151 results on '"Kariyama K"'
Search Results
2. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
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Rimini, M., Kudo, M., Tada, T., Shigeo, S., Kang, W., Suda, G., Jefremow, A., Burgio, V., Iavarone, M., Tortora, R., Marra, F., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Foschi, F.G., Silletta, M., Kumada, T., Iwamoto, H., Aoki, T., Goh, M.J., Sakamoto, N., Siebler, J., Hiraoka, A., Niizeki, T., Ueshima, K., Sho, T., Atsukawa, M., Hirooka, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Takaaki, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Cucchetti, A., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.
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- 2021
- Full Text
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3. Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis
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Yamano, T., Higashi, T., Nouso, K., Nakatsukasa, H., Kariyama, K., Yumoto, E., Kobayashi, Y., Yamamoto, K., Iwagaki, H., Yagi, T., Tanimoto, T., Kurimoto, M., Tanaka, N., and Tsuji, T.
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- 2000
4. Estimation of remnant liver function before hepatectomy using 99mTc-GSA and prognosis of patients after hepatectomy.
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Yumoto, Y, Mitani, K, Higashi, T, Yagi, T, Hiraki, Y, Kurokawa, T, Hanafusa, T, Nakatsukasa, H, Nouso, K, Kobayashi, K, Kariyama, K, Ohmoto, M, and Tsuji, T
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- 2000
5. Expression of telomerase-associated protein 1 and telomerase reverse transcriptase in hepatocellular carcinoma
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Toshikuni, N, primary, Nouso, K, additional, Higashi, T, additional, Nakatsukasa, H, additional, Onishi, T, additional, Kaneyoshi, T, additional, Kobayashi, Y, additional, Kariyama, K, additional, Yamamoto, K, additional, and Tsuji, T, additional
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- 2000
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6. Expression of MAGE-1 and -3 genes and gene products in human hepatocellular carcinoma
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Kariyama, K, primary, Higashi, T, additional, Kobayashi, Y, additional, Nouso, K, additional, Nakatsukasa, H, additional, Yamano, T, additional, Ishizaki, M, additional, Kaneyoshi, T, additional, Toshikuni, N, additional, Ohnishi, T, additional, Fujiwara, K, additional, Nakayama, E, additional, Terracciano, L, additional, Spagnoli, G C, additional, and Tsuji, T, additional
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- 1999
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7. Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma
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Kobayashi, Y., Higashi, T., Nouso, K., Nakatsukasa, H., Ishizaki, M., Kaneyoshi, T., Toshikuni, N., Kariyama, K., Nakayama, E., and Tsuji, T.
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- 2000
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- View/download PDF
8. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
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T. Ishikawa, M. Imai, Noritomo Shimada, Kazuya Kariyama, Shinya Fukunishi, Akemi Tsutsui, Masashi Hirooka, Hideki Iwamoto, Norio Itokawa, Atsushi Hiraoka, Tomomi Okubo, Ei Itobayashi, Kazuhito Kawata, Joji Tani, Yoichi Hiasa, Kouji Joko, N. Sakamoto, F. Marra, Taeang Arai, Koichi Takaguchi, Francesco Giuseppe Foschi, Masanori Atsukawa, Yohei Koizumi, Marianna Silletta, Massimo Iavarone, Takuya Nagano, J. Siebler, Stefano Cascinu, T. Sho, Margherita Rimini, S. Shigeo, T. Aoki, L. Aldrighetti, Toshifumi Tada, G. Suda, A. Jefremow, V. Burgio, Takashi Niizeki, Hidenori Toyoda, Gianluca Masi, Sara Lonardi, Kazuto Tajiri, F. Ratti, Shinichiro Nakamura, W. Kang, A. Cucchetti, Takashi Kumada, Raffaella Tortora, E. Tamburini, Kunihiko Tsuji, Satoshi Yasuda, Fabio Piscaglia, Hiroshi Shibata, Kazuhiro Nouso, Giuseppe Cabibbo, K. Ueshima, Hironori Ochi, Andrea Casadei-Gardini, Hideko Ohama, T. Takaaki, M. Kudo, M.J. Goh, Rimini M., Kudo M., Tada T., Shigeo S., Kang W., Suda G., Jefremow A., Burgio V., Iavarone M., Tortora R., Marra F., Lonardi S., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Foschi F.G., Silletta M., Kumada T., Iwamoto H., Aoki T., Goh M.J., Sakamoto N., Siebler J., Hiraoka A., Niizeki T., Ueshima K., Sho T., Atsukawa M., Hirooka M., Tsuji K., Ishikawa T., Takaguchi K., Kariyama K., Itobayashi E., Tajiri K., Shimada N., Shibata H., Ochi H., Yasuda S., Toyoda H., Fukunishi S., Ohama H., Kawata K., Tani J., Nakamura S., Nouso K., Tsutsui A., Nagano T., Takaaki T., Itokawa N., Okubo T., Arai T., Imai M., Joko K., Koizumi Y., Hiasa Y., Cucchetti A., Ratti F., Aldrighetti L., Cascinu S., Casadei-Gardini A., Rimini, M., Kudo, M., Tada, T., Shigeo, S., Kang, W., Suda, G., Jefremow, A., Burgio, V., Iavarone, M., Tortora, R., Marra, F., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Foschi, F. G., Silletta, M., Kumada, T., Iwamoto, H., Aoki, T., Goh, M. J., Sakamoto, N., Siebler, J., Hiraoka, A., Niizeki, T., Ueshima, K., Sho, T., Atsukawa, M., Hirooka, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Takaaki, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Cucchetti, A., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.
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Oncology ,Phenylurea Compound ,atezolizumab ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Quinoline ,lenvatinib ,bevacizumab ,chemistry.chemical_compound ,Liver disease ,Retrospective Studie ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Medicine ,Humans ,nonalcoholic steatohepatitis ,Original Research ,Retrospective Studies ,Univariate analysis ,Settore MED/12 - Gastroenterologia ,Performance status ,business.industry ,Phenylurea Compounds ,Hazard ratio ,Liver Neoplasms ,Retrospective cohort study ,Hepatitis C ,hepatocellular carcinoma ,medicine.disease ,Prognosis ,digestive system diseases ,advanced hepatocarcinoma ,hepatitis C ,immunotherapy ,sorafenib ,chemistry ,Liver Neoplasm ,Hepatocellular carcinoma ,nonalcoholic steatohepatiti ,Quinolines ,business ,Lenvatinib ,Human - Abstract
Background Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin–bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). Conclusion NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients., Highlights • Evidence supported the idea that etiology could sustain a crucial role in biological behavior. • NASH constitutes one of the more important risk factors for hepatocarcinoma, and its incidence is increasing very fast. • We performed an analysis in patients treated with lenvatinib as the first-line therapy. • NASH was found to be an independent prognostic factor.
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- 2021
9. Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: An inverse probability of treatment weighting analysis
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Andrea Casadei‐Gardini, Mario Scartozzi, Toshifumi Tada, Changhoon Yoo, Shigeo Shimose, Gianluca Masi, Sara Lonardi, Luca Giovanni Frassineti, Silvestris Nicola, Fabio Piscaglia, Takashi Kumada, Hyung‐Don Kim, Hironori Koga, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Yeonghak Bang, Masanori Atsukawa, Takuji Torimura, Kunihiko Tsuj, Ei Itobayashi, Hidenori Toyoda, Shinya Fukunishi, Lorenza Rimassa, Margherita Rimini, Stefano Cascinu, Alessandro Cucchetti, Shinichiro Nakamura, Kojiro Michitaka, Norio Itokawa, Korenobu Hayama, Masashi Hirooka, Yohei Koizumi, Yoichi Hiasa, Toru Ishikawa, Michitaka Imai, Koichi Takaguchi, Akemi Tsutsui, Takuya Nagano, Kazuya Kariyama, Kazuhiro Nouso, Kazuto Tajiri, Noritomo Shimada, Hiroshi Shibata, Hironori Ochi, Kouji Joko, Satoshi Yasuda, Hideko Ohama, Kazuhito Kawata, Casadei-Gardini A., Scartozzi M., Tada T., Yoo C., Shimose S., Masi G., Lonardi S., Frassineti L.G., Nicola S., Piscaglia F., Kumada T., Kim H.-D., Koga H., Vivaldi C., Solda C., Hiraoka A., Bang Y., Atsukawa M., Torimura T., Tsuj K., Itobayashi E., Toyoda H., Fukunishi S., Rimassa L., Rimini M., Cascinu S., Cucchetti A., Nakamura S., Michitaka K., Itokawa N., Hayama K., Hirooka M., Koizumi Y., Hiasa Y., Ishikawa T., Imai M., Takaguchi K., Tsutsui A., Nagano T., Kariyama K., Nouso K., Tajiri K., Shimada N., Shibata H., Ochi H., Joko K., Yasuda S., Ohama H., Kawata K., Casadei-Gardini, A., Scartozzi, M., Tada, T., Yoo, C., Shimose, S., Masi, G., Lonardi, S., Frassineti, L. G., Nicola, S., Piscaglia, F., Kumada, T., Kim, H. -D., Koga, H., Vivaldi, C., Solda, C., Hiraoka, A., Bang, Y., Atsukawa, M., Torimura, T., Tsuj, K., Itobayashi, E., Toyoda, H., Fukunishi, S., Rimassa, L., Rimini, M., Cascinu, S., Cucchetti, A., Nakamura, S., Michitaka, K., Itokawa, N., Hayama, K., Hirooka, M., Koizumi, Y., Hiasa, Y., Ishikawa, T., Imai, M., Takaguchi, K., Tsutsui, A., Nagano, T., Kariyama, K., Nouso, K., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Joko, K., Yasuda, S., Ohama, H., and Kawata, K.
