Faculty Profiles - TOYOOKA Shinichi

Papers - TOYOOKA Shinichi

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Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. International journal

H Yoshioka, M Shimokawa, T Seto, S Morita, Y Yatabe, I Okamoto, J Tsurutani, M Satouchi, T Hirashima, S Atagi, K Shibata, H Saito, S Toyooka, N Yamamoto, K Nakagawa, T Mitsudomi

Annals of oncology : official journal of the European Society for Medical Oncology 30 ( 12 ) 1978 - 1984 2019.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Primary analysis of the phase III study WJTOG 3405 demonstrated superiority of progression-free survival (PFS) for gefitinib (G) in patients treated with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) gefitinib compared with cisplatin plus docetaxel (CD) as the first-line treatment of stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. This report presents final overall survival (OS) data. PATIENTS AND METHODS: Patients were randomized between G (250 mg/day orally) and cisplatin (80 mg/m2 intravenously) plus docetaxel (60 mg/m2 i.v.), administered every 21 days for three to six cycles. After the exclusion of 5 patients, 172 patients (86 in each group, modified intention-to-treat population) were included in the survival analysis. OS was re-evaluated using updated data (data cutoff, 30 September 2013; median follow-up time 59.1 months). The Kaplan-Meier method and the log-rank test were used for analysis, and hazard ratios (HRs) for death were calculated using the Cox proportional hazards model. RESULTS: OS events in the G group and CD group were 68 (79.1%) out of 86 and 59 (68.6%) out of 86, respectively. Median survival time for G and CD were 34.9 and 37.3 months, respectively, with an HR of 1.252 [95% confidence interval (CI): 0.883-1.775, P = 0.2070]. Multivariate analysis identified postoperative recurrence and stage IIIB/IV disease as independent prognostic factors, with an HR of 0.459 (95% CI: 0.312-0.673, P < 0.001). Median survival time (postoperative recurrence versus stage IIIB/IV disease) were 44.5 and 27.5 months in the G group and 45.5 and 32.8 months in the CD group, respectively. CONCLUSION: G did not show OS benefits over CD as the first-line treatment. OS of patients with postoperative recurrence was better than that of stage IIIB/IV disease, even though both groups had metastatic disease.This study was registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539.

DOI： 10.1093/annonc/mdz399

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YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers. Reviewed

Takeda T, Yamamoto H, Suzawa K, Tomida S, Miyauchi S, Araki K, Nakata K, Miura A, Namba K, Shien K, Soh J, Shien T, Kitamura Y, Sendo T, Toyooka S

Cancer science 111 ( 3 ) 849 - 856 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Molecular-targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2-positive breast cancer. However, acquired resistance of various cancers to molecular-targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib-resistant cell lines from HER2-amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib-resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1-amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2-targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome.

DOI： 10.1111/cas.14289

Web of Science

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Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model. Reviewed

Hashimoto K, Yamane M, Sugimoto S, Hirano Y, Kurosaki T, Otani S, Miyoshi K, Ohara T, Okazaki M, Yoshimura T, Oto T, Matsukawa A, Toyooka S

Transplant immunology 57 101242 2019.12

Airway bacteria of the recipient but not the donor are relevant to post-lung transplant pneumonia. Reviewed

Konishi Y, Miyoshi K, Kurosaki T, Otani S, Sugimoto S, Yamane M, Oto T, Toyooka S

General thoracic and cardiovascular surgery 2019.12

N2非小細胞肺癌に対する外科治療

杉本誠一郎, 豊岡伸一

肺癌 59 ( 7 ) 1129 - 1133 2019.12

Language：Japanese Publisher：(NPO)日本肺癌学会

N2陽性の非小細胞肺癌では、局所の制御を目的とした放射線治療や手術と、遠隔転移の制御を目的とした化学療法を組み合わせた集学的治療が行われてきた。N2非小細胞肺癌に対する導入療法後手術の有用性が示唆されていたが、第III相試験では、根治的化学放射線療法と比較した導入療法後手術の優越性は証明されていないのが現状である。しかし、切除可能なN2非小細胞肺癌で、特に肺葉切除術が可能な場合には、導入化学放射線療法後の手術の有用性が示唆されており、治療の選択肢として考慮すべきである。また、最近では新しい治療薬として免疫チェックポイント阻害剤が登場し、切除不能III期非小細胞肺癌に対して、化学放射線療法との逐次併用による有用性が示され、治療の選択肢が増えている。本稿では、N2非小細胞肺癌に対する導入療法後手術の臨床試験を概説し、当院における導入放射線化学療法後手術の周術期管理や手術の工夫を述べるとともに、今後の展望について述べる。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01244&link_issn=&doc_id=20200109370001&doc_link_id=130007775582&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007775582&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Dose-volume parameters predict radiation pneumonitis after induction chemoradiotherapy followed by surgery for non-small cell lung cancer: a retrospective analysis. International journal

Kuniaki Katsui, Takeshi Ogata, Kenta Watanabe, Norihisa Katayama, Junichi Soh, Masahiro Kuroda, Katsuyuki Kiura, Yoshinobu Maeda, Shinichi Toyooka, Susumu Kanazawa

