Annual Report 2019
Department of Thoracic Oncology
Yuichiro Ohe, Noboru Yamamoto, Shintaro Kanda, Hidehito Horinouchi, Yasushi Goto, Tatsuya Yoshida, Yusuke Okuma, Yuki Shinno, Yuji Matsumoto, Masahiro Iwasaku, Masayuki Shirasawa, Sayaka Arakawa
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 to 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 eight 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 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.
Table 1. Number of new patients 2019
Table 2. Type of procedure in 2019
A total of 623 new patients started treatment in 2018, and the backgrounds and initial treatments of these patients are shown in Tables 1 and 2. The initial treatments were chemotherapy in 343 cases, adjuvant chemotherapy after surgery in 60, chemoradiotherapy in 86, curative radiotherapy in 12, and supportive care including palliative radiotherapy in 51. Survival of lung cancer patients treated in 2010-2014 in our department is shown in Table 3.
Table 3. Survival of lung cancer patients treated in 2010-2014
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. Three JCOG phase III studies, namely JCOG1404 (AGAIN), a phase III study for EGFR mutation positive NSCLC, JCOG1408, a phase III study of SBRT for c-stage IA NSCLC and JCOG1701, a phase III study of immune check point inhibitors to evaluate optimal treatment period, 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 3rd generation EGFR-TKIs, anti-PD-1Ab, anti-PD-L1Ab.
Education
In 2019, two chief residents, 14 residents and four trainee doctors are joined the department. A monthly research conference is held to discuss about 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, ROS inhibitor for ROS1 fusion gene positive lung cancer, BRAF plus MEK inhibitor for BRAF V600 positive lung cancer and NTRK inhibitor for NTRK fusion positive lung cancer are already established as a standard treatment. Other rare driver gene alterations such as RET fusion and MET mutation will be good targets for treatment of lung cancer. Immune check point inhibitors, anti-PD-1 Ab and anti-PD-L1 Ab plus chemotherapy have been established as a standard 1st line treatment for NSCLC. A combination of anti-PD-1 Ab and anti-CTLA-4 Ab with or without chemotherapy will be 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 check point inhibitor will also be an incorporated treatment for early stage lung cancer with surgery or SBRT.
List of papers published in 2019
Journal
1. Inoki K, Kakugawa Y, Takamaru H, Sekiguchi M, Matsumoto M, Matsuda T, Ito A, Tanaka T, Inamoto Y, Fuji S, Kurosawa S, Kim SW, Fukuda T, Ohe Y, Saito Y. Capsule Endoscopy after Hematopoietic Stem Cell Transplantation Can Predict Transplant-Related Mortality. Digestion, 101:198-207, 2020
2. Hashimoto H, Abe M, Tokuyama O, Mizutani H, Uchitomi Y, Yamaguchi T, Hoshina Y, Sakata Y, Takahashi TY, Nakashima K, Nakao M, Takei D, Zenda S, Mizukami K, Iwasa S, Sakurai M, Yamamoto N, Ohe Y. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol, 21:242-249, 2020
3. Ida H, Goto Y, Sato J, Kanda S, Shinno Y, Morita R, Murakami S, Matsumoto Y, Yoshida T, Horinouchi H, Fujiwara Y, Yamamoto N, Fukuda T, Ohashi K, Ohe Y. Clinical characteristics of adrenal insufficiency as an immune-related adverse event in non-small-cell lung cancer. Med Oncol, 37:30, 2020
4. Niho S, Yoshida T, Akimoto T, Sakamaki K, Ono A, Seto T, Nishio M, Yamamoto N, Hida T, Okamoto H, Kurata T, Satouchi M, Goto K, Yamanaka T, Ohe Y. Randomized phase II study of chemoradiotherapy with cisplatin + S-1 versus cisplatin + pemetrexed for locally advanced non-squamous non-small cell lung cancer: SPECTRA study. Lung Cancer, 141:64-71, 2020
