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Kazuhiro Yasufuku

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    MS16 - The Interventional Pulmonologist's Contribution to Screen-Detected Nodules: From Diagnosis to Treatment (ID 79)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 6
    • Now Available
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      MS16.01 - Getting to the Target: Transparenchimal Approaches (Now Available) (ID 3530)

      14:30 - 16:00  |  Presenting Author(s): Daniela Gompelmann

      • Abstract
      • Presentation
      • Slides

      Abstract

      The Bronchoscopic Transparenchymal Nodule Access (BTPNA) is a guidance technique that provides to establish tissue diagnosis for peripheral pulmonary nodules. This method differs completely from other guidance techniques as it allows to access nodules via the healthy lung parenchyma and thus is independent on the need to have an airway leading into the lesion [1]. Prior to bronchoscopy, a virtual bronchoscopy navigation system is used that calculates the point of entry (POE) with a straight line, vessel-free access to the lesion and displays the tunnel path from the POE on the airway wall to the target nodule on the basis of the patient´s computed tomography scan. During the endoscopy, the POE is identified under virtual guidance. Then a coring needle is used to penetrate the airway wall and this hole is enlarged by a balloon dilator. Afterwards, a sheath is advanced through the lung parenchyma in order to create a tunnel to the target lesion under fluoroscopic guidance. Once the nodule is achieved, the stylet can be removed and a biopsy forceps is advanced through the sheath in order to sample the lesion. So far, the BTPNA is still investigational and different trials are ongoing to evaluate the diagnostic yield of the BTPNA. Up to date, two prospective trials confirmed the safety and feasibility of the BTPNA in 18 patients with peripheral lesions from suspected lung cancer or metastatic disease [2; 3]. The tunnel path was successfully created in 89% and adequate histological sampling was attained. The only adverse events were pneumothorax in two patients with the need for chest tube insertion in one of them and a transient rise in troponin levels in another patient. In a further prospective trial of BTPNA that was presented on this year´s ATS congress a diagnostic yield of 83.3% was found.

      References:

      [1] Gompelmann D. Upcoming techniques. In: Interventional Pulmonology. Herth, Shah, Gompelmann (eds). ERS monograph 2017.

      [2] Herth FJ, Eberhardt R, Sterman D, Silvestri GA, Hoffmann H, Shah PL. Bronchoscopic transparenchymal nodule access (BTPNA): first in human trial of a novel procedure for sampling solitary pulmonary nodules. Thorax 2015. 70:326-323.

      [3] Harzheim D, Sterman D, Shah PL, Eberhardt R, Herth FJ. Bronchoscopic Transparenchymal Nodule Access: Feasibility and Safety in an Endoscopic Unit. Respiration 2016. 91:302-306.

      [4] Criner G. Bronchoscopic Transparenchymal Access of a Peripheral Pulmonary Nodule. Session D83. ATS 2019.

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      MS16.02 - Robotic Bronchoscopy: Driveless IP? (Now Available) (ID 3531)

      14:30 - 16:00  |  Presenting Author(s): David Fielding

      • Abstract
      • Presentation
      • Slides

      Abstract

      Introduction: Robotic bronchoscopy has been developed in response to challenges which face bronchoscopists in the diagnosis of peripheral pulmonary nodules. Further, such nodules are increasingly presented to bronchoscopists because of CT screening programs, and a general increase in the performance of chest CT in the community with resultant incidental detection of small nodules. Two platforms have undergone preliminary lab evaluations followed by in-human feasibility and safety studies. These are the Auris system and the Intuitive surgical system and the results of these studies are now published (1,2). Both have since had FDA approval and are undergoing post- marketing multicentre studies, the first as the Monarch system, the second as the Ion system.

      The challenges facing bronchoscopists are 1. The small size of nodules, 2. The peripheral nature of the nodules requiring small calibre scopes to reach them, 3. The complex anatomic pathways to reach them, and 4. The position of the nodules in relation to the airway, with many being “extrinsic” to the bronchus, making biopsy sampling difficult.

      Robotic bronchoscopy seeks to answer these challenges by integrating an array of components incorporating small size of the distal scope, excellent manoeuvrability of the distal end of the scope, real time display of CT-derived navigational assistance, and biopsy channel size in the distal end of the scope to allow good quality samples.

