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1. First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE‑048

Author

Oridate, Nobuhiko, Takahashi, Shunji, Tanaka, Kaoru, Shimizu, Yasushi, Fujimoto, Yasushi, Matsumoto, Koji, Yokota, Tomoya, Yamazaki, Tomoko, Takahashi, Masanobu, Ueda, Tsutomu, Hanai, Nobuhiro, Yamaguchi, Hironori, Hara, Hiroki, Yoshizaki, Tomokazu, Yasumatsu, Ryuji, Nakayama, Masahiro, Shiga, Kiyoto, Fujii, Takashi, Mitsugi, Kenji, Takahashi, Kenichi, Nohata, Nijiro, Gumuscu, Burak, Lerman, Nati, and Tahara, Makoto

Published
2024
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10. Early prediction of treatment outcome for lenvatinib using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma refractory to radioiodine treatment: a prospective, multicentre, non-randomised study

Author

Takeuchi, Satoshi, Hirata, Kenji, Magota, Keiichi, Watanabe, Shiro, Moku, Rika, Shiiya, Akihiko, Taguchi, Jun, Ariga, Shin, Goda, Tomohiro, Ohhara, Yoshihito, Noguchi, Takurou, Shimizu, Yasushi, Kinoshita, Ichiro, Honma, Rio, Tsuji, Yasushi, Homma, Akihiro, and Dosaka-Akita, Hirotoshi

Published
2023
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11. Mean first passage times reconstruct the slowest relaxations in potential energy landscapes of nanoclusters

Author

Okushima, Teruaki, Niiyama, Tomoaki, Ikeda, Kensuke S., and Shimizu, Yasushi

Subjects
Physics - Atomic and Molecular Clusters, Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Relaxation modes are the collective modes in which all probability deviations from equilibrium states decay with the same relaxation rates. In contrast, a first passage time is the required time for arriving for the first time from one state to another. In this paper, we discuss how and why the slowest relaxation rates of relaxation modes are reconstructed from the first passage times. As an illustrative model, we use a continuous-time Markov state model of vacancy diffusion in KCl nanoclusters. Using this model, we reveal that all characteristics of the relaxations in KCl nanoclusters come from the fact that they are hybrids of two kinetically different regions of the fast surface and slow bulk diffusions. The origin of the different diffusivities turns out to come from the heterogeneity of the activation energies on the potential energy landscapes. We also develop a stationary population method to compute the mean first passage times as mean times required for pair annihilations of particle-hole pairs, which enables us to obtain the symmetric results of relaxation rates under the exchange of the sinks and the sources. With this symmetric method, we finally show why the slowest relaxation times can be reconstructed from the mean first passage times., Comment: 8 figures

Published
2019
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12. First-line pembrolizumab ± chemotherapy for recurrent/metastatic head and neck cancer: Japanese subgroup of KEYNOTE-048

Author

Takahashi, Shunji, Oridate, Nobuhiko, Tanaka, Kaoru, Shimizu, Yasushi, Fujimoto, Yasushi, Matsumoto, Koji, Yokota, Tomoya, Yamazaki, Tomoko, Takahashi, Masanobu, Ueda, Tsutomu, Hanai, Nobuhiro, Yamaguchi, Hironori, Hara, Hiroki, Yoshizaki, Tomokazu, Yasumatsu, Ryuji, Nakayama, Masahiro, Shiga, Kiyoto, Fujii, Takashi, Mitsugi, Kenji, Takahashi, Kenichi, Nohata, Nijiro, Gumuscu, Burak, Swaby, Ramona F., and Tahara, Makato

Published
2022
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13. Changes of graph structure of transition probability matrices indicate the slowest kinetic relaxations

Author

Okushima, Teruaki, Niiyama, Tomoaki, Ikeda, Kensuke S., and Shimizu, Yasushi

Subjects
Condensed Matter - Disordered Systems and Neural Networks
Abstract

Graphs of the most probable transitions for a transition probability matrix, $e^{\tau K}$, i.e., the time evolution matrix of the transition rate matrix $K$ over a finite time interval $\tau$, are considered. We study how the graph structures of the most probable transitions change as functions of $\tau$, thereby elucidating that a kinetic threshold $\tau_g$ for the graph structures exists. Namely, for $\tau<\tau_g$, the number of connected graph components are constant. In contrast, for $\tau\geq \tau_g$, recombinations of most probable transitions over the connected graph components occur multiple times, which introduce drastic changes into the graph structures. Using an illustrative multi-funnel model, we show that the recombination patterns indicate the existence of the eigenvalues and eigenvectors of slowest relaxation modes quite precisely. We also devise an evaluation formula that enables us to correct the values of eigenvalues with high accuracy from the data of merging processes. We show that the graph-based method is valid for a wide range of kinetic systems with degenerate, as well as non-degenerate, relaxation rates., Comment: 8 figures

Published
2018
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14. Slowest kinetic modes revealed by metabasin renormalization

