TNM Classification For Lung Cancer Research Articles

The 7th edition of TNM for lung cancer: Implications for clinical care and research

The publication of any new TNM classification is always a major event for those clinicians and researchers involved in the study and treatment of a particular cancer. This was especially the case with the launch of the 7th Edition of the TNM Classification for Lung Cancer [1,2], being the first revision for 12 years and the most radical for 35 years. Unfortunately the scientific rigour of the analytical process required that it broke with the convention that each new edition was retrospectively compatible with earlier editions [3], and this will almost certainly be the case with future revisions.

Number of Lymph Nodes and Metastatic Lymph Node Ratio Are Associated With Survival in Lung Cancer

The non-small cell lung cancer TNM classification system uses only the anatomic extent of lymph node (LN) metastases to define the N category. The number of LNs resected and the ratio of positive LNs to total examined LNs are prognostic in other solid tumors. We used the Surveillance, Epidemiology and End Results database to investigate the effect of these factors on the overall survival of non-small cell lung cancer. All patients with non-small cell lung cancer in the Surveillance, Epidemiology and End Results database from 1988 through 2007 who had curative resections and had at least one LN examined were included. The prognostic value of age, race, sex, tumor size, histologic grade, number of examined LNs, and ratio of positive LNs to total examined LNs was assessed using a multivariate Cox proportional hazards model for overall survival. The number of LNs examined was categorized into four levels. The percentage of positive LNs was stratified into three levels. Among patients with localized disease, fewer LNs examined corresponded with a worse prognosis. Prognosis improved as more LNs were examined. For patients with regional disease, the differences were significant only at the extremes. Older patients, males, and those with higher grade or larger tumors did worse. Patients with low or moderate ratios of positive to total LNs had better prognoses than those with high ratios. More LNs resected and lower ratios of positive LNs to total examined LNs are associated with better patient survival after non-small cell lung cancer resection independent of age, sex, grade, tumor size, and stage of disease.

Computed tomographic atlas for the new international lymph node map for lung cancer: A radiation oncologist perspective

PurposeTo develop a reproducible definition for each mediastinal lymph node station based on the new TNM classification for lung cancer. Methods and MaterialsThis paper proposes an atlas using the new international lymph node map used in the seventh edition of the TNM classification for lung cancer. Four radiation oncologists and 1 diagnostic radiologist were involved in the project to put forward a reproducible radiologic description for the lung lymph node stations. ResultsThe International Association for the Study of Lung Cancer lymph node definitions for stations 1 to 11 have been described and illustrated on axial computed tomographic scan images using a certified radiotherapy planning system. ConclusionsThis atlas will assist both diagnostic radiologists and radiation oncologists in accurately defining the lymph node stations on computed tomographic scan in patients diagnosed with lung cancer.

Problems of the New TNM Classification of Lung Cancer from the Standpoint of Radiotherapy

目的．放射線治療からみた新しいTNM病期分類（UICC-7）の問題点と課題について検討した．方法．新分類においてT因子が腫瘍径別に細分化された．また，胸膜播種がT4からM1aに，同一肺葉内結節がT4からT3に変更された．N因子では，新しいリンパ節マップが示された．これら新分類の放射線治療からみた問題点について検討した．結果．腫瘍径3 cm以下のT1は，2 cmでT1aとT1bに細分化されたが，小型肺癌は放射線治療の対象となることが少なかったため，今後は定位放射線治療症例の蓄積と解析が必要である．腫瘍径5 cmで区分されるT2aとT2bは，過去の報告でも放射線治療成績に差がみられており妥当である．また，胸膜播種はM1aに変更されており，もともと根治的放射線治療の適応ではないことから簡便になった．一方，同一肺葉内結節がT4からT3に変更されたこと，従来#7と#10に分けられた気管分岐下リンパ節がすべて#7と定義されたことにより，これらの症例の中に根治的放射線治療の適応とならない症例が含まれる可能性が出てきた．結論．UICC-6と比較して，部分的に放射線治療の適応に即した改訂となったが，新たにT3やN2症例に根治的放射線治療の適応外となる症例が存在することに注意が必要である．

The 7th lung cancer TNM classification and staging system: Review of the changes and implications

Lung cancer is the most common cause of death from cancer in males, accounting for more than 1.4 million deaths in 2008. It is a growing concern in China, Asia and Africa as well. Accurate staging of the disease is an important part of the management as it provides estimation of patient's prognosis and identifies treatment sterategies. It also helps to build a database for future staging projects. A major revision of lung cancer staging has been announced with effect from January 2010. The new classification is based on a larger surgical and non-surgical cohort of patients, and thus more accurate in terms of outcome prediction compared to the previous classification. There are several original papers regarding this new classification which give comprehensive description of the methodology, the changes in the staging and the statistical analysis. This overview is a simplified description of the changes in the new classification and their potential impact on patients' treatment and prognosis.

