Department of Thoracic Oncology
Yuichiro Ohe, Noboru Yamamoto, Hiroshi Nokihara, Yutaka Fujiwara, Hidehito Horinouchi, Shintaro Kanda, Yasushi Goto, Tetsuhiko Asao, Shinsuke Kitahara, Kouta Itahashi
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 elderly people. 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 to our patients through multidisciplinary care, the staff members of the department work closely with thoracic surgeons, radiation oncologists, pharmacists, clinical research coordinators, and psychiatrists who have expertise in these areas. The department includes seven staff physicians. Moreover, residents and trainees from other institutions have joined the Thoracic Oncology Program.
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 five teams. Each team consists of one staff physician and one or two residents and/ or trainee doctors. Protocol and case conferences are scheduled every Monday morning and afternoon, respectively. The journal club is scheduled on Thursday mornings.
A total of 413 new patients were admitted in 2015, and the backgrounds and initial treatments of these patients are shown in tables 1 and 2. The initial treatments were chemotherapy in 230, adjuvant chemotherapy after surgery in 44, chemoradiotherapy in 62, curative radiotherapy in 5, and supportive care including palliative radiotherapy in 49. Survival of lung cancer patients treated in 2006-2010 in our department is shown in Table 3.
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.
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. Three JCOG phase III studies, JCOG1201 for elderly ED-SCLC, JCOG1206 for high-grade neuroendocrine carcinoma and JCOG1210/WJOG7813L for elderly non-squamous NSCLC are ongoing. In addition to these studies, JCOG1404 (AGAIN), a phase III study for EGFR mutation positive NSCLC, was started in December. The department is also participating in a nationwide screening project of lung cancer with rare driver mutation (LC-SCRUM) and phase II studies targeting rare driver mutation. The department carried out many clinical trials using 3rd generation EGFR-TKIs, anti-PD-1Ab, and anti-PD-L1Ab.
In 2015, three chief residents, 16 residents and two research residents joined the department. A monthly research conference is held to discuss clinical and translational research conducted by young doctors.
The recent progression of lung cancer treatment is very rapid. Driver gene alteration targeted therapy such as EGFR-TKIs and ALK inhibitors are already established as a standard treatment for lung cancer patients with EGFR mutation and ALK fusion gene. Other rare driver gene alterations such as ROS1 fusion, RET fusion, and "BRAF mutation can be good targets for treatment of lung cancer." Immunotherapy using anti-PD-1Ab has been established as a standard 2nd or 3rd line treatment for NSCLC. Anti-PD-L1Ab will also be established as a standard treatment of lung cancer in the near future. These immunotherapies could provide a durable response for some lung cancer patients. Establishment of good biomarkers to identify the patients who respond to the immunotherapy is very important.
List of papers published in 2015
- Tsukada H, Yokoyama A, Goto K, Shinkai T, Harada M, Ando M, Shibata T, Ohe Y, Tamura T, Saijo N, Lung Cancer Study Group of the Japan Clinical Oncology Group (JCOG). Randomized controlled trial comparing docetaxel-cisplatin combination with weekly docetaxel alone in elderly patients with advanced non-small- cell lung cancer: Japan Clinical Oncology Group (JCOG) 0207†. Jpn J Clin Oncol, 45:88-95, 2015
- Yoshida T, Yoh K, Niho S, Umemura S, Matsumoto S, Ohmatsu H, Ohe Y, Goto K. RECIST progression patterns during EGFR tyrosine kinase inhibitor treatment of advanced non-small cell lung cancer patients harboring an EGFR mutation. Lung Cancer, 90:477-483, 2015
- Nakata A, Yoshida R, Yamaguchi R, Yamauchi M, Tamada Y, Fujita A, Shimamura T, Imoto S, Higuchi T, Nomura M, Kimura T, Nokihara H, Higashiyama M, Kondoh K, Nishihara H, Tojo A, Yano S, Miyano S, Gotoh N. Elevated β-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs. Sci Rep, 5:13076, 2015
- Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med, 372:1689-1699, 2015