Author

Okushima, Teruaki, Niiyama, Tomoaki, Ikeda, Kensuke S., and Shimizu, Yasushi

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Disordered Systems and Neural Networks
Abstract

Understanding the slowest relaxations of complex systems, such as relaxation of glass-forming materials, diffusion in nanoclusters, and folding of biomolecules, is important for physics, chemistry, and biology. For a kinetic system, the relaxation modes are determined by diagonalizing its transition rate matrix. However, for realistic systems of interest, numerical diagonalization, as well as extracting physical understanding from the diagonalization results, is difficult due to the high dimensionality. Here, we develop an alternative and generally applicable method of extracting the long-time scale relaxation dynamics by combining the metabasin analysis of Okushima et al. [Phys. Rev. E 80, 036112 (2009)] and a Jacobi method. We test the method on a illustrative model of a four-funnel model, for which we obtain a renormalized kinematic equation of much lower dimension sufficient for determining slow relaxation modes precisely. The method is successfully applied to the vacancy transport problem in ionic nanoparticles [Niiyama et al. Chem. Phys. Lett. 654, 52 (2016)], allowing a clear physical interpretation that the final relaxation consists of two successive, characteristic processes., Comment: 5 pages, 3 figures

Published
2018
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15. Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study

Author

Yasumatsu, Ryuji, Shimizu, Yasushi, Hanai, Nobuhiro, Kariya, Shin, Yokota, Tomoya, Fujii, Takashi, Tsukahara, Kiyoaki, Ando, Mizuo, Hanyu, Kenji, Ueda, Tsutomu, Hirakawa, Hitoshi, Takahashi, Shunji, Ono, Takeharu, Sano, Daisuke, Yamauchi, Moriyasu, Watanabe, Akihito, Omori, Koichi, Yamazaki, Tomoko, Monden, Nobuya, Kudo, Naomi, Arai, Makoto, Yonekura, Syuji, Asakage, Takahiro, Nekado, Takahiro, Yamada, Takayuki, and Homma, Akihiro

Published
2022
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17. On the origin of atomistic mechanism of rapid diffusion in alkali halide nanoclusters

Author

Niiyama, Tomoaki, Sawada, Shin-ichi, Ikeda, Kensuke S., and Shimizu, Yasushi

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

To elucidate the atomistic diffusion mechanism responsible for the rapid diffusion in alkali halide nano particles, called Spontaneous Mixing, we execute molecular dynamics simulations with empirical models for KCl-KBr, NaCl-NaBr, RbCl-RbBr and KBr-KI. We successfully reproduce essential features of the rapid diffusion phenomenon. It is numerically confirmed that the rate of the diffusion clearly depends on the size and temperature of the clusters, which is consistent with experiments. A quite conspicuous feature is that the surface melting and collective motions of ions are inhibited in alkali halide clusters. This result indicates that the Surface Peeling Mechanism, which is responsible for the spontaneous alloying of binary metals, does not play a dominant role for the spontaneous mixing in alkali halide nanoclusters. Detailed analysis of atomic motion inside the clusters reveals that the Vacancy Mechanism is the most important mechanism for the rapid diffusion in alkali halide clusters. This is also confirmed by evaluation of the vacancy formation energy: the formation energy notably decreases with the cluster size, which makes vacancy formation easier and diffusion more rapid in small alkali halide clusters., Comment: 12 pages, 14 figures

Published
2016
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18. Effectiveness of nivolumab affected by prior cetuximab use and neck dissection in Japanese patients with recurrent or metastatic head and neck cancer: results from a retrospective observational study in a real-world setting

Author

Kariya, Shin, Shimizu, Yasushi, Hanai, Nobuhiro, Yasumatsu, Ryuji, Yokota, Tomoya, Fujii, Takashi, Tsukahara, Kiyoaki, Yoshida, Masafumi, Hanyu, Kenji, Ueda, Tsutomu, Hirakawa, Hitoshi, Takahashi, Shunji, Ono, Takeharu, Sano, Daisuke, Yamauchi, Moriyasu, Watanabe, Akihito, Omori, Koichi, Yamazaki, Tomoko, Monden, Nobuya, Kudo, Naomi, Arai, Makoto, Yonekura, Shuji, Asakage, Takahiro, Fujiwara, Akinori, Yamada, Takayuki, and Homma, Akihiro

Published
2021
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19. Impact of adaptive radiotherapy on survival in locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy

Author

Uchinami, Yusuke, primary, Yasuda, Koichi, additional, Minatogawa, Hideki, additional, Dekura, Yasuhiro, additional, Nishikawa, Noboru, additional, Kinoshita, Rumiko, additional, Nishioka, Kentaro, additional, Katoh, Norio, additional, Mori, Takashi, additional, Otsuka, Manami, additional, Miyamoto, Naoki, additional, Suzuki, Ryusuke, additional, Kobashi, Keiji, additional, Shimizu, Yasushi, additional, Taguchi, Jun, additional, Tsushima, Nayuta, additional, Kano, Satoshi, additional, Homma, Akihiro, additional, and Aoyama, Hidefumi, additional

