Annual Report 2019
Department of Thoracic Oncology
Koichi Goto, Seiji Niho, Kiyotaka Yoh, Shingo Matsumoto, Keisuke Kirita, Hibiki Udagawa, Yoshitaka Zenke, Takaya Ikeda, Kaname Nosaki, Hiroki Izumi, Eri Sugiyama, Shigeki Umemura, Tomoyuki Naito, Tetsuya Sakai, Akira Sugimoto, Ryo Itotani, Yutaro Tamiya
Introduction
The Department of Thoracic Oncology provides care for patients with primary lung cancer, mediastinal tumors, and pleural tumors. The division aims to provide the highest quality treatment and establish new effective treatments against lung cancer and other thoracic malignancies through innovative clinical and translational research. To provide assistance to our patients through multidisciplinary care, the staff members of the division work closely with thoracic surgeons, radiation oncologists, pathologists, pharmacists, clinical research coordinators, and psychiatrists who have expertise in these areas. Moreover, residents and trainees from other institutions have joined the Thoracic Oncology Program.
The Team and What We Do
Our Outpatient Clinic, managed by the staff members and senior residents, is open from Monday to Friday for the examination of all new referred patients and the evaluation of returning patients. Returning patients also receive oral chemotherapy and/or intravenous chemotherapy in the Ambulatory Care Center. Bronchoscopy with EBUS for diagnosis is performed from Monday to Thursday afternoons. Fluoroscopic-CT guided needle lung biopsies are carried out on Tuesday afternoon. For patient management, we use approximately 60 beds mainly in 8F, 6A, 6B and 5A wards.
Case conferences on thoracic surgery and medical oncology are scheduled on Tuesday evenings and Wednesday evenings, respectively. The staff members and residents of the division participate in a journal club on Monday and Wednesday mornings. At monthly meetings with physicians in private practice, the staff members and residents are teaching methods of reading for chest X-ray and CT scan films.
Research activities
Our research activities are focused on three areas: 1) development of new and effective diagnosis and treatment modalities in lung cancer; 2) collaborative studies with the Research Center for Innovative Oncology in the following areas: detection of biomarkers for the treatment of advanced lung cancer; development of new diagnostic methods of rare driver genomic alteration for lung cancer; correlation between genomic abnormalities and clinical characteristics and treatment in lung cancer; and correlation between pathological features and sensitivity of treatments in lung cancer; and 3) translational research from bench to bed-side or from bed-side to bench for the development of innovative treatment strategies in lung cancer.
Especially, development of target sequence diagnosis methods by next generation sequencing for rare driver genomic alterations of lung cancer such as RET, ROS1, BRAF, MET, and HER2 etc. are currently under investigation collaborating with the Research Center for Innovative Oncology.
Clinical trials
The Department of Thoracic Oncology is currently conducting and participating in multi-institutional clinical studies for advanced lung cancer disease, such as the Japan Clinical Oncology Group (JCOG) trials, West Japan Oncology Group (WJOG) trials, Thoracic Oncology Research Group (TORG) trials, investigator-initiated trials, and pharmaceutical-company-initiated global trials.
A nationwide genomic screening platform established by our department, whose name is LC-SCRUM-Japan, was initiated in 2013 and is now ongoing. As of 2020 March, 212 Japanese institutions participated in LC-SCRUM-Japan and 9725 patients were enrolled. In addition, 6 institutions in Taiwan participated in our genomic screening from March 2019, and LC-SCRUM-Japan became an Asian international genomic screening platform, and its name was changed to LC-SCRUM-Asia. LC-SCRUM-Asia will support the development of novel therapeutic and diagnostic products in Asia and contribute to establish precision medicine in Asian countries. Many lung cancers with rare driver oncogenes, such as RET, ROS1 BRAF, MET, HER2 and KRAS genomic alterations were identified in our screening and they were entered into various clinical trials of molecular targeting agents. Based on the results of clinical trials leveraging genomic screening in LC-SCRUM-Asia, crizotinib was approved for ROS1 fusion positive lung cancer in May 2017, dabrafenib/trametinib was approved for BRAF V600E positive lung cancer in March 2018, entrectinib was approved for NTRK fusion positive lung cancer in June 2019, and entrectinib was also approved for ROS1 fusion positive lung cancer in February 2020. RT-PCR kit, which was adapted in LC-SCRUM-Japan screening for ROS1 fusion, was simultaneously approved using our screening data as a companion diagnostic (CDx) for ROS1 positive lung cancer in January 2017. In the same way, a next generation sequencing (NGS) panel was first approved as a CDx for BRAF mutation positive lung cancer in April 2018 and also approved as a first multi NGS CDx for EGFR/ALK/ROS1/BRAF in February 2019. Through the genomic screening, LC-SCRUM-Asia should play a key role to establish precision medicine in lung cancer in Japan and Asian countries.