      Methods: The robotic aspect of the systems means robotic arms ( 2 with Auris and 1 with Intuitive) drive the scope into the airway under the direction of a physician operated console, as opposed to the hands of a physician holding the scope and advancing and directing the scope. Important in this regard is the system is not “automatic”, meaning the physician is in control of the device at all times, directing the scope into pre-planned airways under direct vision provided by the system. The robotic aspect of the devices means that the driving and directing of the scope are much more precise and not prone to slipping out of airways between biopsy attempts, reducing the need to re-navigate back to a nodule.

      The main difference in the systems relates to the design of the catheter ( Figs 1 and 2). The Auris system has a telescoping end, with a scope extending out of an outer sheath, while the Intuitive scope has a single catheter, within which a removable optic can be removed to allow deployment of biopsy instruments.

      Figure 1: Distal end of the Auris system incorporating a sheath ( light blue) and an inner bronchoscope ( dark blue). The outer sheath(6mm) is wedged in a segmental bronchus, then the inner bronchoscope ( 4.2mm) is advanced to the distal airways.

      Figure 2. The distal catheter tip of the Intuitive system ( outer diameter 3.4mm), showing accompanying shape sensing image which is displayed real time, providing continuous position feedback.

      Results: The Auris study reported 15 patients, and the Intuitive study 29 patients, mean lesion size 26mm ( 1.0-6.3) and 12.2 ± 4.2 mm respectively. Bronchus was sign was absent in all cases with Auris ( predefined) whereas 44% were bronchus sign absent in the Intuitive study. All patients were intubated and the procedure performed under general anaesthesia. Most patients were discharged the same day. Both systems reported no adverse events from the device itself. One SAE was reported in the Intuitive study which was an anaesthetic complication related to use of muscle relaxants from which there were no long term sequelae. Successful navigation to the nodule was made in 14 of 15 and 28 of 29 patients respectively. EBUS Guide sheath confirmation was allowed just before biopsy in the Intuitive study but not the Auris study. The devices allowed multiple samples to be taken quickly; the use of needle sampling was common in the Intuitive study because of the nature of the extrabronchial lesions. Malignancy was confirmed in 7 of 9 cases with the Auris device and 13 of 15 cases with the Intuitive device.

      Conclusions: Robotic bronchoscopy offers unique capability for a proceduralists in combing excellent navigation with thin scopes and stability at the biopsy tip. These early results of sampling difficult nodules need to be followed up in multicentre studies, but suggest a significant potential in dealing with small peripheral nodule biopsy. Further the large size of the biopsy channels and the stability of the tip of the instruments due to the robotics could allow further evaluation of these devices to permit endolumenal therapies for small peripheral lung cancers.

      Rferences:

      1. Rojas-Solano, JR., Ugalde-Gamboa, L, Machuzak M. Robotic Bronchoscopy for Diagnosis of Suspected Lung Cancer: A Feasibility Study. Journal of Bronchology & Interventional Pulmonology25(3):168-175.

      2. Fielding D, Bashirzadeh F, Son JW et al. First human use of a new robotic-assisted fiber optic sensing navigation system for small peripheral pulmonary nodules. Respiration 2018. In press.

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      MS16.03 - Bronchoscopy and Optical Biopsy (Now Available) (ID 3532)

      14:30 - 16:00  |  Presenting Author(s): Lizzy Wijmans

      • Abstract
      • Presentation
      • Slides

      Abstract

      Diagnosing lung cancer in the absence of endobronchial abnormalities is challenging. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic imaging of cells. We assessed the feasibility and safety of using nCLE for real-time identification of lung cancer.

      In patients with suspected or proven lung cancer scheduled for endoscopic ultrasound (EUS), lung tumours and mediastinal lymph nodes were imaged with nCLE before fine-needle aspiration (FNA) was performed. nCLE lung cancer characteristics were identified by comparison with pathology. Multiple blinded raters validated CLE videos of lung tumours and mediastinal nodes twice.

      EUS-nCLE-FNA was performed in 22 patients with suspected or proven lung cancer in whom 27 lesions (six tumours, 21 mediastinal nodes) were evaluated without complications. Three nCLE lung cancer criteria (dark enlarged pleomorphic cells, dark clumps and directional streaming) were identified. The accuracy of nCLE imaging for detecting malignancy was 90% in tumours and 89% in metastatic lymph nodes. Both inter-observer agreement (mean κ=0.68, 95% CI 0.66–0.70) and intra-observer agreement (mean±sd κ=0.70±0.15) were substantial.