- Sekiguchi M, Sekine S, Sakamoto T, Otake Y, Nakajima T, Matsuda T, Taniguchi H, Kushima R, Ohe Y, Saito Y. Excellent prognosis following endoscopic resection of patients with rectal neuroendocrine tumors despite the frequent presence of lymphovascular invasion. J Gastroenterol, 50:1184-1189, 2015
- Yoshida T, Ishii G, Goto K, Neri S, Hashimoto H, Yoh K, Niho S, Umemura S, Matsumoto S, Ohmatsu H, Iida S, Niimi A, Nagai K, Ohe Y, Ochiai A. Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation. Clin Cancer Res, 21:642-651, 2015
- Yagishita S, Horinouchi H, Katsui Taniyama T, Nakamichi S, Kitazono S, Mizugaki H, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Sumi M, Shiraishi K, Kohno T, Furuta K, Tsuta K, Tamura T. Epidermal growth factor receptor mutation is associated with longer local control after definitive chemoradiotherapy in patients with stage III nonsquamous non-small-cell lung cancer. Int J Radiat Oncol Biol Phys, 91:140-148, 2015
- Sugiyama E, Umemura S, Nomura S, Kirita K, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Tsuboi M, Ohe Y, Goto K. Impact of single nucleotide polymorphisms on severe hepatotoxicity induced by EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring EGFR mutations. Lung Cancer, 90:307-313, 2015
- Udagawa H, Ishii G, Morise M, Umemura S, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Tsuboi M, Goto K, Ochiai A, Ohe Y. Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung. J Cancer Res Clin Oncol, 141:1417- 1425, 2015
- Matsumura Y, Umemura S, Ishii G, Tsuta K, Matsumoto S, Aokage K, Hishida T, Yoshida J, Ohe Y, Suzuki H, Ochiai A, Goto K, Nagai K, Tsuchihara K. Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma. J Cancer Res Clin Oncol, 141:2159- 2170, 2015
- Morise M, Hishida T, Takahashi A, Yoshida J, Ohe Y, Nagai K, Ishii G. Clinicopathological significance of cancer stem-like cell markers in high-grade neuroendocrine carcinoma of the lung. J Cancer Res Clin Oncol, 141:2121-2130, 2015
- Nakamichi S, Nokihara H, Yamamoto N, Yamada Y, Fujiwara Y, Tamura Y, Wakui H, Honda K, Mizugaki H, Kitazono S, Tanabe Y, Asahina H, Yamazaki N, Suzuki S, Matsuoka M, Ogita Y, Tamura T. Phase I and pharmacokinetics/pharmacodynamics study of the MEK inhibitor RO4987655 in Japanese patients with advanced solid tumors. Invest New Drugs, 33:641-651, 2015
- Asao T, Nokihara H, Yoh K, Niho S, Goto K, Ohmatsu H, Kubota K, Yamamoto N, Sekine I, Kunitoh H, Fujiwara Y, Ohe Y. Phase II study of amrubicin at a dose of 45 mg/m2 in patients with previously treated small-cell lung cancer. Jpn J Clin Oncol, 45:941-946, 2015
- Fujiwara Y, Kobayashi S, Nagano H, Kanai M, Hatano E, Toyoda M, Ajiki T, Takashima Y, Yoshimura K, Hamada A, Minami H, Ioka T. Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101). PLoS One, 10:e0143072, 2015
- Fujiwara Y, Nokihara H, Yamada Y, Yamamoto N, Sunami K, Utsumi H, Asou H, TakahashI O, Ogasawara K, Gueorguieva I, Tamura T. Phase 1 study of galunisertib, a TGF-beta receptor I kinase inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol, 76:1143-1152, 2015
- Horinouchi H, Yamamoto N, Fujiwara Y, Sekine I, Nokihara H, Kubota K, Kanda S, Yagishita S, Wakui H, Kitazono S, Mizugaki H, Tokudome T, Tamura T. Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer. Invest New Drugs, 33:881-889, 2015
- Kanai M, Hatano E, Kobayashi S, Fujiwara Y, Marubashi S, Miyamoto A, Shiomi H, Kubo S, Ikuta S, Yanagimoto H, Terajima H, Ikoma H, Sakai D, Kodama Y, Seo S, Morita S, Ajiki T, Nagano H, Ioka T. A multi-institution phase II study of gemcitabine/ cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002). Cancer Chemother Pharmacol, 75:293-300, 2015
- Kanda S, Horinouchi H, Fujiwara Y, Nokihara H, Yamamoto N, Sekine I, Kunitoh H, Kubota K, Tamura T, Ohe Y. Cytotoxic chemotherapy may overcome the development of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy. Lung Cancer, 89:287-293, 2015
- Katsuya Y, Fujiwara Y, Sunami K, Utsumi H, Goto Y, Kanda S, Horinouchi H, Nokihara H, Yamamoto N, Takashima Y, Osawa S, Ohe Y, Tamura T, Hamada A. Comparison of the pharmacokinetics of erlotinib administered in complete fasting and 2 h after a meal in patients with lung cancer. Cancer Chemother Pharmacol, 76:125-132, 2015
