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ED05 - The 8th Edition of the TNM Staging System (ID 268)
- Event: WCLC 2016
- Type: Education Session
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:P. Goldstraw, R. Rami-Porta
- Coordinates: 12/05/2016, 16:00 - 17:30, Hall C1
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ED05.03 - The Thymic Epithelial Tumor Staging System (ID 6445)
16:45 - 17:05 | Author(s): K. Kondo
- Abstract
- Presentation
Abstract:
Thymic epithelial tumors are rare tumors. The clinical staging system for thymoma was introduced first by Bergh and associates in 1978 and later modified by Wilkins and Castleman (1), and was almost established by Masaoka and associates in 1981 (2). In France, multiple centers have adopted the Groupe d’Etudes des Tumeurs Thymiques (GETT) staging system (1). The Masaoka classification is the most widely accepted now and is an excellent predictor of the prognosis of thymoma (3, 4). And a modification of this classification was suggested by Koga et al. in 1994 (5) The International Thymic Malignancies Interest Group (ITMIG) has chosen to use the Masaoka-Koga stage classification system (1). There has never been an official TNM system classification of thymic epithelial tumor by American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage classification due to their relative rarity. Yamakawa and Masaoka presented a tentative TNM system classification of thymoma in 1991. Then Tsuchiya et al. (1994) in National Cancer Center Hospital of Japan, the WHO (2004) and Bedini et al.(2005) in National Cancer Institute of Italy proposed a TNM staging system (1). The ITMIG and the International Association for the Study of Lung Cancer (IASLC) simultaneously set out to accomplish a staging system for thymic epithelial neoplasms, and subsequently joined forces in 2010, partnering to create a Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC), charged with the development of proposals to AJCC/UICC for the eight edition of the stage classification system. The ITMIG and IASLC assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. They made a stage classification that was tumor, node, metastasis (TNM) based, and applicable to thymoma as well as thymic carcinoma (6-9) (Tables). The T component is divided into 4 categories (Table 1). A tumor is classified in a particular “level” if one or more structures in that level is involved, regardless of whether other structures of a lower level are involved or not. The encapsulation of the tumor is not included, because this did not have a clinically significant difference of prognosis in the retrospective database. The T1 includes tumors that were classified as stage I or II in the Masoaka or Masaoka-Koga stage classification systems. The involvement of the pericardium pathologically is designated as T2, and several neighboring organs (potentially resectable) are included in the T3 category because they had similar prognosis. The T4 includes several organs with more extensive local invasion (potentially unresectable). The TD-SPFC decided to subcategorize T1 into T1a (no mediastinal pleural involvement) and T1b (involvement of the mediastinal pleura) to gain more prospective data for further testing, as there is a slight difference in cumulative incidence of recurrence in patients from Japan submitted by the Japanese Association for Research in the Thymus (6, 7). Lymph node involvement is common in thymic carcinoma (more than 27%) but is relatively uncommon in thymoma (2%) (4). The N component is divided into 3 categories (Table 1). No lymph node metastasis is classified as N0. Lymph nodes are assigned in 2 groups according to their proximity to the thymus: anterior (perithymic) (N1) and deep cervical or thoracic nodes (N2). The anterior region (N1) encompasses the space surrounding the thymus that is bordered by the hyoid bone and diaphragm craniocaudally, the medial edge of the carotid sheaths and mediastinal pleura laterally, the sternum anteriorly, the pericardium and great vessels posteriorly in the middle, and extending to the level of the phrenic nerves posterolaterally. The deep region (N2) describes the space distant to the anterior region within the mediastinum. It is situated posterior to the anterior mediastinum, anterior to the esophagus, and among the pulmonary hila; it extends into the neck on either side of the anterior cervical nodes. Involved nodes outside these regions are outside the N category and considered a distant