi Ikeda
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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4. Correction: Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study
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Taro Shibuki, Mitsuhito Sasaki, Shota Yamaguchi, Kanae Inoue, Tomonao Taira, Tomoyuki Satake, Kazuo Watanabe, Hiroshi Imaoka, Shuichi Mitsunaga, Takeshi Fujisawa, Kento Tomizawa, Hidekazu Oyoshi, Masaki Nakamura, Hidehiro Hojo, and Masafumi Ikeda
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2023
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5. Development of a nomogram to predict survival in advanced biliary tract cancer
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Hiroshi Imaoka, Masafumi Ikeda, Shogo Nomura, Chigusa Morizane, Takuji Okusaka, Masato Ozaka, Satoshi Shimizu, Kentaro Yamazaki, Naohiro Okano, Kazuya Sugimori, Hirofumi Shirakawa, Nobumasa Mizuno, Sohei Satoi, Hironori Yamaguchi, Rie Sugimoto, Kunihito Gotoh, Keji Sano, Akinori Asagi, Kazuyoshi Nakamura, and Makoto Ueno
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Medicine ,Science - Abstract
Abstract The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno’s concordance index was 0.661 (95% confidence interval [CI] 0.629–0.696) in the training set and 0.640 (95% CI 0.566–0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians’ prognosis-based decision-making.
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- 2023
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6. Covered self‐expandable metallic stent placement for tumor bleeding from duodenal invasion in patients with unresectable pancreatic cancer
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Taro Shibuki, Ko Fukushi, Kanae Inoue, Tomonao Taira, Tomoyuki Satake, Kazuo Watanabe, Mitsuhito Sasaki, Hiroshi Imaoka, Shuichi Mitsunaga, and Masafumi Ikeda
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duodenal stent ,pancreatic cancer ,SEMS ,self‐expandable metallic stent ,tumor bleeding ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Patients with unresectable pancreatic cancer often present with duodenal bleeding, a potentially life‐threatening complication. In our case series of six unresectable pancreatic cancer patients with tumor bleeding, we explored the efficacy and safety of placement of a covered self‐expandable metallic stent in the duodenum as a treatment option; we achieved a hemostasis rate of 67% (4/6), with a rebleeding rate of 50% (2/4). No complications occurred with stent placement, except for food impaction in one patient. Covered self‐expandable metallic stent placement is a moderately effective treatment option for tumor bleeding in patients with unresectable pancreatic cancer. Although its hemostatic efficacy is limited, covered self‐expandable metallic stent placement is safe and beneficial in some cases, warranting consideration in this disease setting with limited treatment options.
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- 2024
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7. Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study
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Taro Shibuki, Mitsuhito Sasaki, Shota Yamaguchi, Kanae Inoue, Tomonao Taira, Tomoyuki Satake, Kazuo Watanabe, Hiroshi Imaoka, Shuichi Mitsunaga, Takeshi Fujisawa, Kento Tomizawa, Hidekazu Oyoshi, Masaki Nakamura, Hidehiro Hojo, and Masafumi Ikeda
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Palliative radiotherapy ,Bleeding ,Pancreatic cancer ,Hemostasis ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Patients with unresectable pancreatic cancer (PC) sometimes experience gastrointestinal bleeding (GIB) due to tumor invasion of the gastrointestinal tract (tumor bleeding); no standard treatment has been established yet for this complication. Palliative radiotherapy (PRT) could be promising, however, there are few reports of PRT for tumor bleeding in patients with unresectable PC. Therefore, we evaluated the outcomes of PRT for tumor bleeding in patients with unresectable PC. Methods We reviewed the medical records of patients with unresectable PC diagnosed at our institution between May 2013 and January 2022, and identified patients with endoscopically confirmed tumor bleeding who had received PRT. PRT was administered at a total dose of 30 Grays (Gy) in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction, and the dose selection was left to the discretion of the attending radiation oncologists. Results During the study period, 2562 patients were diagnosed as having unresectable PC at our hospital, of which 225 (8.8%) developed GIB. Among the 225 patients, 63 (2.5%) were diagnosed as having tumor bleeding and 20 (0.8%) received PRT. Hemostasis was achieved in 14 of the 20 patients (70%) who received PRT, and none of these patients developed grade 3 or more adverse events related to the PRT. The median time to hemostasis was 8.5 days (range 7–14 days). The rebleeding rate was 21.4% (3/14). The median hemoglobin level increased significantly (p
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- 2023
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8. A Phase 1b Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116
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Masatoshi Kudo, Richard S. Finn, Masafumi Ikeda, Max W. Sung, Ari D. Baron, Takuji Okusaka, Masahiro Kobayashi, Hiromitsu Kumada, Shuichi Kaneko, Marc Pracht, Tim Meyer, Satoshi Nagao, Kenichi Saito, Kalgi Mody, Zahra Ramji, Leonid Dubrovsky, and Josep M. Llovet
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Treatment with lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh
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- 2023
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9. Interleukin 6/gp130 axis promotes neural invasion in pancreatic cancer
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Hidetaka Suzuki, Shuichi Mitsunaga, Masafumi Ikeda, Takao Aoyama, Kazumi Yoshizawa, Masayuki Yamaguchi, Masami Suzuki, Minoru Narita, Toshikatsu Kawasaki, and Atsushi Ochiai
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mouse models ,pancreatic cancer ,pancreatic ductal adenocarcinoma ,translational research ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Nerve invasion (N‐inv) is an important prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Elucidation of circulating N‐inv stimulators could provide deeper insights and novel perspectives for PDAC therapy. The interleukin (IL)‐6/gp130 axis was evaluated in this study as a candidate N‐inv stimulator. Methods A human pancreatic cancer (PC) cell, Capan‐1, was confirmed to have the stimulant activity of IL‐6/gp130 axis through the evaluation of mRNA, cell surface protein and intracellular protein levels and chemotaxis and wound healing assay. The upregulation of IL‐6/gp130 axis was evaluated using tumor‐derived IL‐6 level and intratumoral pSTAT3 expression in N‐inv of murine sciatic nerves by intraneural injection of Capan‐1 cell (N‐inv model) and using resected pancreatic cancer tissue and clinical data from 46 PDAC patients. Results mRNA and protein expressions of IL‐6 and IL‐6 receptor were found in whole cell lysate and condition medium from PC cell. Cell surface protein expression of gp130 were clearly detected on PC cell. IL‐6 promoted migration and chemotaxis of PC cell. Serum IL‐6 and tumoral IL‐6 mRNA levels in N‐inv model mice were significantly higher than those in subcutaneous tumor mice (p = 0.004 and p = 0.002, respectively). Silencing of IL‐6 and gp130 on PC cell and administration of an anti‐IL‐6 receptor antibody, tocilizumab, suppressed N‐inv, compared to each control (p = 0.070, p = 0.118 and p = 0.122, respectively). In PDAC patients, the high‐N‐inv group showed poor prognosis (p =0.059) and elevated serum levels of IL‐6 and C‐reactive protein, synthesis of which is promoted by IL‐6, compared to those in the low‐N‐inv group (p = 0.006 and p = 0.075, respectively). Tumoral gp130 expression at N‐inv was higher than that in the primary pancreatic tumor (p = 0.026). Conclusion Biological activity of IL‐6/gp130 axis promoted N‐inv in murine model and was upregulated in PDAC patients with severe N‐inv. This study is the first evidence that the IL‐6/gp130 axis offers a potential therapeutic target in PDAC with N‐inv.
