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Meinoshin Okumura
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MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:K. Shibuya, Francoise Mornex
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 313 + 314
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MA 16.08 - Surgery for Pleural Dissemination of Thymoma; A 20-Year Experience (ID 9191)
16:30 - 16:35 | Author(s): Meinoshin Okumura
- Abstract
- Presentation
Background:
Surgical management of pleural dissemination of thymoma has been recommended in some reports, while reports on the long- term results of pleural dissemination resection are few. The aim of this study was to assess mid- and long- term results of surgical resection of pleural dissemination of thymoma.
Method:
We retrospectively analyzed data from patients with synchronous or metachronous pleural dissemination and primary thymoma who underwent surgical resection between 1996 and 2016 in our hospital.
Result:
During the study period, 38 patients underwent resection of pleural dissemination of thymoma. The synchronous group consisted of 21 patients with a median age of 50.2 years (range: 28—75 years) at the time of resection. The metachronous group consisted of 17 patients with a median age of 46.7 years (range: 30—65 years) at the time of resection of pleural dissemination. The median follow-up was 72.7 months (range: 3—248 months). In the synchronous group, 19 patients were in stage IVa and 2 patients were in stage IVb. The histological type of thymoma was type B1 in 3 patients, type B2 in 9 patients, typeB3 in 9 patients. In the metachronous group, Masaoka stage of the primary thymoma was as follows; 3 patients were in stage I, 5 patients were in stage II, 7 patients were in stage III and 2 patients were in stage IVb. The histological types of the resected dissemination nodule were type AB in 1 patient, type B1 in 1 patient, type B2 in 5 patients, and typeB3 in 10 patients. A macroscopic complete resection of pleural dissemination was achieved in 30 patients (79%) of all the patients. No perioperative deaths occured. Postoperative complications occurred in 5 patients (13.2%). During the observation period, 5 patients died (relation to the tumor in 4) in the synchronous group and 1 patient died (unrelated to the tumor) in the metachronous group. The 5- and 10-year overall survival rates of all the patients were 87.6% and 69.2%, respectively. Of all the patients, 14 received repeated resection of the pleural disseminated nodule. The 5- and 10-year overall survival rates from the first resection of pleural dissemination were 76.6% and 46.0% in the non-repeat resection group and 100% and 88.9% in the repeat resection group, respectively.
Conclusion:
Surgery for pleural dissemination of thymoma was safely performed and provides favorable prognosis. Repeat resection for pleural dissemination could be effective in achieving a prolonged survival.
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MA 17 - Locally Advanced NSCLC (ID 671)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:S. Jheon, Georgios Stamatis
- Coordinates: 10/17/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MA 17.04 - Initial Surgery in Patients with Clinical N2 Non-Small Cell Lung Cancer: A Multi-Institution Retrospective Study (ID 7349)
16:00 - 16:05 | Author(s): Meinoshin Okumura
- Abstract
- Presentation
Background:
There is no large scale study of the initial surgery for patients with cN2 disease who received positron emission tomography (PET). We investigated the outcomes of initial surgery for patients with cN2 disease who had received PET, by conducting a multi-institutional retrospective study.
Method:
Clinical data for 143 patients who had cN2 disease and underwent initial surgery at 12 Japanese institutions in Thoracic Surgery Study Group of Osaka University (TSSGO) between January 2006 and December 2013 were collected. After reviewing all the data for eligibility, completeness, and consistency, 8 cases were excluded. The remaining 135 cases were feasible for analysis. Among these patients, 98 received PET and were analyzed.
