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Y. Nakanishi

Moderator of

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    SC19 - Interventional Pulmonology in Diagnosis and Treatment of Thoracic Malignancies (ID 343)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Pulmonology
    • Presentations: 4
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      SC19.01 - Diagnosis of Lung Cancer: Multimodal Devices for Peripheral Pulmonary Lesions (ID 6677)

      16:00 - 17:30  |  Author(s): N. Kurimoto

      • Abstract
      • Presentation
      • Slides

      Abstract:
      When bronchoscopy is performed for peripheral pulmonary lesions (PPLs), a radial ultrasonic probe can be inserted from the working channel of the bronchoscope to reach the PPL[1]. We began using this technique of endobronchial ultrasonography (EBUS) in 1994. EBUS using a guide sheath (GS) also began in 1996[2]. We would like to explain the technique and advantages of diagnosing PPLs using EBUS, GS, Navigation, and etc. 1) Radial ultrasonic miniature-probe A radial probe emits US while being rotated 360°; the reflected US waveform is rendered as an image. The radial probe scans from the bronchial lumen to provide a short-axis image of the bronchial and para-bronchial tissue. 2) Analyzing the internal structure of peripheral pulmonary lesions with a radial mini-probe EBUS imaging before surgery has been compared with histopathologic findings of surgically resected tissue to determine the internal structures of PPLs that can be depicted by EBUS[3]. PPLs can be classified as heterogeneous or homogeneous based on irregularities in brightness within lesions seen on EBUS. Internal structures within peripheral lesions that can be identified by EBUS include patent blood vessels, patent bronchi, hemorrhage, calcification, dilated bronchi, necrosis, and small amounts of air in alveoli. 3) EBUS using a guide sheath (EBUS-GS)[ 1, 2] The GS-covered probe is advanced to the PPL, then after confirmation by EBUS that the lesion has been reached, the probe is removed before inserting the brush and biopsy forceps through the GS that is held in place in the lesion. This technique enables cytology and biopsy to be performed several times with minimal risk of bleeding. 4) Insertion of the bronchoscope (saline immersion technique) After observing the bronchial lumen, the bronchoscope should be advanced while visualizing the branches to the bronchus near the peripheral lesion. Upon reaching a position where further advancement is not possible, flushing of 1-ml saline (total 5-10 ml) several times is performed through the working channel of the bronchoscope; this is done to fill the bronchus, remove any sputum, and visualize the lumen. The GS-covered probe is then inserted from the working channel into the bronchus. In cases of ground glass nodule (GGN), we do not perform the saline immersion technique. Because the saline immersion technique will occur EBUS images of hyperechoic points which resemble EBUS image of GGN. 5) EBUS visualization The operator advances the US probe from the working channel of the 4-mm bronchoscope towards the periphery and stops when some resistance is felt. The duration of X-ray fluoroscopy should be limited as much as possible; also, an iris of the fluoroscopy machine should be used for fluoroscopy. Scanning while pulling back the probe from the distal site to the proximal site reduces strain on the probe and provides clear EBUS images. We have reported that EBUS imaging of PPLs can be used to diagnose and assess the degree of differentiation between benign and malignant lesions[3]. PPLs are classified as type I if the internal echoes are homogeneous, type III if the internal echoes