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Original Research: Lung Cancer |

Change of Junctions Between Stations 10 and 4 in the New International Association for the Study of Lung Cancer Lymph Node MapLymph Node Map Changes Aid Lung Cancer Prognosis: A Validation Study from a Single, Tertiary Referral Hospital Experience FREE TO VIEW

Sunyoung Lee, MD; Ho Yun Lee, MD; Kyung Soo Lee, MD; Miyeon Yie, MD; Jaeil Zo, MD; Young Mog Shim, MD; Joungho Han, MD; Joong Hyun Ahn, MS
Author and Funding Information

From the Department of Radiology and Center for Imaging Science (Drs S. Lee, H. Y. Lee, K. S. Lee, and Yie), Department of Thoracic and Cardiovascular Surgery (Drs Zo and Shim), Department of Pathology (Dr Han), and Samsung Biomedical Research Institute (Mr Ahn), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

CORRESPONDENCE TO: Ho Yun Lee, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, South Korea; e-mail: hoyunlee96@gmail.com


FOR EDITORIAL COMMENT SEE PAGE 1203

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(5):1299-1306. doi:10.1378/chest.14-0717
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BACKGROUND:  Some tumors previously staged as N2 disease, using the Mountain-Dresler/American Thoracic Society (MD-ATS) map are staged as N1 per the new International Association for the Study of Lung Cancer (IASLC) lymph node (LN) map. We aimed to evaluate the effectiveness of the IASLC LN map in stratifying prognosis in patients with non-small cell lung cancer (NSCLC) and LN metastasis in nodal stations 4 or 10.

METHODS:  Of 2,086 patients undergoing curative surgical resection for NSCLC, we searched for patients who had LNs harboring cancer cells in nodal stations 10 or 4 (n = 531) and reclassified them into three different subgroups (N1 [N1 according to both the MD-ATS and IASLC maps], in-between [N2 according to the MD-ATS map but N1 by the IASLC map], and N2 [N2 according to both maps]) based on histopathologic results. We compared disease-free survival (DFS) among the three subgroups by using the Kaplan-Meier method and log-rank analysis.

RESULTS:  Of 531 patients, 295 belonged to the N1 group, 66 patients belonged to in-between group, and 170 patients belonged to N2 group, according to the IASLC map. The cumulative DFS rates at 5 years for the N1, in-between, and N2 groups were 47%, 39%, and 29%, respectively. In multivariate analysis, LN ratio was identified as significant independent prognostic factor (hazard ratio, 2.877; 95% CI, 1.391-5.950; P = .004).

CONCLUSIONS:  The changed definition between N1 and N2 diseases by the IASLC LN map works well, as expected, in stratifying patient prognosis. Positive LN ratio may be more valuable than the nodal stations involved in predicting patient survival in resectable NSCLC.

Figures in this Article

The map of the mediastinal and pulmonary lymph nodes (LNs), which was proposed by Mountain and Dresler and modified by the American Thoracic Society (MD-ATS map),1 gained wide acceptance and became a standard for nodal staging in non-small cell lung cancer (NSCLC). However, the LN map has some shortcomings in terms of its clarity in describing specific nodal-station localization. Moreover, Japanese surgeons and oncologists continuous to use the Naruke map, as advocated by the Japan Lung Cancer Society.2

Recently, the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Staging Project revised a new LN map to provide more specific anatomic definition and to achieve international uniformity of LN status.3,4 This new map renders important changes compared with the MD-ATS and Naruke maps.5 One of the significant discrepancies in nomenclature between the MD-ATS and new IASLC maps is the junctions between stations 4 and 10 nodes. The previous definition of the lower border of 4R was a horizontal line extending across the right main bronchus at the upper margin of the origin of the upper lobar bronchus. It is currently at the lower border of the azygos vein. Similarly, the definition of the lower border of 4L changed from a horizontal line extending across the left main bronchus at the upper margin of the origin of the upper lobe bronchus to the upper rim of the left main pulmonary artery.6 Consequently some tumors staged as N2 or stage IIIA according to the MD-ATS map may be staged as N1 or stage II when adopting the new LN map.5 To confirm the validity of N descriptors proposed by the IASLC, we compared the prognostic implication of the new IASLC LN map with those of the MD-ATS map in terms of disease-free survival (DFS) between patients classified into having stations 10 and 4 nodes.