Effects of reclassification from the TNM-6 into the TNM-7 staging system in bronchoplastic resection for non-small cell lung cancer

In 2007, the International Association for the Study of Lung Cancer proposed changes to the sixth edition of the lung cancer stage classification system, which were adopted by the Union Internationale Contre le Cancer in 2009 (TNM-7). Using historic patient data, the effects of reclassification from the TNM-6 to the TNM-7 system were researched within a single institution. We retrospectively reclassified the pathological records of 145 patients who underwent bronchoplastic resection for non-small cell lung cancer between 1991 and 2004, by applying the new TNM-7 classification for lung cancer. A comparison between the previous and the new system was conducted. Out of 145 patients, 49 (33.8%) were reclassified into a new stage, 42 (85.7% of reclassified cases) being allocated to a lower and seven (14.3%) being assigned to a higher stage. Most of the patients switched from stage IIB to IIA (n=31, 63.3%). The application of the new TNM-7 staging system resulted in a more accurate stratification of five-year survival curves. The newly revised TNM classification for lung cancer appears to be superior in defining different prognostic groups for this cohort and should lead to an improvement in stage specific tumor therapy.

The Impact of Superior Mediastinal Lymph Node Metastases on Prognosis in Non-small Cell Lung Cancer Located in the Right Middle Lobe

We aimed to assess hilar and mediastinal lymph node involvement and its impact on prognosis in patients with right middle lobe lung cancer. The records of 170 patients undergoing surgery for right middle lobe non-small cell lung cancer from 1980 to December 2007 were retrospectively examined. There were 45 patients found to have hilar or mediastinal lymph nodes metastases. This subgroup included 31 N2 patients and 14 N1 patients, and included 23 women and 22 men, whose ages ranged from 32 to 83 years (median = 61 years). The status of mediastinal, hilar, and interlobar lymph nodes was assessed according to the seventh edition of the TNM classification for lung cancer. Patient records were examined for age, gender, preoperative nodal status, surgical procedure, metastatic status of lymph nodes (distribution and numbers), tumor size, and histologic features (cell type and differentiation degree). Survival duration was defined as the interval between surgery and death from the tumor or the most recent follow-up. For N1 cases (n = 14), the most frequent metastatic site was #12m (lymph nodes adjacent to the middle lobe bronchus), which occurred in 11 cases; there was one case with metastases in #11s (lymph nodes between the upper lobe bronchus and bronchus intermedius), and no case with #11i metastases (lymph nodes between the right middle and lower lobe bronchi). The most frequent metastatic mediastinal zone was the subcarinal zone (25/31), and the superior mediastinal zone also had a high incidence of metastases (22/31). Sixteen cases had metastases to both the superior and subcarinal zones, and six cases had metastasis to superior mediastinal zone without subcarinal zone metastasis. When #11s or #11i was involved, eight of nine or five of five, respectively, were N2 cases. Univariate analyses revealed that tumor diameter, cN, status of lymph node metastases, and operative procedure (pneumonectomy) were significant prognostic factors in N2 cases. Regarding status of lymph node metastases, superior mediastinal zone metastases, both superior and inferior (subcarinal) zone metastases, and #11i were significant prognostic factors. Because #11i metastases and superior mediastinal lymph nodes metastases were highly correlated with each other (p = 0.02), two separate models were used in multivariate analyses. Superior mediastinal metastases (p = 0.03) and #11i metastases (p = 0.015) were revealed to be significant independent prognostic factors, whereas multiple-zone metastases only tended toward significance as an adverse prognostic factor (p = 0.054). Superior mediastinal lymph node metastases and #11i metastases were significant adverse prognostic factors in patients with middle lobe lung cancer, and they were associated with each other.

