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Norihiko Ikeda
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ES 05 - Surgical Skills (ID 514)
- Event: WCLC 2017
- Type: Educational Session
- Track: Surgery
- Presentations: 1
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ES 05.03 - Management of Early Stage Lung Cancer (ID 7601)
16:15 - 16:30 | Presenting Author(s): Norihiko Ikeda
- Abstract
- Presentation
Abstract:
In recent years, the number of early stage lung cancers has enormously increased mainly due to frequent use of chest CT in routine practice or screening purpose. Both curability and non-inavasiveness are required especially for such early disease. Increased number of VATS lobectomy and sublobar resection for selected patients is the international trend in such situation. Diagnosis: Retrospective data revealed that the sensitivity of conventional bronchoscopic examination for peripheral cancer < 2cm is only 34%. The combination of Virtual bronchoscopic navigation and EBUS guide-sheath has demonstrated the improved sensitivity, thus this new combination strategy should be necessary for differential diagnosis of small cancers detected by chest CT[1)]. Surgical procedure: A total of 38000 lung cancers were resected in Japan in 2013 and 70% of surgeries were video-assisted[2)]. 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 survival[3)]. Recently, segmentectomy is selected based on the size and high resolution CT (HRCT) findings of the tumor. The proportion of consolidation diameter to tumor diameter 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 study to recognize the relationship between HRCT finding and pathological non-invasiveness 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 predict early lung cancer preoperatively[5)]. 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 consolidationratio<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. Clinical research: PET-CT has been routinely used for clinical staging and the standardized uptake value (SUV) of the main tumor is recognized to be as a predictor of the clinicopathological characteristics and prognosis. Analyses of 610 resected stage IA adecocarcinoma showed that maxSUV and GGO ratio cutoffs to predict recurrence were 2.9 and 25%, respectively. They were also related to nodal metastasis, histological tumor invasiveness and recurrence. The 5-year RFS of cases with maxSUV <2.9 (n=456) was 95%, while cases with maxSUV>2.9 (n=154), 72% (p<0.001)[7)]. Our result showed that maxSUV cutoff of possibility for recurrence was 2.6 in adenocarcinoma, which was also related to nodal metastasis and histological tumor invasiveness. The 3-year relapse-free survival was 99%/78% (maxSUV lower/higher than 2.6) and following multivariate analysis, pathological nodal status and SUVmax were found to be independent predictive factors for relapse-free survival. Surgical management of early stage lung cancer should be selected based on the tumor size and consolidation ratio on HRCT. The results of RCTs will demonstrate the indication of sublobar resection in near future. Further analysis is encouraged for the evaluation of biological aggressiveness in each case[8)]. References Asano F, Shinagawa N, Ishida T, et al. Virtual bronchoscopic navigation combined with ultrathin bronchoscopy. A randomized clinical trial. Am J Respir Crit Care Med 2013; 188:327-333 Committee for Scientific Affairs The Japanese Association for Thoracic Surgery, Thoracic and cardiovascular surgery in Japan during 2013 : Annual report by the Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg.2015;63:670-701. 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 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 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 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 Uehara H, Tsutani Y, Okumura S, et al. Prognostic Role of Positron Emission Tomographyand High-Resolution Computed Tomography in Clinical Stage IA Lung Adenocarcinoma Ann Thorac Surg 2013;96:1958–1965 Tsutani Y, Miyata Y, Nakayama H,et al.. Sublobar resection for lung adenocarcinoma meeting node-negative criteria on preoperative imaging. The Annals of thoracic surgery. 2014;97:1701-1707
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MA 15 - Lung Cancer Biology II (ID 670)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
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MA 15.13 - The Transfer of Exogenous UCHL-1 via Mesenchymal Lung Cancer Exosomes to Mediate Phenotypic Alterations of Recipients (ID 9094)
17:05 - 17:10 | Author(s): Norihiko Ikeda
- Abstract
- Presentation
Background:
Cancer-derived exosomes are micro-vesicles released by tumor cells and are believed to be involved in intercellular signaling and communication. Recent evidence suggests exosomes help tumor cells invade neighboring tissues and prime metastatic sites for disease spread. Non-small cell lung cancer (NSCLC) is a highly metastatic disease and little is known about how tumor-derived exosomes may influence migration or invasion of lung cancer cells and prime metastatic niches.