are heterogeneous, and type II if there are mainly hyperechoic lines and dots near the probe. About 92% of type I lesions were benign, whereas 99% of type II and type III lesions were malignant. The positional relationship between the probe and a PPL is classified as "within" (probe placement within a lesion), when the 360° area around the probe is entirely surrounded by the lesion; and "adjacent to" (probe is in contact with a lesion) when a lesion is depicted, but the 360° area around the probe is not entirely surrounded by the lesion. Higher diagnostic yields have also been reported for lesions with a positive bronchus sign on computed tomography. Minezawa et al.[4] reported that the CT bronchus sign was a significant predictive factor for successful bronchoscopic diagnosis in the multivariate analysis. We believe that bronchoscopists should trace the accurate bronchus leading to the PPL on CT axial images. When the lesion located in the middle lobe, the lingular segment, or bilateral lower lobes, we inverse CT axial images right to left, or left to right for watching the bronchus from the cranial site. When the lesion located in the right upper lobe, we rotate CT axial images counterclockwise 90 degrees. When the lesion located in the left superior segment, we rotate CT axial images clockwise 90 degrees. While tracing the bronchus on CT images, we could draw the illustration of the bronchus leading to PPLs. We usually use virtual bronchoscopic navigation (VBN) and compare the hand-written illustration of the bronchus leading to PPLs. Asano et al.[5 ]reported that the diagnostic yield by EBUS-GS and VBN was between 63.3 and 84.4% in reports on VBN for PPLs searched in PubMed as of November 2013. When the ultrasonic probe advanced to the different bronchus a little far from the target lesion, EBUS image is invisible. In this case, we should change the direction of the tip of the bronchoscope using the up and down lever of the bronchoscope under fluoroscopy. We select the direction of the tip of the bronchoscope for facing the target lesion, and pull back and push the probe/GS for trying to insert the target lesion. When the ultrasonic probe advanced to the bronchus adjacent to the target lesion, EBUS image is called as “adjacent to”. In this case, we could change the direction of the tip of the bronchoscope using the up and down lever of the bronchoscope under the EBUS image. We use the up or down lever of the bronchoscope for changing the position of the probe and GS (probe/GS) to be close to the target lesion on EBUS image. Then we keep the same angle of the tip of the bronchoscope, and pull back and push the probe/GS for trying to insert the target lesion. 6) Cytology and tissue biopsy from the guide sheath The GS tip is placed within or adjacent to the PPL before passing the brush and biopsy forceps through the GS. References Kurimoto N, Fielding D, Musani A. Endobronchial Ultrasonography. 2011, Willy Blackwell Kurimoto N, Miyazawa T, Okimasa S, Maeda A, Oiwa H, Miyazu Y, Murayama M. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. CHEST 2004; 126: 959-65. Kurimoto N, Murayama M, Yoshioka S, Nishisaka T. Analysis of the internal structure of peripheral pulmonary lesions using endobronchial ultrasonography. CHEST 2002; 122: 1887-94 Minezawa T, Okamura T, Yatsuya H, et al. Bronchus sign on thin-section computed tomography is a powerful predictive factor for successful transbronchial biopsy using endobronchial ultrasound with a guide sheath for small peripheral lung lesions: a retrospective observational study. BMC Med Imaging. 2015 21; 15:21 Asano F, Eberhardt R, Herth F. Virtual Bronchoscopic Navigation for Peripheral Pulmonary Lesions. Respiration 2014; 88: 430-440