      Real-time lung cancer detection by endosonography-guided nCLE was feasible and safe. Lung cancer characteristics were accurately recognised

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      MS16.04 - Bronchoscopic Lung Cancer Ablation (Now Available) (ID 3533)

      14:30 - 16:00  |  Presenting Author(s): Kazuhiro Yasufuku

      • Abstract
      • Presentation
      • Slides

      Abstract

      Lung cancer is the leading cause of cancer mortality in the western world. Around 80% of cases are classified as non-small cell lung cancer (NSCLC). Surgical resection by lobectomy is the standard of care for patients with localized and early stage NSCLC (1). However, patients with comorbidities may not tolerate standard surgery. With the aging population and the wide-spread use of CT scan for lung cancer screening, we are faced with increasing number of patients with early stage lung cancer who are medically inoperable. Currently, stereotactic body radiation therapy (SBRT) is the standard-of-care for treatment of early stage peripheral NSCLC in medically inoperable patients (1). Although SBRT has become a standard option for treatment of peripheral NSCLC, it is still not clear whether the survival rates and recurrence rates are similar to those after standard curative surgical resection. SBRT also has risks such as radiation lung toxicity and therefore it not applicable to all patients as well as limited with location of the tumor (2). Percutaneous thermal ablation typically performed by interventional radiologist is an alternative approach for treatment of medically inoperable patients. Hot therapy such as radiofrequency ablation (RFA) and microwave ablation (MWA) are used for treatment of lung tumors. Cold therapy is also available using the cryotherapy (3). Although thermal therapy has shown good local control rates, complications related to percutaneous ablative approach including pneumothorax, BP fistula, bleeding, needle tract seeding cannot be ignored, since the majority of patients requiring such therapy in general do not have good lung function. A safer approach and therapeutic option for medically inoperable patients with NSCLC is desired.

      Recently we have seen advances in technology that allow bronchoscopists to navigate and approach peripheral lung cancer via transbronchial approach. Development of smaller bronchoscopes allow better manipulation of the scope to reach out to the peripheral lung (4). Navigational bronchoscopy aids bronchoscopist by providing actual pathway to the peripheral nodule (5). The radial probe endobronchial ultrasound (RP-EBUS) allow confirmation of the tumor location during peripheral transbronchial biopsies (6). Combining these bronchoscopic technologies with an ablation catheter that will fit through the channel of the flexible bronchoscope may allow minimally invasive transbronchial ablation of peripheral lung cancer. Fore real-time confirmation of probe positioning during transbronchial ablation, cone-beam CT scan is suitable even during bronchoscopy. The development of such technology is still in its infancy.

      Based on current publications including animal studies and human case studies, possible transbronchial ablative technologies include transbronchial RFA, MWA, cryotherapy, photodynamic therapy (PDT), photothermal therapy (PTT) and thermal vapor ablation (7). Although the evidence is not available yet, multiple clinical trials under way and hopefully these technologies will become available in the future. Details of each modality will be discussed in the presentation.

      Reference

      Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28: 1-21.

      Howington JA, Blum MG, Chang AC, et al. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143: e278S-313S.

      Palussière J, Catena V, Buy X. Percutaneous thermal ablation of lung tumors - Radiofrequency, microwave and cryotherapy: Where are we going? Diagn Interv Imaging. 2017; 98: 619-25.

      Oki M, Saka H, Ando M, et al. Ultrathin Bronchoscopy with Multimodal Devices for Peripheral Pulmonary Lesions. A Randomized Trial. Am J Respir Crit Care Med. 2015; 192(4): 468-76.

      Khandhar SJ, Bowling MR, Flandes J, et al; NAVIGATE Study Investigators. Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study. BMC Pulm Med. 2017 11; 17(1): 59.