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- 2022
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10. Incidence of and risk factors for severe neutropenia during treatment with the modified FOLFIRINOX therapy in patients with advanced pancreatic cancer
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Ai Irisawa, Misaki Takeno, Kazuo Watanabe, Hideaki Takahashi, Shuichi Mitsunaga, and Masafumi Ikeda
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Medicine ,Science - Abstract
Abstract Although FOLFIRINOX (l-Leucovorin/5-FU/Irinotecan/Oxaliplatin) is established as one of the standard therapies for patients with metastatic pancreatic cancer, the modified FOLFIRINOX (mFOLFIRINOX) is often used in clinical practice to reduce the incidence of toxicities. Febrile neutropenia (FN) and severe neutropenia during FOLFIRINOX are especially frequently observed in Japanese patients. In this study, we evaluated the incidence of FN and severe neutropenia, and explored the risk factors for severe neutropenia in patients receiving treatment with mFOLFIRINOX. The data of patients who had received mFOLFIRINOX between December 2013 and December 2014 at the National Cancer Center Hospital East were reviewed retrospectively. We graded the neutropenia severity and defined ≥ Grade 3 neutropenia as severe neutropenia. Univariate and multivariate analysis were undertaken to evaluate the associations with risk of development of severe neutropenia. A total of 122 patients were enrolled in this study. Sixty two patients (51%) and 10 patients (8%) developed severe neutropenia and FN, respectively. Multivariate analysis identified a low baseline white blood cell count (odds ratio [OR], 14.50; 95% confidence interval (CI), 3.27–111.14; p = 0.002) and presence of heterozygosity for UGT1A1*28 or UGT1A1*6 polymorphism (OR, 2.84; 95% CI, 1.18–7.17; p = 0.023) as independent risk factors for severe neutropenia. The incidences of severe neutropenia and FN in patients receiving mFOLFIRINOX in our clinical practice were comparable to previous reports. The risk factors for severe neutropenia in patients receiving mFOLFIRINOX were a low baseline white blood cell count and presence of heterozygosity for UGT1A1*28 or UGT1A1*6 polymorphism.
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- 2022
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11. Case Report: Atezolizumab plus bevacizumab for combined hepatocellular-cholangiocarcinoma
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Tomoyuki Satake, Taro Shibuki, Kazuo Watanabe, Mitsuhito Sasaki, Hiroshi Imaoka, Shuichi Mitsunaga, Motohiro Kojima, and Masafumi Ikeda
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combined hepatocellular-cholangiocarcinoma ,atezolizumab ,bevacizumab ,immunotherapy ,case series ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare subtype of primary liver cancers. Therapeutic strategies for patients with cHCC-CCA are limited, and no standard systemic treatment has been established for unresectable cHCC-CCA. Here, we present six cases of cHCC-CCA treated with atezolizumab plus bevacizumab. We observed three partial responses and one stable disease as the best responses; two of these patients were still being treated with atezolizumab plus bevacizumab at the time of reporting (at least five months of treatment), whereas the remaining two patients were unable to continue treatment owing to adverse events. Atezolizumab plus bevacizumab may be an effective treatment for unresectable cHCC-CCA.
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- 2023
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12. A Phase 2, Prospective, Multicenter, Single-arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-stage Hepatocellular Carcinoma: TACTICS-L Trial
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Masatoshi Kudo, Kazuomi Ueshima, Issei Saeki, Toru Ishikawa, Yoshitaka Inaba, Naoki Morimoto, Hiroshi Aikata, Nobukazu Tanabe, Yoshiyuki Wada, Yasuteru Kondo, Masahiro Tsuda, Kazuhiko Nakao, Takanori Ito, Tetsuya Hosaka, Yusuke Kawamura, Teiji Kuzuya, Shunsuke Nojiri, Chikara Ogawa, Hironori Koga, Keisuke Hino, Masafumi Ikeda, Michihisa Moriguchi, Takashi Hisai, Kenichi Yoshimura, Junji Furuse, and Yasuaki Arai
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase II, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better ORR than sorafenib (jRCTs031180074). Patients and Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy, and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14–21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0–2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0–1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was PFS by RECICL, and secondary endpoints were time to untreatable progression, objective response rate (ORR), OS, and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (95% CI 25.1–31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (95% CI 35.5 months–NR). LEN-TACE achieved a high response rate and high CR rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR) were similar, and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the nonsimple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.
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- 2023
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13. Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 Study
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Masatoshi Kudo, Kaoru Tsuchiya, Yu-Yun Shao, Richard S. Finn, Peter R. Galle, Michel Ducreux, Ann-Lii Cheng, Tatsuya Yamashita, Hironori Koga, Ryosuke Take, Kyoko Yamada, Takashi Asakawa, Yuki Nakagawa, and Masafumi Ikeda
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atezolizumab ,bevacizumab ,unresectable hepatocellular carcinoma ,adverse events of special interest ,skipped bevacizumab ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.
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- 2023
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14. Conventional or Drug-Eluting Beads? Randomized Controlled Study of Chemoembolization for Hepatocellular Carcinoma: JIVROSG-1302
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Masafumi Ikeda, Yasuaki Arai, Yoshitaka Inaba, Toshihiro Tanaka, Shunsuke Sugawara, Yoshihisa Kodama, Takeshi Aramaki, Hiroshi Anai, Shinichi Morita, Yoshinori Tsukahara, Hiroshi Seki, Mikio Sato, Kenya Kamimura, Kimei Azama, Masakatsu Tsurusaki, Eiji Sugihara, Masaya Miyazaki, Tatsushi Kobayashi, and Miyuki Sone
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hepatocellular carcinoma ,transarterial chemoembolization ,drug-eluting beads ,ethiodized oil ,epirubicin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients with hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads (DEB-TACE) loaded with epirubicin or selective conventional TACE (cTACE) with epirubicin-ethiodized oil might be more effective for obtaining complete response(CR) in patients with HCC. Methods: Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events. Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, p = 0.0001), fatigue (5.1% vs. 15.8%, p = 0.0194), malaise (11.1% vs. 25.7%, p = 0.0103), appetite loss (12.1% vs. 28.7%, p = 0.0048), abdominal pain (12.1% vs. 23.8%, p = 0.0423), increased serum bilirubin (22.2% vs. 48.5%, p = 0.0002), hypoalbuminemia (43.4% vs. 60.3%, p = 0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, p < 0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, p < 0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm. Conclusions: Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of postembolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate postembolization syndrome.
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- 2022
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15. The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: an exploratory analysis of JCOG1113
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Ikuhiro Yamada, Chigusa Morizane, Takuji Okusaka, Junki Mizusawa, Tomoko Kataoka, Makoto Ueno, Masafumi Ikeda, Naohiro Okano, Akiko Todaka, Satoshi Shimizu, Nobumasa Mizuno, Mitsugu Sekimoto, Kazutoshi Tobimatsu, Hironori Yamaguchi, Tomohiro Nishina, Hirofumi Shirakawa, Yasushi Kojima, Takamasa Oono, Yasuyuki Kawamoto, Masayuki Furukawa, Tomohisa Iwai, Kentaro Sudo, Keiya Okamura, Tatsuya Yamashita, Naoya Kato, Kazuhiko Shioji, Kyouko Shimizu, Toshio Nakagohri, Ken Kamata, Hiroshi Ishii, Junji Furuse, and JCOG-HBPOG
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Medicine ,Science - Abstract
Abstract In the FUGA-BT trial (JCOG1113), gemcitabine plus S-1 (GS) showed non-inferiority to gemcitabine plus cisplatin (GC) in overall survival (OS) with good tolerance for patients with advanced biliary tract cancer (BTC). We performed a subgroup analysis focused on the elderly cohort of this trial. All 354 enrolled patients in JCOG1113 were classify into two groups;
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- 2022
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16. Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated With Atezolizumab Plus Bevacizumab
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Chiun Hsu, Michel Ducreux, Andrew X. Zhu, Shukui Qin, Masafumi Ikeda, Tae-You Kim, Peter R. Galle, Richard S. Finn, Ethan Chen, Ning Ma, Youyou Hu, Lindong Li, and Ann-Lii Cheng
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: In the Phase 3 IMbrave150 trial (NCT03434379), atezolizumab + bevacizumab demonstrated a clinically meaningful survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (HCC), including those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. We used IMbrave150 data to investigate the safety and risk of viral reactivation or flare in infected patients treated with atezolizumab + bevacizumab or sorafenib. Methods: Patients with unresectable HCC not previously treated with systemic therapy were randomized 2:1 to atezolizumab + bevacizumab or sorafenib. In this exploratory analysis, safety was continually evaluated, including for hepatic adverse events. Patients were monitored for HBV and HCV reactivation and flare at screening, the beginning of Cycles 5 and 9, and at treatment discontinuation. Results: Of 501 enrolled patients, 485 were included in the safety population; 329 (68%) received atezolizumab + bevacizumab and 156 (32%) sorafenib. Overall, 150 (31%) and 58 (12%) patients had HBV and HCV infection, respectively. The safety profiles of atezolizumab + bevacizumab and sorafenib were consistent across patients regardless of viral infection. Overall, hepatic serious adverse events occurred in 11% of patients receiving atezolizumab + bevacizumab and 8% receiving sorafenib. HBV or HCV reactivation occurred in 2% or 16% of atezolizumab + bevacizumab–treated patients, respectively, vs 7% or 14% with sorafenib. There were no instances of hepatitis flare with atezolizumab + bevacizumab. Conclusions: Atezolizumab + bevacizumab had a similar hepatic safety profile in patients with and without HBV or HCV infection. Viral reactivation rates were similar between arms. Overall, these data support the use of atezolizumab + bevacizumab in patients with HCC and HBV or HCV infection without any special precaution.