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      SC19.02 - Invasive Staging of Lung Cancer: EBUS, EUS and Beyond (ID 6678)

      16:00 - 17:30  |  Author(s): K. Yasufuku

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Despite the advances in surgical treatment and multimodality treatment, lung cancer is still the leading cause of death from malignant disease worldwide. Accurate staging is important not only to determine the prognosis but also to decide the most suitable treatment plan. During the staging process of non-small cell lung cancer (NSCLC), mediastinal lymph node staging is one of the most important factors that affect the patient outcome. Non-invasive staging such as computed tomography (CT) and positron emission tomography (PET) indicate size and metabolic activity, respectively. However imaging alone is inaccurate and therefore tissue sampling is the preferred and most reliable. Surgical staging by mediastinoscopy has been the gold standard for mediastinal lymph node staging but requires general anesthesia and complications cannot be ignored. Endoscopic ultrasound techniques provide a minimally invasive alternative for surgical staging. The current available endoscopic ultrasound techniques for mediastinal staging include transesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). Both procedures can be performed in an outpatient setting under local anesthesia. EUS-FNA is a sensitive and safe method of evaluating the inferior mediastinal nodes (stations 7, 8, and 9) and some parts of the anterior mediastinal nodes if the lymph nodes are accessible from the esophagus. However, in spite of the strength of EUS-FNA for evaluating the inferior mediastinal nodes, its ability to evaluate lesions anterior to the trachea is limited. On the other hand, EBUS-TBNA has reach to the paratracheal and subcarinal (stations 2R, 2L, 4R, 4L, 7), as well as the N1 lymph nodes (stations 10, 11, 12). In experienced hands, EBUS can be used through the esophagus for a EUS-like approach to the inferior mediastinal lymph nodes. Thus, EUS-FNA and EBUS-TBNA are complementary methods for lymph node staging in lung cancer and most of the mediastinum and the hilum can be evaluated with these endoscopic procedures. Aortic nodes (stations 5 and 6) are exceptions and must be evaluated by surgical methods (anterior mediastinotomy, VATS, thoracotomy). Based on the current evidence, EBUS-TBNA and EUS-FNA presents a minimally invasive endoscopic procedure as an alternative to mediastinoscopy for mediastinal staging of NSCLC with discrete N2 or N3 lymph node enlargement, provided negative results are confirmed by surgical staging. EBUS-TBNA can access all lymph nodes accessible by mediastinoscopy as well as hilar (N1) lymph nodes. EUS-FNA has access to the inferior mediastinal lymph nodes not accessible by mediastinoscopy. EBUS-TBNA and/or EUS-FNA have in fact replaced mediastinoscopy in many patients with diffuse mediastinal adenopathy, where a simple tissue diagnosis is required to determine treatment. When combined the techniques offer safe and accurate assessment of mediastinum, with accuracy surpassing that of the pervious gold standard – cervical mediastinoscopy. EBUS-TBNA and/or EUS-FNA can also be repeated with ease and have been used for mediastinal restaging in patients who underwent neoadjuvant therapy in preparation for definitive surgical intervention. Ultrasound image analysis of lymph nodes may assist bronchoscopists during EBUS-TBNA or EUS-FNA. Standard sonographic classification of lymph nodes can help characterize mediastinal and hilar lymph nodes as benign or malignant, which may guide the decision on which lymph nodes to sample. Newer imaging technology such as elastography can potentially enhance US guided image analysis of the lymph nodes.

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      SC19.03 - Medical Thoracoscopy (ID 6679)

      16:00 - 17:30  |  Author(s): A. Rozman

      • Abstract
      • Slides

      Abstract not provided

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      SC19.04 - Endobronchial Palliation in Thoracic Malignancies (ID 6680)

      16:00 - 17:30  |  Author(s): Z. Pápai-Székely

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lung cancer is the second most common cancer in both men and women In men prostate cancer, while in women breast cancer is more common. About 14% of all new cancers are lung cancers. The American Cancer Society’s estimates for lung cancer in the United States for 2016 are: About 224,390 new cases of lung cancer (117,920 in men and 106,470 in women) About 158,080 deaths from lung cancer (85,920 in men and 72,160 in women) Lung cancer is by far the leading cause of cancer death among both men and women; about 1 out of 4 cancer deaths are from lung cancer. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. One third of the new lung cancer cases are candidates for surgery, and about half of the rest develops some kind of major airways involvement. This can be endobronchial tumor, extrinsic compression or combined. Besides lung cancer, metastases from other types of tumors are also candidates for intrabronchial treatments. There are different methods available for treating endobronchial malignancies, in most of the cases the combination of two or more procedure needed to reach optimal result. To reestablish the airway patency improves quality of life, and provides sufficient time to apply different lung cancer treatment, chemo, radio and immunotherapy Methods available include mechanical debulking, use of different types of laser, electrocautery, cryotherapy, intraluminal brachytherapy, argon-plasma coagulation, and microvawe instruments. Different types of silicon and self expandable metallic stents are useful for keeping the airways open after successful reopening. Balloon dilatation may help to insert stent to the compressed airways. The use of locally installed substances like chemo, different angiogenesis inhibitors are in the focus again. With the use of endobronchial ultrasound the needle can easily be inserted into the peripheral or central tumor, and lymphnodes. Most of the procedures are done under general anesthesia, with the use of rigid bronchoscope. Ideally the bronchoscopist can choose from the different methods available, using the best appropriate one in the given situation. Sufficient training is necessary before starting each new method. Simulation, low fidelity models are available to learn without having the unnecessary risk in a real case. One has to be prepared for treating different complications, such as heavy bleeding from the tumor, or bleeding caused by the procedure itself. Well trained personnel is a must to start with these kind of procedures. Anesthesiologist, assistants trained in endoscopic procedures are essential before starting the procedure.

