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Y. Matsumura
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MO04 - Lung Cancer Biology I (ID 86)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
- Moderators:G. Sozzi, D.C. Lam
- Coordinates: 10/28/2013, 16:15 - 17:45, Bayside 103, Level 1
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MO04.10 - Identification of biological properties of intralymphatic tumor related to the development of lymph node metastasis in lung adenocarcinoma (ID 1724)
17:10 - 17:15 | Author(s): Y. Matsumura
- Abstract
- Presentation
Background
Intralymphatic tumors in the extratumoral area are considered to represent the preceding phase of lymph node (LN) metastasis. The aim of this study was to clarify the biological properties of intralymphatic tumors susceptible to the development of LN metastasis, with special reference to the expression of cancer initiating/stem cell (CIC/CSC) markers in cancer cells and the number of infiltrating stromal cells.Methods
A total of 2087 consecutive adenocarcinoma patients underwent complete resections and systematic LN dissections between May 1998 and December 2012 were identified. Among these cases, we selected those that had been diagnosed as having lymphatic permeation in the extratumoral area (n = 107). We examined the expression levels of CIC/CSC related markers including ALDH1, OCT4, NANOG, SOX2 and Caveolin-1 in the intralymphatic and primary tumor cells to evaluate their relationship to LN metastasis. The number of infiltrating stromal cells expressing CD34, α-smooth muscle actin, and CD204 were also evaluated. Moreover, we measured E-cadherin expression to identify a correlation between CIC/CSC related molecules and epithelial - mesenchymal transition (EMT) process.Results
Intrathoracic LN metastases were detected in specimens from 86 patients (80%). Among the intralymphatic tissues, low ALDH1 expression in cancer cells, high SOX2 expression in cancer cells, and a high number of CD204(+) macrophages were independent predictive factors for LN metastasis (odds ratio [95%CI] = 3.25 [1.11 – 9.82], P = 0.031 for ALDH1; 4.09 [1.38 – 13.4], P = 0.011 for SOX2; and 3.45 [1.16 – 11.4], P = 0.026 for CD204(+) macrophages). However, in the primary tumors, only a high SOX2 expression level in the cancer cells within the primary tumor was significantly correlated with LN metastasis (p=0.008); ALDH1 expression in the cancer cells and the number of CD204(+) macrophages were not correlated with LN metastasis (P = 0.230 and P = 0.088, respectively). Among these factors, only low ALDH1 expression in intralymphatic cancer cells was significantly correlated with the farther spreading of LN metastasis (mediastinal LN, pN2) (P = 0.046) and higher metastatic LN ratio (metastatic/resected) (P = 0.028). Intralymphatic cancer cells expressing low ALDH1 levels exhibited lower E-cadherin expression levels than cancer cells with high levels of ALDH1 expression (P = 0.015). The expressions of other CIC/CSC related markers, including OCT4, NANOG, SOX2, and Caveolin-1, were not correlated with the E-cadherin expression.Conclusion
Intralymphatic cancer cells expressing low levels of ALDH1 and infiltrating macrophages expressing CD204 have a critical impact on LN metastasis. Especially, intralymphatic cancer cells expressing low levels of ALDH1 might acquire a metastatic aggressiveness by the EMT process. Our study highlighted the significance of evaluating the biological properties of intralymphatic tumors for tumor metastasis and suggested the possibility of usefulness as a new molecular target, especially as an adjuvant therapy.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26 - Anatomical Pathology II (ID 129)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Pathology
- Presentations: 2
- Moderators:E. Brambilla, V.L. Capelozzi
- Coordinates: 10/30/2013, 10:30 - 12:00, Bayside 105, Level 1
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MO26.09 - Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma (ID 2023)
11:15 - 11:20 | Author(s): Y. Matsumura
- Abstract
- Presentation
Background