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- 2022
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17. Cholangioscopic diagnosis of hemobilia: an unusual case of left hepatic portal hypertension by plasma cell tumor
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Kyosuke Goda, MD, Yusuke Hashimoto, MD, MMA, and Masafumi Ikeda, MD, PhD
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2022
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18. Multicenter Phase II Trial of Lenvatinib plus Hepatic Intra-Arterial Infusion Chemotherapy with Cisplatin for Advanced Hepatocellular Carcinoma: LEOPARD
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Masafumi Ikeda, Tatsuya Yamashita, Sadahisa Ogasawara, Masatoshi Kudo, Yoshitaka Inaba, Manabu Morimoto, Kaoru Tsuchiya, Satoshi Shimizu, Yasushi Kojima, Atsushi Hiraoka, Kazuhiro Nouso, Hiroshi Aikata, Kazushi Numata, Tosiya Sato, Takuji Okusaka, and Junji Furuse
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hepatocellular carcinoma ,lenvatinib ,cisplatin ,hepatic arterial infusion chemotherapy ,systemic therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and lenvatinib exhibits strong antitumor effects against advanced hepatocellular carcinoma (HCC). Higher antitumor activity is expected for the combination treatment. The aim of this trial was to evaluate the efficacy and safety of lenvatinib in combination with HAIC using cisplatin in patients with advanced HCC. Methods: In this multicenter, open-labeled, single-arm, phase II trial, patients with advanced HCC categorized as Child-Pugh class A with no prior history of systemic therapy were enrolled. Patients received lenvatinib plus HAIC with cisplatin (lenvatinib: 12 mg once daily for patients ≥60 kg, 8 mg once daily for patients
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- 2023
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19. Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2)
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Masatoshi Kudo, Richard S. Finn, Manabu Morimoto, Kun-Ming Rau, Masafumi Ikeda, Chia-Jui Yen, Peter R. Galle, Josep M. Llovet, Bruno Daniele, Ho Yeong Lim, David W. McIlwain, Reigetsu Yoshikawa, Kenichi Nakamura, Kun Liang, Chunxiao Wang, Paolo Abada, Ryan C. Widau, and Andrew X. Zhu
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ramucirumab ,barcelona clinic liver cancer stage ,α-fetoprotein ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. Methods: A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. Results: Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. Conclusions: Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.
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- 2021
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20. Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113
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Makoto Ueno, Chigusa Morizane, Takuji Okusaka, Junki Mizusawa, Tomoko Kataoka, Masafumi Ikeda, Masato Ozaka, Naohiro Okano, Kazuya Sugimori, Akiko Todaka, Satoshi Shimizu, Nobumasa Mizuno, Tomohisa Yamamoto, Keiji Sano, Kazutoshi Tobimatsu, Akio Katanuma, Atsushi Miyamoto, Hironori Yamaguchi, Tomohiro Nishina, Hirofumi Shirakawa, Yasushi Kojima, Takamasa Oono, Yasuyuki Kawamoto, Masayuki Furukawa, Tomohisa Iwai, Kentaro Sudo, Hiroyuki Miyakawa, Tatsuya Yamashita, Ichirou Yasuda, Hidenori Takahashi, Naoya Kato, Kazuhiko Shioji, Kyoko Shimizu, Toshio Nakagohri, Ken Kamata, Hiroshi Ishii, Junji Furuse, and the members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG).
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Medicine ,Science - Abstract
Abstract JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504–0.937) in the low CCr group. Although the total number of incidences of all Grade 3–4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.
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- 2021
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21. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update
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Masatoshi Kudo, Yusuke Kawamura, Kiyoshi Hasegawa, Ryosuke Tateishi, Kazuya Kariyama, Shuichiro Shiina, Hidenori Toyoda, Yasuharu Imai, Atsushi Hiraoka, Masafumi Ikeda, Namiki Izumi, Michihisa Moriguchi, Sadahisa Ogasawara, Yasunori Minami, Kazuomi Ueshima, Takamichi Murakami, Shiro Miyayama, Osamu Nakashima, Hirohisa Yano, Michiie Sakamoto, Etsuro Hatano, Mitsuo Shimada, Norihiro Kokudo, Satoshi Mochida, and Tetsuo Takehara
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hepatocellular carcinoma ,consensus statement ,japan society of hepatology ,pathology ,diagnosis ,treatment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.
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- 2021
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22. 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
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Makoto Ueno, Chigusa Morizane, Masayuki Furukawa, Daisuke Sakai, Yoshito Komatsu, Yousuke Nakai, Masahiro Tsuda, Masato Ozaka, Nobumasa Mizuno, Manabu Muto, Akira Fukutomi, Masafumi Ikeda, Akihito Tsuji, Akio Katanuma, Toshikazu Moriwaki, Takeshi Kajiwara, Hiroshi Ishii, Yuji Negoro, Satoshi Shimizu, Noriko Nemoto, Shingo Kobayashi, Keigo Makino, and Junji Furuse
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biliary tract cancers ,histone deacetylase inhibitor ,resminostat plus S‐1 ,systemic chemotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Purpose Effective second‐line chemotherapy options are limited in treating advanced biliary tract cancers (BTCs). Resminostat is an oral histone deacetylase inhibitor. Such inhibitors increase sensitivity to fluorouracil, the active form of S‐1. In the phase I study, addition of resminostat to S‐1 was suggested to have promising efficacy for pre‐treated BTCs. This study investigated the efficacy and safety of resminostat plus S‐1 in second‐line therapy for BTCs. Methods Patients were randomly assigned to receive resminostat or placebo (200 mg orally per day; days 1–5 and 8–12) and S‐1 group (80–120 mg orally per day by body surface area; days 1–14) over a 21‐day cycle. The primary endpoint was progression‐free survival (PFS). Secondary endpoints comprised overall survival (OS), response rate (RR), disease control rate (DCR), and safety. Results Among 101 patients enrolled, 50 received resminostat+S‐1 and 51 received placebo+S‐1. Median PFS was 2.9 months for resminostat+S‐1 vs. 3.0 months for placebo+S‐1 (HR: 1.154, 95% CI: 0.759–1.757, p = 0.502); median OS was 7.8 months vs. 7.5 months, respectively (HR: 1.049, 95% CI: 0.653–1.684, p = 0.834); the RR and DCR were 6.0% vs. 9.8% and 70.0% vs. 78.4%, respectively. Treatment‐related adverse events (TrAEs) of grade ≥ 3 occurring more frequently (≥10% difference) in the resminostat+S‐1 than in the placebo+S‐1 comprised platelet count decreased (18.0% vs. 2.0%) and decreased appetite (16.0% vs. 2.0%). Conclusions Resminostat plus S‐1 therapy improved neither PFS nor OS for patients with pre‐treated BTCs. Addition of resminostat to S‐1 was associated with higher incidence of TrAEs, but these were manageable (JapicCTI‐183883).