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Author of

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    MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
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      MA08.10 - Detection of the T790M Mutation of EGFR in Plasma of Advanced NSCLC Patients with Acquired Resistance to EGFR-TKI (WJOG8014LTR) (ID 5377)

      11:00 - 12:30  |  Author(s): Y. Nakanishi

      • Abstract
      • Presentation
      • Slides

      Background:
      NSCLC patients with activating mutations of the EGFR initially respond well to TKIs, but about half such patients develop TKI resistance through acquisition of a secondary T790M mutation. Whereas next-generation EGFR-TKIs have been developed to overcome T790M-mediated resistance, performance of a second tumor biopsy to assess T790M mutation status can be problematic.

      Methods:
      We developed and evaluated liquid biopsy assays for detection of TKI-sensitizing and T790M mutations of EGFR by droplet digital PCR (ddPCR) in EGFR mutation–positive patients with acquired EGFR-TKI resistance.

      Results:
      A total of 260 patients was enrolled between November 2014 and March 2015 at 29 centers for this West Japan Oncology Group (WJOG 8014LTR) study. Plasma specimens from all subjects as well as tumor tissue or malignant pleural effusion or ascites from 41 patients were collected after the development of EGFR-TKI resistance. All plasma samples were genotyped successfully and the results were reported to physicians within 14 days. TKI-sensitizing and T790M mutations were detected in plasma of 120 (46.2%) and 75 (28.8%) patients, respectively. T790M was detected in 56.7% of patients with plasma positive for TKI-sensitizing mutations. For the 41 patients with paired samples obtained after acquisition of EGFR-TKI resistance, the concordance for mutation detection by ddPCR in plasma compared with tumor tissue or malignant fluid specimens was 78.0% for TKI-sensitizing mutations and 65.9% for T790M.

      Conclusion:
      Noninvasive genotyping by ddPCR with cell-free DNA extracted from plasma is a promising approach to the detection of gene mutations during targeted treatment.

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    P2.03a - Poster Session with Presenters Present (ID 464)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03a-056 - Phase II Trial of Weekly Nab-Paclitaxel for Previously Treated Advanced Non–Small Cell Lung Cancer: KTOSG Trial 1301 (ID 4004)

      14:30 - 15:45  |  Author(s): Y. Nakanishi

      • Abstract

      Background:
      We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non–small cell lung cancer (NSCLC).

      Methods:
      Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100 mg/m[2]) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR).

      Results:
      Forty-one patients were enrolled between September 2013 and April 2015. The ORR was 31.7 % (90% confidence interval, 19.3% to 44.1%), which met the primary objective of the study. Median progression-free survival was 4.9 months (95% confidence interval, 2.4 to 7.4 months) and median overall survival was 13.0 (95% confidence interval, 8.0 to 18.0 months) months. The median number of treatment cycles was four (range, 1 to 17) over the entire study period, and the median dose intensity was 89.1 mg/m[2] per week. Hematologic toxicities of grade 3 or 4 included neutropenia (19.5%) and leukopenia (17.1%), with no cases of febrile neutropenia being observed. Individual nonhematologic toxicities of grade 3 or higher occurred with a frequency of <5%.

      Conclusion:
      Weekly nab-paclitaxel was associated with acceptable toxicity and a favorable ORR in previously treated patients with advanced NSCLC. Our results justify the undertaking of a phase III trial comparing nab-paclitaxel with docetaxel in this patient population.