metastasis (M1) (6, 8, 9). The M component is divided into 3 categories (Table 1). Absence of tumor outside the primary mass (or nodal metastases) is classified as M0. M1a is used to designate pleural or pericardial nodules. M1b designates pulmonary intraparenchymal nodules or distant metastases (6, 8). The TNM categories are organized into distinct stage groups as shown in Table 2. Stages I, II, IIIa, and IIIb are determined primarily by the T component. Stages IVa and IVb are determined by the presence of N1 or M1a disease for IVa and N2 or M1b disease for IVb (6-9). Figure 1 Figure 2 References 1. Detterbeck FC, Nicholson AG, Kondo K, Van Schil P, Moran C. The Masaoka-Koga Stage Classification for Thymic Malignancies Clarification and Definition of Terms. J Thorac Oncol. 2011;6: S1710–S1716. 2. Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:2485–92. 3. Detterbeck FC, Parsons AM. Thymic tumors. Ann Thorac Surg 2004;77:1860-9. 4. Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 2003;76:878–84. 5. Koga K, Matsuno Y, Noguchi M, et al. A review of 79 thymomas: modification of staging system and rappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int 1994;44:359–67. 6. Detterbeck FC, Stratton K, Giroux D, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal for an Evidence-Based Stage Classification System for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S65–S72 7.Nicholson AG, Detterbeck FC, Marino M, et al.,,The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: Proposals for the T component for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S73–S80 8. Kondo K, Schil PV, Detterbeck FC, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposals for the N and M Components for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S81-S87 9. Bhora FY, Chen DJ, Detterbeck FD,et al., The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S88–S96
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-081 - The Relationship of CDH3 Expression and DNA Methylation in Thymic Epitherial Tumors (ID 5929)
14:30 - 14:30 | Author(s): K. Kondo
- Abstract
Background:
The genome wide sequence and microarray has performed flourishingly for major cancer specimen in recent day. However, thymic epithelial tumor(TET) was rare tumor comparatively, there are few reports about epigenetic alternation in TET. Cadherin-3, also known as P-cadherin, is a protein encoded by the CDH3 gene. This study was aimed at identifying the relationship DNA methylation and gene expression of CDH3 gene in TET, especially B3 thymoma and thymic cancer.
Methods:
A)DNA methylation 1) DNA were extracted fresh frozen samples of B3 thymoma and thymic cancer, diagnosed as squamous cell carcinoma. These samples collected from the patients, diagnosed as TET, underwent surgery at Tokushima university from 1990 to 2016. 2) DNA was treated by bisulfite conversion. 3) DNA methylation level was measured by infinium methylation assay(Human Methylation 450K DNA Analysis Kit ; Illumina) exhaustively. 7 cases of thymic cancer and 8 cases of B3 thymoma applied this assay. 4) The methylation levels of CpG sites were calculated as β-values (β = Intensity (methylated)/intensity (methylated + unmethylated) by applying default settings of the GenomeStudio Software's DNA methylation module (Illumina). Analysis of this methylation assay used by R package. B) Immunostaining Immunostaining was performed Envision method. It was used Anti-pan-Cadherin antibody (ab16505）, dilution 1300 times as first antibody. DAKO Chemomate EnVsion kit was used as second antibody.
Results:
CDH3 had 2 CpG islands. 450K methylation assay set 5 CpG sites on first CpG island as promoter region. (CpG sites:B3 thymoma averageβ-values : thymic cancer averageβ-values : p-value by t-test)=(cg0900242 : 0.07±0.08 : 0.45±0.05 : 2.7×10[-7]), (cg07061260 : 0.21±0.21 : 0.55±0.09 : 3.3×10[-3]), (cg00748373 : 0.19±0.20 : 0.45±0.07 : 0.01), (cg06575065 : 0.28±0.18 : 0.50±0.07 : 0.02), (cg27417609 : 0.35±0.21 : 0.59±0.09 : 0.02). Immunostaining specimen were classified by scoring system measured by stain intensity and stain expanding. It was classified 2points;strong, 1point;weak, 0point;none, in stain intensity. It was classified 3points;diffuse(>80%), 2point;moderate(50-80%), 1point;focal(20-50%), 0point;none(<20%) in stain stain expanding. Expression rate(stain intensity point and stain expanding point) defined more than 4point as expression promotion. Expression promotion rate is 0% in B3 thymoma and 75% in thymic cancer.