This retrospective study was approved by our institutional review board (approval #2012-05-095). Informed consent was waived.

Patient Population

From 2008 to 2011, a total of 2,086 consecutive patients with primary NSCLC underwent curative surgery at our institution, and complete pathologic staging was available for these patients. All patients received the resection of a primary tumor and complete mediastinal and hilar LN dissection. Among those, 736 patients had LN metastases in the N1 or N2 region (pN1 or pN2) based on the MD-ATS map. Of these 736 patients, we excluded 147 with a prior history of malignant disease, those receiving induction chemotherapy or radiotherapy before curative resection, or those with incomplete resection or microscopic or macroscopic residual disease. Then, we additionally excluded 58 patients with pN1 or N2 disease involving LNs other than stations 10 or 4.

Two chest radiologists (one with 10 and one with 5 years of chest CT scan interpretation experience) reviewed both axial and coronal CT images of the final cohort of 531 patients. Before imaging and surgical correlation for nodes of our interest, we made sure the nodes seen on transverse CT images were located in the peribronchial area on coronal images, by adopting a cross-reference technique (indicating LNs on transverse and coronal images) on picture archiving and communication systems monitors (Figs 1, 2). Individual nodal stations identified on CT images were matched carefully with surgically dissected nodes by reviewing medical records. Pathologic results of the matched nodes were recorded. Thus, we tried to deter mismatching of one nodal station seen on CT imaging with the adjacent nodal station on surgery. In consideration of the proposals of the IASLC staging committee,3,4,6 involved nodal stations on CT scans were reclassified into three subgroups: (1) N1 nodes by both the MD-ATS map and the IASLC map (N1 group), (2) N2 nodes by the MD-ATS map but reclassified nodes as N1 by IASLC map (in-between group), and (3) N2 nodes by both the MD-ATS map and the IASLC map (N2 group) (Figs 1, 2).

Figure Jump LinkFigure 1 –  A, B, Illustrations for station 4 (pink) and station 10 (blue) on the MD-ATS map and the new IASLC map. On the illustration between those two maps, the red area represents the in-between group (N2 by the MD-ATS map and reclassified as N1 by IASLC map). C, D, Coronal CT image and added horizontal and vertical bars for clarifying the distinction between stations 4 and 10 in MD-ATS and IASLC maps and among the three groups (N1, in-between, and N2 stations). Ao = aorta; IASLC = International Association for the Study of Lung Cancer; LN = lymph node; MD-ATS = Mountain-Dresler/American Thoracic Society; mPA = main pulmonary artery.Grahic Jump Location
Figure Jump LinkFigure 2 –  A, Contrast-enhanced coronal image. B, Axial CT image. Both were obtained with mediastinal window settings and show enlarged lymph node (arrows) at the level of left main pulmonary artery. The node was found to be involved on pathologic analysis. Under the MD-ATS map, the LN would have been classified as a 4L (N2) node, but under the new IASLC map, it is classified as a 10L (N1) node. According to the MD-ATS definition, 4R and 10R were separated by a horizontal line extending across the right main bronchus at the upper margin of upper lobar bronchus origin (yellow line below mPA). This line has now moved to the lower border of the azygos vein (red line). Likewise, a landmark between 4L and 10L has been changed from a line extending across the left main bronchus at the upper margin of the upper lobar bronchus (yellow line) to the upper rim of the left main pulmonary artery (red line). Therefore, the enlarged LN (white arrow) in the left mediastinum is classified as 10L with the IASLC map and as 4L with the MD-ATS map. Az = azygos vein; SVC = superior vena cava. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Preoperative Staging