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    P2.08 - Poster Session with Presenters Present (ID 491)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Patient Support and Advocacy Groups
    • Presentations: 1
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      P2.08-007 - Listen Advocate Voice - Web-Survey for the Japanese Model of Lung Cancer Advocacy by Society (ID 5651)

      14:30 - 15:45  |  Author(s): Y. Nakanishi

      • Abstract
      • Slides

      Background:
      In Asian countries, the concept of cancer advocacy has not been sufficiently recognized. In Japan, Lung Cancer Society (JLCS) has led the lung cancer advocacy with a part of the NPO, and adopted the 2014 Kyoto Declaration. To evaluate the awareness and attitude of lung cancer advocacy activity among patients, medical workers, and the general population in Japan, web survey was planned for the perceptions of Kyoto declaration and JLCA (Japanese alliance for lung cancer advocacy) events which were carried out by JLCS in these 2 years.

      Methods:
      An internet survey using survey monkey was conducted which contained 6 closed-ended (selection one or free answers) and open-ended questions, depending on the JLCA network population in June 2016.

      Results:
      109 people of responded involving 36% of patients and their family, 25% of MD and medical worker, 19% of pharmaceutical company officials and 16% of news media. Perception of Kyoto declaration was 21% of attendee, 27% of well-known, 13% of partial known and 39% of non-awareness. Also the number of participants to the events of JLCA is, 49% of 0 times, 17% 0f 1-2 times, 24% of 3-4 times and 11% of more than 5 times. The most sympathy events ware voted to 1) lecture by a physician 57%, 2) lecture by survivor and the participants WCLC of cancer patients 46%, 3) information in the facebook and the web site 46% 4) citizen open lecture of lung cancer 39%, 5) Performance by society ambassador 38%, 6) advocacy program in annual meetings 26% and 7) Medical seminars around the country 26%. The proportion of respondents who have a certain reputation in the activities of JLCA was 76%. The requests to JLCA is, 1) is the most participation opportunities for information of new treatment and participation opportunities to clinical trial, followed by 2) wish to participate to all the programs in the Society.

      Conclusion:
      In Japan, awareness about the advocacy is improved, and it was found that the expect to Society for the diverse needs through the Internet survey.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02c-001 - Phase I Study of Salazosulfapyridine Targeting Cancer Stem Cells in Combination with CDDP and Pemetrexed for Chemo-Naïve Advanced Non-Sq NSCLC (ID 4318)

      14:30 - 15:45  |  Author(s): Y. Nakanishi

      • Abstract

      Background:
      Variant splicing isoforms of CD44 (CD44v) are a marker of cancer stem cells (CSCs) in solid tumors. CD44v stabilizes the glutamate-cystine transporter subunit xCT and thereby promotes synthesis of the intracellular antioxidant glutathione and protects CSCs from oxidative stress. Salazosulfapyridine (SASP) is an inhibitor of xCT activity, and, in combination with cisplatin (CDDP), it attenuates the increase in the proportion of CD44v-positive tumor cells during the growth of tumor xenografts in mice.

      Methods:
      Individuals with advanced (stage IIIB or IV) nonsquamous non–small cell lung cancer are eligible to enroll in a phase I dose-escalation study (standard 3+3 design) of SASP in combination with CDDP and pemetrexed (PEM) as first-line treatment. Patients receive SASP daily as well as CDDP (75 mg/m[2]) and PEM (500 mg/m[2]) on day 1 of a 21-day cycle. The primary end point is the percentage of patients who experience dose-limiting toxicity (DLT) between administration of the first dose of SASP (day 1) and day 21.

      Results:
      From April 2015 to January 2016, 15 patients were enrolled in the study (mean age, 64 years; age range, 42–74 years; male/female ratio, 10/5; ECOG performance status 0/1 ratio, 6/9). Immunohistochemical staining of tumor biopsy specimens revealed that the proportion of CD44v-positive cells was >10% in 9 patients before SASP treatment. No DLT was observed in the first three patients treated at SASP dose level 1 (500 mg TID) or those treated at dose level 2 (1000 mg TID). At dose level 3 (1500 mg TID), two of three patients experienced a DLT (anorexia of grade 3). We enrolled additional patients at dose level 2 and two of the total of five patients treated at this dose level experienced DLTs (hypotension or pneumonitis, each of grade 3). To confirm the safety of dose level 1, we enrolled additional patients at this dose level and one of the total of six patients treated at this dose level experienced DLTs (AST and ALT elevation, each of grade 3). Exposure of SASP following oral administration varied markedly among individuals according to ABCG2 and NAT2 genotypes as previously reported.