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Sorafenib ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Antineoplastic Agents ,lenvatinib ,survival ,trans-arterial chemoembolization ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,performance status ,Humans ,Adverse effect ,Probability ,Hepatology ,Performance status ,business.industry ,Phenylurea Compounds ,Carcinoma ,Liver Neoplasms ,Hepatocellular ,medicine.disease ,extrahepatic disease ,sorafenib ,Quinolines ,chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cohort ,030211 gastroenterology & hepatology ,Lenvatinib ,business ,medicine.drug ,performance statu - Abstract
Purpose Data from common clinical practice were used to generate balanced cohorts of patients receiving either sorafenib or lenvatinib, for unresectable hepatocellular carcinoma, with the final aim to investigate their declared equivalence. Methods Clinical features of lenvatinib and sorafenib patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival was the primary endpoint and occurrence of adverse events was the secondary. Results The analysis included 385 patients who received lenvatinib, and 555 patients who received sorafenib. In the unadjusted cohort, lenvatinib did not show a survival advantage over sorafenib (HR: 0.85, 95% CI 0.70-1.02). After IPTW adjustment, lenvatinib still not returned a survival advantage over sorafenib (HR: 0.82, 95% CI: 0.62-1.07) even in presence of balanced baseline characteristics. Lenvatinib provided longer survival than sorafenib in patients previously submitted to TACE (HR: 0.69), with PS of 0 (HR: 0.73) or without extrahepatic disease (HR: 0.69). Conclusion Present results confirmed randomized controlled trial in the real-life setting, but also suggests that in earlier stages some benefit can be expected.
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- 2021
10. Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib
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Joji Tani, Noritomo Shimada, Taeang Arai, Massimo Iavarone, Valentina Burgio, Koichi Takaguchi, Masanori Atsukawa, Marianna Silletta, Hideko Ohama, Takaaki Tanaka, Hironori Koga, Masashi Hirooka, Emiliano Tamburini, Stefano Cascinu, Ei Itobayashi, Luca Aldrighetti, Gianluca Masi, Takashi Kumada, Kazuhito Kawata, Yoichi Hiasa, Toshifumi Tada, Atsushi Hiraoka, Raffaella Tortora, Shinichiro Nakamura, Kouji Joko, Takuji Torimura, Sara Lonardi, Takuya Nagano, Hironori Ochi, Ilario Giovanni Rapposelli, Francesco Giuseppe Foschi, Akemi Tsutsui, Hideki Iwamoto, Shigeo Shimose, Satoshi Yasuda, Tomomi Okubo, Hiroshi Shibata, Takashi Niizeki, Hidenori Toyoda, Giuseppe Cabibbo, Margherita Rimini, Toru Ishikawa, Shinya Fukunishi, Claudia Campani, Kazuya Kariyama, Kazuto Tajiri, Kunihiko Tsuji, Fabio Piscaglia, Andrea Casadei-Gardini, Kazuhiro Nouso, Yohei Koizumi, Francesca Ratti, Norio Itokawa, Michitaka Imai, Rapposelli I.G., Tada T., Shimose S., Burgio V., Kumada T., Iwamoto H., Hiraoka A., Niizeki T., Atsukawa M., Koga H., Hirooka M., Torimura T., Iavarone M., Tortora R., Campani C., Lonardi S., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Giuseppe Foschi F., Silletta M., Tsuji K., Ishikawa T., Takaguchi K., Kariyama K., Itobayashi E., Tajiri K., Shimada N., Shibata H., Ochi H., Yasuda S., Toyoda H., Fukunishi S., Ohama H., Kawata K., Tani J., Nakamura S., Nouso K., Tsutsui A., Nagano T., Tanaka T., Itokawa N., Okubo T., Arai T., Imai M., Joko K., Koizumi Y., Hiasa Y., Rimini M., Ratti F., Aldrighetti L., Cascinu S., Casadei-Gardini A., Rapposelli, I. G., Tada, T., Shimose, S., Burgio, V., Kumada, T., Iwamoto, H., Hiraoka, A., Niizeki, T., Atsukawa, M., Koga, H., Hirooka, M., Torimura, T., Iavarone, M., Tortora, R., Campani, C., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Giuseppe Foschi, F., Silletta, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Tanaka, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Rimini, M., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.
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Phenylurea Compound ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Multivariate analysis ,predictive factors ,adverse event ,lenvatinib ,Gastroenterology ,predictive factor ,chemistry.chemical_compound ,Quality of life ,Internal medicine ,medicine ,Humans ,Adverse effect ,Retrospective Studies ,adverse events ,hepatocellular carcinoma ,Settore MED/12 - Gastroenterologia ,Hepatology ,business.industry ,Phenylurea Compounds ,Liver Neoplasms ,Hazard ratio ,medicine.disease ,Confidence interval ,Discontinuation ,chemistry ,Liver Neoplasm ,Hepatocellular carcinoma ,Quality of Life ,Quinolines ,Lenvatinib ,business - Abstract
Background and Aim: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. Methods: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). Results: The appearance of arterial hypertension G≥2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46–0.93, P=.0188], whereas decreased appetite G≥2 independently predicted decreased OS (HR 1.70, 95% CI 1.25–2.32, P=.0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56–0.93, P=.0149), whereas decreased appetite G≥2 predicted decreased PFS (HR 1.36, 95% CI 1.04–1.77, P=.0277). Conclusions: Our main findings are that the occurrence of arterial hypertension G≥2 is a predictor of longer survival, whereas decreased appetite G≥2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients’ quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.
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- 2021
11. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis
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M. Rimini, L. Rimassa, K. Ueshima, V. Burgio, S. Shigeo, T. Tada, G. Suda, C. Yoo, J. Cheon, D.J. Pinato, S. Lonardi, M. Scartozzi, M. Iavarone, G.G. Di Costanzo, F. Marra, C. Soldà, E. Tamburini, F. Piscaglia, G. Masi, G. Cabibbo, F.G. Foschi, M. Silletta, T. Pressiani, N. Nishida, H. Iwamoto, N. Sakamoto, B.-Y. Ryoo, H.J. Chon, F. Claudia, T. Niizeki, T. Sho, B. Kang, A. D’Alessio, T. Kumada, A. Hiraoka, M. Hirooka, K. Kariyama, J. Tani, M. Atsukawa, K. Takaguchi, E. Itobayashi, S. Fukunishi, K. Tsuji, T. Ishikawa, K. Tajiri, H. Ochi, S. Yasuda, H. Toyoda, C. Ogawa, T. Nishimur, T. Hatanaka, S. Kakizaki, N. Shimada, K. Kawata, T. Tanaka, H. Ohama, K. Nouso, A. Morishita, A. Tsutsui, T. Nagano, N. Itokawa, T. Okubo, T. Arai, M. Imai, A. Naganuma, Y. Koizumi, S. Nakamura, K. Joko, H. Iijima, Y. Hiasa, F. Pedica, F. De Cobelli, F. Ratti, L. Aldrighetti, M. Kudo, S. Cascinu, A. Casadei-Gardini, M Rimini , L Rimassa, K Ueshima, V Burgio, S Shigeo, T Tada, G Suda, C Yoo, J Cheon, D J Pinato, S Lonardi, M Scartozzi, M Iavarone, G G Di Costanzo, F Marra, C Soldà, E Tamburini, F Piscaglia, G Masi, G Cabibbo, F G Foschi, M Silletta, T Pressiani, N Nishida, H Iwamoto, N Sakamoto, B-Y Ryoo, H J Chon, F Claudia, T Niizeki, T Sho, B Kang, A D'Alessio, T Kumada, A Hiraoka, M Hirooka, K Kariyama, J Tani, M Atsukawa, K Takaguchi, E Itobayashi, S Fukunishi, K Tsuji, T Ishikawa, K Tajiri, H Ochi, S Yasuda, H Toyoda, C Ogawa, T Nishimur, T Hatanaka, S Kakizaki, N Shimada, K Kawata , T Tanaka, H Ohama, K Nouso, A Morishita, A Tsutsui, T Nagano, N Itokawa, T Okubo, T Arai, M Imai, A Naganuma, Y Koizumi, S Nakamura, K Joko, H Iijima, Y Hiasa, F Pedica, F De Cobelli, F Ratti, L Aldrighetti, M Kudo, S Cascinu, A Casadei-Gardini, Rimini M., Rimassa L., Ueshima K., Burgio V., Shigeo S., Tada T., Suda G., Yoo C., Cheon J., Pinato D.J., Lonardi S., Scartozzi M., Iavarone M., Di Costanzo G.G., Marra F., Solda C., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Foschi F.G., Silletta M., Pressiani T., Nishida N., Iwamoto H., Sakamoto N., Ryoo B.-Y., Chon H.J., Claudia F., Niizeki T., Sho T., Kang B., D'Alessio A., Kumada T., Hiraoka A., Hirooka M., Kariyama K., Tani J., Atsukawa M., Takaguchi K., Itobayashi E., Fukunishi S., Tsuji K., Ishikawa T., Tajiri K., Ochi H., Yasuda S., Toyoda H., Ogawa C., Nishimur T., Hatanaka T., Kakizaki S., Shimada N., Kawata K., Tanaka T., Ohama H., Nouso K., Morishita A., Tsutsui A., Nagano T., Itokawa N., Okubo T., Arai T., Imai M., Naganuma A., Koizumi Y., Nakamura S., Joko K., Iijima H., Hiasa Y., Pedica F., De Cobelli F., Ratti F., Alrighetti L., Kudo M., Cascinu S., and Casadei-Gardini A.