Noninvasive clinical staging was conducted with chest CT scans and integrated PET-CT scans in all patients. At our institution, for patients with preoperatively proven NSCLC, cervical mediastinoscopy was routinely performed regardless of the observed findings on CT or PET-CT scans. The mediastinoscopy was waived in following patients: those who were not the candidates for neoadjuvant concurrent chemoradiation therapy for subsequent surgery because of old age or comorbidities (n = 29) and those who underwent endobronchial ultrasound with transbronchial needle aspiration (n = 25). Patients with negative mediastinal nodes underwent directly thoracotomy, whereas those with positive nodes received neoadjuvant therapy and subsequent thoracotomy.

Surgical Approach

The surgery was performed for the affected lung, consisting of segmentectomy, lobectomy, bilobectomy, and pneumonectomy. Segmentectomy was performed only for high-risk patients. All patients received complete mediastinal and hilar LN dissection. The LN dissection criteria include the exploration of the fissures, the hilus of the lung, and all of the ipsilateral mediastinal LN zones and en bloc removal of all LNs.

Analysis of Metastatic LNs

The surgeons labeled the dissected LNs by numbering the nodes based on the LN map. A pathologist with 17 years’ experience in lung cancer diagnosis evaluated the nodes and recorded the absence or presence of tumor cells in the nodes according to how they were numbered in the surgical field by using hematoxylin-and-eosin staining of the specimens.

The number of positive LNs for cancer cells from each defined anatomic nodal location was recorded. The LN ratio was defined as the ratio of positive LNs divided by the total number of harvested LNs.7 The presence of extracapsular extension of the positive LNs was also assessed.

Follow-up and Survival

Postsurgical therapy was administered at the discretion of physicians in charge, and the adjuvant therapy included radiation, chemotherapy, or chemoradiotherapy. The adjuvant treatment was administered in the event of histologically positive N2 status at the surgery, positive multi-N1 status, the presence of extracapsular extension of positive LN, or a positive resection margin at the time of pathologic staging.

After the completion of treatment, patients were followed up at 3-month intervals with chest CT scans to identify any disease recurrence for the following 12 months. Chest CT scans were followed up at 6-month intervals for 3 years and every year thereafter. When recurrence was suggested, additional imaging studies including whole-body PET-CT scans, brain MRI, or bone scan were performed. We diagnosed tumor recurrence based on imaging-study findings, which were confirmed histopathologically when the tumor was clinically and anatomically accessible.

Statistical Analysis

Patient demographics and clinical variables were compared among the three different subgroups based on LN station (ie, N1, in-between, and N2) by using one-way analysis of variance with post hoc test of Bonferroni. DFS was defined as the time from surgery to locoregional or distant relapse of lung cancer, if without relapse; any deaths due to causes other than lung cancer would be censored. The survival curves were estimated by the Kaplan-Meier method, and differences among subgroups in survival were determined by log-rank analysis. Multivariate analysis was also performed using Cox proportional hazards models to evaluate independent prognostic factors. Statistical analysis was performed using SPSS for Windows version 20.0 (IBM Corp). Continuous variables are expressed as the mean ± SD. A P value < .05 was considered statistically significant.

Patient Characteristics

The 531 patients in this study consisted of 390 men and 141 women with a mean age of 62 ± 9 years (range, 24-86 years). The characteristics of the patients are presented in Table 1.

Table Graphic Jump Location
TABLE 1 ]  Patient Characteristics

Data are given as No. (%) unless otherwise indicated. LN = lymph node.

a 

The differences in the distribution between three groups were compared using one-way analysis of variance with post hoc test of Bonferroni.

b 

N1 vs in-between, P = .009; N1 vs N2, P < .001.

c 

N1 vs in-between, P = .047; N1 vs N2, P < .001.

d 

LN ratio was defined as the ratio of positive LNs divided by the total number of harvested LNs.

e 

N1 vs in-between, P = .041; N1 vs N2, P < .001; N2 vs in-between, p < 0.001.

f 

N1 vs in-between, P = .005; N1 vs N2, P < .001.

g 

N1 vs N2, P = .012.

