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The largest randomised controlled trial evaluating results of lung volume reduction surgery (LVRS) was conducted by the National Emphysema Treatment Trial (NETT) that published a series of reports for outcomes up to 24 months. However, patient outcomes were difficult to interpret due to limitations in and the presentation of conventional statistical analyses applied to longitudinal data. We reevaluated the NETT results using longitudinal data methodology to report longer-term outcomes to facilitate interpretation by clinicians and patients who are considering LVRS for emphysema management.Trial data were released by the United States National Institutes of Health and the National Heart, Lung, and Blood Institute and analyzed using a mixed-effects model. Data on the difference in lung function variables between patients receiving LVRS vs medical care out to 5 years were estimated and are presented.The 5-year differences in patients randomised to LVRS were a small but sustained improvement in lung function indicators of forced expiratory volume in 1 second, forced vital capacity, and residual volume of +1.4% (P.001), +3.44% (P.001) and -19.49% (P.001) of the predicted values, respectively. With regards to physiological function, the 5-year difference in patients randomised to LVRS was an overall 0.89 W improvement in maximum workload (P = .069), -4.12 improvement in shortness of breath score (P.001), and 0.088 improvement in quality of well-being score (P = .102).Our results suggest that LVRS continues to have an important role in the treatment of patients with severe emphysema, with long-term benefits to lung function variables and a sustained improvement to the relief of dyspnea.

This primer for eighth edition staging of esophageal and esophagogastric epithelial cancers presents separate classifications for the clinical (cTNM), pathologic (pTNM), and postneoadjuvant pathologic (ypTNM) stage groups, which are no longer shared. For pTNM, pT1 has been subcategorized as pT1a and pT1b for the subgrouping pStage I adenocarcinoma and squamous cell carcinoma. A new, simplified esophagus-specific regional lymph node map has been introduced. Undifferentiated histologic grade (G4) has been eliminated; additional analysis is required to expose histopathologic cell type. Location has been removed as a category for pT2N0M0 squamous cell cancer. The definition of the esophagogastric junction has been revised. ypTNM stage groups are identical for both histopathologic cell types, unlike those for cTNM and pTNM.

Introduction Patients with lung cancer who harbor multiple pulmonary sites of disease have been challenging to classify; a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee was charged with developing proposals for the eighth edition of the tumor, node, and metastasis (TNM) classification to address this issue. Methods A systematic literature review and analysis of the International Association for the Study of Lung Cancer database was performed to develop proposals for revision in an iterative process involving multispecialty international input and review. Results Details of the evidence base are summarized in other articles. Four patterns of disease are recognized; the clinical presentation, pathologic correlates, and biologic behavior of these suggest specific applications of the TNM classification rules. First, it is proposed that second primary lung cancers be designated with a T, N, and M category for each tumor. Second, tumors with a separate tumor nodule of the same histologic type (either suspected or proved) should be classified according to the location of the separate nodule relative to the index tumor—T3 for a same-lobe, T4 for a same-side (different lobe), and M1a for an other-side location—with a single N and M category. Third, multiple tumors with prominent ground glass (imaging) or lepidic (histologic) features should be designated by the T category of the highest T lesion, the number or m in parentheses (#/m) to indicate the multiplicity, and a collective N and M category for all. Finally, it is proposed that diffuse pneumonic-type lung cancers be designated by size (or T3) if in one lobe, T4 if involving multiple same-side lobes, and M1a if involving both lungs with a single N and M category for all areas of involvement. Conclusion We propose to tailor TNM classification of multiple pulmonary sites of lung cancer to reflect the unique aspects of four different patterns of presentation. We hope that this will lead to more consistent classification and clarity in communication and facilitate further research in the nature and optimal treatment of these entities.

Introduction Nodal status is considered to be one of the most reliable indicators of the prognosis in patients with lung cancer and thus is indispensable in determining the optimal therapeutic options. We sought to determine whether the current nodal (N) descriptors should be maintained or revised for the next edition (8th) of the International Lung Cancer Staging System. Methods The new International Association for the Study of Lung Cancer lung cancer database was created from 94,708 patients diagnosed as having lung cancer between 1999 and 2010. Among these, 38,910 and 31,426 patients with non–small-cell lung carcinoma were available for an analysis of the clinical (c)N and pathological (p)N status, respectively. The anatomical location of lymph node involvement was defined by either the Naruke (for Japanese data) or American Thoracic Society (for non-Japanese data) nodal charts. Survival was calculated by the Kaplan–Meier method, and prognostic groups were assessed by a Cox regression analysis. Results The current N0 to N3 descriptors for both the cN and pN status consistently separated prognostically distinct groups. The 5-year survival rates according to the cN and pN status were 60% and 75% (N0), 37% and 49% (N1), 23% and 36% (N2), and 9% and 20% (N3), respectively. The differences in survival between all neighboring nodal categories were highly significant for both the cN and pN status. With regard to pathological staging, additional analyses regarding the prognosis were performed by further dividing N1 into N1 at a single station (N1a) and N1 at multiple stations (N1b); N2 into N2 at a single station without N1 involvement (“skip” metastasis, N2a1), N2 at a single station with N1 involvement (N2a2), and N2 at multiple stations (N2b). The survival curves for N1b and N2a2 overlapped each other, and N2a1 had numerically a better prognosis than N1b, although the difference was not significant. Geographic difference in N-specific prognosis was observed for both c-settings and p-settings. This might have been because of the difference in the used nodal map, surgical technique, and pathologist's handling of the resected specimen. Conclusions Current N descriptors adequately predict the prognosis and therefore should be maintained in the forthcoming staging system. Furthermore, we recommend that physicians record the number of metastatic lymph nodes (or stations) and to further classify the N category using new descriptors, such as N1a, N1b, N2a, N2b, and N3, for further testing.