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atezolizumab ,Cancer Research ,Settore MED/12 - Gastroenterologia ,Oncology ,sorafenib ,NAFLD ,NASH ,advanced HCC ,advanced HCC, NASH, NAFLD, lenvatinib, sorafenib, atezolizumab, bevacizumab ,lenvatinib ,bevacizumab - Abstract
Background: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. Materials and methods: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. Results: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. Conclusions: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.
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- 2022
12. Factors affecting an increase in spleen volume and association of spleen volume variation with the clinical outcomes of atezolizumab and bevacizumab treatment for hepatocellular carcinoma: A retrospective analysis.
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Hatanaka T, Saito N, Kakizaki S, Hiraoka A, Tada T, Kariyama K, Tani J, Takaguchi K, Itobayashi E, Ishikawa T, Toyoda H, Kawata K, Naganuma A, Yata Y, Ohama H, Matono T, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Nakamura S, and Kumada T
- Abstract
Introduction: Gastrointestinal varices rupture is considered to be prone to occur during atezolizumab and bevacizumab (Atez/Bev) treatment. This study aimed to investigate predictive factors affecting the increase in spleen volume (SpV) and the association of SpV variation with the clinical outcomes of Atez/Bev., Methods: A total of 164 HCC patients were included in this retrospective multicenter study. We measured SpV based on CT scans obtained before treatment and at evaluations. We used the inverse probability of treatment weight to address the imbalance between patient characteristics., Results: The median pretreatment SpV was 184 (130-257) cm3 and the median SpV variation was 27 (9-60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. There were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients with SpV variation <25 cm3 and those with SpV variation ≥25 cm3 in the crude (p=0.3 and 0.7) and IPTW-weighted cohorts (p = 0.08 and 0.8, respectively). Regarding pretreatment SpV, there were no significant differences in PFS or OS between patients with and without pretreatment spleen enlargement in the crude (both p = 0.3) and IPTW-weighted cohort (p = 0.6 and 0.3, respectively)., Conclusion: Caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or patients with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy., (S. Karger AG, Basel.)
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- 2024
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13. Identification of risk groups for advanced liver fibrosis in the general population using the Fibrosis-3 index.
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Kariyama K, Kawanaka M, Nouso K, Wakuta A, Shiota S, Kurisu A, Sugiyama A, Akita T, Kumada T, and Tanaka J
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Background and Aim: We conducted a study using the Fibrosis-3 (FIB-3) index, which is the established age-independent index of fibrosis in nonviral liver disease and addresses the limitations of the FIB-4 index in older age group, to assess the liver fibrosis risk among diverse demographic groups in the general population., Methods: We analyzed 31 327 individuals who underwent health examinations between 2013 and 2020 and investigated the distribution of the FIB-3 index by age group. In addition, we examined the age distribution of the FIB-3 index stratified by background factors, such as sex, body mass index (BMI), alcohol consumption habits, and the presence or absence of fatty liver., Results: In terms of age-specific distribution, the FIB-3 index remained below 1.5 in >90% of cases until the age of 50 years but exceeded 1.5 beyond the age of 50 years, in approximately 30% among those aged 70 years. Notably, the FIB-3 index above 31 years old was significantly higher in men than in women. Among the different BMI categories, individuals with BMI < 18.5 exhibited the highest prevalence of fibrosis. Habitual drinkers had a higher proportion with FIB-3. index ≥1.5, and some had FIB-3 index ≥2.5, raising the suspicion of advanced hepatic fibrosis. No distinct association was identified between the FIB-3 index and the presence of fatty liver., Conclusions: The FIB-3 index was useful for identifying cases of advancing hepatic fibrosis in a health checkup population. Liver fibrosis progresses with age in the general population, especially among men, those with low BMI, and habitual drinkers., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2024
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14. A smartphone app-based intervention combined with face-to-face sessions for alcohol dependence at internal medicine clinics: A randomized controlled trial.
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Miyake N, So R, Kariyama K, Itagaki Y, Yamagishi T, Wakuta A, Nishimura M, Murakami S, Ogawa M, Takebayashi Y, Sunami T, Yumoto Y, Ito M, Maesato H, Matsushita S, and Nouso K
- Abstract
Background: Addressing the limited access to treatments for alcohol dependence, we developed ALM-002, a therapeutic application to be "prescribed" for non-abstinence-oriented treatment in internal medicine settings. Our objective was to preliminarily assess the efficacy and safety of ALM-002., Methods: In a multicenter, open-label randomized controlled trial, participants aged ≥20 with alcohol dependence and daily alcohol consumption exceeding 60 g for men and 40 g for women, without severe complications, were randomly assigned to either the intervention group using ALM-002 or the treatment-as-usual control group. Participant in both groups received individual face-to-face sessions by physicians at weeks 0, 4, 8, and 12. The primary endpoint was the change in heavy drinking days (HDDs) from week 0 to week 12. A mixed model for repeated measures was employed., Results: We enrolled 43 participants: 22 in the intervention group and 21 in the control group. A significant reduction in HDDs every 4 weeks from week 0 to week 12 was observed, with a between-group difference of -6.99 days (95% CI: -12.4 to -1.6 days, standardized mean difference: -0.80)., Conclusions: These results indicate the potential of ALM-002 as a viable treatment for alcohol dependence. Further studies are needed to evaluate the clinical potential of ALM-002., Competing Interests: Declaration of competing interest RS reports personal fees from CureApp, Inc., during the conduct of the study; grants from Osake-no-Kagaku Foundation, grants from The Mental Health Okamoto Memorial Foundation, grants from Kobayashi Magobe Memorial Medical Foundation, personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Nippon Shinyaku Co., Ltd., personal fees from Takeda Pharmaceutical Co., Ltd., outside the submitted work; In addition, RS has a patent JP2022049590A, US20220084673A1 pending, a patent JP2022178215A pending, a patent JP2022070086 pending, and a patent JP2023074128A pending. YI, TY received a research funding from CureApp Inc. outside the submitted work. SMa and KN received personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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15. Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Nishikawa H, Tsuji K, Ishikawa T, Tajiri K, Koshiyama Y, Toyoda H, Ogawa C, Hatanaka T, Kakizaki S, Kawata K, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Nishimura T, Imai M, Kosaka H, Naganuma A, Matono T, Aoki T, Kuroda H, Yata Y, Koizumi Y, Nakamura S, Enomoto H, Kaibori M, Hiasa Y, and Kudo M
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- Humans, Male, Female, Middle Aged, Aged, Treatment Outcome, Progression-Free Survival, Adult, Liver Neoplasms drug therapy, Liver Neoplasms mortality, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular mortality, Bevacizumab therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use
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Background: Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC)., Aims: To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial., Methods: A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group)., Results: Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a., Conclusions: Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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16. Prevalence of hazardous drinking and suspected alcohol dependence in Japanese primary care settings.
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So R, Kariyama K, Oyamada S, Matsushita S, Nishimura H, Tezuka Y, Sunami T, Furukawa TA, Kawaguchi M, Kobashi H, Nishina S, Otsuka Y, Tsujimoto Y, Horie Y, Yoshiji H, Yuzuriha T, and Nouso K
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- Humans, Male, Adult, Female, Middle Aged, Japan epidemiology, Cross-Sectional Studies, Aged, Prevalence, Young Adult, Alcohol Drinking epidemiology, East Asian People, Alcoholism epidemiology, Primary Health Care statistics & numerical data
- Abstract
Objective: We aimed to assess the prevalence of hazardous drinking and potential alcohol dependence among Japanese primary care patients, and their readiness to change and awareness of others' concerns., Methods: From July to August 2023, we conducted a multi-site cross-sectional study as a screening survey for participants in a cluster randomized controlled trial. The trial included outpatients aged 20-74 from primary care clinics. Using the Alcohol Use Disorders Identification Test (AUDIT) alongside a self-administered questionnaire, we evaluated the prevalence of hazardous drinking and suspected alcohol dependence, patients' readiness to change, and their awareness of others' concerns., Results: Among the 1388 participants from 18 clinics, 22% (95% confidence interval (CI): 20% to 24%) were identified as engaging in hazardous drinking or suspected of being alcohol dependent. As the AUDIT scores increased, so did their readiness to change. However, only 22% (95%CI: 16% to 28%) of those with scores ranging from 8 to 14 reported that others, including physicians, had expressed concerns about their drinking during the past year. For those with scores of 15 or higher, the figure was 74%., Conclusions: This study underscores the need for universal or high-risk alcohol screening and brief intervention in Japanese primary care settings. Trial registry UMIN-CTR (https://www.umin.ac.jp/ctr/) (UMIN000051388)., Competing Interests: Declaration of competing interest RS and HN were employees of CureApp, Inc. during the conduct of the study. RS reports grants from Osake-no-Kagaku Foundation, grants from The Mental Health Okamoto Memorial Foundation, grants from Kobayashi Magobe Memorial Medical Foundation, personal fees from Otsuka Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Sumitomo Pharma Co., Ltd. outside the submitted work; In addition, RS has a patent JP2022049590A, US20220084673A1 pending, a patent JP2022178215A pending, a patent JP2022070086 pending, and a patent JP2023074128A pending. TAF reports personal fees from Boehringer-Ingelheim, Daiichi Sankyo, DT Axis, Kyoto University Original, Shionogi, SONY and UpToDate, and a grant from DT Axis and Shionogi, outside the submitted work; In addition, TAF has patents 2020–548,587 and 2022–082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. YH and HY report personal fees from Otsuka Pharmaceutical and Cure App Inc. outside the submitted work. SM has received a research grant from Asahi Quality & Innovations, Ltd. and has received speaker's honoraria from EA Pharma, Otsuka Pharmaceutical, Yoshitomi Yakuhin, Eisai, Nippon Shinyaku, Otsuka Pharmaceutical and MSD, and personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work within the past three years. YT reports personal fees from Otsuka Pharmaceutical Co., MSD K.K. TY reports personal fees from Otsuka Pharmaceutical, Cure App Inc., and Nippon Shinyaku Co., Ltd. outside the submitted work. KN received personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work. Other authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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17. Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.
