Department of Thoracic Oncology

Koichi Goto, Kiyotaka Yoh, Shingo Matsumoto, Yoshitaka Zenke, Kaname Nosaki, Hiroki Izumi, Yuji Shibata, Tetsuya Sakai, Hajime Oi, Yutaro Tamiya, Masanobu Okahisa, Yosuke Kagawa, Yu Tanaka, Shingo Kitagawa, Shunta Mori, Fumihiko Okumura, Mao Sasamoto
(Shigeki Umemura, Seiji Niho, Keisuke Kirita, Hibiki Udagawa, Eri Sugiyama)

Introduction

The Department of Thoracic Oncology provides care for patients with primary lung cancer, mediastinal tumors, and pleural tumors. The department 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.

Table 1. Number of patients

The Team and What We Do

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 afternoons. 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 hospitals, the staff members and residents are teaching methods of reading for chest X-ray and CT images.

Table 2. Type of procedure

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 alterations 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, high-spec genomic analysis technologies are being adapted to our research screening for rare driver genomic alterations of lung cancer such as RET, ROS1, BRAF, MET, and HER2 etc. and their clinical development is also being supported in collaboration with some diagnostic companies.

Clinical trials

The Department of Thoracic Oncology is currently conducting and participating in multi-institutional clinical studies for advanced disease of lung cancer, such as the Japan Clinical Oncology Group (JCOG) trials, investigator-initiated trials, and pharmaceutical-company-initiated global trials.

An Asian international genomic screening platform established by our department, whose name is LC-SCRUM-Asia, was initiated in 2013 and is now ongoing. As of March 2022, 182 Japanese institutions participated in LC-SCRUM-Asia and 15,856 patients were enrolled. In addition, 6 institutions in Taiwan have participated in our genomic screening since March 2019 and 394 patients were already enrolled from Taiwan as of February 2022. LC-SCRUM-Asia will support the development of novel therapeutic and diagnostic products and contribute to establishing precision medicine in Asian countries. A lot of lung cancers with rare driver oncogenes, such as RET, ROS1 BRAF, MET, HER2 NTRK and KRAS G12C genomic alterations were identified in our screening and 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 mutation positive lung cancer in March 2018, entrectinib was approved for NTRK and ROS1 fusion positive lung cancer in June 2019 and February 2020, respectively, and tepotinib and capmatinib were approved for MET Ex14 skipping positive lung cancer in March 2020 and June 2020, respectively. In addition, selpercatinib was approved for RET fusion positive lung cancer in September 2021 and sotorasib was approved for KRAS G12C mutation positive lung cancer in January 2022.

Meanwhile, an RT-PCR kit which was adapted to LC-SCRUM-Asia 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. This year, a multi-PCR panel with short turnaround time was approved as a multi CDx for EGFR/ALK/ROS1/BRAF/MET Ex14 skipping in September 2021. As a result of this, we can now get the results of multi genomic analysis in only a week and start precision medicine for lung cancer from first-line treatment in clinical practice. Through the genomic screening and clinical-genomic database which are established, LC-SCRUM-Asia can play a key role toward developing precision medicine in lung cancer in Japan and other Asian countries.

In addition to the targeted genomic screening, to identify some novel oncogenic driver genes, we initiated whole-transcriptome sequencing (WTS) of NSCLC samples negative for known oncogenic drivers in LC-SCRUM-Asia in October 2020. In the WTS, we identified an in-frame fusion transcript of CLIP1 on chromosome 12q24 and LTK on chromosome 15q15 in one patient. The CLIP1-LTK fusion was present in 0.4% of NSCLCs and was mutually exclusive with other known oncogenic drivers. We showed that kinase activity of the CLIP1-LTK fusion protein was constitutively activated and had transformation potential. In in vitro and in vivo analysis, treatment with lorlatinib, an ALK inhibitor, inhibited CLIP1-LTK kinase activity, suppressed proliferation and induced apoptosis. One patient with NSCLC harboring the CLIP1-LTK fusion showed a good clinical response to lorlatinib. This was the first description of LTK alterations with oncogenic activity in cancers and was published in Nature in November 2021.