I started my training in cardiothoracic surgery in 1973 having spent 3 years in the generality of surgery. At that time, a few general surgeons were performing a tiny minority of pulmonary resections.

The revision for the 8 th edition of the tumor, node and metastasis (TNM) classification was based on the analyses of 77,156 patients diagnosed with lung cancer from 1999 to 2010 registered in the International Association for the Study of Lung Cancer database. In the T component there are more tumor-size groups: T1a 1-2 cm; T1c >2-3cm; T2a >3-4cm; T2b >4-5cm; T3 >5-7cm; and T4 >7cm. Endobronchial location 2cm from the carina. Total atelectasis/pneumonitis is grouped with their T2 counterparts as it has a T2 prognosis. Diaphragmatic invasion is T4. Visceral pleura invasion remains the same and mediastinal pleura invasion disappears as a T descriptor because it is rarely used. The N component remains as it is, but quantification of nodal disease impacts prognosis. For the M component, M1a (intrathoracic metastases) remains the same, but extrathoracic metastases are divided into single extrathoracic metastasis (new M1b) and multiple extrathoracic metastases in a single or multiple organs (M1c). Stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1c N0 M0 tumors; all N1 disease is stage IIB except for T3-T4 N1 that are IIIA; a new stage IIIC is created for T3-T4 N3 M0 tumors; and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). This revision enhances our capacity to indicate prognosis and will have an important impact in the management of lung cancer patients.

Modern imaging techniques that can provide functional information on tumor vascularization, metabolic activity, or cellularity have seen significant improvements over the past decade. However, most of these techniques are currently not broadly utilized neither in clinical trials nor in clinical routine, although there is a large agreement on the fact that conventional approaches for therapy response assessment such as Response Evaluation Criteria in Solid Tumors or World Health Organization criteria—that exclusively focus on the change in tumor size—are of less value for response assessment in modern thoracic oncology. The aim of this article comprises two parts: a short review of the most promising state-of-the-art imaging techniques that have the potential to play a larger role in thoracic oncology within the near future followed by a meeting report including recommendations of an interdisciplinary expert panel that discussed the potential of the different techniques during the Dresden 2013 Post World Congress of Lung Cancer (WCLC) - International Association for the Study of Lung Cancer (IASLC) meeting. It is intended to provide a comprehensive summary about ongoing trends and future perspectives on functional imaging in thoracic oncology.

INTRODUCTION: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons.METHODS: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases.RESULTS: The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage.CONCLUSIONS: The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts.

Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma.Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis.There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p0.0001).A recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2.

The anatomic extent of disease, as described by the TNM classification, remains the most powerful prognostic indicator for lung cancer. It is used daily by specialists in all branches of lung cancer care and research. Any new edition of the TNM classification is therefore an important event in the thoracic oncology community and one greeted with mixed feelings. The changes introduced in the seventh edition were the first for 13 years and arguably the most profound since the first data-driven revision more than 40 years earlier. Inevitably there will be concerns that any change in the T, N, or M descriptors and resultant stage groupings will have implications for previous treatment pathways. In this article, the changes to the classification are described, and their possible impacts on clinical care and research are discussed.

Introduction: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM. Methods: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical MO (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases. Results: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggest a possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1). Conclusions: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Immunohistochemical studies using epithelial markers have recently been published which identified micrometastases in lymph nodes that had not been found on routine pathological assessment, therefore increasing the accuracy of staging of non-small cell lung cancers. The presence of these micrometastases was associated with reduced survival. We have therefore performed a retrospective immunohistochemical study on all the lymphoid tissue from five lymph node stations (2 hilar, 3 mediastinal) from 49 patients with T1–2, N0 disease. Before immunohistochemistry was undertaken, all slides were reviewed, with the lymph nodes confirmed as negative. In total, 1447 lymph node slices (average 30 per case, 5.9 per lymph node station) were examined, these figures reflecting sectioning of lymph nodes at approximately 3 mm intervals before processing. MNF116, a broad spectrum anti-keratin antibody was then used to look for occult metastases, with adjacent serial sections being examined to ensure that any positively staining cells were detected solely by immunohistochemistry and not through deeper sectioning. In five cases, lymph nodes contained positively staining cells. Two cases proved to be false positives, further immunohistochemistry identifying the cells as benign mesothelial inclusions. In the remaining three cases, positive staining correlated with tumour cells in the adjacent serial sections. Follow-up on 46 of 49 patients revealed recurrence in 27% (actual survival 68%); however all three cases containing tumour cells on immunohistochemistry were free from recurrence. These results suggest that the use of immunohistochemistry adds little useful information above that of thorough routine examination of lymph nodes. They also document that benign mesothelial inclusions within lymph nodes are more frequent than previously reported.

