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Naohiro Kajiwara
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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 | Author(s): Naohiro Kajiwara
- 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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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): Naohiro Kajiwara
- 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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P1.16 - 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): Naohiro Kajiwara
- 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 | Presenting Author(s): Naohiro Kajiwara
- 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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P2.05 - 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): Naohiro Kajiwara
- 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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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): Naohiro Kajiwara
- 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.