Method:
Exosomes were recovered by a sequential centrifugation schema. Exosomes isolated from lung cancer cell line H1299, A549, H1993, and H2073, and non-malignant, immortalized human bronchial epithelial cell (HBEC) 3KT and 30KT were characterized. We examined the effects of cancer-derived exosomes on HBECs, oncogenically progressed HBECs (HBEC sh-p53+KRAS[v12]; HBEC3KTRL53) in vitro and their influence on metastasis in murine models. Mass spectrometry was performed to identify candidate proteins carried in tumor exosomes that induce phenotypic changes in recipient cells.
Result:
Cancer-derived exosomes but not HBEC-derived exosomes confer invasiveness and increased motility on recipient cells (HBEC3KT, HBEC3KTRL53) in wound healing and Boyden chamber assays. Mesenchymal NSCLC exosomes induce mesenchymal-like phenotypic changes (loss of EPCAM expression and upregulated EMT-transcriptional factors) in HBEC3KT in FACS and qRT-PCR analyses. Cancer-derived exosomes but not HBEC3KT exosomes enhance the lung endothelial permeability, promote lung metastasis, and recruit myeloid-derived suppressor cells in vivo. Mass spectrometry shows that H1299 exosomes contains a wide variety of deubiquitinating enzymes (DUBs) compared to HBEC3KT exosomes, and UCHL-1 (Ubiquitin carboxy-terminal hydrolase L1) is the most highly expressed DUB in H1299 exosomes. UCHL-1 expression is upregulated in mesenchymal NSCLC cells/exosomes, and HBEC3KT cells treated with mesenchymal NSCLC exosomes in vitro, and activated in metastatic sites after cancer-derived exosome treatment in vivo. UCHL-1 knockdown suppresses metastasis induced by cancer-derived exosomes. Exosomes derived from UCHL-1-knockdown H1299 show a decreased effect of the induction of migration, invasiveness, and epithelial/mesenchymal phenotypic changes on recipient cells.
Conclusion:
Mesenchymal NSCLCs-derived exosomes compared to HBECs-derived exosomes induced an increased migratory/invasive phenotype with lung vascular leakiness, metastatic niche formation, and higher xenograft tumor take rates. UHCL-1 was overexpressed only in mesenchymal NSCLCs/exosomes. UCHL-1 knockdown suppressed metastasis, and its exosomes also showed a decreased effect of the induction of tumor progression. These results suggest that understanding and targeting UCHL-1 likely as a key factor of mesenchymal NSCLC-derived exosome behavior could lead to novel therapeutic strategies.
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OA 06 - Global Tobacco Control and Epidemiology I (ID 662)
- Event: WCLC 2017
- Type: Oral
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 1
- Moderators:G. Kovács, Yun Fan
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 511 + 512
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OA 06.09 - Discussant - OA 06.05, OA 06.06, OA 06.07, OA 06.08 (ID 10788)
17:10 - 17:25 | Presenting Author(s): Norihiko Ikeda
- Abstract
- Presentation
Abstract not provided
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-041 - Role of Re-Biopsy During Disease Progression Non-Small Cell Lung Cancer for Acquired Resistance Analysis and Directing Oncology Treatments (ID 10340)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
It is not possible to properly target treatments in cases of relapse without knowing the nature of new lesions. Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can overcome T790M-mediated resistance in non-small-cell lung cancer (NSCLC). But the re-biopsy to confirm T790M status is occasionally difficult. In Japan, transbronchial lung tissue biopsy (TBLB / TBB) is the most common sampling method used for re-biopsy to confirm patients eligible for treatment. We aimed to investigate the success rate of re-biopsy and re-biopsy status of patients with advanced or metastatic NSCLC completing either 1st line chemotherapy or EGFR-TKI therapy.
Method:
We initially screened 39 consecutive patients with NSCLC harboring EGFR-sensitive mutations who had experienced PD after any chemotherapy at Tokyo Medical University Hospital January 2014 and December 2016.