5. Okuno T, Arakawa S, Yoshida T, Ohe Y. Efficacy of osimertinib in a patient with leptomeningeal metastasis and EGFR uncommon S768I mutation. Lung Cancer, 143:95-96, 2020
6. Okamoto I, Nokihara H, Nomura S, Niho S, Sugawara S, Horinouchi H, Azuma K, Yoneshima Y, Murakami H, Hosomi Y, Atagi S, Ozaki T, Horiike A, Fujita Y, Okamoto H, Ando M, Yamamoto N, Ohe Y, Nakagawa K. Comparison of Carboplatin Plus Pemetrexed Followed by Maintenance Pemetrexed With Docetaxel Monotherapy in Elderly Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol, 6:e196828, 2020
7. Shimokawa M, Nosaki K, Seto T, Ohashi K, Morise M, Horinouchi H, Sakakibara J, Murakami H, Yano S, Satouchi M, Matsumoto S, Goto K, Yoh K. Phase II, open-label, multicenter trial of crizotinib in Japanese patients with advanced non-small cell lung cancer harboring a MET gene alteration: Co-MET study. Trials, 21:298, 2020
8. Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol, 21:261-270, 2020
9. Shibaki R, Murakami S, Matsumoto Y, Yoshida T, Goto Y, Kanda S, Horinouchi H, Fujiwara Y, Yamamoto N, Kusumoto M, Yamamoto N, Ohe Y. Association of immune-related pneumonitis with the presence of preexisting interstitial lung disease in patients with non-small lung cancer receiving anti-programmed cell death 1 antibody. Cancer Immunol Immunother, 69:15-22, 2020
10. Shinno Y, Goto Y, Ohuchi M, Hamada A, Nokihara H, Fujiwara Y, Ohe Y. The long half-life of programmed cell death protein 1 inhibitors may increase the frequency of immune-related adverse events after subsequent EGFR tyrosine kinase inhibitor therapy. JTOCRR, 1:2020
11. Morita R, Okishio K, Shimizu J, Saito H, Sakai H, Kim YH, Hataji O, Yomota M, Nishio M, Aoe K, Kanai O, Kumagai T, Kibata K, Tsukamoto H, Oizumi S, Fujimoto D, Tanaka H, Mizuno K, Masuda T, Kozuki T, Haku T, Suzuki H, Okamoto I, Hoshiyama H, Ueda J, Ohe Y. Real-world effectiveness and safety of nivolumab in patients with non-small cell lung cancer: A multicenter retrospective observational study in Japan. Lung Cancer, 140:8-18, 2020
12. Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med, 382:41-50, 2020
13. Lee VHF, Mok TSK, Goto Y, Hsue VCC, Yang L, Jiang Y, Leung DKC, Lau KS, Tse PY. Differences Between the East and the West in Managing Advanced-Stage Non-small Cell Lung Cancer. Clin Oncol (R Coll Radiol), 32:e1-e9, 2020
14. Iwama E, Goto Y, Murakami H, Tsumura S, Sakashita H, Mori Y, Nakagaki N, Fujita Y, Seike M, Bessho A, Ono M, Nishitsuji M, Akamatsu H, Morinaga R, Akagi T, Shimose T, Tokunaga S, Yamamoto N, Nakanishi Y, Sugio K, Okamoto I. Survival Analysis for Patients with ALK Rearrangement-Positive Non-Small Cell Lung Cancer and a Poor Performance Status Treated with Alectinib: Updated Results of Lung Oncology Group in Kyushu 1401. Oncologist, 25:306-e618, 2020
15. Katsuya Y, Horinouchi H, Seto T, Umemura S, Hosomi Y, Satouchi M, Nishio M, Kozuki T, Hida T, Sukigara T, Nakamura K, Kuchiba A, Ohe Y. Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study. Eur J Cancer, 113:78-86, 2019
16. Makino Y, Makihara-Ando R, Ogawa T, Sato H, Goto Y, Kanda S, Horinouchi H, Fujiwara Y, Ohe Y, Yamamoto N. Individual optimal dose of amrubicin to prevent severe neutropenia in Japanese patients with lung cancer. Cancer Sci, 110:3573-3583, 2019
17. Masuda K, Fujiwara Y, Shinno Y, Mizuno T, Sato J, Morita R, Matsumoto Y, Murakami S, Goto Y, Kanda S, Horinouchi H, Yamamoto N, Ohe Y. Efficacy and safety of crizotinib in patients with ROS1 rearranged non-small cell lung cancer: a retrospective analysis. J Thorac Dis, 11:2965-2972, 2019