Prognostic Impact of Angiogenic Markers in Non–Small-Cell Lung Cancer is Related to Tumor Size

BackgroundIt is thought that different families of angiogenic factors stimulate angiogenesis at different stages of tumor development. Our aim was to study whether the prognostic impact of vascular endothelial growth factors (VEGFs) and receptors (VEGFRs), platelet-derived growth factors (PDGFs) and receptors (PDGFRs) and fibroblast growth factor-2 (FGF-2) were associated with tumor size in non–small-cell lung cancer (NSCLC). Patients and MethodsTumor tissue samples were obtained from 335 patients who had undergone resection for stage I-IIIA NSCLC, and tissue microarrays (TMAs) were constructed. Immunohistochemical techniques were used to evaluate the expression of VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, PDGF-A, PDGF-B, PDGFR-α, PDGFR-β, and FGF-2. Tumor size was categorized using the same cutoffs as in the 7th TNM classification for lung cancer. ResultsIn multivariate analysis, high VEGFR-2 (HR, 1.87, [95% CI, 1.02-3.45]; P = .043), VEGFR-3 (HR, 2.18 [95% CI, 1.28-3.71]; P = .004) and the combination of high VEGF-A and high VEGFR-2 expression (low/low vs. high/high; HR, 3.28 [95% CI, 1.47-7.31]; P = .004) were independent negative prognostic factors in T2a tumors. High PDGF-B expression (HR, 11.72 [95% CI, 3.07-44.76]; P < .001) was an independent prognostic factor in T2b tumors. ConclusionThe prognostic impact of angiogenic factors depend in part on tumor size. VEGF-A/VEGFR-2 and VEGFR-3 seem to have their main impact in T2a tumors, while PDGF-B is a strong and independent prognostic factor in T2b tumors.

TNM-Classification for Lung Cancer: From the 7th to the 8th Edition

Most tumors are staged according to the Tumor-Node-Metastasis (TNM) classification. For lung cancer a new edition was introduced in 2009 and generally applied since 2010. This 7th TNM-classification is based on a large, international retrospective database. Important changes were made regarding the T, N, M factors and specific subcategories were added. However, this 7th edition is still purely based on anatomical information. Other prognosticators such as laboratory results, histology, tumor markers and molecular genetic factors are not yet considered. To prepare the 8th TNM classification a prospective database developed by the International Association for the Study of Lung Cancer (IASLC), is currently enrolling patients from all continents. In this way, more precise and reliable data will become available on specific subdivisions of the T, N and M factors. If proven to be prognostically valid, other parameters will be included as histology, demographic data and specific biochemical and molecular predictive and prognostic factors. All centers with a large experience in thoracic oncology are encouraged to participate in this prospective database.

Tumor Size Evaluation according to the T Component of the Seventh Edition of the International Association for the Study of Lung Cancer's TNM Classification: Interobserver Agreement between Radiologists and Computer-Aided Diagnosis System in Patients with Lung Cancer

According to the seventh edition TNM staging system for non-small cell lung cancer (NSCLC), the T component was divided into T1a, T1b, T2a, T2b, and T3, depending on tumor size cut-offs of 2, 3, 5 and 7 cm because of significant differences in the five-year survival rates of patients with lung cancer, which are 53%, 47%, 43%, 36% and 26%, respectively (1). Therefore, accurate assessment of tumor size and staging is essential for patient management and prognosis prediction. Tumor size is affected by the morphology and location of the tumor, as irregular tumors and those in a juxtavascular loOriginal Article

Métastases pleurales des cancers bronchiques : une guérison est-elle possible ?

The 2009 TNM classification of lung cancer reclassified patients with pleural invasion from stage IIIB (T4) to stage IV (M+). However, the 2009 TNM separates patients with pleural metastases (M1a) from patients with others visceral metastases (M1b), the patients with stage M1a having the better prognosis. Two cases are reported of patients with non-small cell lung cancer (NSCLC) metastatic to the pleura, having a long disease free survival (50 and 34 months). Patients with pleural metastases from NSCLC seem to have a better prognosis than other patients with stage IV disease, maybe because of a subgroup of patients with long survival. This long survival is probably related to specific biological characteristics of certain pleural disorders that need to be identified. This would allow a more aggressive treatment of this subgroup of patients regarded today as incurable.