Result:
38 patients who had experienced PD after EGFR-TKI treatment were eligible. Among 30 patients, tumor progression sites included 3 pleural effusion, 9 thoracic primary/metastatic lesions, 2 hepatic metastases, 15 lymph node metastases. Of the 38 patients, 47.3% underwent rebiopsy sucessfully. Of the 38 biopsied patients, 18 (47.3%) were analyzed for EGFR mutation, using tissue or cytology samples; T790M mutations were identified in 10 (55%) of the 18 patients. Of the 38 biopsied patients, 18 (47.3%) were analyzed for EGFR mutation, using tissue or cytology samples; T790M mutations were identified in 10 (55%) of the 18 patients.
Conclusion:
Most re-biopsy samples were diagnosed with malignancy. T790M mutations were identified as much as same in previous studies. However, tissue samples were less available in previous studies. Skill and experience with re-biopsy and noninvasive alternative methods will be increasingly important.
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-025 - A Case of Primary Peripheral Epithelial–Myoepithelial Carcinoma of the Lung (ID 8384)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Primary epithelial-myoepithelial carcinoma (EMC) of the lung is extremely rare carcinoma of salivary type lung cancer. Only 16 cases were reported for peripheral pulmonary EMC in literatures in the world, at present.
Method:
We report a resected case of primary peripheral EMC of the lung existed in right S2 with considerations of literature.
Result:
The patient was 63-year old male, received medical check-up at nearby clinic and an abnormal shadow was pointed out on chest X-ray film. He was referred to our hospital for more detailed examinations and therapy. He had no past history, symptoms nor abnormal physical findings. Chest CT scan showed a 56 x 24 mm mass in right S2. Transbronchial lung biopsy (TBLB) was performed and the tumor was diagnosed as adenoid cystic carcinoma. There was no metastasis to other organs in detailed examinations. Right upper lobectomy and lymph node dissection (ND2a-2) was performed. He was discharged our hospital at 8 post operative days with no post-operative complications. Macroscopically the tumor was 32x30x22 mm in size, white-colored, homogeneous, and well-defined surrounding pulmonary substance. Microscopically the tumor was composed of double tubular layers. Inner tubular layer showed epithelial cell characteristics, whereas the outer layer showed myoepithelial cell characteristics. Immunohistochemical examinations revealed positive for cytokeratin AE1/3 at inner tubular layer, and positive for SMA, p63, and calponin at outer tubular layer. Finally, the diagnosis of the tumor was determined as peripheral pulmonary EMC. There were no metastases in dissected lymph nodes. Epidermal growth factor receptor (EGFR) was wild type and anaplastic lymphoma kinase (ALK) was negative. Pathological stage was IB because of T2aN0M0. He was followed up with no adjuvant therapy, and disease free for 2 years after operation.
Conclusion:
Primary salivary gland type tumors of the lung are rare. Among them, primary peripheral EMC is extremely rare. Differential diagnoses of pulmonary EMC include mucoepidermoid carcinoma, adenoid cystic carcinoma, pleomorphic adenoma and so on. There is a possibility of misdiagnosis in small specimens. EMC of the lung is regarded as a low-grade malignant neoplasm. For diagnosis of EMC, it is necessary to obtain large specimen and/or resect by operation. In this paper, we report a completely resected case of primary peripheral EMC. It is thought that a biological characteristic of EMC will be elucidated by the further accumulation of EMC case.
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-012 - Prediction Sensitivity of PD-1 Checkpoint Blockade Using Pathological Tissues Specimens by Novel Computerized Analysis System (ID 8851)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Recent development of immune checkpoint blockade such as anti-PD-1 antibody brought great benefits to non-small cell lung cancer (NSCLC) patients. However, some population of NSCLC showed resistance and pseudo-progressions against anti-PD-1 checkpoint blockade. Thus, it is very important for developing biomarkers which predict of efficacy of PD-1 checkpoint blockade. In this background, we developed novel digital pathology system that predict for response to anti-PD-1 checkpoint blockade using H&E staining sections and technology of AI.
Method:
In this study, we extract 361 ROIs(Region of Interest) and 254,205 nuclei were measured from NSCLC cases that treated with anti-PD-1 antibody. We used ilastik for nuclei image segmentation, CellProfiler and our CFLCM tool for features measurement, 992 features are evaluated for each ROI. At first, we analyzed by step-wise discriminant analysis for select the effective features, and using canonical discriminant analysis and SVM (Support vector Machine) RBF kernel model discrimination, we analyzed morphological data based PD-1 blockade response on statistical platform R.