Introduction Stage classification provides a consistent language to describe the anatomic extent of disease and is therefore a critical tool in caring for patients. The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer developed proposals for revision of the classification of lung cancer for the eighth edition of the tumor, node, and metastasis (TNM) classification, which takes effect in 2017. Methods An international database of 94,708 patients with lung cancer diagnosed in 1999–2010 was assembled. This article describes the process and statistical methods used to refine the lung cancer stage classification. Results Extensive analysis allowed definition of tumor, node, and metastasis categories and stage groupings that demonstrated consistent discrimination overall and within multiple different patient cohorts (e.g., clinical or pathologic stage, R0 or R-any resection status, geographic region). Additional analyses provided evidence of applicability over time, across a spectrum of geographic regions, histologic types, evaluative approaches, and follow-up intervals. Conclusions An extensive analysis has produced stage classification proposals for lung cancer with a robust degree of discriminatory consistency and general applicability. Nevertheless, external validation is encouraged to identify areas of strength and weakness; a sound validation should have discriminatory ability and be based on an independent data set of adequate size and sufficient follow-up with enough patients for each subgroup.

Introduction It can be difficult to distinguish between a second primary and a metastasis in patients with lung cancer who have more than one pulmonary site of cancer. Methods A systematic review of the literature was conducted by a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee to develop recommendations to identify second primary lung cancers. The process entailed review of knowledge relating to the mechanism of metastasis, determination of clonality, and outcomes of patients with resected tumors. Results It is easier to determine that two tumors are different than that they are the same; finding similarities does not establish that they are the same. For example, most second primary lung cancers are of the same histotype. Few criteria are reliable by themselves; these include different histologic cancer types or matching DNA breakpoints by sequencing and a comprehensive histologic assessment of resected specimens. Characteristics that are suggestive but associated with potential misclassification include the presence or absence of biomarkers, imaging characteristics, and the presence or absence of nodal involvement. Conclusions Clinical and pathologic (i.e., after resection) criteria are presented to identify two foci as separate primary lung cancers versus a metastasis. Few features are definitive; many commonly used characteristics are suggestive but associated with a substantial rate of misclassification. Careful review by a multidisciplinary tumor board, considering all available information, is recommended.

Introduction Small cell lung cancer (SCLC) is commonly classified as either limited or extensive, but the Union for International Cancer Control TNM Classification of Malignant Tumours seventh edition (2009) recommended tumor, node, and metastasis (TNM) staging based on analysis of the International Association for the Study of Lung Cancer (IASLC) database. Methods Survival analyses were performed for clinically and pathologically staged patients presenting with SCLC from 1999 through 2010. Prognosis was compared in relation to the TNM seventh edition staging to serve as validation and analyzed in relation to proposed changes to the T descriptors found in the eighth edition. Results There were 5002 patients: 4848 patients with clinical and 582 with pathological stages. Among these, 428 had both. Survival differences were confirmed for T and N categories and maintained in relation to proposed revisions to T descriptors for seventh edition TNM categories and proposed changes in the eighth edition. There were also survival differences, notably at 12 months, in patients with brain-only single-site metastasis (SSM) compared to SSM at other sites, and SSM without a pleural effusion showed a better prognosis than other patients in the M1b category. Conclusion We confirm the prognostic value of clinical and pathological TNM staging in patients with SCLC, and recommend continued usage for SCLC in relation to proposed changes to T, N, and M descriptors for NSCLC in the eighth edition. However, for M descriptors, it remains uncertain whether survival differences in patients with SSM in the brain simply reflect better treatment options rather than better survival based on anatomic extent of disease.

Introduction: The current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition. Methods: Data elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded. An electronic data capture system was established to facilitate data submission. Results: A total of 3519 cases were submitted to the database. Of those eligible for T-component analysis, 509 cases had only clinical staging, 836 cases had only surgical staging, and 642 cases had both available. Survival was examined for T categories according to the current seventh edition staging system. There was clear separation between all clinically staged categories except T1a versus T1b (hazard ratio = 0.99, p = 0.95) and T3 versus T4 (hazard ratio = 1.22, p = 0.09), although the numbers of T4 cases were small. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category; no current descriptors were shifted or eliminated. Tumor thickness and nodular or rindlike morphology were significantly associated with survival. Conclusions: A recommendation to collapse both clinical and pathological T1a and T1b into a T1 classification will be made for the eighth edition staging system. Simple measurement of pleural thickness has prognostic significance and should be examined further with a view to incorporation into future staging. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition.