Published
2024
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23. Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study

Author

Hanai, Nobuhiro, Shimizu, Yasushi, Kariya, Shin, Yasumatsu, Ryuji, Yokota, Tomoya, Fujii, Takashi, Tsukahara, Kiyoaki, Yoshida, Masafumi, Hanyu, Kenji, Ueda, Tsutomu, Hirakawa, Hitoshi, Takahashi, Shunji, Ono, Takeharu, Sano, Daisuke, Yamauchi, Moriyasu, Watanabe, Akihito, Omori, Koichi, Yamazaki, Tomoko, Monden, Nobuya, Kudo, Naomi, Arai, Makoto, Sakurai, Daiju, Asakage, Takahiro, Doi, Issei, Yamada, Takayuki, and Homma, Akihiro

Published
2021
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25. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study

Author

Lerzo, Guillermo, Tatangelo, Marcelo, Varela, Mirta, Zarba, Juan Jose, Boyer, Michael, Gan, Hui, Gao, Bo, Hughes, Brett, Mallesara, Girish, Rischin, Danny, Taylor, Anne, Burian, Martin, Fuereder, Thorsten, Greil, Richard, Barrios, Carlos Henrique, de Castro Junior, Dalvaro Oliveira, Castro, Gilberto, Franke, Fabio Andre, Girotto, Gustavo, Lima, Iane Pinto Figueiredo, Nicolau, Ulisses Ribaldo, Pinto, Gustavo Dix Junqueira, Santos, Lucas, Victorino, Ana-Paula, Chua, Neil, Couture, Felix, Gregg, Richard, Hansen, Aaron, Hilton, John, McCarthy, Joy, Soulieres, Denis, Ascui, Rodrigo, Gonzalez, Pablo, Villanueva, Luis, Torregroza, Marco, Zambrano, Angela, Holeckova, Petra, Kral, Zdenek, Melichar, Bohuslav, Prausova, Jana, Vosmik, Milan, Andersen, Maria, Gyldenkerne, Niels, Jurgens, Hannes, Putnik, Kadri, Reinikainen, Petri, Gruenwald, Viktor, Laban, Simon, Aravantinos, Gerasimos, Boukovinas, Ioannis, Georgoulias, Vassilis, Psyrri, Amanda, Kwong, Dora, Al-Farhat, Yousuf, Csoszi, Tibor, Erfan, Jozsef, Horvai, Geza, Landherr, Laszlo, Remenar, Eva, Ruzsa, Agnes, Szota, Judit, Billan, Salem, Gluck, Iris, Gutfeld, Orit, Popovtzer, Aron, Benasso, Marco, Bui, Simona, Ferrari, Vittorio, Licitra, Lisa, Nole, Franco, Fujii, Takashi, Fujimoto, Yasushi, Hanai, Nobuhiro, Hara, Hiroki, Matsumoto, Koji, Mitsugi, Kenji, Monden, Nobuya, Nakayama, Masahiro, Okami, Kenji, Oridate, Nobuhiko, Shiga, Kiyoto, Shimizu, Yasushi, Sugasawa, Masashi, Tahara, Makoto, Takahashi, Masanobu, Takahashi, Shunji, Tanaka, Kaoru, Ueda, Tsutomu, Yamaguchi, Hironori, Yamazaki, Tomoko, Yasumatsu, Ryuji, Yokota, Tomoya, Yoshizaki, Tomokazu, Kudaba, Iveta, Stara, Zinaida, Wan Ishak, Wan Zamaniah, Cheah, Soon Keat, Aguilar Ponce, Jose, Gonzalez Mendoza, Rene, Hernandez Hernandez, Carlos, Medina Soto, Francisco, Buter, Jan, Hoeben, Ann, Oosting, S., Suijkerbuijk, Karijn, Bratland, Aase, Brydoey, Marianne, Alvarez, Renzo, Mas, Luis, Caguioa, Priscilla, Querol, John, Regala, Eugenio Emmanuel, Tamayo, Maria Belen, Villegas, Ellie May, Kawecki, Andrzej, Karpenko, Andrey, Klochikhin, Arkadiy, Smolin, Alexey, Zarubenkov, Oleg, Goh, Boon Cher, Cohen, Graham, du Toit, Johanna, Jordaan, Christa, Landers, Gregory, Ruff, Paul, Szpak, Waldemar, Tabane, Neonyana, Brana, Irene, Iglesias Docampo, Lara, Lavernia, Javier, Mesia, Ricard, Abel, Edvard, Muratidu, Valentina, Nielsen, Niels, Cristina, Valerie, Rordorf, Tamara, Rothschild, Sacha, Hong, Ruey-Long, Wang, Hung-Ming, Yang, Muh-Hwa, Yeh, Su-Peng, Yen, Chia-Jui, Ngamphaiboon, Nuttapong, Soparattanapaisarn, Nopadol, Sriuranpong, Virote, Aksoy, Sercan, Cicin, Irfan, Ekenel, Meltem, Harputluoglu, Hakan, Ozyilkan, Ozgur, Harrington, Kevin, Agarwala, Sanjiv, Ali, Haythem, Alter, Robert, Anderson, Daniel, Bruce, Justine, Burtness, Barbara, Campbell, Nicholas, Conde, Miguel, Deeken, John, Edenfield, William, Feldman, Lawrence, Gaughan, Elizabeth, Goueli, Basem, Halmos, Balazs, Hegde, Upendra, Hunis, Brian, Jotte, Robert, Karnad, Anand, Khan, Saad, Laudi, Noel, Laux, Douglas, Martincic, Danko, McCune, Steven, McGaughey, Dean, Misiukiewicz, Krzysztof, Mulford, Deborah, Nadler, Eric, Neupane, Prakash, Nunnink, Johannes, Ohr, James, O'Malley, Meaghan, Patson, Brian, Paul, Doru, Popa, Elizabeta, Powell, Steven, Redman, Rebecca, Rella, Vincent, Rocha Lima, Chaio, Sivapiragasam, Abirami, Su, Yungpo, Sukari, Ammar, Wong, Stuart, Yilmaz, Emrullah, Yorio, Jeffrey, Harrington, Kevin J, Soulières, Denis, de Castro, Gilberto, Jr, Basté, Neus, Bratland, Åse, Hughes, Brett G M, Mesía, Ricard, González Mendoza, René, Roy, Ananya, Zhang, Yayan, Gumuscu, Burak, Cheng, Jonathan D, and Jin, Fan