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- 2021
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23. Relationship between surgical R0 resectability and findings of peripancreatic vascular invasion on CT imaging after neoadjuvant S-1 and concurrent radiotherapy in patients with borderline resectable pancreatic cancer
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Sho Yasuta, Tatsushi Kobayashi, Hidetoshi Aizawa, Shinichiro Takahashi, Masafumi Ikeda, Masaru Konishi, Motohiro Kojima, Hirofumi Kuno, Katsuhiko Uesaka, Soichiro Morinaga, Atsushi Miyamoto, Hirochika Toyama, Norihisa Takakura, Keishi Sugimachi, and Wataru Takayama
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Borderline resectable pancreatic cancer ,Neoadjuvant chemoradiotherapy ,S-1 and concurrent radiotherapy ,Progression of vascular invasion ,R0 resectability ,JASPAC 05 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC. Methods Twenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group. Results There were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%) while 90% (18/20) of the NVI patients underwent an R0 resection. The exact 95% confidence interval of risk difference between those R0 resection rates was − 10.0% [− 31.7–20.4%]. Conclusions Patients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT. Trial registration UMIN-CTR, UMIN000009172 . Registered 23 October 2012
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- 2020
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24. Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results
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Makoto Ueno, Masafumi Ikeda, Takashi Sasaki, Fumio Nagashima, Nobumasa Mizuno, Satoshi Shimizu, Hiroki Ikezawa, Nozomi Hayata, Ryo Nakajima, and Chigusa Morizane
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Lenvatinib ,Biliary tract cancer ,Cholangiocarcinoma ,Gallbladder cancer ,Ampulla of Vater ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Biliary tract cancer (BTC) has a poor prognosis and lacks a standardized second-line therapy. Vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR) 4, and platelet-derived growth factor receptor (PDGFR) are highly expressed in BTC. Therefore, lenvatinib (a known inhibitor of VEGF receptors 1–3, FGFRs 1–4, and PDGFR-α) was evaluated for second-line treatment of BTC. Methods In this single-arm, multicenter, open-label, phase 2 study, patients with BTC received lenvatinib 24 mg orally once daily in 28-day cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), PFS rate at 12 weeks, disease control rate, clinical benefit rate, safety and pharmacokinetic profiles. Results Twenty-six Japanese patients were enrolled and treated; 3 had a confirmed partial response per investigator assessment and per independent imaging review (IIR); ORR was 11.5% (90% confidence interval [CI]: 3.2–27.2). Median PFS was 3.19 months (95% CI: 2.79–7.23) per investigator assessment and 1.64 months (95% CI: 1.41–3.19) per IIR. Median OS was 7.35 months (95% CI: 4.50–11.27). Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 21 patients (80.8%) and included hypertension (n = 10 [38.5%]), proteinuria (n = 3 [11.5%]), palmar-plantar erythrodysesthesia (n = 3 [11.5%]), decreased appetite (n = 3 [11.5%]), and anemia (n = 3 [11.5%]). Two deaths occurred due to TEAEs between treatment initiation and 30 days after last dose, but neither were considered treatment related. Conclusions Lenvatinib demonstrated antitumor activity in BTC, with a tolerable safety profile, and should be further evaluated as potential second-line therapy for this difficult to treat population. Trial registration ClinicalTrials.gov NCT02579616 . Date of registration: October 19, 2015.
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- 2020
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25. Final Results of TACTICS: A Randomized, Prospective Trial Comparing Transarterial Chemoembolization Plus Sorafenib to Transarterial Chemoembolization Alone in Patients with Unresectable Hepatocellular Carcinoma
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Masatoshi Kudo, Kazuomi Ueshima, Masafumi Ikeda, Takuji Torimura, Nobukazu Tanabe, Hiroshi Aikata, Namiki Izumi, Takahiro Yamasaki, Shunsuke Nojiri, Keisuke Hino, Hidetaka Tsumura, Teiji Kuzuya, Norio Isoda, Michihisa Moriguchi, Hajime Aino, Akio Ido, Naoto Kawabe, Kazuhiko Nakao, Yoshiyuki Wada, Sadahisa Ogasawara, Kenichi Yoshimura, Takuji Okusaka, Junji Furuse, Norihiro Kokudo, Kiwamu Okita, Philip James Johnson, and Yasuaki Arai
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction Several clinical trials comparing the efficacy and safety of transarterial chemoembolisation (TACE) plus molecular-targeted agents versus TACE alone revealed no clinical benefits in progression-free survival (PFS) or overall survival (OS). Here, we report the final OS analysis from the TACTICS trial, which previously demonstrated significant improvement in PFS with TACE plus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) (NCT01217034). Methods Patients with unresectable HCC were randomised to a TACE plus sorafenib group(N=80) or a TACE alone group(N=76). Patients in the combination treatment group received sorafenib 400 mg once daily for 2–3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable progression. In this trial, TACE-specific PFS was used. TACE-specific PFS is defined as the time from randomization to progressive disease (PD) or death from any cause, and PD was defined as untreatable (UnTACEable) progression, caused by the inability of a patient to further receive or benefit from TACE for reasons that include intrahepatic tumor progression (25% increase vs baseline) according to RECICL, the detection of extrahepatic spread, vascular invasion or transient deterioration of liver function to Child-Pugh C after TACE. Results At the cut-off date of 31 July 2020, 131 OS events were observed. The median OS was 36.2 months with TACE plus sorafenib and 30.8 months with TACE alone (hazard ratio [HR]=0.861; 95% confidence interval [CI), 0.607–1.223; P=0.40, ΔOS, 5.4 months). The updated PFS was 22.8 months with TACE plus sorafenib and 13.5 months with TACE alone (HR=0.661; 95% CI, 0.466–0.938; P=0.02). Post-trial treatments with active procedures/agents were received by 47 (58.8%) patients in the TACE plus sorafenib group and 58 (76.3%) in the TACE alone group (P=0.01). In post hoc analysis, PFS and OS benefit were shown in HCC patients with tumor burden beyond up-to-7 criteria. Conclusions In TACTICS trial, TACE plus sorafenib did not show significant OS benefit over TACE alone; however, clinical meaningful OS prolongation and significantly improved PFS was observed. Thus, the TACE plus sorafenib can be considered a choice of treatment in intermediate stage HCC, especially in patients with high tumor burden. Trial Registration: NCT01217034
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- 2022
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26. Clinical outcomes of chemotherapy in patients with undifferentiated carcinoma of the pancreas: a retrospective multicenter cohort study
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Hiroshi Imaoka, Masafumi Ikeda, Kosuke Maehara, Kumiko Umemoto, Masato Ozaka, Satoshi Kobayashi, Takeshi Terashima, Hiroto Inoue, Chihiro Sakaguchi, Kunihiro Tsuji, Kazuhiko Shioji, Keiya Okamura, Yasuyuki Kawamoto, Rei Suzuki, Hirofumi Shirakawa, Hiroaki Nagano, Makoto Ueno, Chigusa Morizane, and Junji Furuse
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Undifferentiated carcinoma ,Pancreatic cancer ,Anaplastic carcinoma ,Chemotherapy ,Osteoclast-like giant cells ,Paclitaxel ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas. Methods This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed. Results The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n = 24), S-1 (n = 12), gemcitabine plus nab-paclitaxel (n = 6), and other treatment (n = 8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p = 0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p = 0.033; gemcitabine plus nab-paclitaxel vs. S-1: p = 0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p = 0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076–0.647; p = 0.006) in multiple imputation by chained equation. Conclusions The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.