For nearly 40 years, there was no generally accepted staging system for malignant pleural mesothelioma. In 1994, members of the International Mesothelioma Interest Group, in collaboration with the International Association for the Study of Lung Cancer, proposed a TNM staging system based on analyses of outcomes in retrospective surgical series and small clinical trials. Subsequently accepted by the American Joint Commission on Cancer and the Union for International Cancer Control for the sixth editions of their staging manuals, this system has since been the international staging standard. However, it has significant limitations, particularly with respect to clinical staging and to the categories for lymph node staging. Here we provide an overview of the development of the International Association for the Study of Lung Cancer malignant pleural mesothelioma staging database, which was designed to address these limitations through the development of a large international data set. Analyses of this database, described in papers linked to this overview, are being used to inform revisions in the eighth editions of the American Joint Commission on Cancer and Union for International Cancer Control staging systems. ispartof: Journal of Thoracic Oncology vol:11 issue:12 pages:2082-2088 ispartof: location:United States status: published

In this Study, the historical development of TNM classification and the forming process of final edition of TNM is mentioned. Besides, the use of TNM for small cell lung cancer cases is strongly encouraged in the 7th edition of TNM,and it allows for proposals for new classification to be trialed for a period toassess whether they should be incorporated into future editions.

Nodal status is considered to be one of the most reliable indicators of the prognosis in patients with lung cancer and thus is indispensable in determining the optimal therapeutic options. We sought to determine whether the current nodal (N) descriptors should be maintained or revised for the next edition (8th) of the International Lung Cancer Staging System.The new International Association for the Study of Lung Cancer lung cancer database was created from 94,708 patients diagnosed as having lung cancer between 1999 and 2010. Among these, 38,910 and 31,426 patients with non-small-cell lung carcinoma were available for an analysis of the clinical (c)N and pathological (p)N status, respectively. The anatomical location of lymph node involvement was defined by either the Naruke (for Japanese data) or American Thoracic Society (for non-Japanese data) nodal charts. Survival was calculated by the Kaplan-Meier method, and prognostic groups were assessed by a Cox regression analysis.The current N0 to N3 descriptors for both the cN and pN status consistently separated prognostically distinct groups. The 5-year survival rates according to the cN and pN status were 60% and 75% (N0), 37% and 49% (N1), 23% and 36% (N2), and 9% and 20% (N3), respectively. The differences in survival between all neighboring nodal categories were highly significant for both the cN and pN status. With regard to pathological staging, additional analyses regarding the prognosis were performed by further dividing N1 into N1 at a single station (N1a) and N1 at multiple stations (N1b); N2 into N2 at a single station without N1 involvement ("skip" metastasis, N2a1), N2 at a single station with N1 involvement (N2a2), and N2 at multiple stations (N2b). The survival curves for N1b and N2a2 overlapped each other, and N2a1 had numerically a better prognosis than N1b, although the difference was not significant. Geographic difference in N-specific prognosis was observed for both c-settings and p-settings. This might have been because of the difference in the used nodal map, surgical technique, and pathologist's handling of the resected specimen.Current N descriptors adequately predict the prognosis and therefore should be maintained in the forthcoming staging system. Furthermore, we recommend that physicians record the number of metastatic lymph nodes (or stations) and to further classify the N category using new descriptors, such as N1a, N1b, N2a, N2b, and N3, for further testing.

Introduction Separate tumor nodules with the same histologic appearance occur in the lungs in a small proportion of patients with primary lung cancer. This article addresses how such tumors can be classified to inform the eighth edition of the anatomic classification of lung cancer. Separate tumor nodules should be distinguished from second primary lung cancer, multifocal ground glass/lepidic tumors, and pneumonic-type lung cancer, which are addressed in separate analyses. Methods Survival of patients with separate tumor nodules in the International Association for the Study of Lung Cancer database were analyzed. This was compared with a systematic literature review. Results Survival of clinically staged patients decreased according to the location of the separate tumor nodule relative to the index tumor (same lobe > same side > other side) in N0 and N-any cohorts (all M0 except possible other-side nodules). However, there was also a decrease in the proportion of patients resected; among only surgically resected or among nonresected patients no survival differences were noted. There were no survival differences between patients with same-lobe nodules and those with other T3 tumors, between patients with same-side nodules and those with T4 tumors, and patients with other-side nodules and those with other M1a tumors. The data correlated with those identified in a literature review. Conclusions Tumors with same-lobe separate tumor nodules (with the same histologic appearance) are recommended to be classified as T3, same-side nodules as T4, and other-side nodules as M1a. Thus, there is no recommended change between the seventh and eighth edition of the TNM classification of lung cancer.