Published
2019
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26. Quantum and classical chaos of a two-electron system in a quantum wire

Author

Masuda, Shumpei, Sawada, Shin-ichi, and Shimizu, Yasushi

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Nonlinear Sciences - Chaotic Dynamics
Abstract

We study classical and quantum dynamics of two spinless particles confined in a quantum wire with repulsive or attractive Coulomb interaction. The interaction induces irregular dynamics in classical mechanics, which reflects on the quantum properties of the system in the energy level statistics (the signatures of quantum chaos). We investigate especially closer correspondence between the classical and quantum chaos. The present classical dynamics has some scaling property, which the quantum counterpart does not have. However, we demonstrate that the energy level statistics implies the existence of the corresponding scaling property even in the quantum system. Instead of ordinary maximum Lyapunov exponent (MLE), we introduce a novel kind of MLE, which is shown to be suitable measure of chaotic irregularity for the present classical system. We show that tendency of the energy dependence of the Brody parameter, which characterizes the energy level statistics in the quantum system, is consistent with that of the novel kind of MLE.

Published
2012
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27. A Phase 2 Study of Encorafenib in Combination with Binimetinib in Patients with Metastatic BRAF-Mutated Thyroid Cancer in Japan.

Author

Tahara, Makoto, Kiyota, Naomi, Imai, Hiroo, Takahashi, Shunji, Nishiyama, Akihiro, Tamura, Shingo, Shimizu, Yasushi, Kadowaki, Shigenori, Ito, Ken-ichi, Toyoshima, Masahiro, Hirashima, Yoshinori, Ueno, Shinji, and Sugitani, Iwao

Subjects
THYROID cancer, ANAPLASTIC thyroid cancer, VASCULAR endothelial growth factors
Abstract

Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ≥1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAFV600E-mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4–19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2–75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ≥1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4–5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer. Clinical Trial Registration number: Japan Registry of Clinical Trials: jRCT2011200018 [ABSTRACT FROM AUTHOR]

Published
2024
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28. On a relationship between the collective migration of surface atoms in microclusters and the saddle points on the potential energy surface

Author

Shimizu, Yasushi, Sawada, Shin-ichi, and Ikeda, Kensuke S.

Subjects
Condensed Matter - Materials Science
Abstract

Plenty of saddles on a multidimensional potential energy surface(PES) of two-dimensional microclusters, where atoms are interacting via Morse potential, are numerically located. The reaction paths emanating from the two types of the local minima, which represent the compact and the non-compact shape of Morse clusters, to their neighboring saddles on PES are elucidated. By associating the reaction path crossing these saddles with the atomic rearrangements,we evaluate the barrier height corresponding to various characteristic atomic motion accompanied by the {\it floaters} (i.e. surface atoms popped out of the cluster surface). Our findings are summarized as: (i)The saddle points implying the {\it gliding motion} of a single {\it floater} over the cluster surface yields extremely small values of the energy barriers regardless of the shapes of clusters. In particular, the {\it gliding motion} of a train composed of a few surface atoms also appears as the low-lying saddles. As a result, the barrier height corresponding to the {\it simultaneous gliding motion}, which is a manifestation of the reaction path crossing the higher-index saddles on PES, is significantly low. (ii)A surface rearrangement, where {\it floaters} are created or annihilated, implies relatively high barrier energy which is still accessible below melting point. (iii)On the other hand, the atomic motion, where atoms located deep inside of the clusters are rearranged as well as surface atoms, yields extremely high barrier energies. Some relations between these results and the recent experimental study of the surface cluster diffusion are also pointed out., Comment: 4 pages,5 figures