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Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Rossari F, Yoo C, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Bergamo F, Amadeo E, Vitiello F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Iavarone MA, Cabibbo G, Montes M, Foschi FG, Vivaldi C, Soldà C, Sho T, Niizeki T, Nishida N, Steup C, Bruccoleri M, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Hiraoka A, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Foti S, Camera S, Piscaglia F, Scartozzi M, Cascinu S, and Casadei-Gardini A
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Aged, 80 and over, Adult, Prognosis, Bevacizumab therapeutic use, Bevacizumab pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized adverse effects, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology
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Background: In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors., Objective: This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting., Patients and Methods: The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea)., Results: Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13-0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24-0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43-0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38-0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65-0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52-0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64-0.98; p = 0.03) as independent prognostic factors for progression-free survival., Conclusions: As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab., (© 2024. The Author(s).)
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- 2024
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18. Response to the letter: "Predictive factors for transition to conversion therapy in HCC using atezolizumab plus bevacizumab".
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Kikuchi T, Takeuchi Y, Nouso K, Kariyama K, Kuwaki K, Toshimori J, Iwado S, Moriya A, Hagihara H, Takabatake H, Tada T, Yasunaka T, Sakata M, Sue M, Miyake N, Adachi T, Wada N, Onishi H, Shiraha H, Takaki A, and Otsuka M
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- Humans, Bevacizumab therapeutic use, Bevacizumab administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Liver Neoplasms drug therapy, Carcinoma, Hepatocellular drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use
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- 2024
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19. Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents.
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Ohama H, Hiraoka A, Tada T, Kariyama K, Itobayashi E, Tsuji K, Ishikawa T, Toyoda H, Hatanaka T, Kakizaki S, Naganuma A, Tada F, Tanaka H, Nakamura S, Nouso K, Tanaka K, and Kumada T
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- Humans, Aged, Male, Retrospective Studies, Female, Middle Aged, Japan, Treatment Outcome, Prognosis, Hepatitis C drug therapy, Hepatitis C complications, Age Factors, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic complications, Hepacivirus, Survival Rate, East Asian People, Carcinoma, Hepatocellular virology, Carcinoma, Hepatocellular mortality, Antiviral Agents therapeutic use, Liver Neoplasms virology, Liver Neoplasms mortality, Sustained Virologic Response
- Abstract
Background and Aim: Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development., Methods: A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed., Results: Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 10
4 /μL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0)., Conclusion: The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)- Published
- 2024
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20. The gender difference in expressed concerns about hazardous drinking in primary care settings.
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Nishimura H, So R, Kariyama K, Oyamada S, Matsushita S, Furukawa TA, and Nouso K
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- 2024
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21. Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab.
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Kikuchi T, Takeuchi Y, Nouso K, Kariyama K, Kuwaki K, Toshimori J, Iwado S, Moriya A, Hagihara H, Takabatake H, Tada T, Yasunaka T, Sakata M, Sue M, Miyake N, Adachi T, Wada N, Onishi H, Shiraha H, Takaki A, and Otsuka M
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- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Adult, Multivariate Analysis, Neoplasm Staging, Treatment Outcome, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular therapy, Liver Neoplasms drug therapy, Liver Neoplasms therapy, Liver Neoplasms pathology, Bevacizumab therapeutic use, Bevacizumab administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Background: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC)., Methods: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified., Results: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03)., Conclusion: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2024
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22. mADRES predicts hepatocellular carcinoma development in patients with hepatitis C virus who achieved sustained virological response.
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Tada T, Kumada T, Hiraoka A, Kariyama K, Yasuda S, Tada F, Ohama H, Nouso K, Matono T, Nakamura S, and Toyoda H
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- Humans, Male, Female, Middle Aged, Aged, Proportional Hazards Models, Predictive Value of Tests, Sex Factors, Carcinoma, Hepatocellular virology, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular epidemiology, Liver Neoplasms virology, Liver Neoplasms etiology, Liver Neoplasms epidemiology, Sustained Virologic Response, alpha-Fetoproteins analysis, alpha-Fetoproteins metabolism, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic complications
- Abstract
Background and Aim: The study aims to develop a novel predictive model including the fibrosis (FIB)-3 index for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) who achieved sustained virological response (SVR) with direct-acting antiviral (DAA) therapy., Methods: This study included 2529 patients in whom HCV was eradicated with DAA therapy. The after DAA recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used to predict HCC development. We developed a modified ADRES (mADRES) score, in which the FIB-4 index was replaced by the FIB-3 index, and evaluated its usefulness in predicting HCC development compared with the ADRES score., Results: In the training set (n = 1770), multivariate analysis with Cox proportional hazards modeling showed that male sex (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.48-3.01), FIB-3 index (HR, 1.36; 95% CI, 1.28-1.45), and α-fetoprotein (HR, 1.05; 95% CI, 1.03-1.07) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES or mADRES score in multiple comparisons. Univariate Cox proportional hazards models showed that compared with the mADRES score 0 group, the HR for HCC development was 2.07 (95% CI, 1.02-4.19) for the mADRES score 1 group, 11.37 (95% CI, 5.80-22.27) for the mADRES score 2 group, and 21.95 (95% CI, 10.17-47.38) for the mADRES score 3 group. Similar results were obtained for mADRES score but not for ADRES score in the validation set (n = 759)., Conclusion: The mADRES score is useful for predicting HCC development after SVR., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2024
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23. Impact of body mass index on the prognosis of unresectable HCC patients receiving first-line Lenvatinib or atezolizumab plus bevacizumab.
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Rimini M, Stefanini B, Tada T, Suda G, Shimose S, Kudo M, Finkelmeier F, Yoo C, Presa J, Amadeo E, Genovesi V, De Grandis MC, Iavarone M, Marra F, Foschi F, Tamburini E, Rossari F, Vitiello F, Bartalini L, Soldà C, Tovoli F, Vivaldi C, Lonardi S, Silletta M, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Himmelsbach V, Montes M, Hiraoka A, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Persano M, Camera S, Foti S, Aldrighetti L, Cascinu S, Casadei-Gardini A, and Piscaglia F
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- Humans, Bevacizumab therapeutic use, Body Mass Index, Overweight, Prognosis, Thinness, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Hepatocellular, Liver Neoplasms, Phenylurea Compounds therapeutic use, Quinolines therapeutic use
- Abstract
Introduction: Overweight is a negative prognostic factor in the general population in the long term. However, the role of body mass index (BMI) in the short-mid term in advanced tumours is unclear. The present analysis investigates the role of BMI weight classes in a large sample of patients affected by HCC and receiving atezolizumab plus bevacizumab or lenvatinib as first-line treatment., Methods and Material: The cohort included consecutive patients affected by BCLC-c and BCLC-B HCC patients from a multicenter international study group who received atezolizumab plus bevacizumab or lenvatinib as first-line therapy. Population was stratified according to the BMI in under-, over- and normal-weight according to the conventional thresholds. The primary objective of the study was to evaluate the prognostic and predictive impact of BMI in patients affected by advanced or intermediate HCC. Survival curves were estimated using the product-limit method of Kaplan-Meier. The role of stratification factors was analysed with log-rank tests., Results: 1292 consecutive patients with HCC were analysed. 466 (36%) patients were treated with lenvatinib and 826 (64%) patients were treated with atezolizumab plus bevacizumab. In the atezolizumab plus bevacizumab arm, 510 (62%) patients were normal-weight, 52 (6%) underweight and 264 (32%) overweight. At the univariate analysis for OS, underweight patients had significantly shorter OS compared to normal-weight patients, whereas no differences were found between normal-weight versus overweight. Multivariate analysis confirmed that underweight patients had significantly shorter OS compared to normal-weight patients (HR: 1.7; 95% CI: 1.0-2.8; p = .0323). In the lenvatinib arm, 26 patients (5.6%) were categorized as underweight, 256 (54.9%) as normal-weight, and 184 (39.5%) as overweight. At the univariate analysis for OS, no significant differences were found between normal-weight versus underweight and between normal-weight versus overweight, which was confirmed at multivariate analysis., Conclusion: Our analysis highlighted a prognostic role of BMI in a cohort of patients with advanced HCC who received atezolizumab plus bevacizumab, while no prognostic role for low BMI was apparent in patients who received lenvatinib., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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24. Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease.
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Nouso K, Kawanaka M, Fujii H, Kariyama K, Toyoda H, Iwaki M, Hayashi H, Oeda S, Hyogo H, Morishita A, Munekage K, Kawata K, Tsutsumi T, Sawada K, Maeshiro T, Tobita H, Yoshida Y, Naito M, Araki A, Arakaki S, Kawaguchi T, Noritake H, Ono M, Masaki T, Yasuda S, Tomita E, Yoneda M, Tokushige A, Kamada Y, Takahashi H, Ueda S, Aishima S, Sumida Y, Nakajima A, Kumada T, and Okanoue T
- Abstract
Background and Aims: Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort., Methods: The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study., Results: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001)., Conclusion: The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age., (© 2024 The Japan Society of Hepatology.)
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- 2024
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25. Clinical usefulness of newly developed prognostic predictive score for atezolizumab plus bevacizumab for hepatocellular carcinoma.