Result:
Except undeterminable cases, we got the more than 95% accuracy level discrimination results. The mapping the discriminant scores, SD cases were mapped in the middle of PR and PD. Only using the average and standard deviation of ROIs’ nuclei shape features (size, roundness, perimeter, etc.) and inside nuclei features (mainly chromatin texture) more than 90% discrimination results were obtained. This means the nuclei morphological data is more important than CFLCM (pleomorphism and heterogeneity measurement data). We challenged the prediction for undeterminable cases by using canonical discriminant and SVM.
Conclusion:
This time analysis is small number samples, so the results application robustness may be limited. But our results show the possibility for clinical response prediction even on the pre-treatment pathological tissues specimens.
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P1.13 - Radiology/Staging/Screening (ID 699)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.13-011a - Stratification Based on PET/CT Findings for Malignant Grade of Radiologically Pure Solid Small-Sized (≪ 2cm) Lung Cancer (ID 9372)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Radiologically pure solid tumors are heterogeneity because of including various histological type, however, small-sized tumors are difficult to be preoperatively diagnosed histology. The aim of this study was to identify preoperative predictors for pathological malignant of pure solid lung cancer in clinical early stage.
Method:
The data from a multi-center database of 220 patients who underwent anatomical resection for radiologically pure solid, tumor size 2 cm or less, and clinical N0 lung cancer were retrospectively analysed. Factors affecting survival were assessed using Cox regression analysis. Predictors were found by drawing the receiver operating characteristic curves (ROC) and evaluated the possible cutoff value for independent prognostic factor.
Result:
Pure solid tumors included 164 (74%) adenocarcinoma, 33 (15%) squamous cell carcinoma, 16 (7%) neuroendocrine tumor, 5 (2%) pleomorphic carcinoma, and 3 (1%) adenosquamous cell carcinoma. In multivariate analyses, high malignant grade histology such as micropapillary and solid predominant adenocarcinoma, adenosquamous cell carcinoma, neuroendocrine tumor, or pleomorphic carcinoma and pathological lymph node metastasis were an independent prognostic factors for recurrence-free survival. The ROC showed that 3.55 in maximum standardized uptake value (SUV max) was cut-off value for detecting high malignant grade histology or lymph node metastasis (area under the curve, 0.71; 95% confidence interval, 0.63 – 0.78). Tumors with SUV max ≥ 3.55 had significantly more high-grade histology, the presence of lymphatic and vascular invasion, and lymph node metastasis and poorer recurrence-free survival rate than SUV max < 3.55 (Figure). Figure 1
Conclusion:
The prognosis of radiologically pure solid tumor with small size and clinical N0 lung cancer was stratified according to SUV max. SUV max could evaluate pathological malignant grade and help the decision of appropriate surgical procedure.
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P1.16 - Surgery (ID 702)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.16-010 - Development of a Novel Surgical Marking Method Using Low Power Laser Light (ID 8992)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Small lung nodules which appear to be ground glass opacity in peripheral lung are difficult to identify during surgery. In order to identify the site of such lesions, various types of preoperative or intraoperative marking methods have been reported. However all of them have advantages and disadvantages, so there is no definitive way. Therefore, we developed a new safe and reliable intraoperative marking method using a thin laser fiber. This is a method to confirm a low power laser light from lung surface irradiated from a small diameter laser fiber inserted into or close to the lesion transbronchoscopically using a navigation system. In this study, we conducted an animal experiment to confirm whether the laser light can actually be observed safely from lung surface.
Method:
Bronchoscopy was performed to a hybrid dog under general anesthesia. A plastic laser probe was inserted into a peripheral bronchus from the biopsy channel of the bronchoscope. The plastic laser probe was a very thin (0.8 mm diameter) and flexible cylindrical-type probe. Therefore, it can be inserted into the peripheral lung. It was developed jointly with Keio University. The probe was induced just below the pleura and 50 mW low power laser irradiation was performed. We examined whether laser light could be confirmed from lung surface under thoracotomy. We also examined the difference in appearance from direct-type laser irradiation.
Result:
When the probe was guided to just below the pleura, laser light could be clearly observed from the lung surface. After that, the probe was gradually withdrawn. The laser light could be observed until the depth of 2.0 cm from the pleura. Moreover, laser irradiation was able to be performed safely without any damage around the laser irradiated area. The laser light was observed consistent with laser irradiation site by the cylindrical probe. On the other hands, it was observed on the pleura ahead of laser irradiation by the direct-type probe. Therefore, it is suggested that cylindrical probe might indicate the target area more accuracy.