- Kitazono S, Fujiwara Y, Nakamichi S, Mizugaki H, Nokihara H, Yamamoto N, Yamada Y, Inukai E, Nakamura O, Tamura T. A phase I study of resminostat in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol, 75:1155- 1161, 2015
- Kitazono S, Fujiwara Y, Tsuta K, Utsumi H, Kanda S, Horinouchi H, Nokihara H, Yamamoto N, Sasada S, Watanabe S, Asamura H, Tamura T, Ohe Y. Reliability of Small Biopsy Samples Compared With Resected Specimens for the Determination of Programmed Death-Ligand 1 Expression in Non-Small-Cell Lung Cancer. Clin Lung Cancer, 16:385-390, 2015
- Mizugaki H, Yamamoto N, Fujiwara Y, Nokihara H, Yamada Y, Tamura T. Current Status of Single-Agent Phase I Trials in Japan: Toward Globalization. J Clin Oncol, 33:2051-2061, 2015
- Mizugaki H, Yamamoto N, Nokihara H, Fujiwara Y, Horinouchi H, Kanda S, Kitazono S, Yagishita S, Xiong H, Qian J, Hashiba H, Shepherd SP, Giranda V, Tamura T. A phase 1 study evaluating the pharmacokinetics and preliminary efficacy of veliparib (ABT-888) in combination with carboplatin/paclitaxel in Japanese subjects with non-small cell lung cancer (NSCLC). Cancer Chemother Pharmacol, 76:1063-1072, 2015
- Motonaga M, Yamamoto N, Makino Y, Ando-Makihara R, Ohe Y, Takano M, Hayashi Y. Phase I dose-finding and pharmacokinetic study of docetaxel and gefitinib in patients with advanced or metastatic non-small-cell lung cancer: evaluation of drug-drug interaction. Cancer Chemother Pharmacol, 76:713-721, 2015
- Nakamichi S, Nokihara H, Yamamoto N, Yamada Y, Honda K, Tamura Y, Wakui H, Sasaki T, Yusa W, Fujino K, Tamura T. A phase 1 study of lenvatinib, multiple receptor tyrosine kinase inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol, 76:1153-1161, 2015
- Nishio M, Horiike A, Murakami H, Yamamoto N, Kaneda H, Nakagawa K, Horinouchi H, Nagashima M, Sekiguchi M, Tamura T. Phase I study of the HER3-targeted antibody patritumab (U3- 1287) combined with erlotinib in Japanese patients with nonsmall cell lung cancer. Lung Cancer, 88:275-281, 2015
- Nishio M, Horiike A, Nokihara H, Horinouchi H, Nakamichi S, Wakui H, Ohyanagi F, Kudo K, Yanagitani N, Takahashi S, Kuboki Y, Yamamoto N, Yamada Y, Abe M, Tahata T, Tamura T. Phase I study of the anti-MET antibody onartuzumab in patients with solid tumors and MET-positive lung cancer. Invest New Drugs, 33:632-640, 2015
- Abe T, Takeda K, Ohe Y, Kudoh S, Ichinose Y, Okamoto H, Yamamoto N, Yoshioka H, Minato K, Sawa T, Iwamoto Y, Saka H, Mizusawa J, Shibata T, Nakamura S, Ando M, Yokoyama A, Nakagawa K, Saijo N, Tamura T. Randomized Phase III Trial Comparing Weekly Docetaxel Plus Cisplatin Versus Docetaxel Monotherapy Every 3 Weeks in Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Intergroup Trial JCOG0803/WJOG4307L. J Clin Oncol, 33:575-581, 2015
- Eba J, Shimokawa T, Nakamura K, Shibata T, Misumi Y, Okamoto H, Yamamoto N, Ohe Y, Lung Cancer Study Group of the Japan Clinical Oncology Group. A Phase II/III study comparing carboplatin and irinotecan with carboplatin and etoposide for the treatment of elderly patients with extensive-disease smallcell lung cancer (JCOG1201). Jpn J Clin Oncol, 45:115-118, 2015
- Tamura Y, Fujiwara Y, Yamamoto N, Nokihara H, Horinouchi H, Kanda S, Goto Y, Kubo E, Kitahara S, Tsuruoka K, Tsuta K, Ohe Y. Retrospective analysis of the efficacy of chemotherapy and molecular targeted therapy for advanced pulmonary pleomorphic carcinoma. BMC Res Notes, 8:800, 2015
- Yagishita S, Horinouchi H, Sunami KS, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Sumi M, Shiraishi K, Kohno T, Furuta K, Tsuta K, Tamura T, Ohe Y. Impact of KRAS mutation on response and outcome of patients with stage III non-squamous non-small cell lung cancer. Cancer Sci, 106:1402-1407, 2015
- Fujita Y, Yagishita S, Hagiwara K, Yoshioka Y, Kosaka N, Takeshita F, Fujiwara T, Tsuta K, Nokihara H, Tamura T, Asamura H, Kawaishi M, Kuwano K, Ochiya T. The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther, 23:717-727, 2015
- Takahashi A, Ishii G, Neri S, Yoshida T, Hashimoto H, Suzuki S, Umemura S, Matsumoto S, Yoh K, Niho S, Goto K, Ohmatsu H, Nagai K, Gemma A, Ohe Y, Ochiai A. Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth. Oncotarget, 6:9531-9541, 2015