BMC cancer 19 ( 1 ) 1144 - 1144 2019.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The relationship between lung dose-volume histogram (DVH) parameters and radiation pneumonitis (RP) associated with induction concurrent chemoradiotherapy (CCRT) followed by surgery in patients with non-small cell lung cancer (NSCLC) is unclear, particularly when concerning irradiation of the whole lung prior to resection. We performed this study to identify factors associated with grade ≥ 2 RP in such patients. METHODS: Patients who received induction CCRT (chemotherapy: cisplatin and docetaxel; radiotherapy: 46 Gy/23 fractions) between May 2003 and May 2017 were reviewed. The mean lung dose (MLD) and the percentage of the lung volume that received ≥5 Gy (V5) and ≥ 20 Gy (V20) were calculated. Factors associated with the development of grade ≥ 2 RP were analyzed. RESULTS: One hundred and eight patients were included in this study, 34 (31.5%) of whom experienced grade ≥ 2 RP. A V20 ≥ 21%, an MLD ≥10 Gy, and a lower lobe tumor location were significant predictors of grade ≥ 2 RP on univariate analysis (p = 0.007, 0.002, and 0.004, respectively). Moreover, an MLD ≥10 Gy and lower lobe location were significant predictors of grade ≥ 2 RP on multivariate analysis (p = 0.026 and 0.0043, respectively). The cumulative incidence rates of grade ≥ 2 RP at 6 months were 15.7 and 45.6% in patients with MLDs < 10 Gy and ≥ 10 Gy, respectively, and were 23.5 and 55.6% in patients with upper/middle lobe- vs. lower lobe-located tumors, respectively. CONCLUSIONS: MLD and lower lobe location were predictors of grade ≥ 2 RP in patients who received induction CCRT. It is necessary to reduce the MLD to the greatest extent possible to prevent the occurrence of this adverse event.

DOI： 10.1186/s12885-019-6359-9

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Mortality from extrathymic malignancy after thymic tumour resections: incidences and risk factors. Reviewed International journal

Masatsugu Hamaji, Takashi Sozu, Ryunosuke Machida, Shun-Ichi Watanabe, Kazuo Yoshida, Shinichi Toyooka, Masayuki Tanahashi, Kazuya Kondo, Hirotoshi Horio, Meinoshin Okumura, Hiroshi Date

Interactive cardiovascular and thoracic surgery 29 ( 5 ) 729 - 736 2019.11

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To identify risk factors associated with extrathymic malignancy-related mortality after thymic epithelial tumour resection. METHODS: The Japanese Association for Research on the Thymus database registered the records of 2835 patients collected from 32 Japanese institutions from 1991 to 2010. The cumulative incidence function of death due to extrathymic malignancies or recurrence was calculated, with other causes of death as competing risks. Relevant risk factors associated with extrathymic malignancy-related deaths in patients with thymoma were evaluated using the Fine and Gray model. RESULTS: In total, 2701 patients were eligible for the analysis (thymoma, 2374; thymic carcinoma, 273; thymic neuroendocrine tumour, 54). The median follow-up period was 4.6 years. The cumulative incidence function of death due to extrathymic malignancies at 10 years was 2.2% (3.2% due to recurrence) in patients with thymoma, 1.6% (38.6% due to recurrence) in patients with thymic carcinoma and 0% (36.6% due to recurrence) in patients with thymic neuroendocrine tumour. In the multivariable analysis, age (every 10 years) at thymectomy [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.53-3.14; P < 0.001], male gender (HR 2.62, 95% CI 1.19-5.77; P = 0.017) and previous malignancies (HR 3.09, 95% CI 1.18-8.11; P = 0.022) were significant factors for death due to extrathymic malignancies after thymectomy. CONCLUSIONS: Continued management and early detection of extrathymic malignancies may improve survival of patients with thymoma who are male, of advanced age, or have previous malignancies. Prospective studies are required to further investigate the management of extrathymic malignancies.

DOI： 10.1093/icvts/ivz177

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Impact of pathological stage and histological subtype on clinical outcome of adjuvant chemotherapy of paclitaxel plus carboplatin versus oral uracil-tegafur for non-small cell lung cancer: subanalysis of SLCG0401 trial.

Junichi Soh, Shinichi Toyooka, Norihito Okumura, Hiroshige Nakamura, Masao Nakata, Motohiro Yamashita, Junichi Sakamoto, Motoi Aoe, Katsuyuki Hotta, Satoshi Morita, Hiroshi Date