Published
2002

29. Spontaneous alloying in binary metal microclusters - A molecular dynamics study -

Author

Shimizu, Yasushi, Ikeda, Kensuke S., and Sawada, Shin-ichi

Subjects
Condensed Matter - Materials Science
Abstract

Microcanonical molecular dynamics study of the spontaneous alloying(SA), which is a manifestation of fast atomic diffusion in a nano-sized metal cluster, is done in terms of a simple two dimensional binary Morse model. Important features observed by Yasuda and Mori are well reproduced in our simulation. The temperature dependence and size dependence of the SA phenomena are extensively explored by examining long time dynamics. The dominant role of negative heat of solution in completing the SA is also discussed. We point out that a presence of melting surface induces the diffusion of core atoms even if they are solid-like. In other words, the {\it surface melting} at substantially low temperature plays a key role in attaining the SA., Comment: 15 pages, 12 fgures, Submitted to Phys.Rev.B

Published
2000
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30. A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator’s choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141

Author

Kiyota, Naomi, Hasegawa, Yasuhisa, Takahashi, Shunji, Yokota, Tomoya, Yen, Chia-Jui, Iwae, Shigemichi, Shimizu, Yasushi, Hong, Ruey-Long, Goto, Masahiro, Kang, Jin-Hyoung, Sum Kenneth Li, Wing, Ferris, Robert L., Gillison, Maura, Namba, Yoshinobu, Monga, Manish, Lynch, Mark, and Tahara, Makoto

Published
2017
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31. Correction to: Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real‑world clinical practice: a multicentre retrospective clinical study

Author

Hanai, Nobuhiro, Shimizu, Yasushi, Kariya, Shin, Yasumatsu, Ryuji, Yokota, Tomoya, Fujii, Takashi, Tsukahara, Kiyoaki, Yoshida, Masafumi, Hanyu, Kenji, Ueda, Tsutomu, Hirakawa, Hitoshi, Takahashi, Shunji, Ono, Takeharu, Sano, Daisuke, Yamauchi, Moriyasu, Watanabe, Akihito, Omori, Koichi, Yamazaki, Tomoko, Monden, Nobuya, Kudo, Naomi, Arai, Makoto, Sakurai, Daiju, Asakage, Takahiro, Doi, Issei, Yamada, Takayuki, and Homma, Akihiro

Published
2021
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32. A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring human epidermal growth factor receptor 2 amplification (JUPITER trial)

Author

Takahashi, Kenta, Ishibashi, Eri, Kubo, Toshio, Harada, Yohei, Hayashi, Hideyuki, Kano, Masayuki, Shimizu, Yasushi, Shirota, Hidekazu, Mori, Yukiko, Muto, Manabu, Ishioka, Chikashi, Dosaka-Akita, Hirotoshi, Matsubara, Hisahiro, Nishihara, Hiroshi, Sueoka-Aragane, Naoko, Toyooka, Shinichi, Hirakawa, Akihiro, Tateishi, Ukihide, Miyake, Satoshi, and Ikeda, Sadakatsu

Published
2020
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34. EGFR inhibition in EGFR-mutant lung cancer cells perturbs innate immune signaling pathways in the tumor microenvironment

Author

Shiiya, Akihiko, Noguchi, Takuro, Tomaru, Utano, Ariga, Shin, Takashima, Yuta, Ohhara, Yoshihito, Taguchi, Jun, Takeuchi, Satoshi, Shimizu, Yasushi, Kinoshita, Ichiro, Koizumi, Tomonobu, Matsuno, Yoshihiro, Shinagawa, Naofumi, Sakakibara-Konishi, Jun, 1000070222528, Dosaka-Akita, Hirotoshi, Shiiya, Akihiko, Noguchi, Takuro, Tomaru, Utano, Ariga, Shin, Takashima, Yuta, Ohhara, Yoshihito, Taguchi, Jun, Takeuchi, Satoshi, Shimizu, Yasushi, Kinoshita, Ichiro, Koizumi, Tomonobu, Matsuno, Yoshihiro, Shinagawa, Naofumi, Sakakibara-Konishi, Jun, 1000070222528, and Dosaka-Akita, Hirotoshi