We also initiated another genomic screening project for pre-treated patients to identify resistant genomic alterations after treatment of molecular targeting agents (LC-SCRUM-TRY) in September 2020. A total of 934 pre-treated patients were already enrolled in LC-SCRUM-TRY as of March 2022. We are aiming to establish precision medicine based on the mechanisms of resistance to treatment through LC-SCRUM-TRY.

To select the optimal treatment for individual patients with advanced lung cancer, we currently analyze many biomarkers including EGFR ALK, ROS1, BRAF, MET and NTRK genomic alterations by NGS analysis and PD-L1 immunohistochemical staining using tissue samples in clinical practice. Since we get as large an amount of tissue samples as possible through bronchoscopy for the biomarker analyses, we are conducting a feasibility study of a cutting-edge trans-bronchial biopsy technique 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 clinical and translational research. In addition, one resident is affiliated with the Joint Graduate Program at Juntendo University, and two specialized researchers have been studying in the United States, one at Georgetown University since September 2018 and the other at MD Anderson Cancer Center since October 2020.

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, 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 precision medicine for lung cancer based on biomarkers. Additionally, Asian countries such as Thailand, Malaysia, Vietnam and Singapore are also taking 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 an Asian country, 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

Journal

1. Aokage K, Tsuboi M, Zenke Y, Horinouchi H, Nakamura N, Ishikura S, Nishikawa H, Kumagai S, Koyama S, Kanato K, Kataoka T, Wakabayashi M, Fukutani M, Fukuda H, Ohe Y, Watanabe SI. Study protocol for JCOG1807C (DEEP OCEAN): a interventional prospective trial to evaluate the efficacy and safety of durvalumab before and after operation or durvalumab as maintenance therapy after chemoradiotherapy against superior sulcus non-small cell lung cancer. Japanese journal of clinical oncology, 52:383-387, 2022

2. Ohe Y, Yamazaki N, Yamamoto N, Murakami H, Yoh K, Kitano S, Hashimoto H, Murayama A, Nakane S, Gemma A. The real-world safety of atezolizumab as second-line or later treatment in Japanese patients with non-small-cell lung cancer: a post-marketing surveillance study. Japanese journal of clinical oncology, 52:623-632, 2022

3. Matsumoto Y, Umemura S, Okizaki A, Fujisawa D, Kobayashi N, Tanaka Y, Sasaki C, Shimizu K, Ogawa A, Kinoshita H, Uchitomi Y, Yoshiuchi K, Matsuyama Y, Morita T, Goto K, Ohe Y. Early specialized palliative care for patients with metastatic lung cancer receiving chemotherapy: a feasibility study of a nurse-led screening-triggered programme. Japanese journal of clinical oncology, 52:375-382, 2022

4. Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Pérol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Jänne PA . Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. The New England journal of medicine, 386:241-251, 2022

5. Takamizawa S, Okuma Y, Kato Y, Hakozaki T, Kitagawa S, Zenke Y. First-line osimertinib in EGFR mutation-positive non-small cell lung cancer patients with poor performance status. Future oncology (London, England), 18:291-300, 2022

6. Demetri GD, De Braud F, Drilon A, Siena S, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Lin JJ, Goto K, Lee J, Bazhenova L, John T, Fakih M, Chawla SP, Dziadziuszko R, Seto T, Heinzmann S, Pitcher B, Chen D, Wilson TR, Rolfo C. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors. Clinical cancer research: an official journal of the American Association for Cancer Research, 28:1302-1312, 2022

7. Kunimasa K, Matsumoto S, Nishino K, Honma K, Maeda N, Kuhara H, Tamiya M, Inoue T, Kawamura T, Kimura T, Maniwa T, Okami J, Goto K, Kumagai T. Comparison of sampling methods for next generation sequencing for patients with lung cancer. Cancer medicine, 2022

8. Remon J, Lacas B, Herbst R, Reck M, Garon EB, Scagliotti GV, Ramlau R, Hanna N, Vansteenkiste J, Yoh K, Groen HJM, Heymach JV, Mandrekar SJ, Okamoto I, Neal JW, Heist RS, Planchard D, Pignon JP, Besse B. ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA. European journal of cancer (Oxford, England: 1990), 166:112-125, 2022