The seventh edition of TNM for Lung Cancer came into effect on the first of January 2011. Containing more than 100,000 cases of lung cancer treated by all modalities of care and from around the world, this is the largest database ever accumulated for this purpose. This edition allows detailed analysis and intensive validation such that the resultant classification aligns stage with prognosis more closely than ever before. There have been changes to certain tumor and metastasis descriptors and the resultant stage groupings. This article describes these changes, provides more in-depth discussion of the changes, and provides much additional information.

Educational aims To describe the changes in the 7th edition of the TNM classification of lung cancer To discuss the clinical implications of the incorporation of the new TNM classification in everyday practice To emphasise the key points for a proper pathologic classification Summary The 7th edition of the TNM (tumour, node, metastases) classification of lung cancer incorporates the proposals of the International Association for the Study of Lung Cancer, whose database included more than 100,000 patients from Asia, Australia, Europe, and North America. The changes affect the T and the M components of the classification, and the stage grouping. The N component remained unaltered, although the present descriptors were validated both in the clinical and pathologic settings. This new TNM classification applies to non-small cell lung cancer, small cell lung cancer and, for the first time, to broncho-pulmonary carcinoids. The innovations allow for a better separation of tumours with significantly different prognosis, and imply a more careful determination of tumour size.

This review is trying to address the effectiveness and sustainability of results following minimally invasive repair of pectus excavatum (MIRPE). The aim is to present these results for the benefit of clinicians and the patients. Literature search has revealed 179 hits, which were independently assessed and led to 80 publications being formally reviewed. Studies reporting results from less than 10 patients were excluded. Thirty-five studies were found to be reporting results from patients' and/or surgeons' perspective and they were included in this review. Data from the United Kingdom registry for MIRPE were also included. Results from over 2997 patients (age

Introduction: Approximately 10 to 15% of non-small cell lung cancer patients will be assigned a stage classification according to the 7th edition of TNM that differs from that assigned by the 6th edition (the "stage shifters"). This apparent upstaging or downstaging of tumors may affect patient management, as many clinicians formulate stage-based management strategies. However, the staging system revision was not designed to evaluate treatment, and attempts to make parallel adjustments in treatment plans may not be justified. Methods: Lung cancer clinicians were surveyed at four lung cancer symposia. Treatment of the "stage shift" patients was evaluated in the International Association for the Study of Lung Cancer database and National Cancer Database. Results: Overall, 77% of surveyed clinicians indicated they would alter patient management in response to a change in stage designation. The analysis of the data in the International Association for the Study of Lung Cancer database was not directed at supporting treatment changes. Despite the similar overall prognosis within each of the "stage shift" subgroups in the National Cancer Database, the treatment was decidedly heterogeneous. Conclusions: The perception that a stage change should lead to a change in management exists. The revision of the lung cancer staging system does not provide any direct information to indicate the superiority of one treatment approach over another. Assuming that overall prognosis of a subgroup is strongly linked to a specific treatment and that a particular outcome, therefore, warrants a change in treatment is not justified. Thus, making changes in management solely in response to upstaging or downstaging in the new stage classification system is not justified.

Objective BioGlue (CryoLife, Europa Ltd, Surrey, UK) is effective in reducing alveolar air leak after pulmonary resection. However, concerns exist regarding the use of bovine-derived products. Vivostat (Vivostat A/S, Alleroed, Denmark) is an autologous fibrin sealant that confers certain advantages. It shows superior elastic properties, a faster absorption time, and the absence of risk of transmission of blood-borne diseases. Methods We conducted a randomized, single blind controlled study to compare BioGlue and Vivostat in the control of postoperative air leak. Primary endpoints were duration of air leak, time to intercostal drain removal, and length of hospital stay. Secondary endpoints related to postoperative complications. Results Between December 2005 and December 2007, 103 patients were randomized. The analysis included 102 patients; 67% were male. Median age was 56 ± 19 years. Indications for surgery were primary lung cancer in 41 patients (40%), secondary malignancy in 48 patients (47%), carcinoid in 6 patients (6%), and 7 patients underwent surgery for benign disease (7%). Bilobectomy was performed in 2 patients (2%), lobectomy in 41 patients (40%), lobectomy with lesser resection in 3 patients (3%), segmentectomy in 16 patients (16%), precision excision in 34 patients (33%), and 6 patients underwent other resections (6%). Median duration of air leak was 3 (0–32) days versus 2 (0–33) days for patients who received BioGlue and Vivostat, respectively ( P = .677). Time to intercostal drain removal was 5 (1–32) days in the BioGlue group compared with 5 (1–34) days for the Vivostat group ( P = .473). Median hospital stay was 8 (3–22) days versus 7 (2–29) days for the BioGlue and Vivostat groups, respectively ( P = .382). There was no significant difference in the incidence of complications between the 2 groups (20 patients receiving BioGlue versus 19 patients receiving Vivostat, P = .839). Conclusions There were no significant differences in the 3 clinical outcome measures of duration of air leak, time to intercostal drain removal, and length of hospital stay in those patients receiving BioGlue or Vivostat. Given the inherent advantages of our institutional preference is to use Vivostat in the control of postoperative air leaks after pulmonary resection.