Computed tomography (CT) predicts accurately the pathologic tumour size in stage I non-small-cell lung cancer (NSCLC)

In stage I non-small-cell lung cancer (NSCLC) tumour size has been the most consistent determinant of survival. The choice of therapy option is based on accurate definition of the stage. The aim of our study is to correlate tumour size by computed tomography scan (CT) with pathologic size and to determine possible prognostic factors in surgically resected pathologic stage IA and IB NSCLC patients. Retrospective review of CT scans and medical history data from 89 pathologic stage I NSCLC patients. Clinical prognostic factors analysed were age, gender, smoking status, pulmonary function, performance status (PS), surgical procedure, histopathology, vessel invasion, pleural infi ltration, tumour size and number of lymph nodes resected. According to the new TNM classification for lung cancer, tumour size was divided into five groups (I: <2 cm, II: 2-3 cm, III: 3-5 cm, IV: 5-7 cm and V: >7 cm). After a median surveillance of 55.2 months, 42 patients relapsed and 55 had died. The 5-year progressionfree survival was 55.7% and 5-year overall survival (OS) 49.9% (median 58.97 months). None of the clinical parameters analysed were predictors of OS. Significant correlation was found between tumour size in CT scan and pathologic stage (Pearson 0.75). In our analysis with 89 surgically resected stage IA and IB NSCLC patients we found a good correlation between clinical and pathologic tumour size by CT scan. The prognoses factors analysed had no significant impact on survival.

Prognostic classifications of lymph node involvement in lung cancer and current International Association for the Study of Lung Cancer descriptive classification in zones

The lymphatic drainage of solid organ tumors crosses through the lymph nodes (LNs) whose tumoral involvement may still be considered as local disease. Concerning lung cancer, LN involvement may be intrapulmonary (N1), and mediastinal and/or extra-thoracic. More than 30 years ago, mediastinal involved LNs were all considered as N2, and outside the scope of surgery. In 1978, Naruke presented an original article entitled 'Lymph node mapping and curability at various levels of metastasis in resected lung cancer', demonstrating that N2 was not a contraindication to surgery in all patients. The map permitted to localize the favorable N2 on the lung cancer ipsilateral side of the mediastinum. Several maps ensued aiming to discriminate between right and left involvement (1983), and to distinguish N2 (ipsilateral) and N3 (contralateral) mediastinal LN involvement (1983, 1986). The last map (1997 regional LN classification) was recently replaced by a descriptive classification in anatomical zones. This new LN map of the TNM classification for lung cancer is a step toward using anatomical view points which might be the best way to better understand lung cancer lymphatic spread. Nowadays, the LNs are easily identified by current radiological imaging, and their resectability may be anticipated. Each LN chain may be removed by en-bloc lymphadenectomy performed during radical lung resection, a safe procedure which seems to be more oncological based than sampling, and which avoids the source of discrepancies pointed out during the labeling of LN stations by surgeons.

The impact of stage migration on survival after resection in the UICC 7 TNM classification of lung cancer.

7022 Background: A change of staging classification has been associated with improvements in stage-specific survival without improvement of overall survival (Feinstein, 1985). We aim to estimate in patients with resected non-small cell lung cancer (NSCLC), included in the IASLC staging database (Goldstraw, 2006) 1) the magnitude and direction of stage migration between the 6th and 7th editions of the UICC-TNM classification, and 2) its impact on stage-specific outcome. Methods: Resected NSCLC cases were extracted from the IASLC database and classified according to the 6th and 7th editions of UICC-pTNM. Cases having received preoperative chemotherapy and/or radiotherapy were excluded from the set; postoperative deaths were included, as were substages A and B for stage III only. Migration was estimated by calculating the rate of patients classified in any higher or lower UICC-7 p-stage over the corresponding UICC 6 p-stage. Outcome was estimated by the Kaplan-Meier method and expressed as 5-year survival rate (5y SR) with lower and upper 95% confidence intervals (95%CI). Results: Stage distribution of 15,952 cases with full pathological data, classified according to UICC 6 and 7, with corresponding overall and stage specific 5-y SR are in the Table. Overall, 2,480 cases (16%) migrate, of whom 1,747 (11%) to a higher and 733 (5%) to a lower stage. Substantial changes in 5y SR occur for pI (+3%) and pIIIB (-10%). Conclusions: The change of TNM staging classification of resected NSCLC from UICC6 to 7 results in the net migration of 1 out of 6 cases, to a higher stage in 70% of them, with substantial changes in 5y SR for p-stages I and IIIB. This stage migration should be accounted for when comparing outcome across series using different TNM classifications. UICC 6 UICC 7 Net migration Total 15,952 (100%) 2,480 (16%) 5y SR 47% (46-48) 0% pI 8,092 (51%) 6,766 (42%) - 5y SR 63% (62-64) 66% (65-67) +3% pII 3,544 (22%) 4,831 (30%) 1,476 (9%) 5y SR 39% (37-41) 41% (40-43) +2% pIIIA 3,091 (19%) 3,792 (24%) 701 (4%) 5y SR 25% (23-26) 24% (23-26) −1% pIIIB 1,042 (7%) 297 (2%) 71 (<1%) 5y SR 19% (17-22) 9% (6-13) −10% pIV 183 (1%) 266 (2%) 232 (2%) 5y SR 21% (15-27) 13% (9-17) −8% No significant financial relationships to disclose.