18. Naito T, Udagawa H, Sato J, Horinouchi H, Murakami S, Goto Y, Kanda S, Fujiwara Y, Yamamoto N, Zenke Y, Kirita K, Matsumoto S, Yoh K, Niho S, Motoi N, Ohe Y, Ishii G, Goto K. A Minimum Of 100 Tumor Cells in a Single Biopsy Sample Is Required to Assess Programmed Cell Death Ligand 1 Expression in Predicting Patient Response to Nivolumab Treatment in Nonsquamous Non-Small Cell Lung Carcinoma. J Thorac Oncol, 14:1818-1827, 2019
19. Nokihara H, Nishio M, Yamamoto N, Fujiwara Y, Horinouchi H, Kanda S, Horiike A, Ohyanagi F, Yanagitani N, Nguyen L, Yaron Y, Borgman A, Tamura T. Phase 1 Study of Cabozantinib in Japanese Patients With Expansion Cohorts in Non-Small-Cell Lung Cancer. Clin Lung Cancer, 20:e317-e328, 2019
20. Shibaki R, Murakami S, Matsumoto Y, Goto Y, Kanda S, Horinouchi H, Fujiwara Y, Yamamoto N, Motoi N, Kusumoto M, Yamamoto N, Ohe Y. Tumor expression and usefulness as a biomarker of programmed death ligand 1 in advanced non-small cell lung cancer patients with preexisting interstitial lung disease. Med Oncol, 36:49, 2019
21. Shibaki R, Murakami S, Shinno Y, Matsumoto Y, Goto Y, Kanda S, Horinouchi H, Fujiwara Y, Motoi N, Yamamoto N, Ohe Y. Malignant pleural effusion as a predictor of the efficacy of anti-PD-1 antibody in patients with non-small cell lung cancer. Thorac Cancer, 10:815-822, 2019
22. Shinno Y, Goto Y, Sato J, Morita R, Matsumoto Y, Murakami S, Kanda S, Horinouchi H, Fujiwara Y, Yamamoto N, Ohe Y. Mixed response to osimertinib and the beneficial effects of additional local therapy. Thorac Cancer, 10:738-743, 2019
23. Tamura N, Horinouchi H, Sekine K, Matsumoto Y, Murakami S, Goto Y, Kanda S, Fujiwara Y, Yamamoto N, Ohe Y. Efficacy of subsequent docetaxel +/- ramucirumab and S-1 after nivolumab for patients with advanced non-small cell lung cancer. Thorac Cancer, 10:1141-1148, 2019
24. Yoshida K, Kanda S, Shiraishi H, Goto K, Itahashi K, Goto Y, Horinouchi H, Fujiwara Y, Nokihara H, Yamamoto N, Ohe Y. Difference in central nerve system metastasis during gefitinib or erlotinib therapy in patients with EGFR-mutated non-small cell lung cancer: a retrospective study. J Thorac Dis, 11:1347-1354, 2019
25. Horinouchi H, Nishio M, Hida T, Nakagawa K, Sakai H, Nogami N, Atagi S, Takahashi T, Saka H, Takenoyama M, Katakami N, Tanaka H, Takeda K, Satouchi M, Isobe H, Maemondo M, Goto K, Hirashima T, Minato K, Sumiyoshi N, Tamura T. Three-year follow-up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non-small cell lung cancer: Pooled analysis of ONO-4538-05 and ONO-4538-06 studies. Cancer Med, 8:5183-5193, 2019
26. Niho S, Hosomi Y, Okamoto H, Nihei K, Tanaka H, Hida T, Umemura S, Goto K, Akimoto T, Ohe Y. Carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced non-small cell lung cancer: a multicenter Phase I/II study. Jpn J Clin Oncol, 49:614-619, 2019
27. Sugawara S, Nakagawa K, Yamamoto N, Nokihara H, Ohe Y, Nishio M, Takahashi T, Goto K, Maemondo M, Ichinose Y, Seto T, Sakai H, Gemma A, Imamura F, Shingyoji M, Saka H, Inoue A, Takeda K, Okamoto I, Kiura K, Morita S, Tamura T. Japanese subgroup analysis of a phase III study of S-1 versus docetaxel in non-small cell lung cancer patients after platinum-based treatment: EAST-LC. Int J Clin Oncol, 24:485-493, 2019
28. Masuda N, Ohe Y, Gemma A, Kusumoto M, Yamada I, Ishii T, Yamamoto N. Safety and effectiveness of alectinib in a real-world surveillance study in patients with ALK-positive non-small-cell lung cancer in Japan. Cancer Sci, 110:1401-1407, 2019
29. Baba T, Sakai F, Kato T, Kusumoto M, Kenmotsu H, Sugiura H, Tominaga J, Oikado K, Sata M, Endo M, Yanagawa N, Sasaki S, Iwasawa T, Saito Y, Fujiwara Y, Ohe Y, Yamazaki N, Sakamoto T, Koshiba T, Kuwano K. Radiologic features of pneumonitis associated with nivolumab in non-small-cell lung cancer and malignant melanoma. Future Oncol, 15:1911-1920, 2019