9. Iwama E, Zenke Y, Sugawara S, Daga H, Morise M, Yanagitani N, Sakamoto T, Murakami H, Kishimoto J, Matsumoto S, Nakanishi Y, Goto K, Okamoto I. Trastuzumab emtansine for patients with non-small cell lung cancer positive for human epidermal growth factor receptor 2 exon-20 insertion mutations. European journal of cancer (Oxford, England: 1990), 162:99-106, 2022

10. Kitadai R, Zenke Y, Hishima T, Hosomi Y. Intracranial complete response for non-small-cell lung cancer patient with negative PD-L1 expression of the lung using nivolumab. Cancer reports (Hoboken, N.J.), 5:e1460, 2022

11. McCoach CE, Rolfo C, Drilon A, Lacouture M, Besse B, Goto K, Zhu VW, Tan DSW, Farajian S, Potter LA, Kherani JF, Soldatenkova V, Olek EA, Muehlenbein CE, Park K. Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer, 17:768-778, 2022

12. Seto T, Nosaki K, Shimokawa M, Toyozawa R, Sugawara S, Hayashi H, Murakami H, Kato T, Niho S, Saka H, Oki M, Yoshioka H, Okamoto I, Daga H, Azuma K, Tanaka H, Nishino K, Tohnai R, Yamamoto N, Nakagawa K. Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study). Journal for immunotherapy of cancer, 10:2022

13. Ota T, Kirita K, Matsuzawa R, Udagawa H, Matsumoto S, Yoh K, Niho S, Ishii G, Goto K. Correction to: Validity of using immunohistochemistry to predict treatment outcome in patients with non-small cell lung cancer not otherwise specified. Journal of cancer research and clinical oncology, 148:281-282, 2022

14. Takahashi T, Sakai K, Kenmotsu H, Yoh K, Daga H, Ohira T, Ueno T, Aoki T, Hayashi H, Yamazaki K, Hosomi Y, Chen-Yoshikawa TF, Okumura N, Takiguchi Y, Sekine A, Haruki T, Yamamoto H, Sato Y, Akamatsu H, Seto T, Saeki S, Sugio K, Nishio M, Inokawa H, Yamamoto N, Nishio K, Tsuboi M. Predictive value of EGFR mutation in non-small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy. Cancer science, 113:287-296, 2022

15. Watanabe K, Yoh K, Hosomi Y, Usui K, Naka G, Kishi K, Uemura K, Ohashi Y, Kunitoh H. Efficacy and safety of first-line osimertinib treatment and postprogression patterns of care in patients with epidermal growth factor receptor activating mutation-positive advanced non-small cell lung cancer (Reiwa study): study protocol of a multicentre, real-world observational study. BMJ open, 12:e046451, 2022

16. Shirasawa M, Yoshida T, Shimoda Y, Takayanagi D, Shiraishi K, Kubo T, Mitani S, Matsumoto Y, Masuda K, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Ichikawa H, Kohno T, Yamamoto N, Matsumoto S, Goto K, Watanabe SI, Ohe Y, Motoi N. Differential Immune-Related Microenvironment Determines Programmed Cell Death Protein-1/Programmed Death-Ligand 1 Blockade Efficacy in Patients With Advanced NSCLC. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer, 16:2078-2090, 2021

17. Nishio K, Seto T, Nishio M, Reck M, Garon EB, Sakai K, Goto K, Kato T, Nakanishi Y, Takahashi T, Yamamoto N, Kiura K, Ohe Y, Tamura T, Visseren-Grul C, Frimodt-Moller B, Hozak RR, Wijayawardana SR, Zimmermann A, Homma G, Enatsu S, Nakagawa K. Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated Metastatic EGFR-Mutated NSCLC: RELAY Japanese Subset. JTO clinical and research reports, 2:100171, 2021

18. Yoh K, Hirashima T, Saka H, Kurata T, Ohe Y, Hida T, Mellemgaard A, Verheijen RB, Ou X, Ahmed GF, Hayama M, Sugibayashi K, Oxnard GR. Savolitinib ± Osimertinib in Japanese Patients with Advanced Solid Malignancies or EGFRm NSCLC: Ph1b TATTON Part C. Targeted oncology, 16:339-355, 2021

