Annual Report 2017
Department of Thoracic Oncology
Koichi Goto, Seiji Niho, Kiyotaka Yoh, Shingo Matsumoto, Shigeki Umemura, Yoshitaka Zenke, Keisuke Kirita, Hibiki Udagawa, Masayuki Ishibashi, Kakeru Hisakane, Reiko Matsuzawa, Yuko Usui, Takahiro Ohta, Tomoyuki Naito
Introduction
The Department of Thoracic Oncology provides care for patients with primary lung cancer, mediastinal tumors, and pleural tumors. Our 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 for our patients through multidisciplinary care, the staff members of our department 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 in January 2017 - March 2018
Table 2. Initial treatment for lung cancer in January 2017 - March 2018
Routine activities
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 are also receiving oral chemotherapy and/or intravenous chemotherapy in the Ambulatory Care Center. Bronchoscopy and endobronchial ultrasound (EBUS) for diagnosis are performed from Monday to Thursday afternoon. Fluoroscopic-CT guided needle lung biopsies are carried out on Tuesday afternoon. For patient management, we use approximately 65 beds in mainly 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 our department 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 for reading 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;
2) collaborative studies with the Exploratory Oncology Research & Clinical Oncology (NCC-EPOC) in the following areas: detection of driver mutation for small cell lung cancer, the development of a new diagnostic method of rare driver genomic alterations for lung cancer, correlation between genomic abnormalities and clinical characteristics, and correlation between pathological features and sensitivity of treatments;
3) translational research from bench to bed-side or from bed-side to bench for the development of innovative treatment strategies.
Especially, the 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 in collaboration with the NCC-EPOC.
Clinical trials
The Department of Thoracic Oncology 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, West Japan Oncology Group (WJOG), Thoracic Oncology Research Group (TORG) and global trials conducted by pharmaceutical companies.
To develop useful biomarkers to predict the sensitivity for immune checkpoint inhibitors, we conducted an investigator initiated trial of atezolizumab for advanced non-small-cell lung cancer (NSCLC) in collaboration with the Divison of Cancer Immunology of the NCC-Research Institute. The 28 patients' enrollment with their biopsy samples before and after treatment was completed for only 10 months and the translational research to detect an innovative biomarker for atezolizumab is now ongoing.
In addition, recent many clinical trials indicated that PD-1/PD-L1 immune checkpoint inhibitors combined with chemotherapy showed remarkable clinical response against advanced NSCLC including squamous cell lung cancer as first-line treatment. Nivolumab, pembrolizumab, and atezolizumab were currently approved in Japan for patients with advanced NSCLC as first-line and second-line treatment.
LC-SCRUM-Japan (Lung Cancer Genomic Screening Project for Individualized Medicine in Japan), a nationwide genomic screening project for lung cancer with rare driver oncogenes, such as RET, ROS1 BRAF, MET, and HER2 genomic alterations was initiated from February 2013 and is now ongoing. As of March 2018, 261 institutions participated in LC-SCRUM-Japan and 5,925 patients were enrolled. Many lung cancers with rare driver oncogenes had been detected and they had been entered into various clinical trials of molecular targeting agents. On the basis of the results of clinical trials targeting ROS1 fusion and BRAF mutation, crizotinib was approved for ROS1 fusion positive lung cancer in May 2017 and dabrafenib/trametinib were approved for BRAF V600E positive lung cancer in March 2018. While RT-PCR kit which was adapted in LC-SCRUM-Japan screening for ROS1 fusion was also approved as a companion diagnostic for ROS1 positive lung cancer based on our screening data in January 2017. In the same way, next generation sequencing panel will be approved as a companion diagnostic for BRAF mutation positive lung cancer in April 2018. Through the genomic screening, LC-SCRUM-Japan has contributed to the development of precision medicine in lung cancer in Japan.