To confirm the usefulness of the NGS panel using plasma cell-free DNA (liquid biopsy system), we also started LC-SCRUM-Liquid from December 2017 targeting 2000 advanced lung cancers, and it is now ongoing. As of March 2020, 614 patients were already enrolled in LC-SCRUM-Liquid and a concordance study between tissue and liquid NGS analyses is ongoing to evaluate the sensitivity of the liquid biopsy system. We simultaneously initiated the umbrella-type clinical trials of osimertinib for EGFR mutation positive lung cancer by liquid biopsy from September 2019 and alectinib for ALK fusion positive lung cancer by liquid biopsy from October 2019. We would like to conduct large umbrella trials targeting various types of driver alterations based on our liquid screening.
To select optimal treatment for the individual patients with advanced lung cancer, we currently need to analyze many biomarkers including EGFR ALK, ROS1, BRAF and NTRK genomic alterations by NGS screening and PD-L1 immunohistochemical staining using tissue samples. Since we need to get as many tissue samples as possible by bronchoscopy for the biomarker analyses, we are conducting a feasibility study of trans-bronchial cryobiopsy to evaluate its utility.
Education
Residents, cancer specialists in training, and staff are paired to provide outpatient/inpatient medical care and perform examinations. The aim is to develop clinicians who can provide comprehensive medical care for patients with thoracic malignant tumors, from diagnosis to treatment, and including palliative care, by closely supporting patients with advanced lung cancer for whom a complete cure is difficult. Moreover, in our department, we always try to train specialists to have not only outstanding minds but also strong mental and physical strengths to handle patients’ distress. Residents are required to go on rotation in the Department of Pathology during their training period, and have opportunities to come into contact with basic research from this department. Furthermore, we also actively support the preparation of manuscripts on basic and clinical research, aiming to develop clinicians capable of conducting translational research. In addition, two residents are affiliated with the Joint Graduate Program at Juntendo University, and a specialized researcher has been studying at Georgetown University in the United States since September 2018.
A joint case conference with the Department of Thoracic Surgery is held every Tuesday and a joint case conference with the Department of Radiation Oncology is held every Wednesday to determine treatment policies, and a research conference is held once a month to discuss the progress and schedule of research with all members. A journal club with the Department of Thoracic Oncology is held every Monday, a journal club with the Department of Thoracic Surgery is held every Wednesday, a joint conference with the Departments of Thoracic Surgery and Pathology is held every Friday, and a chest X-ray reading meeting for local clinicians is held on the second Tuesday of each month, and a chest X-ray reading meeting with the Katsushika Medical Association is held on the fourth Tuesday of each month.
Future prospects
Drug therapy for lung cancer has made a major shift to personalized medicine in which therapeutic drugs are selected based on biomarkers in individual patients. In addition, immune checkpoint inhibitors have greatly contributed to the improvement of treatment outcomes in lung cancer as highly effective drugs with a different mechanism of action from conventional drugs. Dramatic advances in these new therapies have greatly changed the treatment structure for advanced lung cancer in the last few years, and treatment outcomes have also significantly improved. In our department, we plan to continue conducting various research studies in the future with the aim of establishing personalized medicine for lung cancer based on biomarkers. Southeast Asian countries are scheduled to take part in LC-SCRUM-Asia, and in collaboration with LC-IRICA, a genomic screening platform in China, a large-scale international genomic screening platform in East Asia, will be established. By utilizing this screening platform, treatment development for advanced lung cancer, which has attracted a great deal of attention worldwide, will be conducted and the results will be released to the world. Moreover, we will continue to promote translational research, conduct innovative and advanced clinical trials that can link the results to clinical development, and pursue research with the aim of overcoming advanced lung cancer.