Adenocarcinoma (52.0%) was the most frequent tumor histology, followed by squamous cell carcinoma (41.0%), large cell carcinoma (6.0%), and undifferentiated carcinoma (1.0%). The most frequent surgery performed was lobectomy (74.8%), followed by pneumonectomy (12.4%). Adjuvant treatment including radiation, chemotherapy, or chemoradiotherapy was performed in 428 patients (80.6%). The median number of LNs resected and examined was 22 per patient (range, 1-83) for both N1 and N2 regions. The median number of LNs, identified as metastatic LNs involving nodal stations 4 and 10 only, was 2.5 per patient (range, 1-14). The LN ratio among all nodes harvested ranged from 0.02 to 1.00, with a mean of 0.14.

LNs in the 531 patients were classified as N1 nodes in 295 patients (55.6%), in-between nodes in 66 patients (12.4%), and N2 nodes in 170 patients (32.0%). The distribution of sex, histopathologic subtype, and metastatic LNs were different among the three groups, but the other main characteristics, including age, T staging, tumor differentiation, type of operation, or the presence of adjuvant therapy, were not different among them. The male to female ratio was higher in the N1 node group compared with the in-between and N2 nodal groups (0.81, 0.64, and 0.64, respectively). Adenocarcinoma was the more frequent cell type in patients in the N2 group. Patients in the N1 nodal group were more likely to have a squamous cell carcinoma. Patients in the N2 nodal group has a significantly higher LN ratio and presence of extracapsular extension than other nodal groups.

All patients were followed until either death or the last follow-up date (December 31, 2012). The median follow-up period was 25 months (range, 1-60 months). During the follow-up period, 254 patients (47.8%) suffered from locoregional or distant recurrence.

Prognosis According to LN Station

DFS curves for 282 N1 and 79 N2 patients, according to the MD-ATS map, are shown in Figure 3A. Patients with N1 and N2 disease showed significant survival differences (P = .002). The DFS curves showed clear survival differences among the three groups classified using the new IASLC map (P = .001) (Fig 3B). The prognoses of patients in the N1, in-between, and N2 groups were analyzed; the results are shown in Figure 3C. The cumulative DFS rates at 5 years of the N1, in-between, and N2 nodal groups were 47%, 39%, and 29%, respectively. The prognosis of the in-between group was between that of N1 disease and N2 disease. No statistically significant difference in survival was observed between the N1 and in-between groups; however, a statistically significant difference was observed between the in-between and N2 groups (P = .042).

Figure Jump LinkFigure 3 –  The survival curves according to different lymph node station. A, Disease-free survival (DFS) curves for the MD-ATS map. B, DFS curves for the new IASLC map. C, DFS curves for reclassified categories. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Multivariate Analysis of Prognostic Factors

In a multivariate analysis, histopathologic subtype and LN ratio were identified as significant prognostic factors (hazard ratio, 1.624; 95% CI, 1.313-2.009; P < .001; and hazard ratio, 2.877; 95% CI, 1.391-5.950; P = .004, respectively) (Table 2).

Table Graphic Jump Location
TABLE 2 ]  Cox Proportional Hazards Model to Predict Survival

PD = poorly differentiated; SCC = squamous cell carcinoma. See Table 1 legend for expansion of other abbreviation.

Accurate staging of LN involvement is critical in patients with NSCLC because it influences the selection of treatment and outcome prediction.3 Although the IASLC Lung Cancer Staging Project established a new LN map to provide internationally uniform and precise anatomic definitions, sufficient external validation studies are required for supporting the new LN map.