Abstract

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) elicit potent cell cycle arrest in EGFR-mutant non-small-cell lung cancer (NSCLC) cells. However, little is known about the mechanisms through which these drugs alter the tumor phenotype that contributes to the immune escape of EGFR-mutant cells. Using EGFR-mutant NSCLC cell lines and tissue samples from patients, we investigated the changes in immune checkpoints expressed in tumor cells following EGFR inhibition. Subsequently, we also analyzed the role of soluble factors from the dying tumor cells in the activation of immune signaling pathways involved in therapy resistance. Upon EGFR-TKI treatment, we found that EGFR-mutant cells upregulated the expression of innate immune checkpoint CD24 in vitro. We then analyzed biopsy samples from six patients who developed resistance to a first-generation EGFR-TKI without the acquired T790M mutation. Immunohistochemistry revealed that levels of tumor CD24 expression were increased upon treatment compared with those from pre-treatment samples. Monocyte-derived macrophages facilitated antibody-dependent cellular phagocytosis when EGFR-TKI-treated EGFR-mutant cells were incubated with anti-CD24 antibodies in vitro, suggesting that CD24 may be a therapeutical target for EGFR-mutant lung cancer. Moreover, EGFR inhibition accelerated the release of cell-free DNA (cfDNA) from dying tumor cells, which activated the type I interferon signaling pathways in human THP-1 monocytes in a stimulator of interferon genes-dependent manner. Our study indicates that EGFR inhibition in EGFR-mutant NSCLC cells fosters a tumor microenvironment associated with immune escape. Thus, CD24 targeted therapy and cfDNA monitoring may contribute to improved treatment outcomes in patients with EGFR-mutant NSCLC.

Published
2023

35. Detailed analysis of failure patterns using deformable image registration in hypopharyngeal cancer patients treated with sequential boost intensity-modulated radiotherapy

Author

Otsuka, Manami, Yasuda, Koichi, Uchinami, Yusuke, Tsushima, Nayuta, Suzuki, Takayoshi, Kano, Satoshi, Suzuki, Ryusuke, Miyamoto, Naoki, Minatogawa, Hideki, Dekura, Yasuhiro, Mori, Takashi, Nishioka, Kentaro, Taguchi, Jun, Shimizu, Yasushi, Katoh, Norio, Homma, Akihiro, Aoyama, Hidefumi, Otsuka, Manami, Yasuda, Koichi, Uchinami, Yusuke, Tsushima, Nayuta, Suzuki, Takayoshi, Kano, Satoshi, Suzuki, Ryusuke, Miyamoto, Naoki, Minatogawa, Hideki, Dekura, Yasuhiro, Mori, Takashi, Nishioka, Kentaro, Taguchi, Jun, Shimizu, Yasushi, Katoh, Norio, Homma, Akihiro, and Aoyama, Hidefumi

Abstract

Introduction Sequential boost intensity-modulated radiotherapy (SQB-IMRT) uses two different planning CTs (pCTs) and treatment plans. SQB-IMRT is a form of adaptive radiotherapy that allows for responses to changes in the shape of the tumour and organs at risk (OAR). On the other hand, dose accumulation with the two plans can be difficult to evaluate. The purpose of this study was to analyse patterns of loco-regional failure using deformable image registration (DIR) in hypopharyngeal cancer patients treated with SQB-IMRT. Methods Between 2013 and 2019, 102 patients with hypopharyngeal cancer were treated with definitive SQB-IMRT at our institution. Dose accumulation with the 1st and 2nd plans was performed, and the dose to the loco-regional recurrent tumour volume was calculated using the DIR workflow. Failure was classified as follows: (i) in-field (>= 95% of the recurrent tumour volume received 95% of the prescribed dose); (ii) marginal (20-95%); or (iii) out-of-field (<20%). Results After a median follow-up period of 25 months, loco-regional failure occurred in 34 patients. Dose-volume histogram analysis showed that all loco-regional failures occurred in the field within 95% of the prescribed dose, with no marginal or out-of-field recurrences observed. Conclusion The dosimetric analysis using DIR showed that all loco-regional failures were within the high-dose region. More aggressive treatment may be required for gross tumours.

Published
2023

39. EGFR inhibition in EGFR ‐mutant lung cancer cells perturbs innate immune signaling pathways in the tumor microenvironment

Author

Shiiya, Akihiko, primary, Noguchi, Takuro, additional, Tomaru, Utano, additional, Ariga, Shin, additional, Takashima, Yuta, additional, Ohhara, Yoshihito, additional, Taguchi, Jun, additional, Takeuchi, Satoshi, additional, Shimizu, Yasushi, additional, Kinoshita, Ichiro, additional, Koizumi, Tomonobu, additional, Matsuno, Yoshihiro, additional, Shinagawa, Naofumi, additional, Sakakibara‐Konishi, Jun, additional, and Dosaka‐Akita, Hirotoshi, additional

Published
2022
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40. Detailed analysis of failure patterns using deformable image registration in hypopharyngeal cancer patients treated with sequential boost intensity‐modulated radiotherapy

Author

Otsuka, Manami, primary, Yasuda, Koichi, additional, Uchinami, Yusuke, additional, Tsushima, Nayuta, additional, Suzuki, Takayoshi, additional, Kano, Satoshi, additional, Suzuki, Ryusuke, additional, Miyamoto, Naoki, additional, Minatogawa, Hideki, additional, Dekura, Yasuhiro, additional, Mori, Takashi, additional, Nishioka, Kentaro, additional, Taguchi, Jun, additional, Shimizu, Yasushi, additional, Katoh, Norio, additional, Homma, Akihiro, additional, and Aoyama, Hidefumi, additional

Published
2022
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42. Early prediction of treatment outcome for lenvatinib using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma refractory to radioiodine treatment: a prospective, multicentre, non-randomised study.