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Ohama H, Hiraoka A, Tada T, Hirooka M, Kariyama K, Hatanaka T, Tani J, Takaguchi K, Atsukawa M, Itobayashi E, Nishimura T, Tsuji K, Tajiri K, Ishikawa T, Yasuda S, Toyoda H, Fukunishi S, Ogawa C, Kakizaki S, Shimada N, Naganuma A, Kawata K, Kosaka H, Kuroda H, Matono T, Yata Y, Ochi H, Tada F, Nouso K, Morishita A, Itokawa N, Okubo T, Arai T, Tsutsui A, Nagano T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, and Kumada T
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- Male, Humans, Aged, Bevacizumab, Prognosis, Retrospective Studies, alpha-Fetoproteins, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Antibodies, Monoclonal, Humanized
- Abstract
Aims: The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment., Methods: A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c-index) and Akaike information criterion (AIC) results., Results: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring system. For IMABALI-De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p < .001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0, 1, and 2, OS was 26.11, 20.29, and 11.32 months, respectively (p < .001; AIC 2864.54, c-index 0.606). PFS periods for those IMABALI-De scores were 21.75, 12.89, 9.18, 8.0, 5.0, and 3.75 months, respectively (p < .001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores were 10.32, 7.68, and 3.57 months, respectively (p < .001; AIC 5246.61, c-index 0.574). As compared with CRAFITY score, IMABALI-De score had better AIC and c-index results for both OS and PFS., Conclusion: The present results indicated that the proposed IMABALI-De score may be favorable for predicting prognosis of uHCC patients receiving Atez/Bev therapy., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)
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- 2024
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26. Comparative analysis of the therapeutic outcomes of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma patients aged 80 years and older: Multicenter study.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Yokohama K, Nishikawa H, Nishimura T, Shimada N, Kawata K, Kosaka H, Naganuma A, Yata Y, Ohama H, Kuroda H, Aoki T, Tanaka K, Tanaka T, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Kudo M, and Kumada T
- Abstract
Aim: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older., Methods: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first-line treatment, respectively, were retrospectively analyzed., Results: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01-86.0) and 83.0 (82.0-86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression-free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group., Conclusions: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first-line treatment even for elderly HCC patients., (© 2023 Japan Society of Hepatology.)
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- 2024
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27. α-FAtE: A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma.
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Rossari F, Tada T, Suda G, Shimose S, Kudo M, Yoo C, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Bergamo F, Amadeo E, Vitiello F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Iavarone M, Cabibbo G, Montes M, Foschi FG, Vivaldi C, Soldà C, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Hiraoka A, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Persano M, Burgio V, Piscaglia F, Scartozzi M, Cascinu S, Casadei-Gardini A, and Rimini M
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- Humans, Bevacizumab therapeutic use, Prospective Studies, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Phenylurea Compounds, Quinolines, Antibodies, Monoclonal, Humanized
- Abstract
Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first-line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real-world AB-treated HCC patients were analyzed in uni- and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α-FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni- and multivariate analyses for OS of a comparable lenvatinib-treated HCC population. Finally, comparison between treatments was performed in patients with low and high α-FAtE scores and predictivity estimated by interaction analysis. Time-to-progression (TTP) was a secondary endpoint. OS of AB-treated HCC patients was statistically longer in those with α-fetoprotein <400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) <125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α-FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p < .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p < .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α-FAtE score resulted as negative predictive factor of response to AB (p = .0004). In conclusion, α-FAtE is a novel prognostic and predictive score of response to first-line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB., (© 2023 UICC.)
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- 2024
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28. Treatment options for solitary hepatocellular carcinoma ≤5 cm: surgery vs. ablation: a multicenter retrospective study.
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Kariyama K, Nouso K, Hiraoka A, Toyoda H, Tada T, Tsuji K, Ishikawa T, Hatanaka T, Itobayashi E, Takaguchi K, Tsutsui A, Naganuma A, Yasuda S, Kakizaki S, Wakuta A, Shiota S, Kudo M, and Kumada T
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Background/aim: The aim of this study was to compare the therapeutic efficacy of ablation and surgery in solitary hepatocellular carcinoma (HCC) measuring ≤5 cm with a large HCC cohort database., Methods: The study included consecutive 2,067 patients with solitary HCC who were treated with either ablation (n=1,248) or surgery (n=819). Th e patients were divided into three groups based on the tumor size and compared the outcomes of the two therapies using propensity score matching., Results: No significant difference in recurrence-free survival (RFS) or overall survival (OS) was found between surgery and ablation groups for tumors measuring ≤2 cm or >2 cm but ≤3 cm. For tumors measuring >3 cm but ≤5 cm, RFS was significantly better with surgery than with ablation (3.6 and 2.0 years, respectively, P=0.0297). However, no significant difference in OS was found between surgery and ablation in this group (6.7 and 6.0 years, respectively, P=0.668)., Conclusion: The study suggests that surgery and ablation can be equally used as a treatment for solitary HCC no more than 3 cm in diameter. For HCCs measuring 3-5 cm, the OS was not different between therapies; thus, ablation and less invasive therapy can be considered a treatment option; however, special caution should be taken to prevent recurrence.
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- 2024
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29. Reply to the Letter regarding "Treatment options for solitary hepatocellular carcinoma ≤5 cm: surgery vs. ablation: a multicenter retrospective study".
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Nouso K and Kariyama K
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- 2024
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30. Safety and Efficacy of Lenvatinib in Very Old Patients with Unresectable Hepatocellular Carcinoma.
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Camera S, Rimini M, Rossari F, Tada T, Suda G, Shimose S, Kudo M, Yoo C, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Bergamo F, Salani F, Marseglia M, Amadeo E, Vitiello F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Iavarone M, Cabibbo G, Montes M, Foschi FG, Vivaldi C, Lonardi S, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Hiraoka A, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Persano M, Foti S, Piscaglia F, Scartozzi M, Cascinu S, and Casadei-Gardini A
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- Humans, Aged, 80 and over, Phenylurea Compounds adverse effects, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Quinolines pharmacology, Quinolines therapeutic use
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Background: Data concerning the use of lenvatinib in very old patients (≥ 80 years) are limited, although the incidence of hepatocellular carcinoma (HCC) in this patient population is constantly increasing., Objective: This analysis aimed to evaluate the efficacy and safety of lenvatinib in a large cohort of very old patients (≥ 80 years) with unresectable HCC., Patients and Methods: The study was conducted on a cohort of 1325 patients from 46 centers in four Western and Eastern countries (Italy, Germany, Japan, and the Republic of Korea) who were undergoing first-line treatment with lenvatinib between July 2010 and February 2022. Patients were stratified according to age as very old (≥ 80 years) and not very old (< 80 years)., Results: The median overall survival (OS) was 15.7 months for patients < 80 years old and 18.4 months for patients ≥ 80 years old [hazard ratio (HR) = 1.02, 95% confidence interval (CI) 0.84-1.25, p = 0.8281]. Median progression free survival (PFS) was 6.3 months for patients < 80 years old and 6.5 months for patients ≥ 80 years old (HR = 1.07, 95% CI 0.91-1.25, p = 0.3954). No differences between the two study groups were found in terms of disease control rate (DCR; 80.8% versus 78.8%; p = 0.44) and response rate (RR; 38.2% versus 37.9%; p = 0.88). Patients < 80 years old experienced significantly more hand-foot skin reaction (HFSR) grade ≥ 2 and decreased appetite grade ≥ 2. Conversely, patients ≥ 80 years old experienced significantly more fatigue grade ≥ 2. In the very old group, parameters associated with prognosis were AFP, albumin-bilirubin (ALBI) grade, Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh score. BCLC stage was the only independent predictor of overall survival (OS; HR = 1.59, 95% CI 1.11-2.29, p = 0.01115)., Conclusions: Our study highlights the same efficacy and safety of lenvatinib between very old and not very old patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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31. Comparison of prognostic impact of atezolizumab plus bevacizumab versus lenvatinib in patients with intermediate-stage hepatocellular carcinoma.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Matono T, Aoki T, Kuroda H, Yata Y, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, and Kudo M
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- Humans, Prognosis, Bevacizumab therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Antineoplastic Agents therapeutic use
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Background & Aims: The study goal was to compare the outcomes of patients with intermediate-stage (Barcelona Clinic Liver Cancer [BCLC]-B) hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic therapy., Methods: A total of 358 patients with BCLC-B HCC treated with Atezo/Bev (n = 177) or LEN (n = 181) as first-line systemic therapy were included., Results: The median progression-free survival (PFS) times in the Atezo/Bev and LEN groups were 10.8 months (95% confidence interval [CI], 7.8-12.6) and 7.3 months (95% CI, 6.3-8.5), respectively (p = .019). In the propensity score-matched cohort, the median PFS times in the Atezo/Bev (n = 151) and LEN (n = 151) groups were 10.2 months (95% CI, 7.0-12.3) and 6.9 months (95% CI, 5.9-8.1), respectively (p = .020). Restricted mean survival times of PFS were significantly higher in the Atezo/Bev group than in the LEN group at landmarks of 12 and 18 months (p = .031 and .012, respectively). In a subgroup analysis of patients with HCC beyond the up-to-seven criteria, the median PFS times in the Atezo/Bev (n = 134) and LEN (n = 117) groups were 10.5 months (95% CI, 7.0-11.8) and 6.3 months (95% CI, 5.5-7.3), respectively (p = .044)., Conclusions: The use of Atezo/Bev as first-line systemic therapy in patients with BCLC-B HCC is expected to result in good PFS., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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32. Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Yokohama K, Nishikawa H, Nishimura T, Shimada N, Kawata K, Kosaka H, Naganuma A, Yata Y, Ohama H, Kuroda H, Tanaka K, Tanaka T, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Kudo M, and Kumada T
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- Humans, Bevacizumab adverse effects, Retrospective Studies, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
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Aim: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma., Methods: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity-score-matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed-effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow-up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups., Results: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were -2.41 ± 0.40 and -2.44 ± 0.42 at baseline, and -2.17 ± 0.56 and -2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN-treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev., Conclusions: Using a nonlinear mixed-effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN-treated patients with BCLC advanced stage or those receiving the full dose of LEN., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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33. Efficacy and safety of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients with esophageal-gastric varices.
