Annual Report 2021

Department of Thoracic Oncology

Yuichiro Ohe, Noboru Yamamoto, Hidehito Horinouchi, Yasushi Goto, Tatsuya Yoshida, Yusuke Okuma, Yuki Shinno, Ken Masuda, Yuji Matsumoto, Keisuke Baba, Ryoko Higashiyama, Yuki Takeyasu, Masahiro Torasawa

Introduction

 Lung cancer is the leading cause of cancer death in Japan and worldwide. The incidence of lung cancer in Japan is still increasing, especially in the elderly. The Department of Thoracic Oncology provides care for patients with primary lung cancer, mediastinal tumors, and pleural tumors. The goals of the department are 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 toward our patients through multidisciplinary care, the staff members of the department work closely with thoracic surgeons, radiation oncologists, pathologists, pharmacists, clinical research coordinators, and psychiatrists who have expertise in these areas. The department includes nine staff physicians. Moreover, residents and trainees from other institutions have joined the Thoracic Oncology Program.

The Team and What We Do

 The staff physicians attend outpatient services for thoracic diseases, and the department has approximately 60 beds in the hospital. Inpatient care is carried out by six teams. Each team consists of one staff physician and one or two residents and/or trainee doctors. Case conferences are scheduled every Monday and Tuesday morning. A protocol conference and the journal club are scheduled every Monday afternoon and Thursday morning, respectively.

 A total of 569 new patients started treatment in 2021, and the backgrounds and initial treatments of these patients are shown in Tables 1 and 2. The initial treatments were chemotherapy in 312 cases, adjuvant chemotherapy after surgery in 65, chemoradiotherapy in 77, curative radiotherapy in 13, and supportive care including palliative radiotherapy in 41. Survival of lung cancer patients treated in 2012-2016 in our department is shown in Table 3.

Table 1. Number of patients in 2021

Table 2. Type of procedure in 2021

Table 3. Survival of lung cancer patients treated in 2012-2016

Research activities

 Research activities of the department can be classified into four categories: (1) multi-institutional phase III studies to establish new standard treatments against lung cancer; (2) phase I and phase II studies to evaluate new anticancer drugs, (3) pharmacokinetic and pharmacodynamic (PK/PD) studies to investigate interpatient variability, optimal administration schedules and drug-drug interactions; and (4) translational research using clinical samples from bench to bed-side or from bed-side to bench for the development of innovative treatment strategies.

Clinical trials

 The department is currently conducting and participating in multi-institutional phase III studies to establish new standard treatments against lung cancer such as the Japan Clinical Oncology Group (JCOG) trials and global trials conducted by pharmaceutical companies. Six JCOG clinical studies, namely JCOG1408 (J-SBRT trial), a phase III study of SBRT for c-stage IA NSCLC, JCOG1701 (SAVE study), a phase III study of immune checkpoint inhibitors to evaluate the optimal treatment period, JCOG1807C (DEEP OCEAN), chemoradiotherapy with durvalumab and surgery for superior sulcus NSCLC, JCOG1914, a phase III study of chemoradiotherapy for elderly patients with locally advanced NSCLC, JCOG2002 (yES-TRT), a phase III study of thoracic radiotherapy for ED-SCLC after chemotherapy with immune checkpoint inhibitors (ICIs), and JCOG2007 (NIPPON), a phase III study of chemotherapy with ICIs for NSCLC, are ongoing. The department is also participating in a nationwide screening project of lung cancer with rare driver mutation (LC-SCRUM). The department carried out many clinical trials using TKIs, ICIs, antibody-drug conjugates (ADCs) and bispecific anti-bodies.

Education

 In 2021, four chief residents, 11 residents, and nine trainee doctors joined the department. A monthly research conference is held to discuss clinical and translational research conducted by young doctors.