Stromal cells, including macrophages, lymphocytes and fibroblasts, are known to interact with cancer cells and to produce a specific microenvironment capable of influencing tumor progression. Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 positive TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 positive TAMs and the clinicopathological features of lung squamous cell carcinoma.Methods
We investigated the relationships between the numbers of CD204 positive TAMs and clinicopathological factors, microvessel density (MVD), and the numbers of Foxp3 positive lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 positive TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 positive TAMs.Results
A high number of CD204 positive TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 positive TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 positive TAMs were correlated with the MVD and the numbers of Foxp3 positive lymphocytes. A high number of CD204 positive TAMs was strongly correlated with the tissue expression level of MCP-1. CD204 positive TAMs were shown to be significant independent prognostic factors in a multivariate analysis.Conclusion
CD204 positive TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 positive TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.12 - Prognostic Impact of Microscopic Vessel Invasion and Visceral Pleural Invasion in Non-small Cell Lung Cancer (ID 2480)
11:35 - 11:40 | Author(s): Y. Matsumura
- Abstract
- Presentation
Background
In non-small cell lung cancer (NSCLC), visceral pleural invasion (VPI) is incorporated as a staging factor in the current TNM classification. Microscopic vessel invasion (MVI: defined collectively as histological blood vessel invasion and lymphatic permeation) has been reported to be a strong independent predictor of poor prognosis, but it has not been incorporated in the TNM classification. We assessed the prognostic significance of MVI as well as VPI.Methods
Between August 1992 to December 2009, 2657 consecutive patients with pathological T1-4N0-2M0 NSCLC underwent complete resection at our institution. We analyzed the prognostic significance of MVI for recurrence in addition to the conventional prognostic factors. The recurrence-free proportion was estimated using the Kaplan-Meier method and differences were analyzed by the log-rank test. Cox regression analyses were used to identify independent risk factors for recurrence.Results
The 5-year recurrence-free proportion for patients with or without MVI was 52.6% and 87.5%, respectively (p < 0.001). On multivariate analysis, MVI, similarly to VPI, was found to be an independently significant predictor of recurrence (HR 2.78). In 1601 patients with pathological stage I disease without adjuvant chemotherapy, MVI and VPI were the two strongest independent predictors of recurrence on multivariate analysis (HR 2.74 and 1.84, respectively). Evident and significant separation of the recurrence-free proportion curves among the following 3 groups according to the number of the two risk factors (VPI and MVI) was observed; both VPI and MVI absent (0), either VPI or MVI present (1), and both VPI and MVI present (2). We compared the recurrence-free proportion of patients stratified by tumor size and the number of the risk factors (0/1/2) (Table 1). The groups of small tumor size without PL and MVI showed the best recurrence-free proportions (T1a_0, T1b_0, and T2a_0). The T1a_1, T1b_1, and T2a_1 subgroups showed poorer outcomes which were comparable with the T2b_0 subgroup. The groups with both PL and MVI, even in small tumor size groups, resulted in poor outcomes equivalent to that of T3_0/1 groups. The T3_2 group showed the poorest outcome equivalent to the T4 group.Conclusion
This study demonstrated that MVI was a significantly independent risk factor for recurrence in resected T1-4N0-2M0 NSCLC patients. We propose the T-classification of tumors with either MVI or VPI (1) should be upgraded to the next T level and that with both MVI and VPI (2) to the second T level (Table 1).Table 1. Incorporation of PL and MVI into T classification