Result:
The median follow-up was 56.5 months (2-110 months). The median age was 67 (35-80) years. There were 71 males and 27 females. The histology was adenocarcinoma (n=66), non-adenocarcinoma (n=33). The tumor location was the right upper lobe and left upper segment (n=66, 67.3%), and the others (n=32, 32.6%). Of 98 patients, 85 (86.7%) had clinical single N2 disease and 80 (81.6%) had no mode of spread lesion and 90 (91.8%) underwent lobectomy. The 5-year relapse free survival (RFS) rate and the 5-year overall survival (OS) rate for patients with cN2 were 34.6% and 46.6%. There were 24 patients (24.9%) with cN2pN0,1 and 74 patients (75.5%) with pN2. Of 74 patients with cN2pN2 disease, 42 (59.5%) had pathological single N2 disease and 40 (54.0%) underwent adjuvant chemotherapy. The 5-year RFS for the patients with cN2 in the cN2pN0,1 and cN2pN2 groups were 62.2% and 26.0%, respectively (p=0.0025). The 5-year OS for the patients with cN2 in the cN2pN0,1 and cN2pN2 groups were 74.8% and 40.0%, respectively (p=0.029). Moreover, we provided the following 3 criteria: primary tumor in right upper lobe or left upper segment, N2 disease with regional mode of spread, and patients who did not undergo pneumonectomy. 60 patients who fulfilled all of these criteria were regarded as specific group. The 5-year OS for the patients with cN2 in the specific group and non-specific group was 55.8% and 32.0%, respectively (p=0.024).
Conclusion:
Among patients with cN2 disease, those with pN2 disease were more in number in our study than in previous reports. Our patients with cN2pN2 had better survival compared with those in previous reports. In particularly, patients with clinical N2 disease in specific group have a favorable prognosis. An initial surgery may be considered as a treatment option for these patients.
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MS 06 - Combined Modality Treatment for Thymic and Pleural Malignancy (ID 528)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:Oscar Arrieta, Scott Swanson
- Coordinates: 10/16/2017, 15:45 - 17:30, F201 + F202 (Annex Hall)
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MS 06.01 - Proposal of Change for Future Staging System for Thymic Tumor (ID 7663)
15:45 - 16:00 | Presenting Author(s): Meinoshin Okumura
- Abstract
- Presentation
Abstract:
Although Masaoka clinic-pathological staging system has been accepted as the global standard staging system for thymic epithelial tumors, several problems of this staging system have been pointed out because clinical practices in diagnosis, medical treatment and surgical procedure has enormously advanced during more than 30 years. Furthermore, there has not been a TNM classification system approved by UICC to describe a tumor’s clinical status adequately. To overcome these situations, International Thymic Malignancy Interest Group (ITMIG) established global database and proposed a novel staging system based on TNM definition in collaboration with IASLC staging committee in 2016. This is a great progress in clinical medicine in the field of thymic epithelial tumor, but as a matter of fact, stage grouping according to this novel TNM classification is mostly defined by tumor invasion to adjacent organs similarly to Masaoka staging system. Japanese Association for Research of the Thymus (JART) established by Akira Masaoka and colleagues contributed to the ITMIG project of global database, and several studies using JART database were performed and reported from Japanese researchers. Novel findings in the JART database study are reviewed and new insights in further modification in TNM staging system are addressed in the present article. The significance of involved organs as a prognostic factor has been a great interest, because some structures are easily resected while others are difficult to be completely resected. Actually, some previous studies showed prognostic significance of involvement of the great vessels. Based on the ITMIG database, involvement of the pericardium alone is defined as T2 in the UICC TNM classification while involvement of SVC and brachiocephalic vein is defined as T3 and involvement of the aorta, aortic branches and intrapericardial vessels is defined as T4. One of the JART database study focusing on the involved organs in Masaoka stage III tumors showed that invasion to the chest wall is an independent prognostic factor by multivariate analysis while involvement of the great vessels is not. The hazard ratio of involvement of the chest wall is 4.07. Invasion to the chest wall is defined as T3, but when invasion to the sternum is extended, resection of the chest wall including sternum is sometimes a difficult procedure, and complete resection is hard to be achieved. Lymphatic channels are distributed in the chest wall, of which involvement by the tumor can result in nodal metastasis. Thus, invasion to the chest wall might be considered as an important