List of papers published in 2019
Journal
1. Sugiyama E, Togashi Y, Takeuchi Y, Shinya S, Tada Y, Kataoka K, Tane K, Sato E, Ishii G, Goto K, Shintani Y, Okumura M, Tsuboi M, Nishikawa H. Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer. Sci Immunol, 5:doi: 10.1126/sciimmunol.aav3937, 2020
2. Wong JYY, Zhang H, Hsiung CA, Shiraishi K, Yu K, Matsuo K, Wong MP, Hong YC, Wang J, Seow WJ, Wang Z, Song M, Kim HN, Chang IS, Chatterjee N, Hu W, Wu C, Mitsudomi T, Zheng W, Kim JH, Seow A, Caporaso NE, Shin MH, Chung LP, An SJ, Wang P, Yang Y, Zheng H, Yatabe Y, Zhang XC, Kim YT, Cai Q, Yin Z, Kim YC, Bassig BA, Chang J, Ho JCM, Ji BT, Daigo Y, Ito H, Momozawa Y, Ashikawa K, Kamatani Y, Honda T, Hosgood HD, Sakamoto H, Kunitoh H, Tsuta K, Watanabe SI, Kubo M, Miyagi Y, Nakayama H, Matsumoto S, Tsuboi M, Goto K, Shi J, Song L, Hua X, Takahashi A, Goto A, Minamiya Y, Shimizu K, Tanaka K, Wei F, Matsuda F, Su J, Kim YH, Oh IJ, Song F, Su WC, Chen YM, Chang GC, Chen KY, Huang MS, Chien LH, Xiang YB, Park JY, Kweon SS, Chen CJ, Lee KM, Blechter B, Li H, Gao YT, Qian B, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Tsai YH, Jung YJ, Guo H, Hu Z, Wang WC, Chung CC, Burdett L, Yeager M, Hutchinson A, Berndt SI, Wu W, Pang H, Li Y, Choi JE, Park KH, Sung SW, Liu L, Kang CH, Zhu M, Chen CH, Yang TY, Xu J, Guan P, Tan W, Wang CL, Hsin M, Sit KY, Ho J, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Lin CC, Park IK, Xu P, Wang Y, He Q, Perng RP, Chen CY, Vermeulen R, Wu J, Lim WY, Chen KC, Li YJ, Li J, Chen H, Yu CJ, Jin L, Chen TY, Jiang SS, Liu J, Yamaji T, Hicks B, Wyatt K, Li SA, Dai J, Ma H, Jin G, Song B, Wang Z, Cheng S, Li X, Ren Y, Cui P, Iwasaki M, Shimazu T, Tsugane S, Zhu J, Chen Y, Yang K, Jiang G, Fei K, Wu G, Lin HC, Chen HL, Fang YH, Tsai FY, Hsieh WS, Yu J, Stevens VL, Laird-Offringa IA, Marconett CN, Rieswijk L, Chao A, Yang PC, Shu XO, Wu T, Wu YL, Lin D, Chen K, Zhou B, Huang YC, Kohno T, Shen H, Chanock SJ, Rothman N, Lan Q. Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women. Genomics, 112:1223-1232, 2020
3. Niho S, Yoshida T, Akimoto T, Sakamaki K, Ono A, Seto T, Nishio M, Yamamoto N, Hida T, Okamoto H, Kurata T, Satouchi M, Goto K, Yamanaka T, Ohe Y. Randomized phase II study of chemoradiotherapy with cisplatin + S-1 versus cisplatin + pemetrexed for locally advanced non-squamous non-small cell lung cancer: SPECTRA study. Lung Cancer, 141:64-71, 2020
4. Nishio M, Kato T, Niho S, Yamamoto N, Takahashi T, Nogami N, Kaneda H, Fujita Y, Wilner K, Yoshida M, Isozaki M, Wada S, Tsuji F, Nakagawa K. Safety and efficacy of first-line dacomitinib in Japanese patients with advanced non-small cell lung cancer. Cancer Sci, 111:1724-1738, 2020
5. Okamoto I, Nokihara H, Nomura S, Niho S, Sugawara S, Horinouchi H, Azuma K, Yoneshima Y, Murakami H, Hosomi Y, Atagi S, Ozaki T, Horiike A, Fujita Y, Okamoto H, Ando M, Yamamoto N, Ohe Y, Nakagawa K. Comparison of Carboplatin Plus Pemetrexed Followed by Maintenance Pemetrexed With Docetaxel Monotherapy in Elderly Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol, 6:e196828, 2020
6. Senan S, Okamoto I, Lee GW, Chen Y, Niho S, Mak G, Yao W, Shire N, Jiang H, Cho BC. Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. Clin Lung Cancer, 21:e84-e88, 2020