Current (7th) T Classification Tumor Size (cm) No. of VPI and MVI Risk Factors Recurrence-free Proportion at 5 Years (%) OurProposalT T1a ≤ 2 0 92.2 T1 ≤ 2 1 72.2 T2 ≤ 2 2 58.2 T3 T1b > 2, ≤ 3 0 89.6 T1 > 2, ≤ 3 1 64.8 T2 > 2, ≤ 3 2 50.9 T3 T2a > 3, ≤ 5 0 87.8 T1 > 3, ≤ 5 1 61.9 T2 > 3, ≤ 5 2 44.8 T3 T2b > 5, ≤ 7 0 75.9 T2 > 5, ≤ 7 1 49.4 T3 > 5, ≤ 7 2 47.5 T3 T3 > 7 0 58.2 T3 > 7 1 50.6 T3 > 7 2 38.8 T4 Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O09 - General Thoracic Surgery (ID 100)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Surgery
- Presentations: 1
- Moderators:G.E. Darling, W. Weder
- Coordinates: 10/28/2013, 16:15 - 17:45, Parkside Ballroom B, Level 1
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O09.05 - Intraoperative autostapling cartridge lavage cytology in surgical resection of pulmonary malignant tumors - possible role in preventing local failure (ID 2543)
17:00 - 17:10 | Author(s): Y. Matsumura
- Abstract
- Presentation
Background
Limited resection of primary lung cancer or sublobar resection of pulmonary metastatic tumor can result in cut-end recurrence. It is important to confirm the absence of tumor cells at the cut-end. Since 2004, all autostapling cartridges used for wedge or segmental resection of pulmonary malignancies are washed with 50 ml saline. Washing saline is centrifuged and the sediment is stained using Papanicolaou’s method and examined for cancer cells during surgery to confirm negative margin. The aim of this study is to evaluate the efficacy of the intraoperative autostapling cartridge lavage cytology in preventing surgical cut-end recurrence.Methods
The intraoperative cytology analysis was performed in 271 patients undergoing wedge or segmental resection for 319 lesions including primary lung cancers and pulmonary metastatic tumors between April 2004 and April 2010. We retrospectively reviewed the clinicopathologic features of patients with positive cytology results and those who developed recurrence at the surgical margins.Results
The median age of the 271 patients at surgery was 67 years (range: 31−92 years). The median size of the 319 lesions was 1.4 cm (range: 0.4−3.5 cm), and there were 149 primary lung cancers and 170 pulmonary metastatic tumors (primary site: 116 colorectal and 54 others). Twenty-two lesions (7%) showed positive cytology results (11 primary and 11 metastatic). In primary lung cancers, tumor size (≧ 21 mm, p = 0.02), moderate to poor differentiation (p ＜ 0.01), vascular invasion or lymphatic permeation (p ＜ 0.01), and visceral pleural invasion (p ＜ 0.01) were significant predictors of a positive result. In contrast, there were no significant predictors in pulmonary metastatic tumors. The cut-ends of the 19 lesions among the 22 positive cytology margin lesions were additionally resected, but those of the remaining 3 lesions were not because of impaired respiratory function. With the median follow-up period of 42 months, surgical cut-end recurrence occurred in 2 of the 19 lesions for which additional resection had been performed (11%, 1 primary and 1 metastatic). Of the 3 lesions for which additional resection was impossible, cut-end recurrence developed in 2 (67%, 1 primary and 1 metastatic). Among the 297 lesions showing negative cytology result, cut-end recurrence occurred in 5 (2%, 4 primary and 1 metastatic).Conclusion
Intraoperative autostapling cartridge lavage cytology in sublobar resection for primary or metastatic lung tumor may be useful in preventing surgical cut-end recurrence.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O13 - Limited Resections (ID 101)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Surgery
- Presentations: 1
- Moderators:G.M. Wright, K. Kernstine
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 204 A+B, Level 2
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O13.03 - Survival of 1963 lobectomy-tolerable patients who underwent limited resection for cStage I non-small cell lung cancer (ID 1030)
10:50 - 11:00 | Author(s): Y. Matsumura
- Abstract
- Presentation
Background
Although the standard operation for lung cancer is lobectomy, precise preoperative diagnosis of the “very early” lung carcinomas may identify patients that can be treated by limited resection. Previous reports on limited resection included patients who were not candidates for lobectomy. The survival of non-small cell lung cancer (NSCLC) patients who were fit for lobectomy and underwent limited resection has not been studied in a large enough scale.Methods