      Sabath BF, Casal RF. Bronchoscopic ablation of peripheral lung tumors. J Thorac Dis 2019. doi: 10.21037/jtd.2019.01.65

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      MS16.05 - Optimal Treatment Selection for Screen-Detected Lung Cancers (Now Available) (ID 3534)

      14:30 - 16:00  |  Presenting Author(s): Norihiko Ikeda

      • Abstract
      • Presentation
      • Slides

      Abstract

      In recent years, the number of early stage lung cancers, especially cases showing ground-glass opacity (GGO) has enormously increased mainly due to frequent use of chest CT in routine practice or screening purpose. The surgical approach has enormously changed to pursue both curability and minimal inavasiveness for such early disease. Increased number of VATS lobectomy and sublobar resection for selected patients is the international trend.Conventional bronchoscopic examination for screening detected tiny cancers shows low diagnostic rate therefore the combination of virtual bronchoscopic navigation (VBN) and EBUS guide-sheath has been employed. A total of 40000 lung cancers were resected in Japan in 2015 and 70% of surgeries were performed by video-assisted1). Although there are a few randomized controlled trial, the evidence of VATS lobectomy is supported many propensity-matched studies, several high quality meta-analyses as well as outcome studies2). Segmentectomy has been performed intentionally mainly for lung cancer 2cm or less in diameter. Several comparative studies between lobectomy and segmentectomy for tumors < 2cm showed no significant difference in survival3). Recently, segmentectomy is selected based on the size, location as well as the consolidation size in the primary lesion in preoperative high resolution CT (HRCT). The proportion of consolidation diameter to tumor diameter (C/T ratio) correlates with biological malignancy and the establishment of robust image criteria predicting non-invasive cancer is desirable to find candidates for segmentectomy. The Japan Clinical Oncology Group (JCOG) conducted a prospective cohort study to recognize the relationship between HRCT finding and pathological non-invasiveness (no lymph node metastasis or vessel invasion) in clicical stage IA cancer (JCOG0201)4). This study revealed that adenocarcinoma <2.0 cm with <0.25 consolidation to the maximum tumor diameter showed pathological non-invasiveness in 98.7% and this criterion could be used to as radiological non-invasive adenocarcinoma5). Based on the result of JCOG0201, two prospective studies were performed and finished recruitment, phase II trial of wide wedge resection for radiological non-invasive adenocarcinoma (tumor diameter 2cm or less and consolidation ratio<0.25) (JCOG0804) and randomised phase III trial for radiological invasive adenocarcinoma (tumor diameter 2cm or less and consolidation ratio>0.25) to evaluate non-inferiority in OS of segmentectomy compared to lobectomy (JCOG0802)6). The indication of segmentectomy will be demonstrated by the results of these studies. Although C/T ratio in the maximum plane of the tumor has been applied clinically as an index of malignancy, objective measurement is sometimes difficult due to the irregular shape of objectives. It should be more accurate to analyze the ratio of the consolidation part volume to whole tumor volume quantitatively by creating 3D-CT image. In our analysis of 252 cases of stage I lung cancer, the solid part volume of the tumor had a statistically significant correlation with prognosis7). In addition, PET-CT has been routinely used for the management of lung cancer and another approach to evaluate the biological aggressiveness. The standardized uptake value (SUV) of the main tumor is recognized to be as a predictor of the clinicopathological characteristics. Our data showed that more accurate prognosis of stage IA adenocarcinoma could be predicted by the combination of SUVmax and solid part volume of the primary tumor8). Since CT reflects the histologic grade of the tumor and SUVmax reflects the intratumoral metabolism, the combined use of these may be expected to evaluate nature of lung cancer more precisely than each alone.The information on the grade of malignancy obtained from preoperative images is useful for selecting appropriate treatment. In the near future, radiomics can analyze the radiologic images and extract important pathological and genomic information non-invasively before treatment. Advances in imaging and quantitative analysis will be powerful support to select interventions of screening detected lung cancer.

      References

      1) Committee for Scientific Affairs The Japanese Association for Thoracic Surgery, Thoracic and cardiovascular surgery in Japan during 2015 : Annual report by the Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg.2018;66:581-615.