Future Prospects

 Recent progression of lung cancer treatment is very rapid. Driver gene alteration targeted therapy such as EGFR-TKIs for EGFR mutation positive lung cancer, ALK inhibitors for ALK fusion gene positive lung cancer, ROS1 inhibitors for ROS1 fusion gene positive lung cancer, BRAF plus MEK inhibitor for BRAF V600E positive lung cancer, NTRK inhibitors for NTRK fusion positive lung cancer, RET inhibitor for RET fusion positive lung cancer, MET inhibitors for MET exon 14 skipping mutation positive lung cancer and KRAS inhibitor for KRAS G12C lung cancer are already established as a standard treatment. Other rare driver gene alterations such as HER2, NRG and CLIP-LTK fusion will be good targets for treatment of lung cancer. Immune checkpoint inhibitors, anti-PD-1 Ab and anti-PD-L1 Ab plus chemotherapy have been established as a standard first line treatment for NSCLC. A combination of anti-PD-1 Ab and anti-CTLA-4 Ab with or without chemotherapy have also been established as a new standard treatment for advanced NSCLC. Anti-PD-L1 Ab and durvalumab for stage III NSCLC after chemoradiotherapy will also be established as a standard treatment. An immune checkpoint inhibitor will also be an incorporated treatment for early stage lung cancer with surgery or SBRT. Moreover, antibody-drug conjugates (ADCs) and bispecific anti-bodies will be now treatment options for lung cancer patients.

List of papers published in 2021

Journal

1. Shiraishi Y, Hakozaki T, Nomura S, Kataoka T, Tanaka K, Miura S, Sekino Y, Ando M, Horinouchi H, Ohe Y, Okamoto I. A Multicenter, Randomized Phase III Study Comparing Platinum Combination Chemotherapy Plus Pembrolizumab With Platinum Combination Chemotherapy Plus Nivolumab and Ipilimumab for Treatment-Naive Advanced Non-Small Cell Lung Cancer Without Driver Gene Alterations: JCOG2007 (NIPPON Study). Clinical lung cancer, 23:e285-e288, 2022

2. 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

3. Takemura C, Kashima J, Hashimoto T, Ichikawa H, Honma Y, Goto Y, Watanabe SI, Yatabe Y. A mimic of lung adenocarcinoma: a case report of histological conversion of metastatic thyroid papillary carcinoma. Histopathology, 80:1004-1007, 2022

4. Shirasawa M, Yoshida T, Imabayashi T, Okuma K, Matsumoto Y, Masuda K, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Tsuchida T, Yamamoto N, Nakayama Y, Watanabe SI, Motoi N, Ohe Y. Baseline PD-L1 expression and tumour-infiltrated lymphocyte status predict the efficacy of durvalumab consolidation therapy after chemoradiotherapy in unresectable locally advanced patients with non-small-cell lung cancer. European journal of cancer (Oxford, England: 1990), 162:1-10, 2022

5. Jo H, Yagishita S, Hayashi Y, Ryu S, Suzuki M, Kohsaka S, Ueno T, Matsumoto Y, Horinouchi H, Ohe Y, Watanabe SI, Motoi N, Yatabe Y, Mano H, Takahashi K, Hamada A. Comparative Study on the Efficacy and Exposure of Molecular Target Agents in Non-small Cell Lung Cancer PDX Models with Driver Genetic Alterations. Molecular cancer therapeutics, 21:359-370, 2022

6. 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

7. So C, Yoshida T, Mizuno T, Yatabe Y, Ohe Y. Rapidly progressing metastatic malignant melanoma mimicking primary pleural tumor: A case report. Thoracic cancer, 13:1423-1426, 2022

8. Muto Y, Okuma Y. Therapeutic options in thymomas and thymic carcinomas. Expert review of anticancer therapy, 22:401-413, 2022

9. Tateishi A, Horinouchi H, Yoshida T, Masuda K, Jo H, Shinno Y, Okuma Y, Goto Y, Yamamoto N, Ohe Y. Correlation between body mass index and efficacy of anti-PD-1 inhibitor in patients with non-small cell lung cancer. Respiratory investigation, 60:234-240, 2022

10. Takumida H, Horinouchi H, Masuda K, Shinno Y, Okuma Y, Yoshida T, Goto Y, Yamamoto N, Ohe Y. Comparison of time to failure of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy: a consecutive analysis of patients having NSCLC with high PD-L1 expression. Cancer immunology, immunotherapy: CII, 71:737-746, 2022

11. Okumura M, Du J, Kageyama SI, Yamashita R, Hakozaki Y, Motegi A, Hojo H, Nakamura M, Hirano Y, Okuma Y, Okuma HS, Tsuchihara K, Akimoto T. Comprehensive screening for drugs that modify radiation-induced immune responses. British journal of cancer, 126:1815-1823, 2022