List of papers published in January 2017 - March 2018
Journal
1. Sekine I, Harada H, Yamamoto N, Wakabayashi M, Murakami H, Goto K, Nogami N, Seto T, Oshita F, Okamoto H, Tanaka H, Tamura T, Ishikura S, Ohe Y. Randomized phase II trial of weekly dose-intensive chemotherapy or amrubicin plus cisplatin chemotherapy following induction chemoradiotherapy for limited-disease small cell lung cancer (JCOG1011). Lung Cancer, 108:232-237, 2017
2. Niho S, Ohe Y, Ohmatsu H, Umemura S, Matsumoto S, Yoh K, Goto K. Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study. Lung Cancer, 108:66-71, 2017
3. Ichikawa T, Saruwatari K, Mimaki S, Sugano M, Aokage K, Kojima M, Hishida T, Fujii S, Yoshida J, Kuwata T, Ochiai A, Suzuki K, Tsuboi M, Goto K, Tsuchihara K, Ishii G. Immunohistochemical and genetic characteristics of lung cancer mimicking organizing pneumonia. Lung Cancer, 113:134-139, 2017
4. Neri S, Miyashita T, Hashimoto H, Suda Y, Ishibashi M, Kii H, Watanabe H, Kuwata T, Tsuboi M, Goto K, Menju T, Sonobe M, Date H, Ochiai A, Ishii G. Fibroblast-led cancer cell invasion is activated by epithelial-mesenchymal transition through platelet-derived growth factor BB secretion of lung adenocarcinoma. Cancer Lett, 395:20-30, 2017
5. Hisakane K, Ohmatsu H, Umemura S, Kirita K, Matsumoto S, Yoh K, Niho S, Goto K. Efficacy of Cell-Free and Concentrated Ascites Reinfusion Therapy for Palliative Care in a Patient with Malignant Pleural Mesothelioma: A Case Report. J Nippon Med Sch, 84:231-236, 2017
6. Takahashi T, Yamanaka T, Seto T, Harada H, Nokihara H, Saka H, Nishio M, Kaneda H, Takayama K, Ishimoto O, Takeda K, Yoshioka H, Tachihara M, Sakai H, Goto K, Yamamoto N. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol, 18:663-671, 2017
7. Hida T, Satouchi M, Nakagawa K, Seto T, Matsumoto S, Kiura K, Nokihara H, Murakami H, Tokushige K, Hatano B, Nishio M. Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset. Jpn J Clin Oncol, 47:618-624, 2017
8. Ishibashi M, Neri S, Hashimoto H, Miyashita T, Yoshida T, Nakamura Y, Udagawa H, Kirita K, Matsumoto S, Umemura S, Yoh K, Niho S, Tsuboi M, Masutomi K, Goto K, Ochiai A, Ishii G. CD200-positive cancer associated fibroblasts augment the sensitivity of Epidermal Growth Factor Receptor mutation-positive lung adenocarcinomas to EGFR Tyrosine kinase inhibitors. Sci Rep, 7:46662, 2017
9. Seow WJ, Matsuo K, Hsiung CA, Shiraishi K, Song M, Kim HN, Wong MP, Hong YC, Wang Z, Chang IS, Wang JC, Chatterjee N, Tucker M, Wei H, Mitsudomi T, Zheng W, Kim JH, Zhou B, Caporaso NE, Albanes D, Shin MH, Chung LP, An SJ, Wang P, Zheng H, Yatabe Y, Zhang XC, Kim YT, Shu XO, Kim YC, Bassig BA, Chang J, Ho JCM, Ji BT, Kubo M, Daigo Y, Ito H, Momozawa Y, Ashikawa K, Kamatani Y, Honda T, Sakamoto H, Kunitoh H, Tsuta K, Watanabe S, Nokihara H, Miyagi Y, Nakayama H, Matsumoto S, Tsuboi M, Goto K, Yin Z, Shi J, Takahashi A, Goto A, Minamiya Y, Shimizu K, Tanaka K, Wu T, Wei F, Wong JYY, Matsuda F, Su J, Kim YH, Oh IJ, Song F, Lee VHF, Su WC, Chen YM, Chang GC, Chen KY, Huang MS, Yang PC, Lin HC, Xiang YB, Seow A, Park JY, Kweon SS, Chen CJ, Li H, Gao YT, Wu C, Qian B, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Tsai YH, Jung YJ, Guo H, Hu Z, Wang WC, Chung CC, Lawrence C, Burdett L, Yeager M, Jacobs KB, Hutchinson A, Berndt SI, He X, Wu W, Wang J, Li Y, Choi JE, Park KH, Sung SW, Liu L, Kang CH, Hu L, Chen CH, Yang TY, Xu J, Guan P, Tan W, Wang CL, Sihoe ADL, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Cai Q, Lin CC, Park IK, Xu P, Dong J, Kim C, He Q, Perng RP, Chen CY, Vermeulen R, Wu J, Lim WY, Chen KC, Chan JKC, Chu M, Li YJ, Li J, Chen H, Yu CJ, Jin L, Lo YL, Chen YH, Liu J, Yamaji T, Yang Y, 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, Jiang G, Fei K, Wu G, Chien LH, Chen HL, Su YC, Tsai FY, Chen YS, Yu J, Stevens VL, Laird-Offringa IA, Marconett CN, Lin D, Chen K, Wu YL, Landi MT, Shen H, Rothman N, Kohno T, Chanock SJ, Lan Q. Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations. Hum Mol Genet, 26:454-465, 2017