      2) Ikeda N Updates on minimally inavasive surgery in non-small cell lung cancer. Curr. Treat. In Oncol. 2019;20:16 (DOI 10.1007/s11864-019-0614-9)

      3) Okada M, Koike T, Higashiyama M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg. 2006; 132: 769-775

      4) Suzuki K, Koike T, Asakawa T, et al.: A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-756

      5) Asamura H, Hishida T, Suzuki K, et al. Radiographically determined noninvasive adenocarcinoma of the lung: Survival outcomes of Japan Clinical Oncology Group 0201 J Thorac Cardiovasc Surg 2013;146:24-30

      6) Nakamura K, Saji H, Nakajima R, et.al. A Phase III Randomized Trial of Lobectomy Versus Limited Resection for Small-sized Peripheral Non-small Cell Lung Cancer (JCOG0802/WJOG4607L) Jpn J Clin Oncol 2010;40:271–274

      7) Shimada Y, Furumoto H, Imai K, et al. Prognostic value of tumor solid-part size and solid-part volume in parients with clinical stage I non-small cell lung cancer. J Thorac Dis 2018;10:6491-6500

      8) Furumoto H, Shimada Y, Imai K, et al. Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung. Lung Cancer 2018;121:91-96

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      MS16.06 - Smoking Cessation in a Pulmonary Clinic (Now Available) (ID 3535)

      14:30 - 16:00  |  Presenting Author(s): Pyng Lee

      • Abstract
      • Presentation
      • Slides

      Abstract

      The National Lung Screening Trial (NLST) demonstrated 20% reduction in lung cancer mortality with low-dose computed tomography (LDCT) screening of current and former smokers. While LDCT screening improves patient outcomes, quitting smoking remains the most effective intervention in reducing lung cancer death. Promoting smoking cessation is an essential component of lung cancer screening program. In the US, Medicare mandates tobacco cessation interventions for current smokers to receive reimbursement for LDCT screening. Quitting smoking would improve mortality benefit and cost-effectiveness of LDCT screening. It is estimated that doubling the quit rate in screening-eligible patients would decrease LCDT screening cost by half, and a simulation model has suggested that addition of behavioral cessation intervention to LDCT screening could reduce the cost per QALY by 25%, and by 50% with pharmacologic therapy. While LDCT screening represents a valuable opportunity to deliver smoking cessation interventions, an aggressive two-pronged approach is necessary to increase success with smoking cessation for this patient population. Counseling is essential to motivate patients to quit by identifying potential barriers and obstacles as well as in formulating an individualized quit plan. Counseling on its own is insufficient to tackle physiologic dependence of smoking. I will review the 5As approach (Ask about smoking, Advise to quit, Assess readiness to quit, Assist with tobacco dependence treatment, and Arrange follow-up) as well as available pharmacomtherapies to help patients achieve tobacco abstinence.

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Author of

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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-03 - The Significance of INSM1 Expression in Small Cell Lung Cancer (Now Available) (ID 2132)

      08:00 - 18:00  |  Author(s): Kazuhiro Yasufuku

      • Abstract
      • Slides

      Background

      We previously demonstrated that INSM1 expressed in NE tumors (NETs) exclusively and INSM1 is a highly sensitive and specific immunohistochemical (IHC) marker in NETs, such as small cell lung cancer (SCLC). In the present study, we investigated 1) diagnostic performance of INSM1 in the diagnosis of SCLC in various types of samples 2) the association of INSM1 with clinical course.

      Method

      We evaluated INSM1 as an IHC marker in 384 formalin-fixed paraffin-embedded lung cancer samples (291 surgically resected samples (90 SCLCs and 201 NSCLCs) and 55 CT-guided biopsy samples (25 SCLCs and 30 NSCLCs)), in 50 cytology samples (25 SCLC metastatic lymph nodes and 25 NSCLCs) obtained by endobronchial ultrasound-guided transbronchial needle aspiration. The mRNA expression levels of INSM1 was examined using qRT-PCR in 37 SCLCs and 40 NSCLCs. We evaluated the association of INSM1 expression (IHC and qRT-PCR data) with clinical course.

      Result

      INSM1 was expressed in 94% of formalin-fixed paraffin-embedded SCLC samples (109/115) and in 92% of cytology SCLC samples (23/25). Whereas, 4 out of 231 formalin-fixed paraffin-embedded NSCLC cases (1.7%) had weak expression of INSM1 and none of the cytology NSCLC samples were positive. The mRNA level of INSM1 was significantly higher in SCLCs including in two cases who were INSM1 negative with IHC. No association between IHC positivity and mRNA expression level of INSM1 with evaluated clinical features including overall survival was observed.

      Conclusion

      Our study suggests INSM1 is a reliable IHC marker for SCLC in various types of clinical samples. There was no association between INSM1 and clinical courses in the present study.