12. Kumagai S, Koyama S, Itahashi K, Tanegashima T, Lin YT, Togashi Y, Kamada T, Irie T, Okumura G, Kono H, Ito D, Fujii R, Watanabe S, Sai A, Fukuoka S, Sugiyama E, Watanabe G, Owari T, Nishinakamura H, Sugiyama D, Maeda Y, Kawazoe A, Yukami H, Chida K, Ohara Y, Yoshida T, Shinno Y, Takeyasu Y, Shirasawa M, Nakama K, Aokage K, Suzuki J, Ishii G, Kuwata T, Sakamoto N, Kawazu M, Ueno T, Mori T, Yamazaki N, Tsuboi M, Yatabe Y, Kinoshita T, Doi T, Shitara K, Mano H, Nishikawa H. Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer cell, 40:201-218.e9, 2022

13. Kaku S, Horinouchi H, Watanabe H, Yonemori K, Okusaka T, Boku N, Yamazaki N, Kawai A, Ohe Y, Kusumoto M. Incidence and prognostic factors in severe drug-induced interstitial lung disease caused by antineoplastic drug therapy in the real world. Journal of cancer research and clinical oncology, 2022

14. Okuma Y, Shimokawa M, Hashimoto K, Mizutani H, Wakui H, Murakami S, Atagi S, Minato K, Seike M, Ohe Y, Kubota K. Uncommon EGFR mutations conducted with osimertinib in patients with NSCLC: a study protocol of phase 2 study (UNICORN/TCOG1901). Future oncology (London, England), 18:523-531, 2022

15. Paz-Ares LG, Ramalingam SS, Ciuleanu TE, Lee JS, Urban L, Caro RB, Park K, Sakai H, Ohe Y, Nishio M, Audigier-Valette C, Burgers JA, Pluzanski A, Sangha R, Gallardo C, Takeda M, Linardou H, Lupinacci L, Lee KH, Caserta C, Provencio M, Carcereny E, Otterson GA, Schenker M, Zurawski B, Alexandru A, Vergnenegre A, Raimbourg J, Feeney K, Kim SW, Borghaei H, O'Byrne KJ, Hellmann MD, Memaj A, Nathan FE, Bushong J, Tran P, Brahmer JR, Reck M. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer, 17:289-308, 2022

16. Jo H, Yoshida T, Horinouchi H, Yagishita S, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Yamamoto N, Takahashi K, Motoi N, Ohe Y. Prognostic significance of cachexia in advanced non-small cell lung cancer patients treated with pembrolizumab. Cancer immunology, immunotherapy: CII, 71:387-398, 2022

17. 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

18. 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

19. Mimori T, Shukuya T, Ko R, Okuma Y, Koizumi T, Imai H, Takiguchi Y, Miyauchi E, Kagamu H, Sugiyama T, Azuma K, Namba Y, Yamasaki M, Tanaka H, Takashima Y, Soda S, Ishimoto O, Koyama N, Kobayashi K, Takahashi K. Clinical Significance of Tumor Markers for Advanced Thymic Carcinoma: A Retrospective Analysis from the NEJ023 Study. Cancers, 14:2022

20. Taniguchi Y, Okamoto H, Shimokawa T, Sasaki T, Seto T, Niho S, Ohe Y, Saigusa Y. Concurrent chemoradiotherapy with cisplatin + S-1 versus cisplatin + other third-generation agents for locally advanced non-small-cell lung cancer: a meta-analysis of individual participant data. BMC pulmonary medicine, 22:31, 2022

21. Goto Y, Arakawa S, Shirasawa M, Higashiyama R, Baba K, Masuda K, Shinno Y, Matsumoto Y, Okuma Y, Yoshida T, Horinouchi H, Yamamoto N, Ohe Y. Performance of Japanese patients in registrational studies. Japanese journal of clinical oncology, 52:53-64, 2022

22. Lee J, Tan AC, Zhou S, Yoon S, Liu S, Masuda K, Hayashi H, Batra U, Kim DW, Goto Y, Tan SH, Wu YL, Lee DH, Tan DSW, Ahn MJ. Clinical Characteristics and Outcomes in Advanced KRAS-Mutated NSCLC: A Multicenter Collaboration in Asia (ATORG-005). JTO clinical and research reports, 3:100261, 2022