Desai S, Dusmet M, Ladas G, Pomplun S, Padley S P G, Griffin N, Badreddine J, Goldstraw P & Nicholson A G (2010) Histopathology 57, 121–127 Secondary vascular changes in pulmonary sequestrations Aims: Whilst parenchymal changes in pulmonary sequestrations are well described, there are comparatively little data on associated vascular changes and their extent. The aim of this study was to retrospectively review morphological changes within sequestrations, concentrating on vascular changes and associations with clinical parameters. Methods and results: Twenty-seven resected cases of sequestrations (intralobar n = 20, extralobar n = 7) showed a male predominance (n = 16) and an age range of 2 months–60 years (average 13 years). Plexogenic vascular changes (medial hypertrophy and intimal fibrosis) were seen in 15 of 27 cases, as well as plexiform lesions in seven cases. Patients with plexogenic changes had a higher mean age compared with those lacking vascular changes (19 versus 6 years) and were more commonly female. Respiratory tract infections were associated solely with intralobar sequestrations. No other associations between presenting symptoms and histopathological parameters were identified. Adjacent lung showed lesser plexogenic changes in six of 22 intralobar cases. There were features of type 2 congenital cystic adenomatoid lesions in 63% of cases. Dissection of the supplying systemic artery (n = 1), intralesional aspergilloma (n = 1) and coexistent lymphangiomatosis (n = 1) were also identified. Conclusions: Hypertensive vascular changes are not uncommon in both intrapulmonary and extrapulmonary sequestrations, although their relative severity seems unrelated to presenting symptoms.

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.

International audience; OBJECTIVE: In the 2003 Supplement for tumor, node, metastasis (TNM) Staging classification it states that TNM staging "applies to all types of carcinoma including small cell carcinoma; however, it does not apply to carcinoids." Despite this caveat, most publications on typical and atypical carcinoids use the TNM staging system for nonsmall cell carcinoma and are able to demonstrate prognostic significance for the different stages. For this reason, as the next TNM Staging proposal is being considered, we sought to investigate the carcinoid cases submitted to the International Association for the Study of Lung Cancer (IASLC) database, as well as the National Cancer Institute Surveillance Epidemiology and End Results (SEER). MATERIALS AND METHODS: In the data collected for the IASLC Staging Project database over the time period 1990 to 2000, there were 513 broncho-pulmonary carcinoids. A total of 1619 broncho-pulmonary carcinoid cases diagnosed over the period 1990-2002 were analyzed from the SEER database, including 1437 surgical cases. Pathologic slides were not available for histologic review. RESULTS: Most of tumors in both the IASLC and SEER databases were Stage I (82% and 78%, respectively), as defined by the IASLC proposals for the 7th edition of TNM staging system. T status was a statistically significant predictor of survival for both the SEER data (p < 0.0001) and the IASLC database (p = 0.0156), though for different reasons. N status showed significant survival correlations in both data sets (p < 0.0001). The effect of M status was significant (p < 0.0001) within the SEER data and not studied in the IASLC cases, which were almost exclusively M0. We found that all three T, N, and M categories as defined for non-small cell lung cancer are generally useful for staging of pulmonary carcinoid tumors. Significant differences in survival for overall stages I versus II versus III/IV were identified in both data sets. Patients with multiple same lobe nodules had a 100% 5-year survival, which may be a reason to reevaluate their status in the IIB category in future analyses. CONCLUSIONS: In summary, the IASLC proposals for the 7th edition of TNM are helpful in predicting prognosis for broncho-pulmonary carcinoid tumors. It is the recommendation of the IASLC Staging project that TNM be applied to broncho-pulmonary carcinoid tumors. A prospective collection of data through an International Registry of Pulmonary Neuroendocrine Tumors planned by the IASLC will allow for further detailed analysis of staging data for broncho-pulmonary carcinoids.

Primary human alveolar type 2 (AT2) cells were immortalized by transduction with the catalytic subunit of telomerase and simian virus 40 large-tumor antigen. Characterization by immunochemical and morphologic methods demonstrated an AT1-like cell phenotype. Unlike primary AT2 cells, immortalized cells no longer expressed alkaline phosphatase, pro-surfactant protein C, and thyroid transcription factor-1, but expressed increased caveolin-1 and receptor for advanced glycation end products (RAGE). Live cell imaging using scanning ion conductance microscopy showed that the cuboidal primary AT2 cells were approximately 15 microm and enriched with surface microvilli, while the immortal AT1 cells were attenuated more than 40 microm, resembling these cells in situ. Transmission electron microscopy highlighted the attenuated morphology and showed endosomal vesicles in some immortal AT1 cells (but not primary AT2 cells) as found in situ. Particulate air pollution exacerbates cardiopulmonary disease. Interaction of ultrafine, nano-sized particles with the alveolar epithelium and/or translocation into the cardiovasculature may be a contributory factor. We hypothesized differential uptake of nanoparticles by AT1 and AT2 cells, depending on particle size and surface charge. Uptake of 50-nm and 1-microm fluorescent latex particles was investigated using confocal microscopy and scanning surface confocal microscopy of live cells. Fewer than 10% of primary AT2 cells internalized particles. In contrast, 75% immortal AT1 cells internalized negatively charged particles, while less than 55% of these cells internalized positively charged particles; charge, rather than size, mattered. The process was rapid: one-third of the total cell-associated negatively charged 50-nm particle fluorescence measured at 24 hours was internalized during the first hour. AT1 cells could be important in translocation of particles from the lung into the circulation.