In our study, we tested the validity of the new IASLC LN map in which the definitions of N1 and N2 nodal stations were reestablished. The meaning of prognostic stratification into previous N1 and N2 nodal stations based on the MD-ATS LN map was also verified. We found that by demonstrating no statistical significance between the N1 and in-between groups and a significant difference between the in-between and N2 groups, the new IASLC LN map better reflects prognosis than the MD-ATS LN map.

Our results are similar to the study of Asamura et al.8 The MD-ATS LN map divides the N1-N2 boundary based on the location of LNs and their relation to pleural reflection. However, in the Naruke-Japanese map, the LN station was defined in consideration of the interrelationship between LNs and the bronchial trees or mediastinal structures without consideration of LNs and the pleural reflection relationship. But, from anatomic and surgical viewpoints, most of the right main stem bronchus is located somewhat beneath the mediastinal pleura and is surgically accessible. Owing to these confusing definitions of the N1-N2 boundary, metastatic LNs around the right main stem bronchus have been considered station 10 (N1) nodes by the Naruke map, but station 4 (N2) nodes by the MD-ATS LN map. Asamura et al8 showed there is no significant difference in patient survival between N1 and N1 with station 10 (peribronchial nodal) involvement, but a significant difference is seen between N1 with station 10 and N2 nodal involvements. Therefore, they concluded that in terms of prognosis, a pleural reflection does not appear to be an appropriate anatomic boundary dividing N1 and N2 stations in NSCLC.

The rationale of the new IASLC LN map for separating these more distal (peripheral) nodal stations from more proximal (central) stations and calling them 10R or 10L LNs rather than 4R and 4L LNs, as in the original Naruke map, was based on the fact that the prognosis of their involvements appears to be between those of N1 and N2 diseases. In other words, like the results of Asamura’s group,8 the progressive degradation of patient prognosis was identified as the disease spreads centrally (proximally) along the lymphatic channels.4 In fact, the Asamura et al8 study was based on LN location classified by the surgeon during LN dissection; therefore, the limitation of determining nodal stations involved during surgery is the lack of reproducibility and the disagreement between surgeons’ calling of the involved LNs. In our study, however, we determined a more precise LN location by reviewing both axial and coronal CT images of involved nodes and correlating the anatomic location with that of pathologic results and surgical reports.

Meanwhile, some studies have suggested that revised N descriptors in the new IASLC lung cancer staging support the idea of calculating overall tumor burden by counting involved nodal station numbers rather than by just the anatomic location of involved LNs, and such an approach can help predict patient prognosis more accurately.3,913 Disease burden of involved LNs is defined as the number of metastatic LNs. Prior studies demonstrated that the number of metastatic LNs is an independent prognostic factor in patients who have undergone resection for NSCLC.9,10,1215 In the latest TNM classification for some other malignancies, including breast, gastric, and colorectal cancers, the number of involved LNs has been considered in the N descriptor, and the category of involved number of LNs has been shown to correlate significantly with patient prognosis.16

Taking a step forward, Bria et al11 also showed that LN ratio was a risk factor for predicting patient prognosis. They demonstrated that LN ratio is an independent factor for survival prediction in 415 patients with N1 and N2 disease. Three studies using the Surveillance, Epidemiology, and End Results-Medicare registry showed that higher LN ratio was associated with worse lung cancer-specific and overall survival in a large cohort of patients with N1 NSCLC.1719 Similarly, in our study, univariate and multivariate analyses disclosed that the positive LN ratio is an independent prognostic factor for survival. In conjunction with previous studies, our results suggest that the overall tumor burden, rather than just the positive nodal status per se, may have the most important clinical implications on patient outcome. Patients with a higher LN ratio appear to have high risk for recurrence and should be considered candidates for more aggressive postsurgical therapies and for increased surveillance for recurrence.

As typical of retrospective studies, our study is limited by biases such as lack of random assignment, patient selection, and incomplete data acquisition. The use of patients from a single large cancer center may reflect a cohort with more aggressive disease, which is the referral pattern for such a center.