7. Shimokawa M, Nosaki K, Seto T, Ohashi K, Morise M, Horinouchi H, Sakakibara J, Murakami H, Yano S, Satouchi M, Matsumoto S, Goto K, Yoh K. Phase II, open-label, multicenter trial of crizotinib in Japanese patients with advanced non-small cell lung cancer harboring a MET gene alteration: Co-MET study. Trials, 21:298, 2020
8. Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol, 21:261-270, 2020
9. Takemoto S, Fukuda M, Yamaguchi H, Ikeda T, Akagi K, Tomono H, Umeyama Y, Dotsu Y, Taniguchi H, Gyotoku H, Senju H, Kitazaki T, Nakatomi K, Nagashima S, Fukuda M, Kinoshita A, Soda H, Mukae H. Phase II study of ramucirumab and docetaxel for previously treated non-small cell lung cancer patients with malignant pleural effusion: Protocol of PLEURAM study. Thorac Cancer, 11:389-393, 2020
10. Nakagawa K, Hida T, Nokihara H, Morise M, Azuma K, Kim YH, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Kumagai T, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Koyama R, Mitsudomi T, Yamamoto N, Asakawa T, Hayashi M, Hasegawa W, Tamura T. Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer, 139:195-199, 2020
11. Naito T, Umemura S, Nakamura H, Zenke Y, Udagawa H, Kirita K, Matsumoto S, Yoh K, Niho S, Motoi N, Aokage K, Tsuboi M, Ishii G, Goto K. Successful treatment with nivolumab for SMARCA4-deficient non-small cell lung carcinoma with a high tumor mutation burden: A case report. Thorac Cancer, 10:1285-1288, 2019
12. Suzuki E, Yamazaki S, Naito T, Hashimoto H, Okubo S, Udagawa H, Goto K, Tsuboi M, Ochiai A, Ishii G. Secretion of high amounts of hepatocyte growth factor is a characteristic feature of cancer-associated fibroblasts with EGFR-TKI resistance-promoting phenotype: A study of 18 cases of cancer-associated fibroblasts. Pathol Int, 69:472-480, 2019
13. Ota T, Niho S, Kirita K, Ishii G, Tsuboi M, Goto K. Impressive response to nivolumab of non-small-cell lung cancer containing sarcomatoid components. Respirol Case Rep, 7:e00477, 2019
14. Hisamitsu S, Miyashita T, Hashimoto H, Neri S, Sugano M, Nakamura H, Yamazaki S, Ochiai A, Goto K, Tsuboi M, Ishii G. Interaction between cancer cells and cancer-associated fibroblasts after cisplatin treatment promotes cancer cell regrowth. Hum Cell, 32:453-464, 201915. Naito T, Udagawa H, Umemura S, Sakai T, Zenke Y, Kirita K, Matsumoto S, Yoh K, Niho S, Tsuboi M, Ishii G, Goto K. Non-small cell lung cancer with loss of expression of the SWI/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden. Lung Cancer, 138:35-42, 2019
16. Katsuya Y, Horinouchi H, Seto T, Umemura S, Hosomi Y, Satouchi M, Nishio M, Kozuki T, Hida T, Sukigara T, Nakamura K, Kuchiba A, Ohe Y. Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study. Eur J Cancer, 113:78-86, 2019
17. Naito T, Udagawa H, Sato J, Horinouchi H, Murakami S, Goto Y, Kanda S, Fujiwara Y, Yamamoto N, Zenke Y, Kirita K, Matsumoto S, Yoh K, Niho S, Motoi N, Ohe Y, Ishii G, Goto K. A Minimum Of 100 Tumor Cells in a Single Biopsy Sample Is Required to Assess Programmed Cell Death Ligand 1 Expression in Predicting Patient Response to Nivolumab Treatment in Nonsquamous Non-Small Cell Lung Carcinoma. J Thorac Oncol, 14:1818-1827, 2019