23. 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

24. Koriyama M, Okamoto Y, Suzuki T, Iinuma T, Yamamoto H, Okuma Y, Hamasaki S, Sakurai D, Hanazawa T, Yonekura S. Characteristics of Japanese cypress pollen-induced allergic rhinitis by environmental challenge chamber. Allergology international: official journal of the Japanese Society of Allergology, 71:144-146, 2022

25. Matsumoto Y, Nakai T, Tanaka M, Imabayashi T, Tsuchida T, Ohe Y. Diagnostic Outcomes and Safety of Cryobiopsy Added to Conventional Sampling Methods: An Observational Study. Chest, doi.org/10.1016/j.chest.2021.05.015, 2021

26. Mizuno T, Yoshida T, Sunami K, Koyama T, Okita N, Kubo T, Sudo K, Shimoi T, Ueno H, Saito E, Katanoda K, Shibata T, Yonemori K, Okusaka T, Boku N, Ohe Y, Hiroshima Y, Ueno M, Kuboki Y, Doi T, Nakamura K, Kohno T, Yatabe Y, Yamamoto N. Study protocol for NCCH1908 (UPFRONT-trial): a prospective clinical trial to evaluate the feasibility and utility of comprehensive genomic profiling prior to the initial systemic treatment in advanced solid tumour patients. Japanese journal of clinical oncology, 51:1757-1760, 2021

27. Yazaki S, Yoshida T, Kojima Y, Yagishita S, Nakahama H, Okinaka K, Matsushita H, Shiotsuka M, Kobayashi O, Iwata S, Narita Y, Ohba A, Takahashi M, Iwasa S, Kobayashi K, Ohe Y, Yoshida T, Hamada A, Doi T, Yamamoto N. Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan. JAMA oncology, 7:1141-1148, 2021

28.  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

29. Kobayashi AK, Nakagawa K, Nakayama Y, Ohe Y, Yotsukura M, Uchida S, Asakura K, Yoshida Y, Watanabe SI. Salvage Surgery Compared to Surgery After Induction Chemoradiation Therapy for Advanced Lung Cancer. The Annals of thoracic surgery, 2021

30. Kashima J, Hishima T, Okuma Y, Horio H, Ogawa M, Hayashi Y, Horiguchi SI, Motoi T, Ushiku T, Fukayama M. CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets. Frontiers in oncology, 11:808396, 2021

31. Fukuda A, Okuma Y, Hakozaki T, Mirokuji K, Yomota M, Hishima T, Hosomi Y. Cisplatin and Irinotecan as First-Line Chemotherapy for Previously Untreated Metastatic Thymic Carcinoma: Updated Analysis. Frontiers in oncology, 11:779700, 2021

32. Solomon BJ, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Shaw AT. Plain language summary of the CROWN study comparing lorlatinib with crizotinib for people with untreated non-small cell lung cancer. Future oncology (London, England), 17:4649-4656, 2021

33. Teishikata T, Shiraishi K, Shinno Y, Kobayashi Y, Kashima J, Ishiyama T, Yoshida T, Mori T, Yatabe Y. An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer, 16:2133-2138, 2021

34. Ogiwara T, Kawazoe H, Egami S, Hashimoto H, Saito Y, Sakiyama N, Ohe Y, Yamaguchi M, Furukawa T, Hara A, Hiraga Y, Jibiki A, Yokoyama Y, Suzuki S, Nakamura T. Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study. Frontiers in oncology, 11:770268, 2021

35. Shimoda Y, Yoshida T, Shirasawa M, Mizuno T, Jo H, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Yamamoto N, Yatabe Y, Ohe Y, Motoi N. Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients. Anticancer research, 41:5739-5747, 2021

36. Yamamoto N, Nakanishi Y, Gemma A, Nakagawa K, Sakamoto T, Akamatsu A, Ohe Y. Real-world safety of nivolumab in patients with non-small-cell lung cancer in Japan: Postmarketing surveillance. Cancer science, 112:4692-4701, 2021

37. Ito K, Kitajima K, Toriihara A, Ishibashi M, Nakahara T, Daisaki H, Ohe Y, Honda R, Kijima T, Hasegawa S, Nakajo M. 18F-FDG PET/CT for monitoring anti-PD-1 therapy in patients with non-small cell lung cancer using SUV harmonization of results obtained with various types of PET/CT scanners used at different centers. Annals of nuclear medicine, 35:1253-1263, 2021