In conclusion, the changed definition between N1 and N2 disease by IASLC LN map works well, as expected, in stratifying patient prognosis. Positive LN ratio may be more valuable than nodal stations involved in predicting patient survival in resectable NSCLC.

Author contributions: H. Y. L. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. S. L. served as principal author. S. L., H. Y. L., K. S. L., M. Y., J. Z., Y. M. S., J. H., and J. H. A. contributed to the study design, data collection, and writing the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The authors gratefully thank to Sung-kab Kim, BA, Department of Medical Information & Media Services, Samsung Medical Center, Seoul, South Korea, for beautiful illustrations.

DFS

disease-free survival

IASLC

International Association for the Study of Lung Cancer

LN

lymph node

MD-ATS

Mountain-Dresler modification of the American Thoracic Society

NSCLC

non-small cell lung cancer

Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest. 1997;111(6):1718-1723. [CrossRef] [PubMed]
 
Naruke T, Suemasu K, Ishikawa S. Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg. 1978;76(6):832-839. [PubMed]
 
Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2007;2(7):603-612. [CrossRef] [PubMed]
 
Zieliński M, Rami-Porta R. Proposals for changes in the Mountain and Dresler mediastinal and pulmonary lymph node map. J Thorac Oncol. 2007;2(1):3-6. [CrossRef] [PubMed]
 
Pitson G, Lynch R, Claude L, Sarrut D. A critique of the international association for the study of lung cancer lymph node map: a radiation oncology perspective. J Thorac Oncol. 2012;7(3):478-480. [CrossRef] [PubMed]
 
Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4(5):568-577. [CrossRef] [PubMed]
 
Qiu C, Dong W, Su B, Liu Q, Du J. The prognostic value of ratio-based lymph node staging in resected non-small-cell lung cancer. J Thorac Oncol. 2013;8(4):429-435. [CrossRef] [PubMed]
 
Asamura H, Suzuki K, Kondo H, Tsuchiya R. Where is the boundary between N1 and N2 stations in lung cancer? Ann Thorac Surg. 2000;70(6):1839-1845. [CrossRef] [PubMed]
 
Fukui T, Mori S, Yokoi K, Mitsudomi T. Significance of the number of positive lymph nodes in resected non-small cell lung cancer. J Thorac Oncol. 2006;1(2):120-125. [CrossRef] [PubMed]
 
Lee JG, Lee CY, Park IK, et al. Number of metastatic lymph nodes in resected non-small cell lung cancer predicts patient survival. Ann Thorac Surg. 2008;85(1):211-215. [CrossRef] [PubMed]
 
Bria E, Milella M, Sperduti I, et al. A novel clinical prognostic score incorporating the number of resected lymph-nodes to predict recurrence and survival in non-small-cell lung cancer. Lung Cancer. 2009;66(3):365-371. [CrossRef] [PubMed]
 
Wei S, Asamura H, Kawachi R, Sakurai H, Watanabe S. Which is the better prognostic factor for resected non-small cell lung cancer: the number of metastatic lymph nodes or the currently used nodal stage classification? J Thorac Oncol. 2011;6(2):310-318. [CrossRef] [PubMed]
 
Macia I, Ramos R, Moya J, et al. Survival of patients with non-small cell lung cancer according to lymph node disease: single pN1 vs multiple pN1 vs single unsuspected pN2. Ann Surg Oncol. 2013;20(7):2413-2418. [CrossRef] [PubMed]
 
Ruffini E, Filosso PL, Bruna MC, et al. Recommended changes for T and N descriptors proposed by the International Association for the Study of Lung Cancer - Lung Cancer Staging Project: a validation study from a single-centre experience. Eur J Cardiothorac Surg. 2009;36(6):1037-1044. [CrossRef] [PubMed]
 