International journal of clinical oncology 24 ( 11 ) 1367 - 1376 2019.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Pathological stage (pStage) and histological subtype are strong determinants of the treatment strategy for non-small cell lung cancer (NSCLC). Setouchi Lung Cancer study Group (SLCG) recently reported the results of a multicenter trial (SLCG0401) indicating that paclitaxel plus carboplatin (CBDCA/PTX) as adjuvant chemotherapy does not yield better survival than uracil-tegafur (UFT) in NSCLC patients with pStage IB-IIIA disease, while stratified analyses considering the pStage and histological subtype have not been performed. METHODS: We reanalyzed the overall survival (OS) and relapse-free survival (RFS) in 402 patients who had been randomly assigned to receive CBDCA/PTX or UFT by multivariate analysis with adjustments for the pStage and histological subtype. RESULTS: There were no significant differences in the OS or RFS between the two treatment settings either in the entire cohort (n = 402) and in some of subsets: pStage IB (n = 228), pStage II (n = 117), adenocarcinoma (AD, n = 265), and squamous cell carcinoma (SQ, n = 101). In pStage IIIA patients (n = 57), CBDCA/PTX yielded superior RFS to UFT [hazard ratio (HR) 0.44; P = 0.016]. Among the patients with non-AD and non-SQ histology (n = 36), UFT yielded both superior OS and RFS to CBDCA/PTX (HRs 0.16 and 0.23; P = 0.046 and 0.011, respectively). CONCLUSIONS: There are subsets of patients in which one or the other between UFT and CBDCA/PTX is significantly more effective. Selection of adjuvant therapy for NSCLC patients needs to be made taking into consideration the pStage and histological subtype.

DOI： 10.1007/s10147-019-01508-9

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臨床的疑問より発した研究-Reverse translational research High tumor mutation burdenのALK陽性肺癌におけるアレクチニブ早期耐性について

槇本剛, 大橋圭明, 冨田秀太, 二宮貴一朗, 久保寿夫, 頼冠名, 市原英基, 堀田勝幸, 田端雅弘, 豊岡伸一, 木浦勝行

肺癌 59 ( 6 ) 571 - 571 2019.11

Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine model. Reviewed

Irie M, Otani S, Kurosaki T, Tanaka S, Ohki T, Miyoshi K, Sugimoto S, Yamane M, Oto T, Toyooka S

General thoracic and cardiovascular surgery 2019.11

Favorable survival even with high disease-specific complication rates in lymphangioleiomyomatosis after lung transplantation - long-term follow-up of a Japanese center. Reviewed

Kurosaki T, Otani S, Miyoshi K, Okazaki M, Sugimoto S, Suno M, Yamane M, Kobayashi M, Oto T, Toyooka S

The clinical respiratory journal 2019.11

c-I期非小細胞肺癌における予後因子としてのスリガラス様陰影第7次全国肺癌登録

朝倉啓介, 新谷康, 岡見次郎, 奥村明之進, 伊藤宏之, 大塚崇, 豊岡伸一, 森毅, 渡辺俊一, 伊達洋至, 横井香平, 淺村尚生, 永安武, 宮岡悦良, 吉野一郎, 肺癌登録合同委員会

肺癌 59 ( 6 ) 696 - 696 2019.11

Bリンパ球過形成を伴う小結節性胸腺腫瘍の1切除例

上山廉起, 岡崎幹生, 塩谷俊雄, 諏澤憲, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

肺癌 59 ( 6 ) 923 - 923 2019.11

肺癌との鑑別が困難であった肺結節性リンパ過形成の1例

富岡泰章, 山本寛斉, 松原慧, 山本治慎, 塩谷俊雄, 難波圭, 諏澤憲, 三好健太郎, 大谷真二, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

肺癌 59 ( 6 ) 878 - 878 2019.11

サルベージ治療・オリゴ再発に対する局所治療戦略術前化学放射線療法後手術を行った局所進行肺癌術後再発症例の臨床経過

諏澤憲, 枝園和彦, 三好健太郎, 大谷真二, 山本寛斉, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

肺癌 59 ( 6 ) 586 - 586 2019.11

腹臥位による後方アプローチ併用ロボット支援下ダンベル型神経鞘腫摘出術

岡崎幹生, 諏澤憲, 塩谷俊雄, 三好健太郎, 大谷真二, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

肺癌 59 ( 6 ) 745 - 745 2019.11

定型カルチノイドを伴うびまん性特発性肺神経内分泌過形成の1例

富岡泰章, 山本寛斉, 松原慧, 山本治慎, 塩谷俊雄, 難波圭, 諏澤憲, 三好健太郎, 大谷真二, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

肺癌 59 ( 6 ) 878 - 878 2019.11

肉腫多発肺転移に対する肺切除術

山本寛斉, 諏澤憲, 三好健太郎, 大谷真二, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

肺癌 59 ( 6 ) 684 - 684 2019.11

頭頸部癌治療歴を有する非小細胞肺がん患者に対する手術症例の検討

高津史明, 諏澤憲, 枝園和彦, 三好健太郎, 大谷真二, 山本寛斉, 岡崎幹生, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

肺癌 59 ( 6 ) 711 - 711 2019.11

完全切除II-IIIA期の非扁平上皮非小細胞肺癌に対するPEM/CDDPとVNR/CDDPを比較する第III相試験(JIPANG)

駄賀晴子, 釼持広知, 山本信之, 山中竹春, 岡本勇, 光冨徹哉, 瀬戸貴司, 杉尾賢二, 豊岡伸一, 伊達洋至, 坂英雄, 横井香平, 岡本浩明, 滝口裕一, 坪井正博, JIPANG運営委員会

肺癌 59 ( 6 ) 594 - 594 2019.11

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Papers - TOYOOKA Shinichi