factor to determine the tumor spread, and therefore, as one factor in T definition. Involvement of SVC and brachiocephalic vein is defined as T3, but is heterogenous variable because some tumors invade to the outer surface of the vessel but others enter the lumen of the vessel, which can result in pulmonary metastasis. The extent in involvement of the great vessels could be a significant factor in T definition. Tumor size could reflect the time from initiation of the tumor and the larger tumor is more likely to be in an advanced status. Actually, tumor size is a critical factor in T definition in lung cancers. In thymic epithelial tumors, however, T definition does not reflect the tumor size. Using JART database, oncological significance of the tumor size was examined in thymoma and thymic carcinoma, separately. In thymoma, the rate of R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 94.4%, 91.3%, and 84.0%, respectively. Recurrence rate after R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 3.0%, 8.9% and 27.2%, respectively. In thymic carcinoma, the rate of R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 80.2%, 63.2%, and 62.5%, respectively. Recurrence rate after R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 28.2%, 53.7% and 62.5%, respectively. Thus, there was apparent difference in oncological behavior between tumors less than 5.0 cm and those more than 5.1 cm both in thymoma and thymic carcinoma. These observations suggest that tumors size also should be included in T definition in thymic epithelial tumors. Finally, the category of Masaoka stage IVA disease includes pleural dissemination, but the situation of pleural dissemination varies greatly from a single lesion to numerous lesions. Furthermore, some disseminations are resectable while others are not. JART study revealed that the number of disseminated lesions on the pleura In conclusion, T definition remains to be further evaluated in reference to tumor size, chest wall invasion and extent of involvement of the great vessels. M definition also remains to be further discussed in terms of extent of the pleural dissemination.
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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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P1.02-068 - Effects of Pirfenidone Targeting EMT and Tumor-Stroma Interaction as Novel Treatment for Non-Small Cell Lung Cancer (ID 8983)
09:30 - 09:30 | Author(s): Meinoshin Okumura
- Abstract
Background:
Epithelial-to-mesenchymal transition (EMT) is related to the malignant behavior of cancer. Interaction between cancer-associated fibroblasts (CAFs) and tumor cells has been shown to increase tumor cell survival via several pathways including EMT. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis and one of its functions may be to inhibit fibrotic EMT. We evaluated the effects of PFD on EMT using non-small cell lung cancer (NSCLC) cells, as well as interactions between CAFs and NSCLC cells in vitro and in vivo.
Method:
NSCLC cells (A549, NCI-H358) were used to evaluate the effects of PFD on EMT. Primary human fibroblasts obtained from tumors as well as normal tissues were isolated from surgically resected lungs of three patients with lung cancer, and defined as CAFs and LNFs, respectively. The effects of PFD on activation of CAFs and LNFs were determined by analyzing the expression of hallmarks of fibroblast activation and pro-inflammatory markers. In addition, the impact of PFD on interactions between NSCLC cells and CAFs was also determined in vitro using a co-culture technique, as well as in vivo using co-implantation of those cells.
Result:
PFD significantly inhibited TGF-β1-induced EMT in NSCLC cells, and also the activation levels of α-SMA and collagen I, as well as cytokine productions of IL-6 and TGF-β1 by LNFs and CAFs. qRT-PCR results showed that the median diminution rates for three patients by PFD were 0.303 in LNFs and 0.69 in CAFs for α-SMA, and 0.316 in LNFs and 0.627 in CAFs for collagen I. Medium conditioned with LNFs or CAFs significantly induced EMT in NSCLC cells, while pretreatment of LNFs or CAFs with PFD inhibited the EMT change in NSCLC cells. In vivo findings showed that co-implantation of CAFs promoted tumor progression, which was suppressed by PFD via inhibition of EMT and stroma outgrowth. Immunohistological analysis showed that the Ki67 labelling index was higher in the co-implantation group than in the control group. Administration of PFD reduced the Ki67 labelling index by 27.1% in A549 tumors and 27.0% in NCI-H358 tumors in the co-implantation group. PFD also decreased α-SMA positive area with restoration of E-cadherin expression.
Conclusion:
Our findings suggest that PFD inhibits EMT and fibroblast activity, as well as cross-talk between cancer cells and fibroblasts. PFD may have great potential as a novel agent with a wide variety of actions for treatment of NSCLC.