      Conclusion:
      SASP 500 mg TID was the recommended dose when administered with CDDP plus PEM.

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    SC13 - Interaction of COPD and Lung Cancer - Consequences for Early Diagnosis and Management (ID 337)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      SC13.04 - Limitations by COPD for Treatment (ID 6652)

      11:00 - 12:30  |  Author(s): Y. Nakanishi

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The most common cause of death among patients with COPD is lung cancer as well as respiratory failure, and COPD often co-exists with lung cancer with a range of 40 to 70% (1). While lung cancer survival is generally very low, survival is even lower among patients with COPD, i.e. in one study, it is reported that 26% of lung cancer patients without COPD were still alive 3 years after their diagnosis compared to 15% of lung cancer patients with COPD (2). One of the reasons why prognoses of lung cancer patients with COPD are worse is that treatment options are limited due to affected lung function. For surgical treatment for lung cancer patients with COPD, post-operative residual lung function should be maintained within a certain level. Therefore, patients with severely reduced lung function may be rejected for surgical treatment, or at least they may not able to receive standard surgical procedures. For patients rejected for surgery because of poor lung function, radiotherapy is an alternative treatment option. However, radiotherapy itself affects lung function because of post treatment radiation pneumonia. For drug therapy, drug-induced lung toxicities are emerging issues, especially due to the use of EGF receptor tyrosine kinase inhibitors, ALK inhibitors or immune check point inhibitors (3). In cases whose lung function is severely affected, drug-induced lung toxicities may be lethal, and special attention should be payed to such patients. Therefore, to overcome these limitations of treatment is an urgent issue in the daily practice. For surgical treatment, assessment of preoperative lung function is essential to judge its indication. Both predicted post-operative lung function and DLco values are mainly used as parameters for the indication of surgical treatment. Therefore, optimization of these functions by medical therapy, pulmonary rehabilitation and smoking cessation may extend the opportunities of surgical treatment, resulting in better patients’ outcomes. Regarding with medical therapy, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (4) and American Thoracic Society and the European Respiratory Society guidelines for COPD management point out the usefulness of bronchodilators as well as inhaled corticosteroids. In addition, pulmonary rehabilitations would be recommended for pre-operative lung cancer patients with poor lung function because of its safety, although there are no data clearly showing the efficacy of pulmonary rehabilitations on patients’ outcome. For radiotherapy for lung cancer patients with COPD, newly developed devices appear to show promising outcome. Both stereotactic body radiotherapy (SBRT) and ion beam radiotherapy have such a nice radiation dose distribution that high doses of irradiation are possible with low impact to normal tissues. Some reports suggest that patients’ outcomes by these treatment modalities may be not worse or sometimes better than surgical treatment (5). In addition, smoking cessation is, of course, important issue as a pre- and post- operative management. Since lung cancer patients with COPD are increasing over all area in the world, appropriate treatment should be chosen with the utmost care and attention. In addition, it is an urgent issue to establish more effective and safe treatment modalities to these patients. References 1) Young RP, Hopkins RJ, Christmas T, et al. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J. 2009;34(2):380-6. 2) Kiri VA, Soriano J, Visick G, Fabbri L. Recent trends in lung cancer and its association with COPD: an analysis using the UK GP Research Database. Prim Care Respir J. 2010;19(1):57-61. 3) De Sanctis A, Taillade L, Vignot S, et al. Pulmonary toxicity related to systemic treatment of nonsmall cell lung cancer. Cancer. 2011;117(14):3069-80. 4) Rabe KF, Hurd S, Anzueto A, Barnes PJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532-55. 5) Chehade S and Palma DA. Stereotactic radiotherapy for early lung cancer: Evidence-based approach and future directions. Rep Pract Oncol Radiother. 2015;20(6):403-10..

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