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Department of Thoracic Oncology

Koichi Goto, Hironobu Ohmatsu, Seiji Niho, Kiyotaka Yoh, Shigeki Umemura, Shingo Matsumoto, Keisuke Kirita, Eri Sugiyama, Yoshitaka Zenke

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 Department work closely with thoracic surgeons, radiation oncologists, 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.

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 also receive oral chemotherapy and/or intravenous chemotherapy in the Ambulatory Care Center. Bronchoscopy and EBUS for diagnosis is performed on Monday, Tuesday, and Thursday afternoon. Fluoroscopic-CT guided needle lung biopsies are carried out on Tuesday afternoon. For patient management, we use approximately 70 beds in 8F, 6A, 5A and 5B 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 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 four areas: 1) development of new and effective diagnosis and treatment modalities; 2) detection, diagnosis, and treatment of peripheral-type minute lung cancers that are not visible in plain chest X-rays; 3) collaborative studies with the Research Center for Innovative Oncology in the following areas: detection of driver mutation for small cell lung cancer; development of a new diagnostic method of rare driver gene alterations for lung cancer; correlation between gene abnormalities and clinical characteristics; correlation between sensitivity of EGFR-TKI and CAF (cancer-associated fibroblasts); and 4) translational research from bench to bed-side or from bed-side to bench for the development of innovative treatment strategies.

Especially, hole genome analysis of small cell cancer to detect new driver mutations and establishment of multiplex diagnosis methods for rare gene alteration of lung cancer such as ALK, RET and ROS1 fusion gene and BRAF mutation are under investigation as a collaboration with the Research Center for Innovative Oncology.

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.

Recently, the usefulness of TS-1 and pemetrexed combined with thoracic radiotherapy has been reported for locally advanced NSCLC. Therefore, a randomized phase II study of cisplatin plus TS-1 vs. cisplatin plus pemetrexed combined with thoracic radiotherapy for stage III nonsquamous NSCLC is now ongoing.

Alectinib is a newly developing selective ALK inhibitor and very effective for ALK fusion positive NSCLC, although 4-5% of NSCLC are positive for ALK fusion protein. A phase I/II study of alectinib demonstrated durable response and higher than 90% response rate without severe toxicity. A phase III study of alectinib comparing with crizotinib for ALK positive lung cancer was conducted and the patient enrollment was completed. The study of AZD9291, 3rd generation EGFR-TKI, was conducted and a good response for T790M-resistant mutation positive lung cancer was observed with minimal toxicities.

In addition, many recent clinical trials indicated that PD-1/PD-L1 immune checkpoint inhibitors showed remarkable clinical response against advanced NSCLC including squamous cell lung cancer. Nivolumab, one of the PD-1 antibodies, was approved in December 2015, in Japan.

LC-SCRUM-Japan (Lung Cancer Genomic Screening Project for Individualized Medicine in Japan), a nationwide genomic screening project of lung cancer with rare driver oncogenes, such as ALK, RET and ROS1 fusion, and BRAF mutation was started in February 2013. As of December 2015, 2,301 patients were enrolled and 51 (3%) RET and 86 (4%) ROS1 fusion positive patients were detected. Many lung cancers with oncogenic alterations detected in LC-SCRUM-Japan had been entered into clinical trials of molecular targeting agents. In addition, from February 2015, to further develop genomic screening and to establish precision medicine in Japan, LC-SCRUM-Japan and genomic screening network for gastrointestinal cancer (GI-SCREEN), developed the collaborative genomic screening organization between academia and 14 pharmaceutical companies, named SCRUM-Japan.