Conclusion:
It might be possible to confirm the localization of small nodules in peripheral lung using low power laser light during surgery.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-009 - Metabolomic Analysis in Lung Cancer (ID 8521)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Metabolomics measures low weight molecules, generally called metabolites, and it is an effective technique to understand how metabolism is changed by various factors, including environment and disease, particularly malignant disease. Body fluids, for example sputum or urine, harvested non-invasively havebeen used in remarkable recent developments of omics analysis technology, yielding highly precise results for diagnosis of oral cancer, breast cancer, and pancreatic cancer. Metabolomic analysis has begun to be reported based on the pattern information of metabolites. It can be used for practical clinical early detection of carcinoma of various organs. However, practical metabolomic analysis regarding lung cancer has not been repored yet. We used surgically resected specimen of lung cancer to analyze and clarify metabolomics as an aspect of lung cancer.
Method:
We obtained resected specimens from patients with lung cancer after obtaining informed consent for this study, and compared the metabolism profile of the normal tissue portion with carcinoma tissue in 80 patients in terms of various clinical aspects. Metabolomic analysis was performed by capillary electrophoresis / time-of-flight mass spectrometry (CE-TOFMS) of metabolites of the lung tissue and analysed ionized tissue which contained the most main metabolites.
Result:
Analysis of serum and metabolite organization by CE-TOFMS revealed that the intermediate metabolite levels of several pathways changed markedly in lung cancer tissue. We can identify a characteristic metabolic marker in advanced lung cancer tissue with metabolomic clinical information by analysing the association with the overall metabolism profile.
Conclusion:
We identified metabolomic biomarkers which were characteristic of lung cancer using resected tissue in this study. At present, we are analysing various body fluids for analysis of lung cancer cases including prognostic implications. Applications to non-invasive, simple, easy and cheap cancer screening are expected in the future.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-019 - Sizing Capillary Electrophoresis with PCR to Detect Various EGFR Exon 19 Deletions in Non-Small Cell Lung Cancer (ID 8614)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
This study points out an issue of PCR-based methods to detect exon 19 deletions. PCR methods are used for clinical examination, because they are useful, rapid and cost-effective to detect EGFR mutations. Exon 19 deletions are most important among EGFR mutations to dictate EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy in non-small cell lung cancer (NSCLC), and have various species. The sensitive PCR methods select major exon 19 deletions, but cannot detect unusual variants. We investigated the clinical significance of minority exon 19 deletions.
Method:
A series of 73 NSCLC patients, which were treated with EGFR-TKI for recurrent disease after they had undergone surgery from 1992 to 2004. In all cases, Microdissenction and direct sequence were performed. Scorpion Amplification Refractory Mutation System (ARMS) and cobas version 2.0, as sensitive PCR methods, were performed in 47 patients along with sizing capillary electrophoresis for the exhaustive detection of exon 19 deletions.
Result:
EGFR mutations were detected from 35 patients (47.9%), which were one exon 18 mutation, 23 exon 19 deletions, and 11 exon 21 mutations in all 73 cases. The catalog of somatic mutation in cancer (COSMIC) database included 174 different exon 19 deletions in 4190 submitted cases at December 2014. E746_A750 deletion was most common deletion of exon 19, accounting for 70% of the total exon 19 deletions (2931/4190). Predicted frequency of exon 19 tested by Scorpion-ARMS was 81.6% (3419/4190), and that of cobas version 2.0 had 82.5% (3457/4190) in the detection of various exon 19 deletions. In clinical samples of this study, Scorpion-ARMS and cobas version 2.0 failed to detect four exon 19 deletions, in two squamous cell carcinomas (EGFR-TKI effects were stable disease and no assessable patient) and two papillary adenocarcinomas (EGFR-TKI effects were stable disease and no assessable patient). One of papillary adenocarcinoma had minority deletion ‘T751_I759 deletion and insertion S’, which had long stable disease for 43.4 months in EGFR-TKI therapy. Sizing capillary electrophoresis was able to detect this deletion.