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Tada F, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, and Kumada T
- Abstract
Background: Bevacizumab inhibits vascular endothelial growth factor-A (VEGF-A), though is known to increase bleeding risk as an adverse event (AE). This study examined whether atezolizumab/bevacizumab (Atez/Bev) for unresectable hepatocellular carcinoma (uHCC) can be used for patients with esophageal-gastric varices (EGV)., Methods: From October 2020 to December 2022, 506 uHCC patients (median 74 years) underwent an upper gastrointestinal endoscopy examination were enrolled, after exclusion of those with portal vein tumor thrombus (PVTT). Patients with EGV (≧ F1) were defined as EGV positive, and the cohort was divided into non-EGV (n = 355) and EGV (n = 151). Before introducing Atez/Bev, endoscopic treatment was performed, when necessary. Prognosis was evaluated, retrospectively., Results: The EGV group had significantly worse hepatic function, lower platelet count, elevated alpha-fetoprotein, and lower rate of extrahepatic metastasis, and lower rate of first-line use (each P < 0.05) than the other. However, progression-free survival (PFS) was also not a significantly difference between the EGV and non-EGV groups in analyses with (PFS rate at 6/12/18 months: 60%/38%/30% vs. 65%/46%/34%, P = 0.29) or without inverse probability weighting adjustment [median: 10.6 months (95% CI 8.3-14.0) vs. 10.5 months (95% CI 7.8-13.7), P = 0.79]. As for AEs, diarrhea was more frequent in the EGV group (≧ G3: 2.0% vs. 0.3%, P = 0.036), while no significant difference was noted for EGV hemorrhage (≧ G3: 1.3% vs. 0.6%, P = 0.345). Of 28 patients who underwent endoscopic treatments before introducing Atez/Bev, none showed EGV-associated hemorrhage., Conclusions: Atez/Bev might be an effective therapeutic option in patients with EGV, when appropriate endoscopic treatment for EGV is performed., (© 2023. Japanese Society of Gastroenterology.)
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- 2023
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34. Geriatric nutritional risk index as an easy-to-use assessment tool for nutritional status in hepatocellular carcinoma treated with atezolizumab plus bevacizumab.
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Hiraoka A, Kumada T, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, and Hiasa Y
- Abstract
Aim: The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy-to-use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC)., Methods: A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child-Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI., Results: Atez/Bev was used in 338 of the present cohort as first-line systemic chemotherapy (64.4%). Median progression-free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c-index) values of GNRI for predicting prognosis (progression-free survival/overall survival) were superior to those of Child-Pugh class and albumin-bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649-0.781; specificity/sensitivity = 0.644/0.688)., Conclusion: These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev., (© 2023 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)
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- 2023
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35. The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab.
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Takeuchi Y, Nouso K, Fujioka SI, Kariyama K, Kobashi H, Uematsu S, Moriya A, Hagihara H, Takabatake H, Nakamura S, Yabushita K, Kikuchi T, Oyama A, Adachi T, Wada N, Onishi H, Shiraha H, and Takaki A
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- Humans, Bevacizumab adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Albumins, Bilirubin, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Background and Aims: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice., Methods: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD., Results: There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001)., Conclusions: The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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36. Effect of butyrate-producing enterobacteria on advanced hepatocellular carcinoma treatment with atezolizumab and bevacizumab.
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Nouso K, Shiota S, Fujita R, Wakuta A, Kariyama K, Hiraoka A, Atsukawa M, Tani J, Tada T, Nakamura S, Tajiri K, Kaibori M, Hirooka M, Itobayashi E, Kakizaki S, Naganuma A, Ishikawa T, Hatanaka T, Fukunishi S, Tsuji K, Kawata K, Takaguchi K, Tsutsui A, Ogawa C, Ochi H, Yata Y, Kuroda H, Iijima H, Matono T, Shimada N, Yasuda S, Toyoda H, and Kumada T
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- Humans, Bevacizumab adverse effects, Butyric Acid, Enterobacteriaceae, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Drug-Related Side Effects and Adverse Reactions
- Abstract
Aim: Multiple studies have revealed the correlation between gut microbiome and the response to checkpoint inhibitors (CPIs) in patients with cancer, and oral administration of butyrate-producing enterobacteria has been reported to enhance the efficacy of CPIs. However, the effects of enterobacteria on patients with hepatocellular carcinoma (HCC) are not well understood., Methods: In this retrospective multicenter study, we enrolled 747 patients with advanced HCC, treated with atezolizumab and bevacizumab combination therapy. Tumor response, survival, and adverse effects were compared between 99 patients who ingested drugs containing butyric acid-producing enterobacteria (butyric acid group) and the remaining patients (control group)., Results: Objective response and disease control rates in butyric acid group (29.7% and 77.8%, respectively) were higher than those in the control group (26.4% and 72.7%, respectively). However, the differences were not statistically significant (p = 0.543 and p = 0.222, respectively). No difference in median survival time was observed between the two groups (20.0 months and 21.4 months, respectively; p = 0.789), even after matching the backgrounds of the patients with propensity scores (p = 0.714). No adverse effects occurred upon the administration of butyrate-producing bacteria. However, proteinuria (41.4% vs. 30.9%; p = 0.041), fever (17.2% vs. 10.2%, p = 0.036), and diarrhea (15.2% vs. 6.2%; p = 0.001) occurred more frequently in the butyric acid group., Conclusion: Butyrate-producing bacteria does not enhance the efficacy of atezolizumab-bevacizumab combination therapy in patients with HCC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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37. Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.
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Tanaka K, Tsuji K, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Ishikawa T, Tajiri K, Ochi H, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, and Kumada T
- Abstract
Aim: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment., Materials/methods: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively., Results: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively ( p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively ( p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a., Conclusions: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.
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- 2023
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38. Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients.
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Rimini M, Persano M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Salani F, Lonardi S, Piscaglia F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Schirripa M, Montes M, Vivaldi C, Soldà C, Hiraoka A, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Burgio V, Scartozzi M, Cascinu S, and Casadei-Gardini A
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- Humans, Bevacizumab, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
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Introduction: The best first-line treatment for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class B remains unknown. The aim of the present study was to perform a real-world analysis on a large sample of patients with unresectable HCC with CP B treated with atezolizumab plus bevacizumab Vs Lenvatinib., Methods: The study population included patients affected by advanced (BCLC-C) or intermediate (BCLC-B) HCC patients not suitable for locoregional therapies from both the Western and Eastern world (Italy, Germany, Republic of Korea and Japan), who received atezolizumab plus bevacizumab or Lenvatinib as first-line treatment. All the study population presented a CP class of B. The primary endpoint of the study was the overall survival (OS) of CP B patients treated with Lenvatinib compared to atezolizumab plus bevacizumab. Survival curves were estimated using the product-limit method of Kaplan-Meier. The role of stratification factors was analyzed with log-rank tests. Finally, an interaction test was performed for the main baseline clinical characteristics., Results: 217 CP B HCC patients were enrolled in the study: 65 (30%) received atezolizumab plus bevacizumab, and 152 (70%) received lenvatinib. The mOS for patients receiving Lenvatinib was 13.8 months (95% CI: 11.6-16.0), compared to 8.2 months (95% CI 6.3-10.2) for patients receiving atezolizumab plus bevacizumab as first-line treatment (atezolizumab plus bevacizumab Vs Lenvatinib: HR 1.9, 95% CI 1.2-3.0, p = 0.0050). No statistically significant differences were highlighted in terms of mPFS. The multivariate analysis confirmed that patients receiving Lenvatinib as first-line treatment have a significantly longer OS compared to patients receiving atezolizumab plus bevacizumab (HR 2.01; 95% CI 1.29-3.25, p = 0.0023). By evaluating the cohort of patients who received atezolizumab plus bevacizumab, we found that Child B patients with ECOG PS 0, or BCLC B stage or ALBI grade 1 were those who had benefited from the treatment thus showing survival outcomes no significantly different compared to those receiving Lenvatinib., Conclusion: The present study suggests for the first time a major benefit from Lenvatinib compared to atezolizumab plus bevacizumab in a large cohort of patients with CP B class HCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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39. Impact of first-line systemic therapy with atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Matono T, Koizumi Y, Nakamura S, Kaibori M, Iijima H, and Hiasa Y
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- Humans, Bevacizumab adverse effects, Ambulatory Care Facilities, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Background and Aim: The study goal was to compare the outcomes of patients with unresectable hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) as either first- or later-line systemic therapy., Methods: A total of 430 patients with HCC treated with Atezo/Bev at 22 institutions in Japan were included. Patients treated with Atezo/Bev as first-line therapy for HCC were defined as the first-line group (n = 268) while those treated with Atezo/Bev as second- or later-line therapy were defined as the later-line group (n = 162)., Results: The median progression-free survival times in the first- and later-line groups were 7.7 months (95% confidence interval [CI], 6.7-9.2) and 6.2 months (95% CI, 5.0-7.7) (P = 0.021). Regarding treatment-related adverse events, hypertension of any grade was more common in the first-line group than in the later-line group (P = 0.025). Analysis adjusted by inverse probability weighting, including patient and HCC characteristics, showed that the later-line group (hazard ratio, 1.304; 95% CI, 1.006-1.690; P = 0.045) was significantly associated with progression-free survival. In patients with Barcelona Clinic Liver Cancer stage B, the median progression-free survival times in the first- and later-line groups were 10.5 months (95% CI, 6.8-13.8) and 6.8 months (95% CI, 5.0-9.4) (P = 0.021). Among patients with a history of lenvatinib therapy, the median progression-free survival times in the first- and later-line groups were 7.7 months (95% CI, 6.3-9.2) and 6.2 months (95% CI, 5.0-7.7) (P = 0.022)., Conclusion: The use of Atezo/Bev as first-line systemic therapy in patients with HCC is expected to prolong survival., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2023
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40. Association of proton pump inhibitor and antibiotic use with the clinical outcomes of hepatocellular carcinoma patients receiving atezolizumab and bevacizumab: A multicenter analysis.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Shimada N, Kawata K, Kosaka H, Naganuma A, Yata Y, Tanaka T, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, and Kumada T
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Aim: This retrospective study aimed to investigate the impact of proton pump inhibitor treatment (PPI) and antibiotic treatment on the therapeutic outcomes of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/Bev)., Methods: The present study included a total of 441 HCC patients who were treated with Atez/Bev in 20 Japanese institutions from September 2020 to April 2022. We adopted the inverse probability of treatment weight to adjust for imbalance in the baseline characteristics of patients with and without PPI treatment as well as patients with and without antibiotic treatment., Results: The progression-free survival (PFS) and overall survival (OS) of patients with and without PPI treatment did not differ to a statistically significant extent. In the weighted cohort, the difference in PFS and OS between the patients with and without PPI did not reach statistical significance (median PFS, 7.0 vs. 6.5 months, p = 0.07; 1-year survival rate 66.3% and 73.8%, p = 0.9). The PFS and OS in patients with antibiotic treatment were worse in comparison to patients without antibiotic treatment (median PFS, 3.8 vs. 7.0 months, p = 0.007; 1-year survival rate 58.8% and 70.3%, p = 0.01). In the weighted cohort, the PFS and OS of the two groups did not differ to a statistically significant extent (median PFS, 3.8 vs. 6.7 months, p = 0.2; 1-year survival rate, 61.8% and 71.0%, p = 0.6)., Conclusions: The therapeutic outcomes of Atez/Bev in HCC patients did not differ between patients with and without PPI treatment or between patients with and without antibiotic treatment., (© 2023 Japan Society of Hepatology.)