Author

Takeuchi, Satoshi, Hirata, Kenji, Magota, Keiichi, Watanabe, Shiro, Moku, Rika, Shiiya, Akihiko, Taguchi, Jun, Ariga, Shin, Goda, Tomohiro, Ohhara, Yoshihito, Noguchi, Takurou, Shimizu, Yasushi, Kinoshita, Ichiro, Honma, Rio, Tsuji, Yasushi, Homma, Akihiro, and Dosaka-Akita, Hirotoshi

Subjects
THYROID cancer, TREATMENT effectiveness, IODINE isotopes, POSITRON emission tomography, RECEIVER operating characteristic curves, UNIVERSITY hospitals
Abstract

Background: Lenvatinib is widely used to treat unresectable and advanced thyroid carcinomas. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) performed 1 week after lenvatinib treatment initiation could predict treatment outcomes. Results: This was a prospective, nonrandomised, multicentre study. Patients with pathologically confirmed differentiated thyroid carcinoma (DTC) and lesions refractory to radioiodine treatment were eligible for inclusion. Patients were treated with 24 mg lenvatinib as the initial dose and underwent PET/CT examination 1 week after treatment initiation. Contrast-enhanced CT was scheduled at least 4 weeks later as the gold standard for evaluation. The primary endpoint was to evaluate the discrimination power of maximum standardised uptake value (SUVmax) obtained by PET/CT compared to that obtained by contrast-enhanced CT. Evaluation was performed using the area under the receiver operating characteristic (ROC-AUC) curve. Twenty-one patients were included in this analysis. Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.714 for SUVmax after 1 week of lenvatinib treatment. The best cut-off value for the treatment response for SUVmax was 15.211. The sensitivity and specificity of this cut-off value were 0.583 and 0.857, respectively. The median progression-free survival was 26.3 months in patients with an under-cut-off value and 19.7 months in patients with an over-cut-off value (P = 0.078). Conclusions: The therapeutic effects of lenvatinib were detected earlier than those of CT because of decreased FDG uptake on PET/CT. PET/CT examination 1 week after the initiation of lenvatinib treatment may predict treatment outcomes in patients with DTC. Trial registration: This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (number UMIN000022592) on 6 June, 2016. [ABSTRACT FROM AUTHOR]

Published
2023
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44. Diabetes mellitus degenerates cisplatin-induced nephrotoxicity in short hydration method: a propensity score-matching analysis

Author

1000000835001, Saito, Yoshitaka, Sakamoto, Tatsuhiko, 1000000396293, Takekuma, Yoh, 1000070431319, Kobayashi, Masaki, Okamoto, Keisuke, 1000020431372, Shinagawa, Naofumi, 1000010374513, Shimizu, Yasushi, 1000040343008, Kinoshita, Ichiro, 1000060332467, Sugawara, Mitsuru, 1000000835001, Saito, Yoshitaka, Sakamoto, Tatsuhiko, 1000000396293, Takekuma, Yoh, 1000070431319, Kobayashi, Masaki, Okamoto, Keisuke, 1000020431372, Shinagawa, Naofumi, 1000010374513, Shimizu, Yasushi, 1000040343008, Kinoshita, Ichiro, 1000060332467, and Sugawara, Mitsuru

Abstract

Cisplatin (CDDP)-induced nephrotoxicity (CIN) is dose-limiting. We revealed that co-administration of non-steroid anti-inflammatory drugs and baseline comorbidity of diabetes mellitus (DM) are associated with CIN development in the short hydration method; however, the results were accessorily obtained without appropriate power calculation. This study aimed to demonstrate the influence of DM complications on CIN incidence in a real-world setting. Lung cancer patients receiving CDDP (>= 75 mg/m2)-containing regimens with a short hydration method (n = 227) were retrospectively evaluated. The patients were divided into control and baseline DM complication groups. The primary endpoint was the evaluation of CIN incidence between the groups. Propensity score-matching was performed to confirm the robustness of the primary analysis results. CIN occurred in 6.8% of control and 27.0% of DM patients, respectively, with a significant difference in all-patient populations (P = 0.001). In addition, variation of serum creatinine and creatinine clearance significantly worsened in DM patients. Similar results were obtained in a propensity-matched population. Multivariate logistic regression analysis found that DM complication is a singular risk factor for CIN development (adjusted odds ratio; 4.31, 95% confidence interval; 1.62-11.50, P = 0.003). In conclusion, our study revealed that baseline DM complications significantly worsen CIN.