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P1.17 - Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies (ID 703)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.17-002 - Clinicopathological Significance of Epithelial Mesenchymal Transition in Thymic Cancer (ID 8019)
09:30 - 09:30 | Author(s): Meinoshin Okumura
- Abstract
Background:
The epithelial to mesenchymal transition (EMT) is a fundamental biological process during which epithelial cells change to a mesenchymal phenotype which has a profound impact on cancer progression. It has been proposed that increased expressions of EMT markers, loss of epithelial markers such as E-cadherin, and altered expressions of mesenchymal markers such as N-cadherin are called as cadherin switching and associated with poor prognosis in cancer case. We analyzed the expression of E-cadherin and N-cadherin in thymic cancer to determine the relationship to clinicopthological factors and prognosis.
Method:
We collected the data of 31 patients with thymic cancer from our institution between 2000 and 2014. Immunohistochemistry was used to examine the expression of EMT markers, E-cadherin and N-cadherin in tumor specimens. We evaluated the correlation between EMT and prognosis in patients with thymic cancer. We also compared expressions of the cadherins in tumor specimens obtained both before and after preoperative chemoradiotherapy or chemotherapy from 14 patients with thymic cancer who underwent preoperative biopsy in our hospital.
Result:
Eighteen patients underwent preoperative treatment. The resection was extended to the surrounding organs in addition to thymectomy including thymic tumor and anterior mediastinal lymphadenectomy. Twenty-six patients had a R0 resection. Pathological findings revealed that one patient had Masaoka stage I disease, one had II, 20 had III, one had IVa, and 8 had IVb. The histological diagnosis was squamous cell carcinoma in 24, undifferentiated carcinoma in 4, and others in 3 patients. Immunohistochemically, decreased expression of E-cadherin or upregulation of N-cadherin was detected in surgically resected specimens in 15 patients whose tumor was classified as EMT marker-positive. According to a clinicopathological comparison of these groups, EMT status was not related to preoperative therapy, Masaoka staging, or histology. The 5-year survival rate for all patients was 86 %, 63 % for EMT marker-positive, and 100 % for EMT marker-negative. The survival rate of patients with EMT marker-positive tumors was significantly lower than that of those with EMT marker-negative tumors. Decreased expression of E-cadherin or upregulation of N-cadheirn was detected in surgically resected specimens after preopetative treatment compared with biopsy specimens obtained before treatment in 10 of 14 patients.
Conclusion:
EMT marker expression such as cadherin switching was detected in thymic cancer tumor and was more often detected after preoperative treatment, indicating that EMT may affect the degree of malignant potential in thymic cancer and make them insensitive to treatment.
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P1.17-013 - Prognostic Impact of Programmed Cell Death-1 (PD-1) and PD-Ligand 1 (PD-L1) Expression in Thymic Cancer (ID 9655)
09:30 - 09:30 | Author(s): Meinoshin Okumura
- Abstract
Background:
Thymic cancer is one of the aggressive thoracic malignancies. Chemotherapy, radiation therapy, and surgery are the main therapeutic options. However, no standard therapy has not been established because of the rarity, and the mortality rate remains high. Therefore, additional therapeutic options are needed. Recently, cancer immunotherapy has been developed and shown promising results against some malignancies in clinical trials. One of the immuno-check point proteins; the programmed cell death 1/ Programmed cell death 1-Ligand 1 (PD-1/PD-L1) pathways play one of the main role in cancer immunology. The expression of PD-L1 in cancer cells and PD-1 positive tumor infiltrating lymphocytes (TIL) are reportedly one of the useful prognostic and predictive factor for the therapeutic effect of anti-PD-1 or anti-PD-L1 immunotherapies in several malignancies. However, clinical significance of PD-1 and PD-L1 in thymic cancer remains unclear. In this present study, we retrospectively investigated the relationships between the expression of PD/1PD-L1 and clinical backgrounds in thymic cancer.