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- 2020
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27. Clinical impact of radiofrequency ablation and stereotactic body radiation therapy for colorectal liver metastasis as local therapies for elderly, vulnerable patients
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Naoto Gotohda, Shogo Nomura, Manami Doi, Katsuyuki Karasawa, Takamasa Ohki, Yasuhiro Shimizu, Yoshitaka Inaba, Atsuya Takeda, Haruyuki Takaki, Hiroshi Anai, Masafumi Ikeda, Motokazu Sugimoto, and Tetsuo Akimoto
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colorectal liver metastases ,elderly patients ,radiofrequency ablation ,stereotactic body radiation therapy ,vulnerable patients ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim Surgical resection is the standard local therapy for patients with colorectal liver metastases (CRLM). However, elderly and vulnerable patients sometimes have various organ dysfunctions. We have to conduct nonsurgical local therapies for those patients who might not tolerate surgery or systemic chemotherapy. Methods We retrospectively reviewed medical records of 254 patients who underwent local therapies, including surgery, radiofrequency ablation (RFA), and stereotactic body radiation therapy (SBRT), for CRLM from January 2010 to December 2016, at seven tertiary‐care institutions in Japan. This study was designed to include elderly, vulnerable patients who received local therapy for CRLM. For those undergoing liver resection, only those having one or more points of the Charlson comorbidity index (CCI) were enrolled. Results Of the total 169 enrolled patients, 122 patients underwent surgery, 42 RFA, and 5 SBRT as the first local therapy for CRLM. Median overall survival from the first local therapy was 5.9 years for the surgery group, 2.7 years for the RFA group, and 3.8 years for the SBRT group. The proportion of the patients with CCI ≧3 was significantly higher in the group of RFA/SBRT than surgery (P
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- 2020
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28. Hepatic Arterial Infusion Chemotherapy versus Sorafenib in Patients with Advanced Hepatocellular Carcinoma
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Kazuomi Ueshima, Sadahisa Ogasawara, Masafumi Ikeda, Yutaka Yasui, Takeshi Terashima, Tatsuya Yamashita, Shuntaro Obi, Shinpei Sato, Hiroshi Aikata, Takumi Ohmura, Hidekatsu Kuroda, Takamasa Ohki, Kengo Nagashima, Yoshihiko Ooka, Masahiro Takita, Masayuki Kurosaki, Kazuaki Chayama, Shuichi Kaneko, Namiki Izumi, Naoya Kato, Masatoshi Kudo, and Masao Omata
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hepatic arterial infusion chemotherapy ,sorafenib ,advanced hepatocellular carcinoma ,macrovascular invasion ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Prior to the approval of sorafenib, hepatic arterial infusion chemotherapy (HAIC) was offered to patients with advanced hepatocellular carcinoma (HCC) in East Asia, particularly Japan. According to the Japanese guidelines, HAIC is recommended as one of the treatment options in patients without extrahepatic metastasis (EHM). Methods: The present cohort study compared the use of HAIC and sorafenib on outcomes of patients with advanced HCC. Consecutive patients with advanced HCC who received HAIC or sorafenib as a first-line systemic therapy were enrolled from 10 Japanese institutions. The primary outcomes were overall survival (OS) in patients with macrovascular invasion (MVI), but without EHM, and OS in patients without both MVI and EHM. Results: Between 2009 and 2016, 2,006 patients were enrolled (541 HAIC patients, 1,465 sorafenib patients). After propensity score matching, the OS of patients with MVI but without EHM was significantly longer in the HAIC group compared with the sorafenib group (10.1 vs. 9.1 months for the HAIC and sorafenib groups, respectively; n = 170 for each group; hazard ratio [HR] 0.668; 95% confidence interval [95% CI] 0.475–0.935; p = 0.018). There was no significant difference in OS between patients without both MVI and EHM (12.2 vs. 15.4 months for the HAIC and sorafenib groups, respectively; n = 76 in each cohort after propensity score matching; HR 1.227; 95% CI 0.699–2.155; p = 0.475). Conclusion: HAIC is a potential front-line treatment choice in a subpopulation of patients with advanced HCC with MVI but without EHM.
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- 2020
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29. The 'histological replacement growth pattern' represents aggressive invasive behavior in liver metastasis from pancreatic cancer
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Kazuo Watanabe, Shuichi Mitsunaga, Motohiro Kojima, Hidetaka Suzuki, Ai Irisawa, Hideaki Takahashi, Mitsuhito Sasaki, Yusuke Hashimoto, Hiroshi Imaoka, Izumi Ohno, Masafumi Ikeda, Tetsuo Akimoto, and Atsushi Ochiai
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liver metastasis ,pancreatic cancer ,prognostic factor ,replacement growth pattern ,tumor microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background In the case of liver metastasis (LM), tumors showing the replacement growth pattern (RGP), in which metastatic cells infiltrate and replace hepatocytes with minimal desmoplastic reaction and inflammatory cell infiltration, associate with a poor prognosis. The heterogeneity, frequency, and prognostic value of the RGP in LM from pancreatic cancer (PCa) are not well known. Methods In the circumference of treatment‐naïve resected LMs from patients with PCa, the heterogeneity of the GP was assessed. Next, the clinicopathological features of LMs showing the RGP in needle biopsy specimens were investigated in patients with treatment‐naïve advanced PCa. Results Thirteen of the 14 (93%) in all resected LMs and 7 of the 9 (78%) in RGP component GP in resected LMs showed homogeneous GP. A RGP was found in 50% of the needle biopsy specimens of LMs obtained from 107 patients. The median overall survival times in the RGP group and non‐RGP group were 3.6 and 10.4 months. Multivariate analysis identified RGP as an independent poor prognostic factor. Median value of CD8 positive percentage in RGP was lower than that in non‐RGP (0.75 vs 1.46, P = .04). Median overall survival times in low CD8 groups tend to be shorter than those in high CD8 group (8.2 vs 4.2 months). Conclusion Most LMs from PCa show a homogeneous GP. The RGP was observed in about a half of the LMs from PCa patients, and was identified as a poor prognostic factor.
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- 2020
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30. A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements
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Masatoshi Kudo, Kwang-Hyub Han, Sheng-Long Ye, Jian Zhou, Yi-Hsiang Huang, Shi-Ming Lin, Chung-Kwe Wang, Masafumi Ikeda, Stephen Lam Chan, Su Pin Choo, Shiro Miyayama, and Ann Lii Cheng
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asia-pacific primary liver cancer expert ,hepatocellular carcinoma ,intermediate stage ,systemic therapy ,transarterial chemoembolization ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement on the treatment strategy for patients with intermediate-stage hepatocellular carcinoma (HCC) was established on August 31, 2019, in Sapporo, Hokkaido during the 10th Annual APPLE Meeting. This manuscript summarizes the international consensus statements developed at APPLE 2019. Transarterial chemoembolization (TACE) is the only guideline-recommended global standard of care for intermediate-stage HCC. However, not all patients benefit from TACE because intermediate-stage HCC is a heterogeneous disease in terms of tumor burden and liver function. Ten important clinical questions regarding this stage of HCC were raised, and consensus statements were generated based on high-quality evidence. In intermediate-stage HCC, preservation of liver function is as important as achieving a high objective response (OR) because the treatment goal is to prolong overall survival. Superselective conventional TACE (cTACE) is recommended as the first choice of treatment in patients eligible for effective (curative) TACE, whereas in patients who are not eligible, systemic therapy is recommended as the first choice of treatment. TACE is not indicated as the first-line therapy in TACE-unsuitable patients. Another important statement is that TACE should not be continued in patients who develop TACE failure/refractoriness in order to preserve liver function. Targeted therapy is the recommended first-line treatment for TACE-unsuitable patients. Especially, the drug, which can have higher OR rate, is preferred. Immunotherapy, transarterial radioembolization, TACE + targeted therapy or other modalities may be considered alternative options in TACE-unsuitable patients who are not candidates for targeted therapy. Better liver function, such as albumin-bilirubin grade 1, is an important factor for maximizing the therapeutic effect of systemic therapy.
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- 2020
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31. IMbrave150: Efficacy and Safety of Atezolizumab Plus Bevacizumab vs Sorafenib in Patients With Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma—An Exploratory Analysis of the Phase III Study
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Masatoshi Kudo, Richard S. Finn, Peter R. Galle, Andrew X. Zhu, Michel Ducreux, Ann-Lii Cheng, Masafumi Ikeda, Kaoru Tsuchiya, Ken-ichi Aoki, Jing Jia, and Riccardo Lencioni
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: The Phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) Stage B disease. Methods: Patients with systemic treatment-naive unresectable HCC and Child-Pugh Class A liver function were randomized 2:1 to receive 1200 mg of atezolizumab plus 15 mg/kg of bevacizumab or 400 mg of sorafenib. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) per independent review facility (IRF)–assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in the BCLC Stage B subgroup. Patients in this analysis had BCLC Stage B disease at baseline per electronic case report form. Secondary efficacy endpoints included objective response rate (ORR) and change in the sum of longest diameter (SLD) of target lesions from baseline per IRF RECIST 1.1 and modified RECIST (mRECIST) for HCC. Results: Of 501 enrolled patients, 74 (15%) had BCLC Stage B disease at baseline (atezolizumab + bevacizumab, n=49; sorafenib, n=24). For this group, median follow-up was 19.7 months. A trend toward improved OS and PFS per IRF RECIST 1.1 was observed with atezolizumab + bevacizumab vs sorafenib (OS: HR, 0.63; 95% CI: 0.29, 1.34; PFS: HR, 0.64; 95% CI: 0.36, 1.12). ORRs per IRF RECIST 1.1 and HCC mRECIST were 43% and 50% with atezolizumab + bevacizumab and 26% and 30% with sorafenib, respectively. Percentage change in SLD of target lesions from baseline per IRF RECIST 1.1 and HCC mRECIST showed durable responses with atezolizumab + bevacizumab treatment. Safety data were consistent with known profiles of atezolizumab and bevacizumab, as seen in the overall study population. Discussion/Conclusion: Efficacy benefits were observed with atezolizumab + bevacizumab in patients with baseline BCLC Stage B disease, consistent with the intention-to-treat population.