      図1.jpg

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    MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
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      MA18.07 - Identification of Neuroendocrine Transformation in Anaplastic Lymphoma Kinase Rearranged (ALK+) Tumors After Tyrosine Kinase Inhibitors (Now Available) (ID 1137)

      11:30 - 13:00  |  Author(s): Kazuhiro Yasufuku

      • Abstract
      • Presentation
      • Slides

      Background

      Acquired resistance after ALK tyrosine kinase inhibitors treatment has multiple known mechanisms: new mutations or gene amplifications, bypass signaling and rarely neuroendocrine histological transformation. Here we describe results of a program utilizing routine biopsy post-progression in ALK+ patients for clinical and research purposes.

      Method

      Since 2014, ALK+ lung cancer patients treated at the Princess Margaret Cancer Centre have undergone routine biopsies at disease progression time points upon failure of an ALK-tyrosine kinase inhibitor (TKI) for both clinical purposes and research purposes, in particular to obtain tissue for primary derived xenograft (PDX) engraftment.

      Result

      All 9/9 patients consented for research sampling during clinical biopsy procedures (median 2 extra cores/passes); 2 patients were biopsied more than once; 3 PDX models from 2 patients have engrafted; 3 additional models are too early to assess engraftment. Engraftment occurred in patients with clinically aggressive tumors and poor survival outcomes. In this process, we identified 2 patients with neuroendocrine transformation post-second generation ALK TKI: (a) a 59 yo Asian female, never smoker, diagnosed six years prior with metastatic disease, heavily pretreated with crizotinib (12 months), pemetrexed (16 months), ceritinib (25 months), alectinib (6 months) and brigatinib (3 months); post-alectinib biopsy showed no transformation, while post-brigatinib liver biopsy demonstrated transformation to large cell neuroendocrine carcinoma; (b) a 75 yo Caucasian female, never smoker, diagnosed eight months prior and started on alectinib with a partial response, progressed in a single site; endobronchial biopsy demonstrated high grade neuroendocrine transformation. Both biopsies were positive for neuroendocrine markers (chromogranin and synaptophysin), TTF-1 and diffusely co-expressed ALK on immunohistochemistry. Assessment of PDX engraftment of these models is ongoing.

      Conclusion

      Routine combined clinical and research biopsy of ALK+ patients at time of TKI failure helped to identify these recent cases of neuroendocrine transformation as a possible mode of resistance and provide tissue for model development. This is the first time that ALK+ transformation to large cell neuroendocrine carcinoma is reported in the literature. (PP, AFF, SNMF, LN contributed equally).

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    MS16 - The Interventional Pulmonologist's Contribution to Screen-Detected Nodules: From Diagnosis to Treatment (ID 79)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 1
    • Now Available
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      MS16.04 - Bronchoscopic Lung Cancer Ablation (Now Available) (ID 3533)

      14:30 - 16:00  |  Presenting Author(s): Kazuhiro Yasufuku

      • Abstract
      • Presentation
      • Slides

      Abstract

      Lung cancer is the leading cause of cancer mortality in the western world. Around 80% of cases are classified as non-small cell lung cancer (NSCLC). Surgical resection by lobectomy is the standard of care for patients with localized and early stage NSCLC (1). However, patients with comorbidities may not tolerate standard surgery. With the aging population and the wide-spread use of CT scan for lung cancer screening, we are faced with increasing number of patients with early stage lung cancer who are medically inoperable. Currently, stereotactic body radiation therapy (SBRT) is the standard-of-care for treatment of early stage peripheral NSCLC in medically inoperable patients (1). Although SBRT has become a standard option for treatment of peripheral NSCLC, it is still not clear whether the survival rates and recurrence rates are similar to those after standard curative surgical resection. SBRT also has risks such as radiation lung toxicity and therefore it not applicable to all patients as well as limited with location of the tumor (2). Percutaneous thermal ablation typically performed by interventional radiologist is an alternative approach for treatment of medically inoperable patients. Hot therapy such as radiofrequency ablation (RFA) and microwave ablation (MWA) are used for treatment of lung tumors. Cold therapy is also available using the cryotherapy (3). Although thermal therapy has shown good local control rates, complications related to percutaneous ablative approach including pneumothorax, BP fistula, bleeding, needle tract seeding cannot be ignored, since the majority of patients requiring such therapy in general do not have good lung function. A safer approach and therapeutic option for medically inoperable patients with NSCLC is desired.