Conclusion:
DNA methylation of CDH3 was increasing and P-cadherin protein expression was increasing in thymic cancer compared to B3 thymoma.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-030 - FDG-PET/CT Might Be a Predictor for Residual Disease in Advanced NSCLC after Chemoradiotherapy (ID 6299)
14:30 - 14:30 | Author(s): K. Kondo
- Abstract
Background:
The standard treatment for locally advanced non-small-cell lung cancer (NSCLC) is chemoradiotherapy (CRT), some patients are considered for trimodality therapy represented by concurrent CRT followed by surgical resection. However, there is no validated clinical predictor for surgical resection after CRT. In the present study, we analyzed that the correlation between SUVmax of FDG-PET/CT in pre/post CRT and treatment effect.
Methods:
22 patients with advanced NSCLC underwent CRT in Tokushima University Hospital between February 2006 to March 2016. we reviewed the medical records of 22 patients to obtain information on age, gender, histological type, clinical stage, adverse events, reduction ratio of tumor, SUVmax of FDG-PET/CT in pre/post CRT. Radiographic response was assessed by Modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Toxicities were assessed according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE).
Results:
Patient characteristics were as follows: average age of 65; male/female: 21/1, histologic type adenocarcinoma/squamous cell carcinoma/other: 14/5/3; clinical stage IB/IIB/IIIA: 1/3/18. Chemotherapy were platinum doublets regimen in almost cases. The average amounts of radiotherapy were 42Gy. The response rate was 29%. The number of PR/SD were 10/22 in RECIST. The adverse events were following: G2;11(50%), G3;8(36%), G4;5(23%). 2cases stopped treatment because of adverse events. Operative procedure were followings: lobectomy/bilobectomy/pneumonectomy: 17/2/3. The complication rate of operation was 27.2%, however, there was no hospital death. Overall survival was 69.7±10.3 months. Relapse free survival was 64.5±12.3 months. Pathological Complete Response(pCR) was recognized in 10cases(45.5%). The 4cases in 10cases of pCR got recurrence as distant metastasis, without local recurrence. The SUVmax decreasing rate was 69.8% in CRT. The SUVmax decreasing rate was 79% in the patients of pCR(n=5), however, this decreasing rate was 65% in not pCR(n=7, p=0.059). All cases of pCR indicated the SUVmax decreasing rate was more than 70%.
Conclusion:
The pCR were recognized in 10/22(45/5%) cases, underwent CRT. The treatment response in localregion was good in all cases. The SUVmax decreasing rate was more than 70% in all pCR cases.
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P1.08 - Poster Session with Presenters Present (ID 460)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.08-005 - Stratification of pStage I Lung Adenocarcinoma by the Scoring System Based on Prognostic Factors (ID 5168)
14:30 - 14:30 | Author(s): K. Kondo
- Abstract
Background:
In Stage I lung cancer, tumor size and PL factors are only reflected by the TNM staging system. However, other clinicopathological factors have the potential to influence recurrence and prognosis, especially in pStage I lung adenocarcinoma. This study aimed to evaluate prognostic factors, and to thereby stratify pStage I lung adenocarcinoma patients.
Methods:
A total of 203 patients who underwent curative resection for Stage I invasive adenocarcinoma, from 2006 to 2013, were retrospectively reviewed. [18]F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was performed in 194 patients and the maximum standardized uptake value (SUVmax) of the tumor was calculated. Invasive adenocarcinoma was classified into 3 predominant subtypes (lepidic, papillary and others) according to the IASLC/ATS/ERS classification. The associations between various clinicopathological factors and recurrence were evaluated, and disease-free survival (DFS) was analyzed.