19. Calvo E, Spira A, Miguel M, Kondo S, Gazzah A, Millward M, Prenen H, Rottey S, Warburton L, Alanko T, Cassier PA, Yoh K, Italiano A, Moreno V, Peltola K, Seto T, Toyozawa R, Afar DE, Englert S, Komarnitsky P, Lambert S, Parikh A, Vosganian G, Gao B . Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Cancer treatment and research communications, 28:100405, 2021

20. Oiwa H, Aokage K, Suzuki A, Sato K, Kuroe T, Mimaki S, Tane K, Miyoshi T, Samejima J, Tsuchihara K, Goto K, Funai K, Tsuboi M, Nakai T, Ishii G. Clinicopathological, gene expression and genetic features of stage I lung adenocarcinoma with necrosis. Lung cancer (Amsterdam, Netherlands), 159:74-83, 2021

21. Izumi H, Matsumoto S, Liu J, Tanaka K, Mori S, Hayashi K, Kumagai S, Shibata Y, Hayashida T, Watanabe K, Fukuhara T, Ikeda T, Yoh K, Kato T, Nishino K, Nakamura A, Nakachi I, Kuyama S, Furuya N, Sakakibara-Konishi J, Okamoto I, Taima K, Ebi N, Daga H, Yamasaki A, Kodani M, Udagawa H, Kirita K, Zenke Y, Nosaki K, Sugiyama E, Sakai T, Nakai T, Ishii G, Niho S, Ohtsu A, Kobayashi SS, Goto K. The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer. Nature, 600:319-323, 2021

22. Takamochi K, Suzuki K, Tsuboi M, Niho S, Ishikura S, Oyamada S, Yamaguchi T, Okada M. Randomized phase II trial of pemetrexed-cisplatin plus bevacizumab or thoracic radiotherapy followed by surgery for stage IIIA (N2) nonsquamous non-small cell lung cancer. The Journal of thoracic and cardiovascular surgery, 2021

23. Yamaguchi H, Wakuda K, Fukuda M, Kenmotsu H, Mukae H, Ito K, Chibana K, Inoue K, Miura S, Tanaka K, Ebi N, Suetsugu T, Harada T, Kirita K, Yokoyama T, Nakatani Y, Yoshimura K, Nakagawa K, Yamamoto N, Sugio K. A Phase II Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis From NSCLC: Results for the T790M Cohort of the OCEAN Study (LOGIK1603/WJOG9116L). Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer, 16:2121-2132, 2021

24. Yasuda H, Ichihara E, Sakakibara-Konishi J, Zenke Y, Takeuchi S, Morise M, Hotta K, Sato M, Matsumoto S, Tanimoto A, Matsuzawa R, Kiura K, Takashima Y, Yano S, Koyama J, Fukushima T, Hamamoto J, Terai H, Ikemura S, Takemura R, Goto K, Soejima K. A phase I/II study of osimertinib in EGFR exon 20 insertion mutation-positive non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands), 162:140-146, 2021

25. Ninomiya K, Teraoka S, Zenke Y, Kenmotsu H, Nakamura Y, Okuma Y, Tamiya A, Nosaki K, Morise M, Aokage K, Oya Y, Kozuki T, Sakamoto T, Tanaka K, Tanaka H, Tanizaki J, Miura S, Mizutani H, Miyauchi E, Yamaguchi O, Ebi N, Goto Y, Sasaki T, Daga H, Morita S, Yamanaka T, Amano S, Hasegawa K, Imamura CK, Suzuki K, Nakajima K, Nishimoto H, Oizumi S, Hida T, Hotta K, Takiguchi Y. Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations. JTO clinical and research reports, 2:100107, 2021

26. Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, Sabari JK, Spira AI, Yang TY, Kim DW, Lee KH, Sanborn RE, Trigo J, Goto K, Lee JS, Yang JC, Govindan R, Bauml JM, Garrido P, Krebs MG, Reckamp KL, Xie J, Curtin JC, Haddish-Berhane N, Roshak A, Millington D, Lorenzini P, Thayu M, Knoblauch RE, Cho BC . Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 39:3391-3402, 2021