30. Uchida S, Yoshida Y, Ohe Y, Nakayama Y, Motoi N, Kobayashi A, Asakura K, Nakagawa K, Watanabe SI. Trimodality therapy for superior sulcus tumour: experience of a single institution over 19 years. Eur J Cardiothorac Surg, 56:167-173, 2019
31. Nakai T, Matsumoto Y, Sasada S, Tanaka M, Tsuchida T, Ohe Y, Motoi N. Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology. Jpn J Clin Oncol, 49:559-566, 2019
32. Nishio M, Murakami H, Ohe Y, Hida T, Sakai H, Kasahara K, Imamura F, Baba T, Kubota K, Hosomi Y, Shimokawa T, Hayashi H, Miyadera K, Tamura T. Phase I study of TAS-121, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with non-small-cell lung cancer harboring EGFR mutations. Invest New Drugs, 37:1207-1217, 2019
33. Takeda M, Ohe Y, Horinouchi H, Hida T, Shimizu J, Seto T, Nosaki K, Kishimoto T, Miyashita I, Yamada M, Kaneko Y, Morimoto C, Nakagawa K. Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma. Lung Cancer, 137:64-70, 2019
34. Ogura T, Takigawa N, Tomii K, Kishi K, Inoue Y, Ichihara E, Homma S, Takahashi K, Akamatsu H, Ikeda S, Inase N, Iwasawa T, Ohe Y, Ohta H, Onishi H, Okamoto I, Ogawa K, Kasahara K, Karata H, Kishimoto T, Kitamura Y, Gemma A, Kenmotsu H, Sakashita H, Sakamoto S, Sekine K, Takiguchi Y, Tada Y, Toyooka S, Nakayama Y, Nishioka Y, Hagiwara K, Hanibuchi M, Fukuoka J, Minegishi Y, Yanagihara T, Yamamoto N, Yamamoto H, Gaga M, Fong KM, Powell CA, Kiura K. Summary of the Japanese Respiratory Society statement for the treatment of lung cancer with comorbid interstitial pneumonia. Respir Investig, 57:512-533, 2019
35. Thomas M, Thatcher N, Goldschmidt J, Ohe Y, McBride HJ, Hanes V. Totality of evidence in the development of ABP 215, an approved bevacizumab biosimilar. Immunotherapy, 11:1337-1351, 2019
36. Udagawa C, Horinouchi H, Shiraishi K, Kohno T, Okusaka T, Ueno H, Tamura K, Ohe Y, Zembutsu H. Whole genome sequencing to identify predictive markers for the risk of drug-induced interstitial lung disease. PLoS One, 14:e0223371, 2019
37. Okada M, Kijima T, Aoe K, Kato T, Fujimoto N, Nakagawa K, Takeda Y, Hida T, Kanai K, Imamura F, Oizumi S, Takahashi T, Takenoyama M, Tanaka H, Hirano J, Namba Y, Ohe Y. Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT). Clin Cancer Res, 25:5485-5492, 2019
38. Shibaki R, Murakami S, Oki K, Ohe Y. Nivolumab-induced autoimmune encephalitis in an anti-neuronal autoantibody-positive patient. Jpn J Clin Oncol, 49:793-794, 2019
39. Akamatsu H, Ninomiya K, Kenmotsu H, Morise M, Daga H, Goto Y, Kozuki T, Miura S, Sasaki T, Tamiya A, Teraoka S, Tsubata Y, Yoshioka H, Hattori Y, Imamura CK, Katsuya Y, Matsui R, Minegishi Y, Mizugaki H, Nosaki K, Okuma Y, Sakamoto S, Sone T, Tanaka K, Umemura S, Yamanaka T, Amano S, Hasegawa K, Morita S, Nakajima K, Maemondo M, Seto T, Yamamoto N. The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV. Int J Clin Oncol, 24:731-770, 2019
40. Mizuno T, Fujiwara Y, Yoshida K, Kohno T, Ohe Y. Next-Generation Sequencer Analysis of Pulmonary Pleomorphic Carcinoma With a CD74-ROS1 Fusion Successfully Treated With Crizotinib. J Thorac Oncol, 14:e106-e108, 2019
41. Ito K, Nishio M, Kato M, Murakami H, Aoyagi Y, Ohe Y, Okayama T, Hashimoto A, Ohsawa H, Tanaka G, Nonoshita K, Ito S, Matsuo K, Miyadera K. TAS-121, A Selective Mutant EGFR Inhibitor, Shows Activity Against Tumors Expressing Various EGFR Mutations Including T790M and Uncommon Mutations G719X. Mol Cancer Ther, 18:920-928, 2019
42. Planchard D, Boyer MJ, Lee JS, Dechaphunkul A, Cheema PK, Takahashi T, Gray JE, Tiseo M, Ramalingam SS, Todd A, McKeown A, Rukazenkov Y, Ohe Y. Postprogression Outcomes for Osimertinib versus Standard-of-Care EGFR-TKI in Patients with Previously Untreated EGFR-mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res, 25:2058-2063, 2019