Takamochi K, Oh S, Suzuki K. Prognostic evaluation of nodal staging based on the new IASLC lymph node map for lung cancer. Thorac Cardiovasc Surg. 2010;58(6):345-349. [CrossRef] [PubMed]
 
Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 2010;17(12):3077-3079. [CrossRef] [PubMed]
 
Wisnivesky JP, Arciniega J, Mhango G, Mandeli J, Halm EA. Lymph node ratio as a prognostic factor in elderly patients with pathological N1 non-small cell lung cancer. Thorax. 2011;66(4):287-293. [CrossRef] [PubMed]
 
Jonnalagadda S, Arcinega J, Smith C, Wisnivesky JP. Validation of the lymph node ratio as a prognostic factor in patients with N1 nonsmall cell lung cancer. Cancer. 2011;117(20):4724-4731. [CrossRef] [PubMed]
 
Nwogu CE, Groman A, Fahey D, et al. Number of lymph nodes and metastatic lymph node ratio are associated with survival in lung cancer. Ann Thorac Surg. 2012;93(5):1614-1619. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  A, B, Illustrations for station 4 (pink) and station 10 (blue) on the MD-ATS map and the new IASLC map. On the illustration between those two maps, the red area represents the in-between group (N2 by the MD-ATS map and reclassified as N1 by IASLC map). C, D, Coronal CT image and added horizontal and vertical bars for clarifying the distinction between stations 4 and 10 in MD-ATS and IASLC maps and among the three groups (N1, in-between, and N2 stations). Ao = aorta; IASLC = International Association for the Study of Lung Cancer; LN = lymph node; MD-ATS = Mountain-Dresler/American Thoracic Society; mPA = main pulmonary artery.Grahic Jump Location
Figure Jump LinkFigure 2 –  A, Contrast-enhanced coronal image. B, Axial CT image. Both were obtained with mediastinal window settings and show enlarged lymph node (arrows) at the level of left main pulmonary artery. The node was found to be involved on pathologic analysis. Under the MD-ATS map, the LN would have been classified as a 4L (N2) node, but under the new IASLC map, it is classified as a 10L (N1) node. According to the MD-ATS definition, 4R and 10R were separated by a horizontal line extending across the right main bronchus at the upper margin of upper lobar bronchus origin (yellow line below mPA). This line has now moved to the lower border of the azygos vein (red line). Likewise, a landmark between 4L and 10L has been changed from a line extending across the left main bronchus at the upper margin of the upper lobar bronchus (yellow line) to the upper rim of the left main pulmonary artery (red line). Therefore, the enlarged LN (white arrow) in the left mediastinum is classified as 10L with the IASLC map and as 4L with the MD-ATS map. Az = azygos vein; SVC = superior vena cava. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3 –  The survival curves according to different lymph node station. A, Disease-free survival (DFS) curves for the MD-ATS map. B, DFS curves for the new IASLC map. C, DFS curves for reclassified categories. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Patient Characteristics

Data are given as No. (%) unless otherwise indicated. LN = lymph node.

a 

The differences in the distribution between three groups were compared using one-way analysis of variance with post hoc test of Bonferroni.

b 

N1 vs in-between, P = .009; N1 vs N2, P < .001.

c 

N1 vs in-between, P = .047; N1 vs N2, P < .001.

d 

LN ratio was defined as the ratio of positive LNs divided by the total number of harvested LNs.

e 

N1 vs in-between, P = .041; N1 vs N2, P < .001; N2 vs in-between, p < 0.001.

f 

N1 vs in-between, P = .005; N1 vs N2, P < .001.

g 

N1 vs N2, P = .012.

Table Graphic Jump Location
TABLE 2 ]  Cox Proportional Hazards Model to Predict Survival

PD = poorly differentiated; SCC = squamous cell carcinoma. See Table 1 legend for expansion of other abbreviation.