A nationwide multi-institutional project collected clinical data of patients who underwent limited resection (segmentectomy or partial resection) for clinical T1-2N0M0 non-small cell lung carcinoma, who were 75 years old or younger at the time of operation and were considered fit for lobectomy by the physician. Overall and disease free survival, freedom from recurrence were analyzed and factors affecting survival or recurrence were identified.Results
The median age of 1963 patients was 63 years. The mean maximal diameter of the tumor was 1.4 ± 0.6 cm. The overall and recurrence free survival after limited lung resection was 93.7 % and 90.4 % at 5 years, respectively. The recurrence free proportion and local recurrence free proportion were 93.3 % and 98.4 % at 5 years, respectively. Prognostic factors in overall survival were pathologically proven lymph node metastasis, interstitial pneumonia, male gender, older age, complications (cardiac disease, diabetes etc.), radiological invasive cancer, and multiple lesions. The consolidation/tumor ratio on CT of ≤ 0.25 predicted good outcome especially in cT1aN0M0 disease. Prognosis and recurrence was not affected by the method of limited resection (segmentectomy (n=1225) or partial resection (n=738)).Conclusion
If the patient was 75 years old or younger and was judged fit for lobectomy, the result of limited resection for cStage I NSCLC was excellent and was not inferior to the reported result of lobectomy for small sized NSCLC. The radiological noninvasive carcinomas rarely recur and are especially good candidates for limited resection.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.12-007 - The Predictors of Early Recurrence in Patients with Completely Resected p-stage I Non-Small Cell Lung Cancer (ID 1256)
09:30 - 09:30 | Author(s): Y. Matsumura
- Abstract
Background
The objective of this study was to identify the risk factors for early (within 2 years after surgery) recurrence in patients with completely resected pathological stage I (p-stage I) non-small cell lung cancer (NSCLC).Methods
We reviewed retrospectively 864 consecutive patients with p-stage I NSCLC who underwent complete resection between 1992 and 2012 at our institution. The correlation between clinicopathologic factors (sex, age, preoperative CEA level, tumor laterality, primary lobe, smoking history, histological type, histological differentiation, p-T status, lymphatic permeation, vascular invasion, pleural invasion) and early recurrence was evaluated using chi-square test and multivariate analysis.Results
There were 498 men and 366 women, with an average age of 67 years. (range: 33-87). The median follow up period was 78 months. Histologically, 659 patients had adenocarcinomas, 189 squamous cell carcinomas, and 16 other types. T status was 1a in 230 patients, 1b in 274, and 2a in 360. Vascular invasion was observed in 326 patients, and lymphatic permeation in 169. Recurrence developed in 208 patients (24.1%), and 64 (7.4%) of them developed within 2 years after surgery. By multivariate analysis, vascular invasion (hazard ratio 3.441, 95% confidence interval 1.892-6.428) and moderate to poor differentiation (hazard ratio 3.252, 95% confidence interval 1.242-8.512) were shown to be independently significant risk factors for early recurrence. In patients with vascular invasion, distant failure occurred significantly more frequently than locoregional recurrence. The early recurrences were distant failure in 46 patients (72%). Of the 18 patients with locoregional recurrence only, 13 had malignant pleural effusion or pleural dissemination.Conclusion
Moderate to poor differentiation and vascular invasion were the significant predictors of early recurrence within 2 years after complete resection of p-stage I NSCLC. More than 90% of the early recurrences were disseminated diseases. Therefore, adjuvant chemotherapy after complete resection may be beneficial for p-stage I NSCLC patients with vascular invasion or moderately to poorly differentiated tumors.