Aim To determine whether similarities exist in both the imaging and histopathological features of congenital cystic lung lesions and whether a more appropriate classification would be to adopt the theory of “malinosculation”. Material and methods From the histopathology and computed tomography (CT) database, 24 patients (16 male, median age 3 years) with congenital cystic lung lesions were identified. CT studies were reviewed for site and characteristics of the lesions, parenchymal features, bronchial anatomy, and the presence of a feeding systemic vessel. Individual histopathological parameters were also correlated with CT data. Results There were five type 1 congenital cystic adenomatoid malformations (CCAMs), six type 2 CCAMs, one type 4 CCAM, one bronchial atresia, four pleuropulmonary blastomas (PPBs), and seven sequestrations. CCAMs (types 1, 2 and 4), sequestrations and PPBs appeared as cystic lesions, with cyst size less than 2 cm in type 2 CCAMs. Sequestrations were distinguished radiologically from CCAMs by systemic vessels. Reduced pulmonary attenuation was seen in bronchial atresia, type 2 CCAMs and in sequestrations. Histopathology showed an overlap in entities with sequestrations demonstrating CCAM type 2 histology and segmental atresia noted in both type 2 CCAMs and sequestrations. PPBs showed histological and imaging overlap with type 4 CCAMs and were distinguished on histology by the presence of blastematous proliferation. Conclusions This study demonstrates overlap in the CT appearances of congenital cystic lesions. The similarity in CT and histopathology findings across the spectrum of developmental lesions supports the hypothesis of a common aetiology.

Background Abnormal plasma and lung iron mobilization is associated with the onset and progression of ARDS and is detectable in specific at-risk populations. Patients with ARDS also have pronounced oxidative and nitrosative stress that can be catalyzed and thereby aggravated by the bioavailability of redox active iron. ARDS of pulmonary and extrapulmonary origin may differ pathophysiologically and require different ventilatory strategies. Evidence suggests that genetic predisposition is relevant to the pathogenesis of ARDS. We therefore explored the hypothesis that polymorphisms from a panel of genes encoding iron-metabolizing proteins determine susceptibility to ARDS. Methods Retrospective case-control study conducted at the adult ICUs of two university hospitals. Patients with ARDS (n = 122) and healthy control subjects (n = 193) were genotyped. Sequence-specific primer polymerase chain reaction was used to genotype selected biallelic single-nucleotide polymorphisms. An audit of the patient database was conducted, and 104 of the 122 ARDS patients were eligible for the final data analysis. Results Preliminary analysis indicated differences between ARDS and healthy control subjects in the incidence of polymorphism of the gene encoding ferritin light chain. Subgroup analysis indicated the prevalence of ferritin light-chain gene −3381GG homozygotes was increased in patients with ARDS of extrapulmonary origin compared to healthy control subjects. Secondly, a common haplotype in the heme oxygenase 2 gene was reduced in patients with ARDS compared to healthy control subjects and was more evident in those with ARDS of direct or pulmonary etiology. Conclusions These results provide preliminary evidence to suggest a distinction in the genetic background of the subpopulations studied, inferring that the ferritin light-chain gene genotype confers susceptibility to ARDS, while the heme oxygenase 2 haplotype is protective against the onset of the syndrome. Such data support further previous findings that suggest abnormalities in iron handling resulting in redox imbalance are implicated in the pathogenesis of ARDS.