References

Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest. 1997;111(6):1718-1723. [CrossRef] [PubMed]
 
Naruke T, Suemasu K, Ishikawa S. Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg. 1978;76(6):832-839. [PubMed]
 
Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2007;2(7):603-612. [CrossRef] [PubMed]
 
Zieliński M, Rami-Porta R. Proposals for changes in the Mountain and Dresler mediastinal and pulmonary lymph node map. J Thorac Oncol. 2007;2(1):3-6. [CrossRef] [PubMed]
 
Pitson G, Lynch R, Claude L, Sarrut D. A critique of the international association for the study of lung cancer lymph node map: a radiation oncology perspective. J Thorac Oncol. 2012;7(3):478-480. [CrossRef] [PubMed]
 
Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4(5):568-577. [CrossRef] [PubMed]
 
Qiu C, Dong W, Su B, Liu Q, Du J. The prognostic value of ratio-based lymph node staging in resected non-small-cell lung cancer. J Thorac Oncol. 2013;8(4):429-435. [CrossRef] [PubMed]
 
Asamura H, Suzuki K, Kondo H, Tsuchiya R. Where is the boundary between N1 and N2 stations in lung cancer? Ann Thorac Surg. 2000;70(6):1839-1845. [CrossRef] [PubMed]
 
Fukui T, Mori S, Yokoi K, Mitsudomi T. Significance of the number of positive lymph nodes in resected non-small cell lung cancer. J Thorac Oncol. 2006;1(2):120-125. [CrossRef] [PubMed]
 
Lee JG, Lee CY, Park IK, et al. Number of metastatic lymph nodes in resected non-small cell lung cancer predicts patient survival. Ann Thorac Surg. 2008;85(1):211-215. [CrossRef] [PubMed]
 
Bria E, Milella M, Sperduti I, et al. A novel clinical prognostic score incorporating the number of resected lymph-nodes to predict recurrence and survival in non-small-cell lung cancer. Lung Cancer. 2009;66(3):365-371. [CrossRef] [PubMed]
 
Wei S, Asamura H, Kawachi R, Sakurai H, Watanabe S. Which is the better prognostic factor for resected non-small cell lung cancer: the number of metastatic lymph nodes or the currently used nodal stage classification? J Thorac Oncol. 2011;6(2):310-318. [CrossRef] [PubMed]
 
Macia I, Ramos R, Moya J, et al. Survival of patients with non-small cell lung cancer according to lymph node disease: single pN1 vs multiple pN1 vs single unsuspected pN2. Ann Surg Oncol. 2013;20(7):2413-2418. [CrossRef] [PubMed]
 
Ruffini E, Filosso PL, Bruna MC, et al. Recommended changes for T and N descriptors proposed by the International Association for the Study of Lung Cancer - Lung Cancer Staging Project: a validation study from a single-centre experience. Eur J Cardiothorac Surg. 2009;36(6):1037-1044. [CrossRef] [PubMed]
 
Takamochi K, Oh S, Suzuki K. Prognostic evaluation of nodal staging based on the new IASLC lymph node map for lung cancer. Thorac Cardiovasc Surg. 2010;58(6):345-349. [CrossRef] [PubMed]
 
Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 2010;17(12):3077-3079. [CrossRef] [PubMed]
 
Wisnivesky JP, Arciniega J, Mhango G, Mandeli J, Halm EA. Lymph node ratio as a prognostic factor in elderly patients with pathological N1 non-small cell lung cancer. Thorax. 2011;66(4):287-293. [CrossRef] [PubMed]
 
Jonnalagadda S, Arcinega J, Smith C, Wisnivesky JP. Validation of the lymph node ratio as a prognostic factor in patients with N1 nonsmall cell lung cancer. Cancer. 2011;117(20):4724-4731. [CrossRef] [PubMed]
 
Nwogu CE, Groman A, Fahey D, et al. Number of lymph nodes and metastatic lymph node ratio are associated with survival in lung cancer. Ann Thorac Surg. 2012;93(5):1614-1619. [CrossRef] [PubMed]
 
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