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- 2022
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32. Conversion of percutaneous cholecystostomy to transmural endoscopic ultrasound-guided gallbladder drainage in malignant biliary obstruction
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Motoyasu Kan, Yusuke Hashimoto, Taro Shibuki, Gen Kimura, Kumiko Umemoto, Kazuo Watanabe, Mitsuhito Sasaki, Hideaki Takahashi, Hiroshi Imaoka, Izumi Ohno, Shuichi Mitsunaga, and Masafumi Ikeda
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Cholecystitis ,Endosonography ,Fistula and drainage ,Medicine ,Internal medicine ,RC31-1245 ,Specialties of internal medicine ,RC581-951 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background : In patients with distal malignant biliary obstruction, it is a challenge to manage acute cholecystitis secondary to cystic duct obstruction associated with tumor progression or stent compression. Percutaneous transhepatic gallbladder drainage (PTGBD) has been used as the treatment option of choice, because of its ease of performance and safety, but because of the use of an external drainage tube, some patients experience a decreased quality of life. We report the technical success and clinical success of conversion from PTGBD to endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) for the treatment of acute cholecystitis in patients with unresectable malignant biliary obstruction. Methods : We included the patients with cholecystitis secondary to unresectable malignant biliary obstruction who underwent conversion from PT-GBD to EUS-GBD in the study. After PTGBD for the treatment of acute cholecystitis, we performed EUS-GBD and a plastic stent or a self-expandable metal stent (SEMS) was placed for fistulostomy. Results : Fourteen patients (median age, 69 years; 9 males and 5 females) underwent conversion to EUS-GBD after clinical improvement of cholecystitis by PTGBD. The technical success rate of the conversion from PTGBD to EUS-GBD was 100% (14/14). EUS-GBD was performed in a median of 9.5 days (range, 3-51 days) after PTGBD procedure, using mainly a plastic stent (13 patients) and a covered SEMS in one patient. The early (within 24 hours) adverse events rate was 14.3% (2/14), and the late (after 24 hours) adverse events rate was 7.1% (1/14). The rate of recurrence of cholecystitis was 28.6% (4/14). These patients underwent endoscopic re-intervention and there were no cases of further recurrence of cholecystitis. Conclusion : Conversion of PTGBD to EUS-GBD demonstrated a feasible and safe technique for acute cholecystitis in non-surgical candidates with malignant biliary obstruction.
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- 2019
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33. Endoscopic Ultrasound-Guided Gallbladder Drainage for Aberrant Right Posterior Duct Obstruction Developing after Placement of a Covered Self-Expandable Metallic Stent in a Patient with Distal Biliary Obstruction
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Yuko Suzuki, Yusuke Hashimoto, Taro Shibuki, Motoyasu Kan, Gen Kimura, Kumiko Umemoto, Kazuo Watanabe, Mitsuhito Sasaki, Hideaki Takahashi, Hiroshi Imaoka, Izumi Ohno, Shuichi Mitsunaga, and Masafumi Ikeda
- Subjects
Endoscopic ultrasound-guided gallbladder drainage ,Anatomical anomaly of the bile duct ,Aberrant hepatic duct ,Biliary drainage ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been utilized as an alternative endoscopic technique for patients with acute cholecystitis. In addition to EUS-guided hepaticogastrostomy and EUS-guided cystogastrostomy, EUS-GBD has been reported as being useful for biliary drainage in cases with distal malignant biliary obstruction instead of conventional endoscopic retrograde cholangiopancreatography. We present a case of successful EUS-GBD for malignant obstruction of an aberrant hepatic duct draining directly into the cystic duct.
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- 2018
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34. Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2
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Masatoshi Kudo, Peter R. Galle, Giovanni Brandi, Yoon-Koo Kang, Chia-Jui Yen, Richard S. Finn, Josep M. Llovet, Eric Assenat, Philippe Merle, Stephen L. Chan, Daniel H. Palmer, Masafumi Ikeda, Tatsuya Yamashita, Arndt Vogel, Yi-Hsiang Huang, Paolo B. Abada, Reigetsu Yoshikawa, Kenta Shinozaki, Chunxiao Wang, Ryan C. Widau, and Andrew X. Zhu
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ALBI ,Liver function ,Prognosis ,Safety ,Survival ,Tumour response ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: The albumin–bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). In this post hoc analysis, we assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using the ALBI score in patients with advanced HCC. Methods: Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomised in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2 weeks. Data were analysed by trial and as a meta-analysis of individual patient-level data (pooled population) from REACH (alpha-fetoprotein ≥400 ng/ml) and REACH-2. Patients from REACH with Child-Pugh class B were analysed as a separate cohort. The ALBI grades and scores were calculated at baseline and before each treatment cycle. Results: Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; hazard ratio [HR]: 1.38 [1.13–1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared with baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumour response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445–0.824]) and ALBI grade 2 (HR 0.814 [0.630–1.051]). Conclusions: Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade. Lay summary: Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide. Prognosis is affected by many clinical factors including liver function both before and during anticancer treatment. Here we have used a validated approach to assess liver function using 2 laboratory parameters, serum albumin and bilirubin (ALBI), both before and during treatment with ramucirumab in 2 phase III placebo-controlled studies. We confirm the practicality of using this more simplistic approach in assessing liver function prior to and during anticancer therapy, and demonstrate ramucirumab did not impair liver function when compared with placebo.
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- 2021
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35. Integrated communication support program for oncologists, caregivers and patients with rapidly progressing advanced cancer to promote patient-centered communication: J-SUPPORT 1904 study protocol for a randomised controlled trial
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Makoto Ueno, Takuhiro Yamaguchi, Tempei Miyaji, Yosuke Uchitomi, Takuji Okusaka, Masafumi Ikeda, Ayako Sato, Sayaka Jinno, Masato Ozaka, Yukiko Takayama, and Yoshiyuki Majima
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Medicine - Abstract
Introduction Communication is an essential aspect of care for patients with progressive serious illnesses. This study aims to evaluate the efficacy of a new, integrated communication support program for oncologists, patients with rapidly progressing advanced cancer and their caregivers.Methods and analysis The proposed integrated communication support programme is in the randomised control trial stage. It comprises a cluster of oncologists from comprehensive cancer centre hospitals in a metropolitan area in Japan. A total of 20 oncologists, 200 patients with advanced pancreatic cancer and the patients’ caregivers are enrolled in this study as of the writing of this protocol report. Oncologists are randomly assigned to the intervention group (IG) or control group (CG). Patients and caregivers are allocated to the same group as their oncologists. The IG oncologists receive a 2.5-hour individual communication skills training, and patients and caregivers receive a half-hour coaching intervention to facilitate prioritising and discussing questions and concerns; the CG participants do not receive any training. Follow-up data will be collected quarterly for 6 months for a year and then annually for up to 3 years. The primary endpoint is the intergroup difference between before-intervention and after-intervention patient-centred communication behaviours during oncology visits.Ethics and dissemination This study is conducted in accordance with the ethical guidelines for clinical studies published by Japan’s Ministry of Education, Cultural, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the ethical principles established for research on humans stipulated in the Declaration of Helsinki and further amendments thereto. The protocol was approved by the Institutional Review Board of National Cancer Center, Japan on 4 July 2018 (ID: 2017-474).Trial status This study is currently enrolling participants. Enrolment period ends 31 July 2020; estimated follow-up date is 31 March 2023.Trial registration number UMIN Clinical Trial Registry (UMIN000033612); pre-results.