18. Kenmotsu H, Yoh K, Mori K, Ono A, Baba T, Fujiwara Y, Yamaguchi O, Ko R, Okamoto H, Yamamoto N, Ninomiya T, Ogura T, Kato T. Phase II study of nab-paclitaxel + carboplatin for patients with non-small-cell lung cancer and interstitial lung disease. Cancer Sci, 110:3738-3745, 2019
19. Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol, 20:1655-1669, 2019
20. Yoshino T, Kotaka M, Shinozaki K, Touyama T, Manaka D, Matsui T, Ishigure K, Hasegawa J, Inoue K, Munemoto Y, Takagane A, Ishikawa H, Ishida H, Ogata Y, Oba K, Goto K, Sakamoto J, Maehara Y, Ohtsu A. JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer. Cancer Chemother Pharmacol, 84:1269-1277, 2019
21. Shimada M, Yamaguchi H, Fukuda M, Tomono H, Honda N, Dotsu Y, Taniguchi H, Gyotoku H, Senju H, Takemoto S, Ikeda T, Nakatomi K, Nakamura Y, Nagashima S, Yamazaki T, Mukae H. Dose escalation study of amrubicin and cisplatin with concurrent thoracic radiotherapy for limited-disease small cell lung cancer. Cancer Chemother Pharmacol, 84:1059-1064, 2019
22. Tsutani Y, Suzuki K, Koike T, Wakabayashi M, Mizutani T, Aokage K, Saji H, Nakagawa K, Zenke Y, Takamochi K, Ito H, Aoki T, Okami J, Yoshioka H, Okada M, Watanabe SI. High-Risk Factors for Recurrence of Stage I Lung Adenocarcinoma: Follow-up Data From JCOG0201. Ann Thorac Surg, 108:1484-1490, 2019
23. Udagawa H, Hasako S, Ohashi A, Fujioka R, Hakozaki Y, Shibuya M, Abe N, Komori T, Haruma T, Terasaka M, Fujita R, Hashimoto A, Funabashi K, Yasuda H, Miyadera K, Goto K, Costa DB, Kobayashi SS. TAS6417/CLN-081 Is a Pan-Mutation-Selective EGFR Tyrosine Kinase Inhibitor with a Broad Spectrum of Preclinical Activity against Clinically Relevant EGFR Mutations. Mol Cancer Res, 17:2233-2243, 2019
24. Ota T, Kirita K, Matsuzawa R, Udagawa H, Matsumoto S, Yoh K, Niho S, Ishii G, Goto K. Validity of using immunohistochemistry to predict treatment outcome in patients with non-small cell lung cancer not otherwise specified. J Cancer Res Clin Oncol, 145:2495-2506, 2019
25. Horinouchi H, Nishio M, Hida T, Nakagawa K, Sakai H, Nogami N, Atagi S, Takahashi T, Saka H, Takenoyama M, Katakami N, Tanaka H, Takeda K, Satouchi M, Isobe H, Maemondo M, Goto K, Hirashima T, Minato K, Sumiyoshi N, Tamura T. Three-year follow-up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non-small cell lung cancer: Pooled analysis of ONO-4538-05 and ONO-4538-06 studies. Cancer Med, 8:5183-5193, 2019
26. Sakakibara-Konishi J, Kitai H, Ikezawa Y, Hatanaka Y, Sasaki T, Yoshida R, Chiba S, Matsumoto S, Goto K, Mizugaki H, Shinagawa N. Response to Crizotinib Re-administration After Progression on Lorlatinib in a Patient With ALK-rearranged Non-small-cell Lung Cancer. Clin Lung Cancer, 20:e555-e559, 2019
27. Taniguchi H, Yamaguchi H, Dotsu Y, Shimada M, Gyotoku H, Senju H, Takemoto S, Kitazaki T, Fukuda M, Ogawara D, Soda H, Nakatomi K, Sugasaki N, Kinoshita A, Nagashima S, Ikeda T, Nakamura Y, Sakamoto N, Obase Y, Fukuda M, Mukae H. Phase II study of nedaplatin and amrubicin as first-line treatment for advanced squamous cell lung cancer. Thorac Cancer, 10:1764-1769, 2019