27. Cho BC, Yoh K, Perets R, Nagrial A, Spigel DR, Gutierrez M, Kim DW, Kotasek D, Rasco D, Niu J, Satouchi M, Ahn MJ, Lee DH, Maurice-Dror C, Siddiqi S, Ren Y, Altura RA, Bar J. Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer. Lung cancer (Amsterdam, Netherlands), 159:162-170, 2021

28. Kashima Y, Shibahara D, Suzuki A, Muto K, Kobayashi IS, Plotnick D, Udagawa H, Izumi H, Shibata Y, Tanaka K, Fujii M, Ohashi A, Seki M, Goto K, Tsuchihara K, Suzuki Y, Kobayashi SS. Single-Cell Analyses Reveal Diverse Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer. Cancer research, 81:4835-4848, 2021

29. Sakai T, Udagawa H, Kirita K, Nomura S, Itotani R, Tamiya Y, Sugimoto A, Ota T, Naito T, Izumi H, Nosaki K, Ikeda T, Zenke Y, Matsumoto S, Yoh K, Niho S, Nakai T, Ishii G, Goto K. Comparison of the efficiency of endobronchial ultrasound-guided transbronchial needle aspiration using a 22G needle versus 25G needle for the diagnosis of lymph node metastasis in patients with lung cancer: a prospective randomized, crossover study. Translational lung cancer research, 10:3745-3758, 2021

30. Yoh K, Matsumoto S, Furuya N, Nishino K, Miyamoto S, Oizumi S, Okamoto N, Itani H, Kuyama S, Nakamura A, Nishi K, Fukuda I, Tsuta K, Hayashi Y, Motoi N, Ishii G, Goto K. Comprehensive assessment of PD-L1 expression, tumor mutational burden and oncogenic driver alterations in non-small cell lung cancer patients treated with immune checkpoint inhibitors. Lung cancer (Amsterdam, Netherlands), 159:128-134, 2021

31. Kunimasa K, Nishino K, Kukita Y, Matsumoto S, Kawachi H, Kawamura T, Inoue T, Tamiya M, Honma K, Sugimoto N, Yamasaki T, Imamura F, Goto K, Kumagai T. Late recurrence of lung adenocarcinoma harboring EGFR exon 20 insertion (A763_Y764insFQEA) mutation successfully treated with osimertinib. Cancer genetics, 256-257:57-61, 2021

32. Murata S, Sasada S, Usui Y, Sakai T, Kirita K, Ishioka K, Takahashi S, Nakamura M. Omission of Throat Anesthesia Using Jackson's Spray Prior to Bronchoscopy for Preventing Aerosol Generation: A Survey Through Patient Distress Questionnaire. Cureus, 13:e17231, 2021

33. Sakai H, Morise M, Kato T, Matsumoto S, Sakamoto T, Kumagai T, Tokito T, Atagi S, Kozuki T, Tanaka H, Chikamori K, Shinagawa N, Takeoka H, Bruns R, Straub J, Schumacher KM, Paik PK. Tepotinib in patients with NSCLC harbouring MET exon 14 skipping: Japanese subset analysis from the Phase II VISION study. Japanese journal of clinical oncology, 51:1261-1268, 2021

34. Miura K, Sano Y, Niho S, Kawasumi K, Mochizuki N, Yoh K, Matsumoto S, Zenke Y, Ikeda T, Nosaki K, Kirita K, Udagawa H, Goto K, Kawasaki T, Hanada K. Impact of concomitant medication on clinical outcomes in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: A retrospective study. Thoracic cancer, 12:1983-1994, 2021

35. Sugimoto A, Umemura S, Miyoshi T, Nakai T, Kuroe T, Nosaki K, Ikeda T, Udagawa H, Kirita K, Zenke Y, Matsumoto S, Yoh K, Niho S, Tsuboi M, Goto K, Ishii G. High proportion of tumor necrosis predicts poor survival in surgically resected high-grade neuroendocrine carcinoma of the lung. Lung cancer (Amsterdam, Netherlands), 157:1-8, 2021