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- 2020
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36. Clinical characteristics of Japanese patients with epithelioid hemangioendothelioma: a multicenter retrospective study
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Satoshi Shiba, Hiroshi Imaoka, Kazuhiko Shioji, Eiichiro Suzuki, Shigeru Horiguchi, Takeshi Terashima, Yasushi Kojima, Tatsuya Okuno, Yasutaka Sukawa, Kunihiko Tsuji, Kumiko Umemoto, Akinori Asagi, Akiko Todaka, Makoto Ueno, Masafumi Ikeda, Chigusa Morizane, and Junji Furuse
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Epithelioid hemangioendothelioma ,Prognosis ,Tumor size ,Ki-67 index ,Sarcoma ,Chemotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Epithelioid hemangioendothelioma is an exceedingly rare sarcoma often occurring as an indolent angiocentric vascular tumor at various anatomic sites. Few reports have evaluated large case series of epithelioid hemangioendothelioma. Methods We conducted a retrospective analysis of the clinical data of 42 consecutive patients with epithelioid hemangioendothelioma who were pathologically diagnosed between 1990 and 2014 at 13 Japanese tertiary hospitals. We analyzed their clinical characteristics, tumor features and prognostic factors. Results The study included 22 men and 20 women, with a median age of 54 (range, 18–78) years. Pain was the most common symptom, occurring in 15 (68%) of the 22 symptomatic patients. The median maximum tumor diameter was 4.0 (range, 1.0–12.8) cm. The most commonly involved organs were the liver (81%), lungs (57%), and bones (12%). The overall survival rates were 79.5% at 1 year and 72.0% at 5 years. Substantially better survival was observed in asymptomatic patients than in symptomatic patients (P = 0.03), and better survival was also ovserved in patients with Ki-67 index ≤10% than in those with Ki-67 index > 10% (P = 0.04). By multivariate analysis, tumor size > 3.0 cm was associated with decreased survival (P = 0.049, hazard ratio 13.33). Conclusions This study showed the clinical characteristics of Japanese patients with epithelioid hemangioendothelioma. Tumor size > 3.0 cm is an independent indicator of a poor prognosis in epithelioid hemangioendothelioma. The presence of symptoms at the time of diagnosis and high Ki-67 index implied poor survival.
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- 2018
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37. Successful endoscopic closure of an esophageal leak after endoscopic ultrasound-guided hepaticoesophagostomy by using n-butyl-2 cyanoacrylate
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Renma Ito, Yusuke Hashimoto, and Masafumi Ikeda
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Endoscopic ultrasound-guided hepaticoesophagostomy ,Esophageal leak ,N-butyl-2 cyanoacrylate ,Medicine ,Internal medicine ,RC31-1245 ,Specialties of internal medicine ,RC581-951 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Endoscopic ultrasound-guided hepaticoesophagostomy (EUS-HES) refers to EUS-guided biliary access from the abdominal part of the esophagus, an uncommon choice of route for biliary drainage. In the patient reported herein, an esophageal laceration and leakage at the site of placement of a metal stent occurred a few days after EUS-HES. To plug the laceration, 0.5 mL of n-butyl-2 cyanoacrylate mixed with 1 mL of lipiodol was injected through an endoscopic retrograde cholangiopancreatography catheter. We performed EUS-guided transgastric drainage for drainage of the peritoneal fluid collection. The procedures were successful and the laceration eventually healed, with no further leakage.
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- 2019
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38. Impact of Endoscopic Ultrasound-Guided Tissue Acquisition on Decision-Making in Precision Medicine for Pancreatic Cancer: Beyond Diagnosis
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Hiroshi Imaoka, Mitsuhito Sasaki, Yusuke Hashimoto, Kazuo Watanabe, Shoichi Miyazawa, Taro Shibuki, Shuichi Mitsunaga, and Masafumi Ikeda
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endoscopic ultrasound-guided tissue acquisition ,endoscopic ultrasound-guided fine needle aspiration ,endoscopic ultrasound-guided fine needle biopsy ,next-generation sequencing ,precision medicine ,pancreatic cancer ,Medicine (General) ,R5-920 - Abstract
Precision medicine in cancer treatment refers to targeted therapy based on the evaluation of biomarkers. Although precision medicine for pancreatic cancer (PC) remains challenging, novel biomarker-based therapies, such as pembrolizumab, olaparib, and entrectinib, have been emerging. Most commonly, endoscopic ultrasound-guided tissue acquisition (EUS-TA) had been used for the diagnosis of PC until now. However, advances in EUS-TA devices and biomarker testing, especially next-generation sequencing, have opened up the possibility of sequencing of various genes even in limited amounts of tissue samples obtained by EUS-TA, and identifying potential genetic alterations as therapeutic targets. Precision medicine benefits only a small population of patients with PC, but biomarker-based therapy has shown promising results in patients who once had no treatment options. Now, the role of EUS-TA has extended beyond diagnosis into decision-making regarding the treatment of PC. In this review, we mainly discuss tissue sampling by EUS-TA for biomarker testing and the current status of precision medicine for PC.
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- 2021
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39. Endoscopic unroofing drainage with a needle-knife for gastric wall abscess: a rare adverse event that developed after EUS-FNA
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Gen Kimura, MD, Yusuke Hashimoto, MD, and Masafumi Ikeda, MD, PhD
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2019
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40. Successful obliteration of bleeding duodenal varices by EUS-guided injection of N-butyl-2-cyanoacrylate
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Gen Kimura, MD, Yusuke Hashimoto, MD, and Masafumi Ikeda, MD
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2017
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41. Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
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Masafumi Ikeda, Shuichi Mitsunaga, Izumi Ohno, Yusuke Hashimoto, Hideaki Takahashi, Kazuo Watanabe, Kumiko Umemoto, and Takuji Okusaka
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hepatocellular carcinoma ,chemotherapy ,sorafenib ,immune-oncologic agents ,individualized treatment ,Medicine - Abstract
Systemic chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). Before the introduction of sorafenib, cytotoxic agents, hormonal therapies, or many combinations of these were the mainly used modalities for systemic chemotherapy of advanced HCC. However, such regimens were of only limited value in clinical practice, because some randomized controlled studies comparing promising regimens with no treatment or doxorubicin alone failed to show any overall survival advantage. In two pivotal phase III placebo-controlled studies, the SHARP trial and the Asia-Pacific trial, sorafenib was demonstrated to significantly delay the time to progression and the overall survival time in patients with advanced HCC. Therefore, sorafenib therapy has come to be acknowledged as a standard therapy for advanced HCC worldwide. After the introduction of sorafenib, a number of phase III trials of various molecular-targeted agents vs. sorafenib as first-line chemotherapy and of various molecular-targeted agents vs. placebo as second-line chemotherapy have been conducted to determine if any of these agents could offer a survival benefit, however, none of the agents examined so far has been demonstrated to provide any survival benefit over sorafenib or placebo. Recently, favorable treatment efficacies have been reported in some clinical trials of molecular-targeted agents in the biomarker-enriched population. Development of individualized cancer treatments using molecular-targeted agents based on the results of genome-sequencing is aggressively ongoing. Furthermore, immune-oncologic agents, such as anti-CTLA-4 antibody and anti-PD-1/PD-L1 antibody, have been reported to provide promising outcomes. Thus, various novel systemic chemotherapeutic agents are currently under development, and further improvements in the treatment outcomes are expected.
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- 2015
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42. Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.
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Rumi Fujioka, Nobuo Mochizuki, Masafumi Ikeda, Akihiro Sato, Shogo Nomura, Satoshi Owada, Satoshi Yomoda, Katsuya Tsuchihara, Satoshi Kishino, and Hiroyasu Esumi
- Subjects
Medicine ,Science - Abstract
Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.
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- 2018
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43. Early Relapse of Unresectable Gallbladder Cancer after Discontinuation of Gemcitabine Monotherapy Administered for 5 Years in a Patient Who Had Complete Response to the Treatment
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Koichi Suyama, Masafumi Ikeda, Eiichiro Suzuki, Motohiro Kojima, Shuichi Mitsunaga, Satoshi Shimizu, Izumi Ohno, Hideaki Takahashi, Hiroyuki Okuyama, Akiko Kuwahara, Takuji Okusaka, and Junji Furuse
- Subjects
Gemcitabine ,Chemotherapy ,Complete response ,Early relapse ,Gallbladder cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The tumor shrinkage effect of gemcitabine is considered to be limited in cases of advanced gallbladder cancer, and there are few reports of complete response to gemcitabine therapy in patients with this cancer. Therefore, the treatment continuation strategy in these patients, after a complete response has been achieved, still remains to be established. Here, we present the case of a 77-year-old patient with unresectable gallbladder cancer, who after showing complete response to gemcitabine monotherapy administered for 5 years, showed early relapse within only 11 months of discontinuation of the drug. Thus, it is necessary to establish a suitable treatment continuation strategy for patients who show complete response to gemcitabine treatment.