Method:
A total of 30 patients of thymic cancer surgically resected from 1998 to 2016 in our institutes were retrospectively analyzed. Median follow up periods was 4.2 years. The expression of PD-L1 and PD-1positve TIL was evaluated by immunohistochemical staining using formalin-fixed paraffin embedded surgically resected tissues and analyzed the relationships between those expressions and clinical backgrounds. A Pearson's chi-square test was used to compare the variances. Disease-free survival (DFS) were analyzed by using the Kaplan–Meier method, and the Log-rank test was used to compare the survival distributions of subgroup.
Result:
14 cases were positive in immunohistochemistry staining of PD-L1 (47%). While, 16 cases were positive in PD-1 TIL staining (55%). There were no significant relationships between PD-1/PD-L1 positive staining and Masaoka-Koga stage. In tumor size, age and gender, there were also no significant difference among IHC results of PD-1/PD-L1. While, in disease free survival rate (DFS), the PD-1 and PD-L1-positive cases were significantly worse as compared to negative cases (PD-1; P=0.001, PD-L1; P=0.03). Uni- and multivariant analysis showed the PD-1 and PD-L1 expression were independent prognostic factors (P < 0.05).
Conclusion:
Our results suggested that the high PD-L1 expression and the PD-1 positive TIL are indicators of poor prognosis, and anti PD-1/PD-L1 immunotherapy may be reliable option to treatment in thymic cancer.
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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-050 - Stromal PDGFR-β Expression Influences Postoperative Survival of NSCLC Patients Receiving Preoperative Chemo- or Chemo-Radiotherapy (ID 8871)
09:30 - 09:30 | Author(s): Meinoshin Okumura
- Abstract
Background:
Platelet-Derived growth factor beta (PDGFR-β) is a functional regulator of mesenchymal cells. It is reported that PDGFR-β is expressed by cancer associated fibroblasts, and PDGFR signaling supports cancer cells. Stromal expression of PDGFR-β is reported to be associated with poor prognosis in prostate, breast, pancreas, and gastric cancers. However, the significance of stromal PDGFR-β expression in non-small cell lung cancer (NSCLC) in patients undergoing preoperative chemo- or chemoradio-therapy had not been undetermined.
Method:
Seventy-two patients with NSCLC undergoing preoperative chemo- or chemoradio-therapy between 1996 and 2006 were assessed for expression of stromal PDGFR-β by immunohistochemistry using resected specimens. After cancer cells and stromal tissues were identified by HE staining, stromal PDGFR-β expression was defined as positive when it was observed in >5% of the stromal area. Relationships between stromal PDGFR-β expression and disease-free survival (DFS) and disease-specific survival (DSS) were analyzed.
Result:
The mean age of the 72 patients was 59.7 years. Sixty-one (85%) were male and 11 (15%) female. Forty patients (56%) underwent preoperative chemoradiotherapy and 32 patients (44%) underwent preoperative chemothearapy. Indications for preoperative chemotherapy were N2 disease in 51 (71%), T3 or T4 disease in 20 (28%), and other reasons in the remaining patient (1%). Regimens for preoperative chemotherapy were cisplatin (CDDP)-based in 34 patients (47%) and carboplatin (CBDCA)-based in 37 (52%). Type of resection were pneumonectomy in 7 (10%), bilobectomy in 6 (8%), lobectomy in 57 (79%), and sublobar resection in 2 (3%) patients. Complete resection were achieved in 59 patients (82%). The pathologic stage (7[th] ed.) was IA in 11 (15%), IB in 12 (17%), IIA in 6 (8%), IIB in14 (19%), IIIA in 19 (27%), IIIB in 5 (7%), and IV in 5 (7%) patients. The histological type were adenocarcinoma in 32 (44%), squamous cell carcinoma in 35 (49%), and others in 5 (7%) patients. On immunohitological examination, stromal cells expressed PDGFR-β in 47 cases (65%). Five-year DFS and DSS in the stromal PDGFR-β-positive group was significantly worse than in the negative group (29.1%-vs-64.6%, p=0.01 and 40.2%-vs-66.1%, p=0.02, respectively).
Conclusion:
Stromal PDGFR-β expression is negatively associated with DFS and DSS in patients with NSCLC undergoing preoperative chemo- or chemoradio-therapy.