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- 2023
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41. Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients.
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Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Yoo C, Lonardi S, Tovoli F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Niizeki T, Montes M, Vivaldi C, Soldà C, Stefanini B, Hiraoka A, Sho T, Nishida N, Steup C, Iavarone M, Di Costanzo G, Marra F, Tamburini E, Cabibbo G, Foschi FG, Silletta M, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Campani C, Amadeo E, Rossari F, Burgio V, Cascinu S, Scartozzi M, and Casadei-Gardini A
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- Humans, Bevacizumab adverse effects, Sorafenib, Retrospective Studies, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab., Materials and Methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line., Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6months) and atezolizumab plus bevacizumab first-line (15.7months; p = 0.12; hazard ratio [HR]= 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who underwent trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8months, p < 0.01; HR=0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0months) and those who underwent TACE (15.9months) had a significative longer OS than patients treated with sorafenib (14.2months; respectively, p = 0.01; HR=0.45, and p < 0.05; HR=0.46)., Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.C.G. is an advisor for AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, GSK, and MSD; received grants and personal fees from Bayer, Eisai, and MSD. M.S. is an advisor for AMGEN, Eisai, MERCK, MSD, and SERVIER. M.K. received research grant from AbbVie, Astellas Pharma, Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Medico’s Hirata, MSD, Otsuka, Sumitomo Dainippon, Takeda, and Taiho; received advisory consulting fee from BMS, Chugai, Eisai, MSD, Ono pharmaceutical, and Taiho; received lecture fee from Bayer, Chugai, EA Pharma, Eisai, and MSD. The other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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42. Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study.
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Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Rimassa L, Presa J, Masi G, Yoo C, Lonardi S, Tovoli F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Kawaguchi T, Montes M, Vivaldi C, Soldà C, Piscaglia F, Hiraoka A, Sho T, Niizeki T, Nishida N, Steup C, Iavarone M, Di Costanzo G, Marra F, Scartozzi M, Tamburini E, Cabibbo G, Foschi FG, Silletta M, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Cammarota A, Burgio V, Cascinu S, and Casadei-Gardini A
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- Humans, Bevacizumab therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Purpose: The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting., Methods: Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea)., Results: 1312 patients were treated with lenvatinib, and 823 patients were treated with atezolizumab plus bevacizumab. Objective response rate (ORR) was 38.6% for patients receiving lenvatinib, and 27.3% for patients receiving atezolizumab plus bevacizumab (p < 0.01; odds ratio 0.60). For patients who achieved complete response (CR), overall survival (OS) was not reached in both arms, but the result from univariate Cox regression model showed 62% reduction of death risk for patients treated with atezolizumab plus bevacizumab (p = 0.05). In all multivariate analyses, treatment arm was not found to be an independent factor conditioning OS. Comparing ORR achieved in the two arms, there was a statistically significant difference in favor of lenvatinib compared to atezolizumab plus bevacizumab in all subgroups except for Eastern patients, Child-Pugh B patients, presence of portal vein thrombosis, α-feto-protein ≥ 400 ng/mL, presence of extrahepatic disease, albumin-bilirubin (ALBI) grade 2, and no previous locoregional procedures., Conclusion: Lenvatinib achieves higher ORR in all patient subgroups. Patients who achieve CR with atezolizumab plus bevacizumab can achieve OS so far never recorded in HCC patients. This study did not highlight any factors that could identify patient subgroups capable of obtaining CR., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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43. Attempt to Establish Prognostic Predictive System for Hepatocellular Carcinoma Using Artificial Intelligence for Assistance with Selection of Treatment Modality.
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Hiraoka A, Kumada T, Tada T, Toyoda H, Kariyama K, Hatanaka T, Kakizaki S, Naganuma A, Itobayashi E, Tsuji K, Ishikawa T, Ohama H, Tada F, and Nouso K
- Abstract
Introduction: Because of recent developments in treatments for hepatocellular carcinoma (HCC), methods for determining suitable therapy for initial or recurrent HCC have become important. This study used artificial intelligence (AI) findings to establish a system for predicting prognosis of HCC patients at time of reoccurrence based on clinical data as a reference for selection of treatment modalities., Methods: As a training cohort, 5,701 observations obtained at the initial and each subsequent treatment for recurrence from 1,985 HCC patients at a single center from 2000 to 2021 were used. The validation cohort included 5,692 observations from patients at multiple centers obtained at the time of the initial treatment. An AI calculating system (PRAID) was constructed based on 25 clinical factors noted at each treatment from the training cohort, and then predictive prognostic values for 1- and 3-year survival in both cohorts were evaluated., Results: After exclusion of patients lacking clinical data regarding albumin-bilirubin (ALBI) grade or tumor-node-metastasis stage of the Liver Cancer Study Group of Japan, 6th edition (TNM-LCSGJ 6th), ALBI-TNM-LCSGJ 6th (ALBI-T) and modified ALBI-T scores confirmed that prognosis for patients in both cohorts was similar. The area under the curve for prediction of both 1- and 3-year survival in the validation cohort was 0.841 (sensitivity 0.933 [95% CI: 0.925-0.940], specificity 0.517 [95% CI: 0.484-0.549]) and 0.796 (sensitivity 0.806 [95% CI: 0.790-0.821], specificity 0.646 [95% CI: 0.624-0.668]), respectively., Conclusion: The present PRAID system might provide useful prognostic information related to short and medium survival for decision-making regarding the best therapeutic modality for both initial and recurrent HCC cases., Competing Interests: Atsushi Hiraoka, MD, PhD, received lecture fees from Chugai, Bayer, and Eli Lilly. None of the other authors have potential conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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44. Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, and Hiasa Y
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- Humans, Bevacizumab adverse effects, alpha-Fetoproteins, Fatigue chemically induced, Proteinuria, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Hypertension chemically induced
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Aim: To investigate the possible correlation between the development of adverse events (AEs) and prognosis in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev)., Methods: A total of 286 patients with unresectable HCC treated with Atez/Bev as first-line systematic therapy were included., Results: Regarding treatment-related AEs, decreased appetite of any grade, proteinuria of any grade, and fatigue of any grade were found with a frequency of ≥20%. Multivariate analysis adjusted for immune-related liver injury, immune-related endocrine dysfunction, proteinuria, fatigue, decreased appetite, hypertension, sex, age, Eastern Cooperative Oncology Group performance status, HCC etiology, HCC stage, Child-Pugh score, and α-fetoprotein showed that hypertension of any grade (hazard ratio [HR], 0.527; 95% confidence interval [CI], 0.326-0.854; p = 0.009) and α-fetoprotein ≥100 ng/ml (HR, 1.642; 95% CI, 1.111-2.427; p = 0.013) were independently associated with progression-free survival. Multivariate analysis adjusted for the same AEs showed that fatigue (HR, 2.354; 95% CI, 1.299-4.510; p = 0.010) was independently associated with overall survival. Median progression-free survival was 6.5 months (95% CI, 5.2-8.1) in patients without hypertension of any grade and 12.6 months (95% CI, 6.7-not available) in patients with hypertension of any grade (p = 0.035). The overall survival was significantly shorter in patients in whom treatment-related fatigue of any grade was observed (p < 0.001). Regarding response rates, the disease control rate of patients who developed treatment-related hypertension (94.2%) was significantly higher than those who did not (79.1%) (p = 0.009)., Conclusions: Treatment-related hypertension is associated with good outcomes in patients with HCC treated with Atez/Bev., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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45. Predictive Factors for Recovery from Alcoholic Liver Failure.