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P1.19 - Poster Session 1 - Imaging (ID 179)
- Event: WCLC 2013
- Type: Poster Session
- Track: Imaging, Staging & Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.19-005 - Computer-aided lung nodule analysis focused on ground glass opacity and consolidation on thin-section computed tomography. (ID 1447)
09:30 - 09:30 | Author(s): Y. Matsumura
- Abstract
Background
Ground-glass opacity (GGO) component in a nodule on thin-section computed tomography (TSCT) often corresponds to a lepidic growth pattern of adenocarcinoma. In contrast, solid attenuation or consolidation on TSCT corresponds to invasive components. Many researchers reported consolidation tumor ratio (CTR; defined as the ratio of the size of solid attenuation to the maximum tumor dimension) was a reliable parameter in predicting tumor invasiveness. However, it has been pointed out that inter-/intra-observer variability in CTR measurement is a major problem in precise and reproducible evaluation of tumor characteristics. The aim of this study was to determine the optimal CT settings to reproducibly diagnose GGO and consolidation areas on TSCT by using an imaging software.Methods
We reviewed preoperative TSCT images of the patients undergoing surgical resection for T1 lung adenocarcinoma in our institution between 2005 and 2009. The TSCT images were obtained without contrast enhancement and reconstructed in 1.0 or 2 mm thickness, using several CT systems. The imaging software colored GGO areas with cut-off CT levels of -800, -700 and -600 HU. Consolidation areas were colored with cut-off CT levels of -300, -200 and -100 HU. These GGO/consolidations identified by the software were compared with those visually determined by the consensus of the 4 authors (EY, KA, YM, HO). The 4 authors scored the correspondence between visual evaluation and software identification according to the cut-off levels. The scores were summarized to determine the optimal cut-off CT levels.Results
We have reviewed 20 patients so far. Figure 1 shows a TSCT image and software-yielded image showing good correspondence with each other of GGO and consolidation areas. The best score was obtained when the cut-off level was -700 HU for GGO and -200 HU for consolidation. Figure1. Figure 1Conclusion
Although based on a small cohort, we found optimal cut-off CT levels to identify GGO and consolidation areas using an imaging software. We need to analyze more cases, but this image analysis method is promising in determining CTR reproducibly.
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P3.07 - Poster Session 3 - Surgery (ID 193)
- Event: WCLC 2013
- Type: Poster Session
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.07-045 - Thin-section computed tomography findings of lung adenocarinoma inherent with metastatic potential (ID 3259)
09:30 - 09:30 | Author(s): Y. Matsumura
- Abstract
Background
Pulmonary solid nodules on chest computed tomography (CT) included inflammatory nodule, benign tumor, carcinoid tumor, small cell lung cancer, large cell carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, and poorly-differentiated adenocarcinoma, and so on. If the solid nodule was highly suspicious of malignant tumor or diagnosed as being primary lung cancer, a surgical resection would be recommended as expeditiously as practicable because of its metastatic potential. On the other hand, most well-defined ground-glass nodules including part-solid nodules were atypical adenomatous hyperplasias or lung adenocarcinomas. The development of spatial resolution on CT had provided improvement in predicting malignancy of these nodule shadow suspected of lung cancer. The aim of this study was to elucidate the preoperative chest thin-section CT (TSCT) findings of lung nodules which were inherent with metastatic potential from the perspective of recurrence and long term results.Methods
We reviewed 392 primary lung adenocarcinomas with clinical T1N0M0 who underwent surgery between 2003 and 2007. Independent recurrence predicting parameters were extracted from the following ten parameters by using logistic regression analysis; sex, age, smoking index, preoperative serum carcinoembryonic antigen level, tumor location, maximum tumor size, consolidation tumor ratio (C/T ratio), tumor disappearance rate (TDR), the maximum size of consolidation at lung window setting (lung consolid), and the maximum size of consolidation at mediastinal window setting (med consolid). We evaluated extracted parameters by using receiver operating characteristic area under the curve (ROC-AUC) for recurrence prediction and identified these optimal cut-off levels of these parameters for prediction of whether patients had a good chance of being cured by surgical resection from their recurrence rate and survival.Results
The median follow-up period was seven years. The 75 of 392 patients recurred. C/T ratio, lung consolid, and TDR were extracted as an independent recurrence predictor. ROC-AUC of these parameters was 0.70, 0.71, and 0.64 for predicting recurrence, respectively. If C/T ratio was 0.5 or less, distant metastatic recurrence was observed in only one of 75 patients and if lung consolid was 10 mm or less, it was also observed in only one of 82 patients. There were significant differences in overall survival and recurrence free survival among two populations divided by these cut-off levels of C/T ratio and lung consolid.Conclusion
If the C/T ratio was 0.5 or less and/or lung consolid size was10 mm or less in cT1N0M0 lung adenocarcinoma patients, the recurrence rate was extremely low if they underwent a standard surgical resection. But when TSCT parameters of lung nodules exceeded these cut-off values, the recurrence rate wound increase and the prognosis would become worse even if they underwent complete resection. In these cases a prompt surgical resection would be recommended.