38. Ito T, Yokomichi N, Ishiki H, Kawaguchi T, Masuda K, Tsukuura H, Funaki H, Suzuki K, Oya K, Nakagawa J, Mori M, Yamaguchi T. Optimal Paracentesis Volume for Terminally Ill Cancer Patients With Ascites. Journal of pain and symptom management, 62:968-977, 2021

39. Kitadai R, Okuma Y. Future Perspective of Chemotherapy and Pharmacotherapy in Thymic Carcinoma. Cancers, 13:2021

40. Hasegawa N, Kohsaka S, Kurokawa K, Shinno Y, Takeda Nakamura I, Ueno T, Kojima S, Kawazu M, Suehara Y, Ishijima M, Goto Y, Kojima Y, Yonemori K, Hayashi T, Saito T, Shukuya T, Takahashi F, Takahashi K, Mano H. Highly sensitive fusion detection using plasma cell-free RNA in non-small-cell lung cancers. Cancer science, 112:4393-4403, 2021

41. Seike Y, Fukuda T, Yokawa K, Horinouchi H, Inoue Y, Shijo T, Uehara K, Sasaki H, Matsuda H. Severe intraluminal atheroma and iliac artery access affect spinal cord ischemia after thoracic endovascular aortic repair for degenerative descending aortic aneurysm. General thoracic and cardiovascular surgery, 69:1367-1375, 2021

42. Morita C, Yoshida T, Shirasawa M, Masuda K, Matsumoto Y, Shinno Y, Yagishita S, Okuma Y, Goto Y, Horinouchi H, Yamamoto N, Motoi N, Yatabe Y, Ohe Y. Clinical characteristics of advanced non-small cell lung cancer patients with EGFR exon 20 insertions. Scientific reports, 11:18762, 2021

43. Noda-Narita S, Kawachi A, Okuyama A, Sadachi R, Hirakawa A, Goto Y, Fujiwara Y, Higashi T, Yonemori K. First-line treatment for lung cancer among Japanese older patients: A real-world analysis of hospital-based cancer registry data. PloS one, 16:e0257489, 2021

44. Nishii T, Okuyama S, Horinouchi H, Chikuda R, Kamei E, Higuchi S, Ohta Y, Fukuda T. A Real-World Clinical Implementation of Automated Processing Using Intelligent Work Aid for Rapid Reformation at the Orbitomeatal Line in Head Computed Tomography. Investigative radiology, 56:599-604, 2021

45. Yoshimura A, Yamada T, Okuma Y, Fukuda A, Watanabe S, Nishioka N, Takeda T, Chihara Y, Takemoto S, Harada T, Hiranuma O, Shirai Y, Nishiyama A, Yano S, Goto Y, Shiotsu S, Kunimasa K, Morimoto Y, Iwasaku M, Kaneko Y, Uchino J, Kenmotsu H, Takahashi T, Takayama K. Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study. Translational lung cancer research, 10:3582-3593, 2021

46. Kubo Y, Ito K, Fujiwara Y, Yoshida T, Kusumoto M. Case Report: SAPHO Syndrome Mimicking Bone Metastases During Treatment With Pembrolizumab for Non-small Cell Lung Cancer. Frontiers in medicine, 8:679111, 2021

47. Nakagawa K, Kijima T, Okada M, Morise M, Kato M, Hirano K, Fujimoto N, Takenoyama M, Yokouchi H, Ohe Y, Hida T, Aoe K, Kishimoto T, Hirokawa M, Matsuki H, Kaneko Y, Yamada T, Morimoto C, Takeda M. Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma. JTO clinical and research reports, 2:100178, 2021

48. 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

49. Watanabe K, Okuma Y, Kawai S, Nagamata M, Hosomi Y. Premature phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma. Thoracic cancer, 12:1668-1672, 2021

50. Egami S, Kawazoe H, Hashimoto H, Uozumi R, Arami T, Sakiyama N, Ohe Y, Nakada H, Aomori T, Ikemura S, Fukunaga K, Yamaguchi M, Nakamura T. Absolute Lymphocyte Count Predicts Immune-Related Adverse Events in Patients With Non-Small-Cell Lung Cancer Treated With Nivolumab Monotherapy: A Multicenter Retrospective Study. Frontiers in oncology, 11:618570, 2021