10. Usui Y, Udagawa H, Matsumoto S, Imai K, Ohashi K, Ishibashi M, Kirita K, Umemura S, Yoh K, Niho S, Osame K, Goto K. Association of Serum Anti-GAD Antibody and HLA Haplotypes with Type 1 Diabetes Mellitus Triggered by Nivolumab in Patients with Non-Small Cell Lung Cancer. J Thorac Oncol, 12:e41-e43, 2017
11. Kubota K, Yoshioka H, Oshita F, Hida T, Yoh K, Hayashi H, Kato T, Kaneda H, Yamada K, Tanaka H, Ichinose Y, Park K, Cho EK, Lee KH, Lin CB, Yang JC, Hara K, Asato T, Nakagawa K. Phase III, Randomized, Placebo-Controlled, Double-Blind Trial of Motesanib (AMG-706) in Combination With Paclitaxel and Carboplatin in East Asian Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol, 35:3662-3670, 2017
12. Sekihara K, Hishida T, Yoshida J, Oki T, Omori T, Katsumata S, Ueda T, Miyoshi T, Goto M, Nakasone S, Ichikawa T, Matsuzawa R, Aokage K, Goto K, Tsuboi M. Long-term survival outcome after postoperative recurrence of non-small-cell lung cancer: who is 'cured' from postoperative recurrence? Eur J Cardiothorac Surg, 52:522-528, 2017
13. Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet, 390:29-39, 2017
14. Takeuchi S, Murayama T, Yoshimura K, Kawakami T, Takahara S, Imai Y, Kuribayashi Y, Nagase K, Goto K, Nishio M, Hasegawa Y, Satouchi M, Kiura K, Seto T, Yano S. Phase I/II study of alectinib in lung cancer with RET fusion gene: study protocol. J Med Invest, 64:317-320, 2017
15. Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol, 18:1454-1466, 2017
16. Nukaga S, Yasuda H, Tsuchihara K, Hamamoto J, Masuzawa K, Kawada I, Naoki K, Matsumoto S, Mimaki S, Ikemura S, Goto K, Betsuyaku T, Soejima K. Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors. Cancer Res, 77:2078-2089, 2017
17. Goto Y, Tanai C, Yoh K, Hosomi Y, Sakai H, Kato T, Kaburagi T, Nishio M, Kim YH, Inoue A, Hasegawa Y, Isobe H, Tomizawa Y, Mori Y, Minato K, Yamada K, Ohashi Y, Kunitoh H. Continuing EGFR-TKI beyond radiological progression in patients with advanced or recurrent, EGFR mutation-positive non-small-cell lung cancer: an observational study. ESMO open, 2:e000214, 2017
18. Yang JC, Ahn MJ, Kim DW, Ramalingam SS, Sequist LV, Su WC, Kim SW, Kim JH, Planchard D, Felip E, Blackhall F, Haggstrom D, Yoh K, Novello S, Gold K, Hirashima T, Lin CC, Mann H, Cantarini M, Ghiorghiu S, Janne PA. Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component. J Clin Oncol, 35:1288-1296, 2017
19. Nakaoku T, Kohno T, Araki M, Niho S, Chauhan R, Knowles PP, Tsuchihara K, Matsumoto S, Shimada Y, Mimaki S, Ishii G, Ichikawa H, Nagatoishi S, Tsumoto K, Okuno Y, Yoh K, McDonald NQ, Goto K. A secondary RET mutation in the activation loop conferring resistance to vandetanib. Nat Commun, 9:625, 2018
20. Kato T, Seto T, Nishio M, Goto K, Yamamoto N, Okamoto I, Tao L, Yu W, Khaznadar T, Tajima K, Shibata M, Seki A, Yamamoto N. Erlotinib Plus Bevacizumab Phase ll Study in Patients with Advanced Non-small-Cell Lung Cancer (JO25567): Updated Safety Results. Drug Saf, 41:229-237, 2018
21. Seto T, Hirai F, Saka H, Kogure Y, Yoh K, Niho S, Fukase K, Shimada H, Sasai M, Fukino K. Safety and tolerability of selumetinib as a monotherapy, or in combination with docetaxel as second-line therapy, in Japanese patients with advanced solid malignancies or non-small cell lung cancer. Jpn J Clin Oncol, 48:31-42, 2018
22. Taira T, Yoh K, Nagase S, Kubota K, Ohmatsu H, Niho S, Onozawa M, Akimoto T, Ohe Y, Goto K. Long-term results of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer. Cancer Chemother Pharmacol, 81:565-572, 2018