      Recently we have seen advances in technology that allow bronchoscopists to navigate and approach peripheral lung cancer via transbronchial approach. Development of smaller bronchoscopes allow better manipulation of the scope to reach out to the peripheral lung (4). Navigational bronchoscopy aids bronchoscopist by providing actual pathway to the peripheral nodule (5). The radial probe endobronchial ultrasound (RP-EBUS) allow confirmation of the tumor location during peripheral transbronchial biopsies (6). Combining these bronchoscopic technologies with an ablation catheter that will fit through the channel of the flexible bronchoscope may allow minimally invasive transbronchial ablation of peripheral lung cancer. Fore real-time confirmation of probe positioning during transbronchial ablation, cone-beam CT scan is suitable even during bronchoscopy. The development of such technology is still in its infancy.

      Based on current publications including animal studies and human case studies, possible transbronchial ablative technologies include transbronchial RFA, MWA, cryotherapy, photodynamic therapy (PDT), photothermal therapy (PTT) and thermal vapor ablation (7). Although the evidence is not available yet, multiple clinical trials under way and hopefully these technologies will become available in the future. Details of each modality will be discussed in the presentation.

      Reference

      Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28: 1-21.

      Howington JA, Blum MG, Chang AC, et al. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143: e278S-313S.

      Palussière J, Catena V, Buy X. Percutaneous thermal ablation of lung tumors - Radiofrequency, microwave and cryotherapy: Where are we going? Diagn Interv Imaging. 2017; 98: 619-25.

      Oki M, Saka H, Ando M, et al. Ultrathin Bronchoscopy with Multimodal Devices for Peripheral Pulmonary Lesions. A Randomized Trial. Am J Respir Crit Care Med. 2015; 192(4): 468-76.

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    OA01 - Advanced Diagnostic Approaches for Intrathoracic Lymph Nodes and Peripheral Lung Tumors (ID 117)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 1
    • Now Available
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      OA01.02 - Endobronchial Ultrasound Staging of Operable NSCLC: Triple Negative Lymph Nodes May Not Require Routine Biopsy (Now Available) (ID 2621)

      10:30 - 12:00  |  Author(s): Kazuhiro Yasufuku

      • Abstract
      • Presentation
      • Slides

      Background

      Current staging guidelines with endobronchial ultrasound (EBUS) still recommend systematic biopsy of at least 3 mediastinal stations prior to surgical resection. Recently, a 4-point ultrasonographic score (Canada Lymph Node Score- CLNS) was developed to determine the probability of nodal metastasis in any given lymph node. A LN with CLNS<2 is considered very low probability for malignancy. We hypothesized that, during EBUS assessment of patients with cN0 non-small cell lung cancer, individual nodal stations that have CLNS<2 do not require routine biopsy because they are likely to represent true pN0 disease.

      iaslc 2019 - clns lymph node figure.png

      Method

      The CLNS is a prospectively validated score that uses four ultrasonographic features to accurately predict LN malignancy. LNs were evaluated for ultrasonographic features at the time of EBUS and the CLNS was applied. “Triple Negative” LNs were defined as cN0 on CT (LN≤1cm), PET (no hypermetabolic activity) and EBUS (CLNS<2). Specificity, NPV, and false-negative rates were calculated against the gold-standard pathological diagnosis from surgically excised specimens.

      Result

      In total, 122 LNs in 58 cN0 patients were assessed. Triple Negative LNs were associated with the following T-stage distribution (T1a=12.07%, T1b=24.14%, T2a=34.38%, T2b=10.34%, T3=17.24%, T4=1.72%). Triple Negative LNs had a specificity, NPV, and false-negative rate of 86.10% (95%CI: 78.40-91.80%), 93.40% (95%CI: 86.90-97.30%), and 6.60%, respectively when using <2 as the CLNS malignancy cut-off. In total, only 5.74%(n=7) Triple Negative nodes were actually proven to be malignant, 6/7 (85.71%) on EBUS-TBNA, and 1/7 (14.29%) only after surgical resection.

      Conclusion

      Triple Negative LNs have a high NPV for malignancy. At the time of EBUS in cN0 patients, it may be possible that Triple Negative LNs do not require tissue sampling, thereby saving procedural time, cost, and discomfort. Findings also suggest that Triple Negative LNs with inconclusive biopsy results may not require repeat sampling. A prospective comparative trial is required to confirm these findings.

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