Published
2022

46. Feasibility and efficacy of induction docetaxel, cisplatin, and 5-fluorouracil chemotherapy combined with concurrent weekly cisplatin chemoradiotherapy for locally advanced head and neck squamous cell carcinoma

Author

Mizumachi, Takatsugu, Homma, Akihiro, Kakizaki, Tomohiko, Sakashita, Tomohiro, Kano, Satoshi, Hatakeyama, Hiromitsu, Tsuchiya, Kazuhiko, Yasuda, Koichi, Onimaru, Rikiya, Shirato, Hiroki, Taguchi, Jun, Shimizu, Yasushi, Kinoshita, Ichiro, Akita, Hirotoshi, and Fukuda, Satoshi

Published
2015
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47. Abstract 5210: Tumor immune characterization identifies age-stratified biomarkers for nivolumab in patients with head and neck squamous cell carcinoma: A nationwide collaborative study in Japan

Author

Tsujikawa, Takahiro, primary, Ohno, Kazuchika, additional, Saburi, Sumiyo, additional, Mitsuda, Junichi, additional, Yoshimura, Kanako, additional, Kimura, Alisa, additional, Morimoto, Hiroki, additional, Ohmura, Gaku, additional, Arai, Akihito, additional, Ogi, Hiroshi, additional, Shibata, Saya, additional, Ariizumi, Yosuke, additional, Tasaki, Akihisa, additional, Takahashi, Ryosuke, additional, Tateishi, Yumiko, additional, Kawabe, Hiroaki, additional, Ikeda, Sadakatsu, additional, Morita, Kei-ichi, additional, Tsunoda, Tatsuhiko, additional, Akashi, Takumi, additional, Kurata, Morito, additional, Imoto, Issei, additional, Shimizu, Yasushi, additional, Watanabe, Akihito, additional, Asada, Yukinori, additional, Hayashi, Ryuichi, additional, Saito, Yuki, additional, Ozawa, Hiroyuki, additional, Tsukahara, Kiyoaki, additional, Oridate, Nobuhiko, additional, Horii, Arata, additional, Maruo, Takashi, additional, Hanai, Nobuhiro, additional, Inohara, Hidenori, additional, Iwai, Hiroshi, additional, Fujii, Takashi, additional, Nibu, Ken-ichi, additional, Iwae, Shigemichi, additional, Ueda, Tsutomu, additional, Yasumatsu, Ryuji, additional, Umeno, Hirohito, additional, Masuda, Muneyuki, additional, Itoh, Kyoko, additional, Hirano, Shigeru, additional, and Asakage, Takahiro, additional

Published
2022
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48. Primary results from JUPITER, a phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with HER2-amplified solid tumors.

Author

Ikeda, Sadakatsu, primary, Kudo, Ryo, additional, Yamashita, Yamato, additional, Kubo, Toshio, additional, Mori, Yukiko, additional, Harada, Yohei, additional, Shirota, Hidekazu, additional, Hayashi, Hideyuki, additional, Kano, Masayuki, additional, Shimizu, Yasushi, additional, Ishibashi, Eri, additional, Tateishi, Ukihide, additional, Hirakawa, Akihiro, additional, Akita, Hirotoshi, additional, Matsubara, Hisahiro, additional, Nishihara, Hiroshi, additional, Ishioka, Chikashi, additional, Sueoka-Aragane, Naoko, additional, Muto, Manabu, additional, and Toyooka, Shinichi, additional

Published
2022
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50. Two-year follow-up of a randomized phase III clinical trial of nivolumab vs. the investigator's choice of therapy in the Asian population for recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141)

Author

Yen, Chia-Jui, Kiyota, Naomi, Hanai, Nobuhiro, Takahashi, Shunji, Yokota, Tomoya, Iwae, Shigemichi, Shimizu, Yasushi, Hong, Ruey-Long, Goto, Masahiro, Kang, Jin-Hyoung, Li, Wing Sum Kenneth, Ferris, Robert L., Gillison, Maura, Endo, Toshimitsu, Jayaprakash, Vijayvel, and Tahara, Makoto

Subjects
nivolumab, squamous cell carcinoma of the head and neck, Asian population, clinical trial, immunotherapy
Abstract

Background The present study evaluated the 2-year survival of the Asian population in the CheckMate 141 trial. Methods The CheckMate 141 trial included patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). In the present study, 34 Asian patients (nivolumab group: 23 patients; investigator's choice of therapy [IC] group: 11 patients) were analyzed. Results The median overall survival (OS) was 12.1 and 6.2 months for the nivolumab and IC groups, respectively. The estimated 2-year OS rates were 22.7% and 0% for the nivolumab and IC groups, respectively. In the nivolumab group, the patients with any treatment-related adverse events (TRAEs), including skin-related disorders, showed better OS than the patients without any TRAEs. Conclusions Nivolumab demonstrated prolonged OS benefits in the Asian population with platinum-refractory R/M SCCHN and a favorable safety profile. TRAEs, including skin-related disorders, may be favorable prognostic factors for nivolumab efficacy. Clinical trial registration NCT02105636.

Published
2020

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