A Radiologic Review of the New TNM Classification for Lung Cancer

In 2009, a new TNM staging system was published by the International Union Against Cancer and the American Joint Committee on Cancer. The new edition will encompass non-small cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoids. This article will review many important changes that have been made in the revised staging system. It is important that radiologists learn the new system and understand the reasons for the changes to provide more accurate clinical staging.

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

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

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

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

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

The accurate assessment of lymph node involvement is an important part of the management of lung cancer. Lymph node "maps" have been used to describe the location of nodal metastases. However, discrepancies in nomenclature among maps used by Asian and Western countries hinder analyses of lung cancer treatment outcome. To achieve uniformity and to promote future analyses of a planned prospective international database, the International Association for the Study of Lung Cancer proposes a new lymph node map which reconciles differences among currently used maps, and provides precise anatomic definitions for all lymph node stations. A method of grouping lymph node stations together into "zones" is also proposed for the purposes of future survival analyses.

Intraoperative pleural lavage cytology after lung resection as an independent prognostic factor for staging lung cancer

Although malignant pleural effusion or dissemination is regarded as T4 per TNM classification of lung cancer, the prognostic significance in staging of pleural lavage cytologic examination remains undetermined. The purpose of this study was to clarify the utility of pleural lavage cytologic staging as a prognostic factor in patients with non-small cell lung cancer. In 1271 patients with lung cancer who underwent curative resection, intraoperative pleural lavage cytologic examination was performed at thoracotomy (first cytologic examination), immediately after pulmonary resection and mediastinal lymph node dissection (second cytologic examination), and after last washing of pleural cavity (third cytologic examination). Positive first cytologic result represented cytologic positive result before lung resection; positive second and third cytologic results were regarded as cytologic positive results after lung resection. Eighty-nine patients (7.0%) had positive findings of pleural lavage cytologic examination before or after lung resection. Five-year survivals were 44.1% for patients with positive results before lung resection and 23.4% for patients with positive results after lung resection, both significantly worse than that for patients with negative results. Multivariate analyses revealed that positive lavage result after lung resection was an independent prognostic factor. We found significantly greater pleural recurrence among patients with positive pleural lavage cytologic results after lung resection than among those with negative results. In addition to TNM classification, results of pleural lavage cytologic examination after lung resection should be considered when staging non-small cell lung cancer. Adjuvant systemic therapy may improve outcome for patients with positive results.

Prognostic significance of visceral pleural invasion in the forthcoming (seventh) edition of TNM classification for lung cancer

Background The next revision to the TNM classification for lung cancer (the seventh edition) is scheduled to be released in 2009. However, the definition of visceral pleural invasion (VPI), which is a non-size-based T2 descriptor, still lacks in detail, and its validation is not included. Methods We analyzed 1046 cases of non-small cell lung cancer (NSCLC) with T1, T2, or T3 diseases from 1990 to 2005, and subclassified into p0–p3 according to the degrees of pleural invasion. Survival analyses were performed using Kaplan–Meier method. Then, all patients were subdivided into nine groups according to tumor size and pleural invasion, and we compared survival differences, primarily focusing on T2a and T2b diseases according to the seventh edition. Results There was no survival difference between patients with p1 and p2, thus we regarded p1 or p2 as VPI. There was survival difference between two groups, which are expected to be classified as T2b. The behavior of tumors larger than 5 cm but 7 cm or less with VPI was similar to T3 tumors. Conclusions VPI is a poor prognostic factor of NSCLC, and the penetration through the elastic layer of the visceral pleura regardless of its exposure on the pleural surface (pl and p2) should be defined as VPI. This study also indicates that VPI influences T stage dependent on tumor size, and it can be suggested that tumors of larger than 5 cm but 7 cm or less with VPI should be upgraded to T3 stage.