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- 2013
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44. Hepatitis B Virus Reactivation during Treatment with Multi-Tyrosine Kinase Inhibitor for Hepatocellular Carcinoma
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Satoshi Shiba, Shunsuke Kondo, Hideki Ueno, Chigusa Morizane, Masafumi Ikeda, and Takuji Okusaka
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Hepatitis B virus reactivation ,Hepatocellular carcinoma ,Multi-tyrosine kinase inhibitor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Hepatitis B virus (HBV) reactivation is well documented in individuals with cancer who receive certain cytotoxic or immunosuppressive therapies including rituximab treatment. As a general rule, the risk is greatest upon withdrawal of chemotherapy. The risk ranges from approximately 20 to 50% among HBsAg-positive carriers. A 67-year-old man was diagnosed with inoperable multiple hepatocellular carcinoma accompanied by an increase in alpha-fetoprotein and protein induced by vitamin K absence or antagonist II level. Eighteen weeks after starting on the oral multi-tyrosine kinase inhibitor TSU-68, laboratory investigations showed a substantial increase in serum transaminase levels (AST: 302 IU/l; ALT: 324 IU/l) and an elevation of the HBV-DNA level (6.9 log copies/ml). The diagnosis was that the cause of the acute hepatitis was HBV reactivation and we immediately administered entecavir. Two months after the initiation of daily entecavir treatment, laboratory findings showed that the serum levels of transaminases and ALP had improved (AST: 18 IU/l; ALT: 10 IU/l; ALP: 197 U/l). When the HBV markers were examined 4 months later, they were altered: HBeAg was negative and HBeAb was positive. Entecavir treatment was discontinued after 6 months. Although reactivation with rituximab has been reported, reactivation with a tyrosine kinase inhibitor is extremely unusual in a patient who is HBsAg negative but anti-HBc positive. This is the first report describing HBV reactivation with an increasing HBV-DNA level in a HBsAg-negative/HBcAb-positive/HBsAb-positive patient who was treated with TSU-68 for hepatocellular carcinoma.
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- 2012
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45. Revisions of the clinical practice guidelines for hepatocellular carcinoma in 2021 version
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Nobuyuki Takemura, Ryosuke Tateishi, Tatsuya Yamashita, Takeyuki Watadani, Masaki Kaibori, Shoji Kubo, Mitsuo Shimada, Hiroaki Nagano, Etsuro Hatano, Hiroshi Aikata, Hiroko Iijima, Kazuomi Ueshima, Kazuyoshi Ohkawa, Takuya Genda, Kaoru Tsuchiya, Takuji Torimura, Masafumi Ikeda, Junji Furuse, Masaaki Akahane, Satoshi Kobayashi, Hideyuki Sakurai, Atsuya Takeda, Takamichi Murakami, Utaroh Motosugi, Yutaka Matsuyama, Masatoshi Kudo, and Kiyoshi Hasegawa
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Hepatology - Published
- 2023
46. Clinical significance of circulating-tumour DNA analysis by metastatic sites in pancreatic cancer
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Kumiko Umemoto, Yu Sunakawa, Makoto Ueno, Masayuki Furukawa, Nobumasa Mizuno, Kentaro Sudo, Yasuyuki Kawamoto, Takeshi Kajiwara, Koushiro Ohtsubo, Naohiro Okano, Nobuhisa Matsuhashi, Shinji Itoh, Toshihiko Matsumoto, Satoshi Shimizu, Toru Otsuru, Hiroko Hasegawa, Hiroyuki Okuyama, Hideko Ohama, Toshikazu Moriwaki, Takashi Ohta, Justin I. Odegaard, Yoshiaki Nakamura, Hideaki Bando, Takayuki Yoshino, Masafumi Ikeda, and Chigusa Morizane
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Cancer Research ,Oncology - Published
- 2023
47. Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: Final results of a multicenter phase II study
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Naoya Kato, Masatoshi Kudo, Kaoru Tsuchiya, Atsushi Hagihara, Kazushi Numata, Hiroshi Aikata, Yoshitaka Inaba, Shunsuke Kondo, Kenta Motomura, Naohiro Okano, Masafumi Ikeda, Manabu Morimoto, Shingo Kuroda, and Akiko Kimura
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Infectious Diseases ,Hepatology - Published
- 2023
48. Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial
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Kohei Nakachi, Masafumi Ikeda, Masaru Konishi, Shogo Nomura, Hiroshi Katayama, Tomoko Kataoka, Akiko Todaka, Hiroaki Yanagimoto, Soichiro Morinaga, Shogo Kobayashi, Kazuaki Shimada, Yu Takahashi, Toshio Nakagohri, Kunihito Gotoh, Ken Kamata, Yasuhiro Shimizu, Makoto Ueno, Hiroshi Ishii, Takuji Okusaka, Junji Furuse, Keiya Okamura, Yasuyuki Kawamoto, Akio Katanuma, Michiaki Unno, Hirofumi Shirakawa, Hironori Yamaguchi, Amane Takahashi, Hiroo Yanagibashi, Naoya Kato, Yoshihiro Sakamoto, Yasushi Kojima, Ryota Higuchi, Naoki Sasahira, Keiji Sano, Yu Sunakawa, Yusuke Kumamoto, Kazuya Sugimori, Tatsuya Nomura, Kazuto Shibuya, Isamu Makino, Kentaro Yamazaki, Nobumasa Mizuno, Hiroshi Wada, Mitsugu Sekimoto, Tetsuo Ajiki, Ikuo Nakamura, Ikuya Miki, Hiroaki Nagano, Koji Ohta, Takehiro Okabayashi, Masayuki Furukawa, and Nao Fujimori
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General Medicine - Published
- 2023
49. Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis
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Yukio Yoshida, Satoshi Kobayashi, Makoto Ueno, Chigusa Morizane, Kunihiro Tsuji, Yuta Maruki, Keita Mori, Kazuo Watanabe, Akihiro Ohba, Mitsuhiro Furuta, Akiko Todaka, Akiko Tsujimoto, Masato Ozaka, Naohiro Okano, Kei Yane, Kumiko Umemoto, Yasuyuki Kawamoto, Takeshi Terashima, Hidetaka Tsumura, Keitaro Doi, Kazuhiko Shioji, Akinori Asagi, Yasushi Kojima, Eiichiro Suzuki, Reishi Toshiyama, Masayuki Furukawa, Atsushi Naganuma, Rei Suzuki, Haruo Miwa, Masafumi Ikeda, and Junji Furuse
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Pancreatic Neoplasms ,Carcinoma, Adenosquamous ,Hepatology ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Humans ,Retrospective Studies ,Carcinoma, Pancreatic Ductal - Abstract
Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC.We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions.Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively.This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.
- Published
- 2022
50. Liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy in Japanese patients with metastatic pancreatic cancer: additional safety analysis of a randomized phase 2 trial
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Junji Furuse, Makoto Ueno, Masafumi Ikeda, Takuji Okusaka, Zhaoyang Teng, Momoko Furuya, and Tatsuya Ioka
- Subjects
Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging ,General Medicine - Abstract
Background Nanoliposomal irinotecan (nal-IRI) was recently authorized in Japan for unresectable pancreatic cancer after disease progression following chemotherapy. Physicians now consider certain aspects of nal-IRI safety profile as slightly different from conventional irinotecan. This report aims to explore additional aspects of the nal-IRI safety in Japanese phase 2 study. Methods We analyzed the incidence, time to first onset, and time to resolution for adverse events that require special attention and other selected toxicities in the nal-IRI combination group (n = 46). Results Leukopenia/neutropenia (76.1%/71.7%), diarrhea (58.7%) and hepatic dysfunction (41.3%) were the most commonly reported treatment-emergent adverse events, with a median time to onset of 21.0 days (range: 8, 97), 9.0 days (1, 61) and 22.0 days (2, 325), respectively, and a median time to resolution of 8.0 days (95% confidence intervals: 8, 9), 4.0 days (4, 8) and 40.0 days (9, –), respectively. Eight patients experienced Grade ≥ 3 diarrhea and their symptoms were well controlled by dose modification except one patient who had drug withdrawal. The median time to resolution for Grade ≥ 3 and Grade ≤ 2 diarrhea was 17.5 days (95% confidence intervals: 1, 31) and 4 days (3, 7), respectively. Anorexia occurred in 28/46 patients (60.9%) with a median time to onset of 4.0 days (range: 2, 132) and a median time to resolution of 12.0 days (95% confidence intervals: 6, 26). Conclusions We explored safety profile of nal-IRI combination regimen recognized as effective and tolerable treatment for Japanese unresectable pancreatic cancer patients. Although the treatment-emergent adverse events occurred were controllable, patients with prolonged toxicities should be closely managed.
- Published
- 2022
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