  • Table 1. Number of patients in 2015
  • Table 2. Initial treatment for lung cancer in 2015

List of papers published in 2015

Journal

  1. Watanabe N, Umemura S, Niho S, Kirita K, Matsumoto S, Yoh K, Ohmatsu H, Goto K. Docetaxel for platinum-refractory advanced thymic carcinoma. Jpn J Clin Oncol, 45:665-669, 2015
  2. 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
  3. 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
  4. Daga H, Takeda K, Okada H, Miyazaki M, Ueda S, Kaneda H, Okamoto I, Yoh K, Goto K, Konishi K, Sarashina A, Tanaka T, Kaiser R, Nakagawa K. Phase I study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol, 76:1225-1233, 2015
  5. 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
  6. 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
  7. Hishida T, Tsuboi M, Shukuya T, Takamochi K, Sakurai H, Yoh K, Ohashi Y, Kunitoh H. Multicenter observational cohort study of post-operative treatment for completely resected non-smallcell lung cancer of pathological stage I (T1 >2 cm and T2 in TNM classification version 6). Jpn J Clin Oncol, 45:499-501, 2015
  8. 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
  9. Koriyama H, Ishii G, Yoh K, Neri S, Morise M, Umemura S, Matsumoto S, Niho S, Ohmatsu H, Tsuboi M, Goto K, Ochiai A. Presence of podoplanin-positive cancer-associated fibroblasts in surgically resected primary lung adenocarcinoma predicts a shorter progression-free survival period in patients with recurrences who received platinum-based chemotherapy. J Cancer Res Clin Oncol, 141:1163-1170, 2015
  10. 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
  11. 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
  12. Makinoshima H, Takita M, Saruwatari K, Umemura S, Obata Y, Ishii G, Matsumoto S, Sugiyama E, Ochiai A, Abe R, Goto K, Esumi H, Tsuchihara K. Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma. J Biol Chem, 290:17495-17504, 2015
  13. Umemura S, Tsuchihara K, Goto K. Genomic profiling of smallcell lung cancer: the era of targeted therapies. Jpn J Clin Oncol, 45:513-519, 2015
  14. Kubota K, Sakai H, Katakami N, Nishio M, Inoue A, Okamoto H, Isobe H, Kunitoh H, Takiguchi Y, Kobayashi K, Nakamura Y, Ohmatsu H, Sugawara S, Minato K, Fukuda M, Yokoyama A, Takeuchi M, Michimae H, Gemma A, Kudoh S, Tokyo Cooperative Oncology Group. A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial. Ann Oncol, 26:1401-1408, 2015
  15. Shukuya T, Yamanaka T, Seto T, Daga H, Goto K, Saka H, Sugawara S, Takahashi T, Yokota S, Kaneda H, Kawaguchi T, Nagase S, Oguri T, Iwamoto Y, Nishimura T, Hattori Y, Nakagawa K, Nakanishi Y, Yamamoto N, West Japan Oncology Group. Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial. Lancet Oncol, 16:1630-1638, 2015
  16. Kohno T, Nakaoku T, Tsuta K, Tsuchihara K, Matsumoto S, Yoh K, Goto K. Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res, 4:156-164, 2015
  17. Shimizu K, Nakaya N, Saito-Nakaya K, Akechi T, Ogawa A, Fujisawa D, Sone T, Yoshiuchi K, Goto K, Iwasaki M, Tsugane S, Uchitomi Y. Personality traits and coping styles explain anxiety in lung cancer patients to a greater extent than other factors. Jpn J Clin Oncol, 45:456-463, 2015
  18. Enomoto Y, Kenmotsu H, Watanabe N, Baba T, Murakami H, Yoh K, Ogura T, Takahashi T, Goto K, Kato T. Efficacy and Safety of Combined Carboplatin, Paclitaxel, and Bevacizumab for Patients with Advanced Non-squamous Non-small Cell Lung Cancer with Pre-existing Interstitial Lung Disease: A Retrospective Multi-institutional Study. Anticancer Res, 35:4259-4263, 2015
  19. Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol, 16:990-998, 2015
  20. 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
  21. Watanabe N, Niho S, Kirita K, Umemura S, Matsumoto S, Yoh K, Ohmatsu H, Goto K. Second-line docetaxel for patients with platinum-refractory advanced non-small cell lung cancer and interstitial pneumonia. Cancer Chemother Pharmacol, 76:69-74, 2015
  22. Watanabe N, Niho S, Kirita K, Umemura S, Matsumoto S, Yoh K, Ohmatsu H, Goto K. Vinorelbine and cisplatin in patients with advanced non-small cell lung cancer with interstitial pneumonia. Anticancer Res, 35:1697-1701, 2015