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Inoue K, Fujita R, Nagahara T, Murakami S, Nagai Y, Moriwake R, Miyake N, Wakuta A, Kariyama K, Nishimura M, and Nouso K
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- Humans, Liver, Risk Factors, gamma-Glutamyltransferase, Carcinoma, Hepatocellular, Liver Neoplasms, Liver Diseases, Alcoholic, Liver Failure
- Abstract
Alcoholic liver disease is a risk factor for non-virus-related hepatocellular carcinoma (HCC), which is increasing in prevalence. This study aimed to identify the factors for recovery from alcoholic liver failure. Sixty-two consecutive patients hospitalized for alcoholic liver failure at Okayama City Hospital were enrolled. The characteristics of patients who survived to the 1-month follow-up and whose liver function improved to Child-Pugh A at 3 months (CPA3) and 12 months (CPA12) were compared with the rest of the patients. The survivors at 1 month (50 patients) were significantly younger than the deceased patients and had better liver and renal function with higher levels of γ-glutamyl transferase (GGT). The same factors, except renal function, were correlated with achieving CPA3. High AST, ALT, and GGT levels as well as short spleen length, total abstinence, and good Child-Pugh scores at admission were identified as factors for achieving CPA12. The extent of alcohol intake before admission was not identified as a risk factor in any analysis. In conclusion, baseline liver function is crucial for survival and achieving CPA3, whereas high transaminase and γ-GTP levels, the absence of splenomegaly, and total abstinence are significant factors for achieving CPA12., Competing Interests: No potential conflict of interest relevant to this article was reported.
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- 2023
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46. New prognostic system based on inflammation and liver function predicts prognosis in patients with advanced unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A validation study.
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Tada T, Kumada T, Hiraoka A, Kariyama K, Tani J, Hirooka M, Takaguchi K, Atsukawa M, Fukunishi S, Itobayashi E, Tsuji K, Tajiri K, Ochi H, Ishikawa T, Yasuda S, Ogawa C, Toyoda H, Hatanaka T, Nishimura T, Kakizaki S, Kawata K, Shimada N, Tada F, Nouso K, Tsutsui A, Ohama H, Morishita A, Nagano T, Itokawa N, Okubo T, Arai T, Kosaka H, Imai M, Naganuma A, Nakamura S, Koizumi Y, Kaibori M, Iijima H, and Hiasa Y
- Subjects
- Humans, Prognosis, Bevacizumab therapeutic use, Serum Albumin analysis, Inflammation, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology
- Abstract
Aim: Recently, the neo-Glasgow prognostic score (GPS), a composite biomarker determined by the C-reactive protein level and albumin-bilirubin grade, was developed to predict outcomes in hepatocellular carcinoma (HCC) patients who undergo hepatic resection. The present research investigated whether the neo-GPS could predict prognosis in HCC patients treated with atezolizumab plus bevacizumab (Atez/Bev)., Methods: A total of 421 patients with HCC who were treated with Atez/Bev were investigated., Results: Multivariate Cox hazards analysis showed that a GPS of 1 (hazard ratio (HR), 1.711; 95% confidence interval (CI), 1.106-2.646) and a GPS of 2 (HR, 4.643; 95% CI, 2.778-7.762) were independently associated with overall survival. Conversely, multivariate Cox hazards analysis showed that a neo-GPS of 1 (HR, 3.038; 95% CI, 1.715-5.383) and a neo-GPS of 2 (HR, 5.312; 95% CI, 2.853-9.890) were also independently associated with overall survival in this cohort. Additionally, cumulative overall survival rates differed significantly by GPS and neo-GPS (p < 0.001). The neo-GPS, compared with the GPS, had a lower Akaike information criterion (1207 vs. 1,211, respectively) and a higher c-index (0.677 vs. 0.652, respectively) regarding to overall survival. In a subgroup analysis of patients considered to have a good prognosis as confirmed using a Child-Pugh score of 5 (p = 0.001), a neutrophil-to-lymphocyte ratio <3 (p = 0.001), or an α-fetoprotein level < 100 ng/mL (p < 0.001), those with a high neo-GPS (≥1) had a statistically poorer overall survival than those with a low neo-GPS., Conclusions: The neo-GPS can predict prognosis in advanced unresectable HCC patients treated with Atez/Bev., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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47. Comparative efficacy and safety of atezolizumab and bevacizumab between hepatocellular carcinoma patients with viral and non-viral infection: A Japanese multicenter observational study.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Shimada N, Kawata K, Kosaka H, Tanaka T, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Naganuma A, Koizumi Y, Nakamura S, Joko K, Kaibori M, Iijima H, Hiasa Y, and Kumada T
- Subjects
- Humans, Bevacizumab adverse effects, Retrospective Studies, East Asian People, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology
- Abstract
Aim: This study compared the efficacy and safety of atezolizumab and bevacizumab (Atez/Bev) in patients with viral and non-viral infection in clinical settings., Methods: We conducted the retrospective cohort study of 323 BCLC stage B or C hepatocellular carcinoma (HCC) patients with Child-Pugh class A, and a performance status of 0 or 1 who started Atez/Bev from September 2020 to December 2021 at 22 institutions in Japan. Patients with viral infection was defined as those who were either serum anti-HCV- Ab or HBs-Ag-positive, while patients with non-viral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. We constructed a propensity-score-matched cohort to minimize the risk of observable potential confounders., Results: Propensity score matching produced 126 matched pairs for patients with viral versus non-viral infection. After matching, the significant differences in baseline demographic features did not exist between the two groups. The objective response rate was 20.6% and 24.6% in viral- and non-viral-related HCC patients, respectively, without a significant difference (p = 0.55). The disease control rate was not also significantly different (68.3% vs 69.0%, p = 1.00). The median progression-free survival was 7.0 months (95% confidence interval [CI] 6.0-9.6) and 6.2 months (95% CI 5.1-7.8) in patients with viral and non-viral infection, and the 12-month survival rates were 65.5% (95% CI 50.8-76.8) and 71.7% (95% CI 57.3-81.9) in those with viral and non-viral infection, respectively, which were not significantly different (p = 0.33, p = 0.38). No significant difference in treatment-related adverse events was found between the two groups., Conclusions: Our etiology-based study demonstrated that Atez/Bev showed good efficacy and safety for HCC patient with non-viral infection as well as those with viral infection., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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48. Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?
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Rimini M, Persano M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Yoo C, Lonardi S, Piscaglia F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Montes M, Vivaldi C, Soldà C, Hiraoka A, Sho T, Niizeki T, Nishida N, Steup C, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Burgio V, Rimassa L, Scartozzi M, Cascinu S, and Casadei-Gardini A
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- Humans, Bevacizumab pharmacology, Bevacizumab therapeutic use, Prognosis, Albumins, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Background: Atezolizumab plus bevacizumab has recently been approved as a new first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC)., Objective: We performed a real-world study to evaluate the impact of the IMbrave150 trial inclusion criteria on the safety and efficacy of treatment outside of clinical trials., Methods: We analyzed patients treated with atezolizumab plus bevacizumab for unresectable HCC from four different countries. No specific inclusion and exclusion criteria were applied, except for the absence of previous systemic therapies for HCC. The entire population was split into two groups according to concordance with the inclusion criteria as reported in the IMbrave150 trial in 'IMbrave150-in' and 'IMbrave150-out' patients, and safety and efficacy in the two groups of patients were evaluated., Results: Overall, 766 patients were included in the analysis: 561/766 (73%) in the 'IMbrave150-in' group and 205/766 (27%) in the 'IMbrave150-out' group. Median overall survival (OS) and median progression-free survival (PFS) were 16.3 versus 14.3 months (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.35-0.65; p < 0.0001] and 8.3 versus 6.0 months (HR 0.79, 95% CI 0.63-0.99; p = 0.0431) in 'IMbrave150-in' and 'IMbrave150-out' patients, respectively. Multivariate analysis confirmed that patients included in the 'IMbrave150-in' group had significantly longer OS compared with patients included in the 'IMbrave150-out' group (HR 0.76, 95% CI 0.47-0.97; p = 0.0195). In 'IMbrave150-in' patients, the albumin-bilirubin (ALBI) grade was not associated with OS, whereas in 'IMbrave150-out' patients, those with ALBI grade 1 reported a significant benefit in terms of OS compared with those with ALBI grade 2 (16.7 vs. 5.9 months; HR 4.40, 95% CI 2.40-8.08; p > 0.0001). No statistically significant differences were reported in the 'IMbrave150-in' and 'IMbrave150-out' groups in terms of safety profile., Conclusion: Adherence to the IMbrave150 trial inclusion criteria favorably impacts the prognosis of patients receiving atezolizumab plus bevacizumab. Among patients who did not meet the IMbrave150 inclusion criteria, those with ALBI grade 1 could benefit from the treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2023
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49. Correction to: Development and validation of a modified albumin-bilirubin grade and α-fetoprotein score (mALF score) for hepatocellular carcinoma patients receiving atezolizumab and bevacizumab.
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Hatanaka T, Kakizaki S, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Shimada N, Kawata K, Kosaka H, Tanaka T, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, and Kumada T
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- 2023
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50. Letter: rising incidence and poor survival in patients with non-viral HCC - better HCC surveillance and treatment for alcohol-associated and non-alcohol fatty liver diseases are needed. Authors' reply.
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Toyoda H, Kariyama K, and Hiraoka A
- Subjects
- Humans, Incidence, Risk Factors, Ethanol, Carcinoma, Hepatocellular etiology, Liver Neoplasms etiology, Non-alcoholic Fatty Liver Disease epidemiology, Non-alcoholic Fatty Liver Disease complications
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- 2023
- Full Text
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