28. Udagawa H, Akamatsu H, Tanaka K, Takeda M, Kanda S, Kirita K, Teraoka S, Nakagawa K, Fujiwara Y, Yasuda I, Okubo S, Shintani M, Kosloski MP, Scripture C, Tamura T, Okamoto I. Phase I safety and pharmacokinetics study of rovalpituzumab tesirine in Japanese patients with advanced, recurrent small cell lung cancer. Lung Cancer, 135:145-150, 2019
29. Otsubo K, Sakai K, Takeshita M, Harada D, Azuma K, Ota K, Akamatsu H, Goto K, Horiike A, Kurata T, Nakagaki N, Nosaki K, Iwama E, Nakanishi Y, Nishio K, Okamoto I. Genetic Profiling of Non-Small Cell Lung Cancer at Development of Resistance to First- or Second-Generation EGFR-TKIs by CAPP-Seq Analysis of Circulating Tumor DNA. Oncologist, 24:1022-1026, 2019
30. Niho S, Hosomi Y, Okamoto H, Nihei K, Tanaka H, Hida T, Umemura S, Goto K, Akimoto T, Ohe Y. Carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced non-small cell lung cancer: a multicenter Phase I/II study. Jpn J Clin Oncol, 49:614-619, 2019
31. Sakai T, Miyoshi T, Umemura S, Suzuki J, Nakasone S, Okada S, Tane K, Aokage K, Goto K, Motoi N, Ishii G, Tsuboi M. Large pulmonary sclerosing pneumocytoma with massive necrosis and vascular invasion: a case report. Oxf Med Case Reports, 2019:doi:10.1093/omcr/omz066, 2019
32. Doi T, Yoh K, Shitara K, Takahashi H, Ueno M, Kobayashi S, Morimoto M, Okusaka T, Ueno H, Morizane C, Okano N, Nagashima F, Furuse J. First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors. Invest New Drugs, 37:507-518, 2019
33. Watanabe S, Yoshioka H, Sakai H, Hotta K, Takenoyama M, Yamada K, Sugawara S, Takiguchi Y, Hosomi Y, Tomii K, Niho S, Yamamoto N, Nishio M, Ohe Y, Kato T, Takahashi T, Kamada A, Suzukawa K, Omori Y, Enatsu S, Nakagawa K, Tamura T. Corrigendum to “Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan” [Lung Cancer, 129 (March) (2019) 55-62]. Lung Cancer, 132:157-158, 2019
34. Ikemura S, Yasuda H, Matsumoto S, Kamada M, Hamamoto J, Masuzawa K, Kobayashi K, Manabe T, Arai D, Nakachi I, Kawada I, Ishioka K, Nakamura M, Namkoong H, Naoki K, Ono F, Araki M, Kanada R, Ma B, Hayashi Y, Mimaki S, Yoh K, Kobayashi SS, Kohno T, Okuno Y, Goto K, Tsuchihara K, Soejima K. Molecular dynamics simulation-guided drug sensitivity prediction for lung cancer with rare EGFR mutations. Proc Natl Acad Sci U S A, 116:10025-10030, 2019
35. Nakamura M, Kageyama SI, Niho S, Okumura M, Hojo H, Motegi A, Nakamura N, Zenda S, Yoh K, Goto K, Akimoto T. Impact of EGFR Mutation and ALK Translocation on Recurrence Pattern After Definitive Chemoradiotherapy for Inoperable Stage III Non-squamous Non-small-cell Lung Cancer. Clin Lung Cancer, 20:e256-e264, 2019
36. Sugawara S, Nakagawa K, Yamamoto N, Nokihara H, Ohe Y, Nishio M, Takahashi T, Goto K, Maemondo M, Ichinose Y, Seto T, Sakai H, Gemma A, Imamura F, Shingyoji M, Saka H, Inoue A, Takeda K, Okamoto I, Kiura K, Morita S, Tamura T. Japanese subgroup analysis of a phase III study of S-1 versus docetaxel in non-small cell lung cancer patients after platinum-based treatment: EAST-LC. Int J Clin Oncol, 24:485-493, 2019
37. Esaki T, Hirai F, Makiyama A, Seto T, Bando H, Naito Y, Yoh K, Ishihara K, Kakizume T, Natsume K, Myers A, Doi T. Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors. Cancer Sci, 110:1340-1351, 2019