51. 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

52. Shaikh FY, White JR, Gills JJ, Hakozaki T, Richard C, Routy B, Okuma Y, Usyk M, Pandey A, Weber JS, Ahn J, Lipson EJ, Naidoo J, Pardoll DM, Sears CL. A Uniform Computational Approach Improved on Existing Pipelines to Reveal Microbiome Biomarkers of Nonresponse to Immune Checkpoint Inhibitors. Clinical cancer research: an official journal of the American Association for Cancer Research, 27:2571-2583, 2021

53. Maruyama K, Kawasaki R, Koide Y, Horinouchi H, Sasaki K, Gentsu T, Okada T, Yamaguchi M, Sugimoto K. Preoperative Magnetic Resonance Imaging (MRI) for Predicting Thromboembolic Complications during Endovascular Treatment for Iliac Artery Occlusions. Annals of vascular surgery, 73:211-221, 2021

54. Satoh H, Okuma Y, Kashima J, Konnno-Yamamoto A, Yatabe Y, Ohe Y. Alectinib for Miliary Lung Metastasis in ALK-Positive Lung Adenocarcinoma. OncoTargets and therapy, 14:2911-2915, 2021

55. Hase I, Tanaka H, Sekine K, Yoshida S, Maitani F, Horinouchi H, Tateno H. Successful Removal of Mucoid Impaction by Bronchoscope-guided Modified Nasogastric Tube Suctioning: A Case of Allergic Bronchopulmonary Mycosis. Journal of bronchology & interventional pulmonology, 28:e33-e35, 2021

56. Hibino H, Makino Y, Sakiyama N, Makihara-Ando R, Hashimoto H, Akiyoshi T, Imaoka A, Fujiwara Y, Ohe Y, Yamaguchi M, Ohtani H. Exacerbation of atrioventricular block associated with concomitant use of amlodipine and aprepitant in a lung cancer patient: A case report. International journal of clinical pharmacology and therapeutics, 59:328-332, 2021

57. Sata M, Sasaki S, Oikado K, Saito Y, Tominaga J, Sakai F, Kato T, Iwasawa T, Kenmotsu H, Kusumoto M, Baba T, Endo M, Fujiwara Y, Sugiura H, Yanagawa N, Ito Y, Sakamoto T, Ohe Y, Kuwano K. Treatment and relapse of interstitial lung disease in nivolumab-treated patients with non-small cell lung cancer. Cancer science, 112:1506-1513, 2021

58. Saito Y, Sasaki S, Oikado K, Tominaga J, Sata M, Sakai F, Kato T, Iwasawa T, Kenmotsu H, Kusumoto M, Baba T, Endo M, Fujiwara Y, Sugiura H, Yanagawa N, Ito Y, Sakamoto T, Ohe Y, Kuwano K. Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer. Cancer science, 112:1495-1505, 2021

59. Shirasawa M, Yoshida T, Takayanagi D, Shiraishi K, Yagishita S, Sekine K, Kanda S, Matsumoto Y, Masuda K, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Hamada A, Kohno T, Yamamoto N, Watanabe SI, Ohe Y, Motoi N. Activity and Immune Correlates of Programmed Death-1 Blockade Therapy in Patients With Advanced Large Cell Neuroendocrine Carcinoma. Clinical lung cancer, 22:282-291.e6, 2021

60.  Shibayama T, Makise N, Motoi T, Mori T, Hiraoka N, Yonemori K, Watanabe SI, Esaki M, Morizane C, Okuma T, Kawai A, Ushiku T, Yatabe Y, Yoshida A. Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases: A Proposal of Risk Stratification and Identification of a Synaptophysin-positive Aggressive Subset. The American journal of surgical pathology, 45:616-626, 2021

61.  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

62. Takeyasu Y, Yoshida T, Motoi N, Teishikata T, Tanaka M, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Kakishima H, Tsuchida T, Yamamoto N, Ohe Y, Yatabe Y. Feasibility of next-generation sequencing (Oncomine DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. Japanese journal of clinical oncology, 51:1114-1122, 2021

63. Nakamura IT, Ikegami M, Hasegawa N, Hayashi T, Ueno T, Kawazu M, Yagishita S, Goto Y, Shinno Y, Kojima Y, Takamochi K, Takahashi F, Takahashi K, Mano H, Kohsaka S. Development of an optimal protocol for molecular profiling of tumor cells in pleural effusions at single-cell level. Cancer science, 112:2006-2019, 2021

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