36. Takeda M, Shimokawa M, Nakamura A, Nosaki K, Watanabe Y, Kato T, Hayakawa D, Tanaka H, Takahashi T, Kogure Y, Tachihara M, Fujimoto D, Yamaguchi K, Hamaguchi N, Okamoto I, Azuma K, Hasegawa K, Yamamoto N, Nakagawa K. A Phase II Study to Assess the Efficacy of Osimertinib in Patients With EGFR Mutation-positive NSCLC Who Developed Isolated CNS Progression (T790M-negative or Unknown) During First- or Second-generation EGFR-TKI or Systemic Disease Progression (T790M-negative) After Treatment With First- or Second-generation EGFR-TKI and Platinum-based Chemotherapy (WJOG12819L). Clinical lung cancer, 22:376-380, 2021

37. Udagawa H, Sugiyama E, Harada T, Atagi S, Koyama R, Watanabe S, Nakamura Y, Harada D, Hataji O, Tanaka F, Kida H, Satouchi M, Maeno K, Inoue A, Yoh K, Yamane Y, Urata Y, Yoshioka H, Yamanaka T, Goto K. Bevacizumab plus platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer: a randomized, open-label phase 2 study (CLEAR). Translational lung cancer research, 10:3059-3070, 2021

38. Nakasuka T, Ohashi K, Watanabe H, Kubo T, Matsumoto S, Goto K, Hotta K, Maeda Y, Kiura K. A case of dramatic reduction in cancer-associated thrombus following initiation of pembrolizumab in patient with a poor performance status and PD-L1+ lung adenocarcinoma harboring CCDC6-RET fusion gene and NF1/TP53 mutations. Lung cancer (Amsterdam, Netherlands), 156:1-4, 2021

39. Yoneshima Y, Iwama E, Matsumoto S, Matsubara T, Tagawa T, Ota K, Tanaka K, Takenoyama M, Okamoto T, Goto K, Mori M, Okamoto I. Paired analysis of tumor mutation burden for lung adenocarcinoma and associated idiopathic pulmonary fibrosis. Scientific reports, 11:12732, 2021

40. Zenke Y, Tsuboi M, Chiba Y, Tsujino K, Satouchi M, Sawa K, Shimizu J, Daga H, Fujimoto D, Mori M, Aoki T, Sawa T, Omori S, Saka H, Iwamoto Y, Okuno M, Hirashima T, Kashiwabara K, Tachihara M, Ymamoto N, Nakagawa K. Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial. JAMA oncology, 7:904-909, 2021

41. Shibata Y, Murakami S, Kato T. Overview of checkpoint inhibitor pneumonitis: incidence and associated risk factors. Expert opinion on drug safety, 20:537-547, 2021

42. Kok PS, Lee K, Lord S, Yang JC, Rosell R, Goto K, John T, Wu YL, Mok TSK, Lee CK. Clinical utility of plasma EGFR mutation detection with quantitative PCR in advanced lung cancer: A meta-analysis. Lung cancer (Amsterdam, Netherlands), 154:113-117, 2021

43. Nishio M, Saito H, Goto K, Watanabe S, Sueoka-Aragane N, Okuma Y, Kasahara K, Chikamori K, Nakagawa Y, Kawakami T. IMpower132: Atezolizumab plus platinum-based chemotherapy vs chemotherapy for advanced NSCLC in Japanese patients. Cancer science, 112:1534-1544, 2021

44. Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Eba J, Asamura H, Ohe Y, Watanabe SI. Reply to J. L. Derks et al. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 39:1509-1510, 2021

45. Yoh K, Seto T, Satouchi M, Nishio M, Yamamoto N, Murakami H, Nogami N, Nosaki K, Kohno T, Tsuta K, Nomura S, Ikeno T, Wakabayashi M, Sato A, Matsumoto S, Goto K. Final survival results for the LURET phase II study of vandetanib in previously treated patients with RET-rearranged advanced non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands), 155:40-45, 2021

46. Sakai T, Udagawa H, Matsumoto S, Yoh K, Nosaki K, Ikeda T, Zenke Y, Kirita K, Niho S, Akimoto T, Goto K, Ishii G. Morphological, immune and genetic features in biopsy sample associated with the efficacy of pembrolizumab in patients with non-squamous non-small cell lung cancer. Journal of cancer research and clinical oncology, 147:1227-1237, 2021