Conclusion:
This study suggests sizing capillary electrophoresis is necessary for the exhaustive detection of exon 19 deletions, and may identify tumors responsive to EGFR-TKIs therapy, especially those with unusual deletions.
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P2.05 - Early Stage NSCLC (ID 706)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.05-012 - Prognostic Factors for Surgically Resected Non-Small Cell Lung Cancer with Cavity Formation (ID 8763)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Small pulmonary nodules have been detected frequently by computed tomography (CT). Lung cancers with cavity formation are also easily detected. There are a few reports focused on the cavity wall, although cancer cells exist along the cavity wall, not inside. We evaluated the impact of cavity wall thickness on prognosis and assessed the clinicopathological features in non-small cell lung cancer (NSCLC) with cavity formation.
Method:
Between 2005 and 2011, 1313 patients underwent complete resection for NSCLC. Of these cases, we reviewed 65 patients (5.0%) diagnosed with NSCLC with cavity formation by chest CT. We classified the patients into three groups based on the maximum cavity wall thickness, namely, ≤ 4 mm (Group 1, 8 patients), > 4 mm and ≤ 15 mm (Group 2, 33 patients), and > 15 mm (Group 3, 24 patients).
Result:
The number of patients with pathological whole tumor size > 3 cm was 2 (25%) in Group 1, 17 (52%) in Group 2, and 23 (96%) in Group 3 (p < 0.001). Cases with lymph node metastasis were 0 (0%) in Group 1, 5 (15%) in Group 2, and 10 (42%) in Group 3 (p = 0.016). The 5-year overall survival (OS) rates were 100% in Group 1, 84.0% in Group 2, and 52.0% in Group 3, with significant differences between Group 1 and Group 3 (p = 0.044) and between Group 2 and Group 3 (p = 0.034). In univariate analysis, neither whole tumor size nor lymph node metastasis was a prognostic factor for OS (p = 0.505, p = 0.274). Only cavity wall thickness was a significant prognostic factor by multivariate analysis (p = 0.009).Figure 1
Conclusion:
Maximum cavity wall thickness was an important prognostic factor in NSCLCs with cavity formation, comparable with other established prognostic factors.
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P2.16 - Surgery (ID 717)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.16-012 - Does Percutaneous Ultrasound Predict Tumor Site and Internal Tumor Properties? (ID 9493)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
The lung contains a large volume of air and have thus been unsuitable for observation with ultrasound. However, recent advancements in ultrasound have enabled the diagnosis of pneumothorax and tumor invasion of the chest wall, and fine-needle aspiration of tumors abutting the pleura can now be performed using ultrasound. Here, we investigated whether ultrasound is capable of predicting internal tumor properties.
Method:
TOSHIBA aplio 400 was used. Of 64 patients with tumor lesions undergoing preoperative ultrasound at our hospital between June 2015 and April 2017, we investigated 42 patients in whom internal tumor properties were visualized before surgery. There were 27 men and 15 women; 37 patients had malignant and 5 had benign lung tumors. Solid components were present in the tumor in 25 patients, liquid components in 3, a cavernous lesion in 9, a ground-glass opacity (GGO) lesion in 4, and pulmonary sequestration in 1. The tumor diameters ranged from 0.7 to 10.4 cm (median, 2.4 cm), and the distances from the lung surface ranged from 0 to 8.9 cm (median, 0.57 cm).
Result:
Ultrasound was useful for identifying an anomalous vessel originating from the aorta in a case with pulmonary sequestration. According to internal tumor properties, lesions containing a large volume of air (cavernous or GGO lesions) were visualized as hyperechoic areas, while many solid lesions appeared hypoechoic with a hyperechoic periphery on images. The posterior echo was enhanced in tumors containing liquid components and also in many cases with benign tumors. Thus, ultrasound is potentially useful for determining whether tumors are malignant or benign before surgery.
Conclusion:
Although ultrasound was not capable of visualizing the internal tumor structures in all cases, the internal tumor structure, if visualized by ultrasound, could be assessed. Moreover, ultrasound has the potential for differentiating benign from malignant tumors. Our results suggest that ultrasound merits future study, with further accumulation of cases.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-012 - Liquid Based Cytology (LBC) Specimens Were Useful for EGFR Mutation Test (ID 10305)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Reliable EGFR mutation testing techniques are required to identify eligible patients for EGFR-TKI treatment. Nowadays, surgically resected tissues or biopsy specimens are mainly used for the molecular testing. However, the biopsy samples sometimes have a certain limitation and so the cytology specimens are chosen for EGFR testing instead. Plasma sample has also become an option in EGFR-TKI resistant cases in which often have difficulties to obtain the inadequate tumor yield. In this study, we evaluated the feasibilities of using cytology samples and plasma specimens the EGFR molecular testing.