Results:
Twenty-eight patients had recurrent disease during the follow-up period (mean; 59.3±25 months). Univariable analysis showed male gender, smoking history >20 pack-years, BMI≦20, CEA>5ng/ml, T classification, tumor size>20mm, predominant histologic subtype (lepidic, papillary, others), pleural invasion, vascular invasion, and SUVmax>3.0 to be significantly associated with worse DFS. On multivariable analysis, tumor size>20mm (P=0.006), papillary predominant (P=0.023), other predominant (P=0.008), and SUVmax>3.0 (P=0.008) were extracted as independent prognostic factors associated with worse DFS. Predictive variables were scored as follows; tumor size>20mm (1 point), papillary predominant (1 point), other predominant (2 points) and SUVmax >3.0 (1 point). Patients were classified into 3 risk groups (low-risk; 0-2, intermediate-risk; 3, high-risk; 4) according to their aggregate scores. The 5-year DFS rate was 91% in the low-risk group, 55% in the intermediate group and 36% in the high-risk group. The 5-year DFS rates during the same period in our institute were 88% in pStage IA, 69.5% in pStage IB, 53% in pStage II, and 38% in pStage IIIA patients. Therefore, the DFS rate in the intermediate-risk group was comparable to that of pStage II, and the DFS rate in the high-risk group was comparable to that of pStage IIIA.
Conclusion:
In Stage I lung adenocarcinoma, tumor size, SUVmax and histologic subtypes were suggested to be prognostic factors. This scoring system may predict the groups, such as patients with pStage II and IIIA, requiring platinum based post-operative chemotherapy.
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P2.04 - Poster Session with Presenters Present (ID 466)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.04-052 - Promoter Hypermethylation of DNA Mismatch Repair Gene hMLH1 of Lung Cancer in Chromate-Exposed Workers (ID 6112)
14:30 - 14:30 | Author(s): K. Kondo
- Abstract
Background:
Although it is known that chromium is an important inhaled carcinogen for lung cancer, there are few reports about genetic effects of chromium in oncogenic process. Our previous studies revealed that chromate lung cancer frequently had microsatellite instability (MSI), and that MSI was associated with the loss of expression of MLH1, which is one of the essential DNA mismatch repair proteins. Inactivation of MLH1 due to promoter methylation causes high level of microsatellite instability in hereditary nonpolyposis colorectal cancer (HNPCC). Therefore, we hypothesized that loss of expression of MLH1 in chromate lung cancer is caused by MLH1 promoter methylation similar to HNPCC. In the present study, we analyze DNA methylation of MLH1 promoter regions in chromate and non-chromate lung cancers and clarify whether methylation of MLH1 has the influence on MLH1 protein expression and MSI.
Methods:
Thirty-three tumor samples from chromate workers with lung cancer and thirteen tumor samples from lung cancer patients without chromate exposure (non-chromate group) were obtained. DNA was extracted from chromate and non-chromate lung cancer and bisulfite pyrosequencing was used to examine DNA methylation levels of MLH1 promoter regions. MSI, MLH1 protein expression of these tumor samples have been investigated in our previous studies.
Results:
High methylation levels of MLH1 promoter regions were found in 42.4% (7/33) of chromate lung cancers and 15.4% (2/13) of non-chromate lung cancers. Methylation rates of MLH1 promoter region and the grade of MSI were related to positive correlation in chromate lung cancers. Immunohistochemistry for MLH1 was performed in 24 chromate lung cancer, High methylation of MLH1 was found in 27.3% (3/11) of tumors with repression of MLH1 protein and 4.3% (1/13) of tumors with normal expression of MLH1 protein.
Conclusion:
According to the present data, DNA methylation of MLH1 promoter regions might contribute to loss of expression of MLH1 protein and MSI. We speculate that in addition to genetic changes, epigenetic events have emerged in chromium carcinogenesis.