Method:
Cytology samples were obtained from biopsy and cells were suspended into liquid-based cytology (LBC) media. Tumor contents in the samples were confirmed with Papanicolaou stained slides. Plasma samples were also collected from patients shortly before the tissue biopsy. EGFR mutations in these samples were analyzed by cobas EGFR Mutation Test v2. Also, EGFR testing result of tissue specimens of the patients corresponded were collected from the medical records measured by cobas EGFR Mutation Test v2 as references.The feasibilities of both cytology and plasma specimen were evaluated comparing the results with the tissue samples.
Result:EGFR mutation rate of tissue, plasma and LBC
One-hundred seven patients were registered to this study. 60 patients were enrolled to this study. EGFR mutation rates in tissue, cytology, and plasma were 30.0, 23.3 and 15.0 %, respectively. Concordance analysis was performed comparing cytology specimens and plasma specimens to the tissue samples. Overall concordance EGFR mutation status was 85.0 and 81.7%, respectively. A total 7 cytology specimens had discordances and 3 were invalid results. For plasma samples, discordants were found in11 samples but no invalids.Tissue Plasma LBC EGFR mutation + 18 9 14 EGFR mutation - 42 51 43 Invalid 0 0 3 Total 60 60 60 Positive rate (%) 30.0 15.0 23.3
Conclusion:
Plasma was easy to obtain sample, but rate of detection was low. If a cancer cell is detected enough, LBC is useful for the examination for EGFR. Preservation of sample is easy, and re-useful for the examination, repeatedly.
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-003 - Analysis of Dendritic Cell Derived Exosomes That Suppressed Tumor Growth (ID 8062)
09:30 - 09:30 | Author(s): Norihiko Ikeda
- Abstract
Background:
Because dendritic cells (DCs) play a key role in immune reactions to activate T cells against cancer cells by cancer antigen presentation at cellular membrane, DCs have been used in clinical trials as cellular mediators for therapeutic vaccination. It has reported that the exosomes released from vaccinated DCs are responsible for the persistence of antigen presentation. Cancer cells derived exosomes play an immunosuppressive. We considered that whether DCs-derived exosomes could induce suppress cancer cells and more effective response of immune system against cancer with control for the cancer cells-derived exosomes. Because dendritic cells (DCs) play a key role in immune reactions to activate T cells against cancer cells by cancer antigen presentation at cellular membrane, DCs have been used in clinical trials as cellular mediators for therapeutic vaccination. It has reported that the exosomes released from vaccinated DCs are responsible for the persistence of antigen presentation. Cancer cells derived exosomes play an immunosuppressive. We considered that whether DCs-derived exosomes could induce suppress cancer cells and more effective response of immune system against cancer with control for the cancer cells-derived exosomes.
Method:
DCs were generated from bone marrow cells in C57BL/6J by stimulation with GM-CSF and IL-4 mice for 6 days. Murine lung cancer cell line (3LL) was cultured in RPMI1640 medium containing 10%FCS. 3LL cells-derived exosomes and DCs-derived ones were isolated by ultracentrifugation methods and exosomes purification kit (Qiagen). 3LL cells were injected to C57BL/6J mice by intraperitoneal administration. DCs, DCs-exosomes or 3LL-exosmes were weekly administrated to cancer bearing mice. Tumor growth inhibition by exosomes was evaluated measurement of luciferase activity by in vivo image analyzing system.
Result:
DCs and DCs-derived exosomes inhibited lung cancer cell growth, on the other hand, lung cancer derived-exosomes increased in compared with DCs, DCs-exosomes and non-treated.
Conclusion:
For cancer immunotherapy, DC-exosomes and cancer-exosomes play important roles in cancer immune reactions. Further examination, we are going on analyze immunosuppressive molecules possessing cancer cell-derived exosomes, and immune activation molecules in DCs-exosomes.