The contractile and actomyosin ATPase properties of single fibres were examined in human diaphragm muscle obtained from patients with and without chronic obstructive pulmonary disease (COPD). Costal diaphragm biopsies were taken from five patients without evidence of COPD and from 11 age-matched individuals with varying degrees of the disease. Our aim was to establish whether changes in contractile properties of COPD diaphragm could be fully explained by the previously documented shift towards a greater proportion of type I myosin heavy chain isoform in COPD. The relative proportion of type I diaphragm fibres from non-COPD and COPD patients was measured by gel electrophoresis, and was negatively correlated with FEV1 over the full range of values investigated. There was also significant atrophy of the type I fibre population in COPD diaphragms. Isometric tension was similar among the fibre types and between the COPD and non-COPD patients. The intrinsic energetic properties of diaphragm fibres were examined by monitoring the time-resolved actomyosin ATPase activity in COPD and non-COPD fibres that produced similar isometric forces. The isometric ATPase rate in COPD fibres was reduced to 50% of the rate in non-COPD fibres; hence, the cost of isometric contraction in type I and type IIA COPD fibres was reduced to between one-third and one-half of the tension cost calculated for non-COPD fibres. The rate of force development in type I COPD fibres was reduced to 50% of the rate seen in non-COPD type-I fibres. No difference in the rate of ATP consumption between COPD and non-COPD fibres was evident during isovelocity shortening. These data extend previous findings showing that aspects of breathing mechanics during progressive COPD are associated with remodelling of the diaphragm fibre-type distribution; on top of the increase in type I fibres there are fibre-specific reductions in force development rate (type I fibres) and ATPase rate that are consistent with the impairment of cross-bridge cycling kinetics.

Purpose To explore the clinical significance of enlarged regional lymph nodes in patients with pathological stage I non-small cell lung cancer (NSCLC). Material and Methods We retrospectively reviewed the tumor registry of the International Association for the Study of Lung Cancer (IASLC) Staging Database to identify 6995 patients between January 1, 1990 and December 31, 2000 with clinical stage I, II, and IIIA tumors (cT1-2N0-2M0, excluding T3N0-2M0 cases) who proved to have pathological stage I NSCLC (T1-2N0M0, pStage I). The frequency of enlarged nodes in patients with pStage I disease is reported, and the overall survival of these patients who had enlarged regional lymph nodes was compared with that of patients with pStage I disease with normal size regional lymph nodes. Results Enlarged regional lymph nodes (cN1-2) were seen in approximately 12% of patients with pStage I disease. Median survival for patients with enlarged versus normal nodes was 102 versus 107 months (hazard ratio 1.16, p = 0. 01). Survival curves converged at 8 years postsurgery. Conclusions Enlarged regional lymph nodes are uncommon in patients with pStage I NSCLC, and the size of regional lymph nodes in these early stage patients does not seem to provide clinically useful prognostic information.

Oesophageal rupture is a serious and lifethreatening condition. It usually presents to non-specialist medical and surgical staff through the emergency department. The clinical features are non-specific and can be easily confused with more common conditions. However, once considered the diagnosis is easily made. Untreated, the condition is rapidly fatal and delay in diagnosis rapidly adds to problems of treatment, and is associated with escalating morbidity and mortality risk. This article will focus on the presentation, investigation and initial management of ‘spontaneous’ rupture of the oesophagus. The management options that are available in specialist centres will then be considered in brief.

The purpose of this presentation is three-fold: (a) to inform the lung cancer community of the proposals submitted by the International Association for the Study of Lung Cancer (IASLC) to the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) for the Lung Cancer section of the forthcoming (7th) Edition of the TNM Classification of Malignant Tumours, (b) to stimulate discussion within the lung cancer community ahead of these revisions being enacted, and (c) to describe to the wider oncological community the IASLC Lung Cancer Staging Project in the hope that it might provide a useful template by which revisions to the TNM Classification for other tumours could be better informed. This last issue will entail a description of the development of TNM staging in lung cancer, which, inevitably will be somewhat critical of the pre-existing process for revision. The UICC has sought to improve this and the previous speaker will address their process for change initiative. However, the relevant specialist associations and National groups can help to inform such revisions by stimulating collaborative, international efforts for data collection.

International audience; PURPOSE: To analyze all nonlymphatic metastatic components (T4 and M1) of the current TNM system of lung cancer, with the objective of providing suggestions for the next edition of the TNM classification for lung cancer. MATERIAL AND METHODS: Data on 100,809 patients were submitted to the International Association for the Study of Lung Cancer International Database. Of these, 5592 selected T4M0 and M1 patients fulfilled the inclusion criteria for the analysis. Specific categories of clinically staged T4 (lesions not continuous with the primary tumor) and M1 cases were compared with respect to overall survival using Kaplan-Meier survival estimates and comparisons via Cox regression analysis. Relevant findings were validated internally by geographic area and type of database and were validated externally by the North American Surveillance, Epidemiology and End Results Registries. RESULTS: Median survival for cT4M0 with malignant pleural effusion was significantly worse than that of other cT4M0 patients (8 months versus 13 months) and was more comparable with M1 cases with metastases to the contralateral lung only (10 months). M1 cases with metastases outside the lung/pleura had a significantly poorer prognosis than those with metastases confined to the lung, with a median survival of 6 months. CONCLUSIONS: Revisions to the TNM classification system for lung cancer should include grouping cases with malignant pleural effusions and cases with nodules in the contralateral lung in the M1a category, and cases with distant metastases should be designated M1b. In addition, cases with nodule(s) in the ipsilateral lung (nonprimary lobe), currently staged M1, should be reclassified as T4M0, in accordance with the recommendations of the T descriptor subcommittee of the IASLC international staging committee.

IntroductionAccurate staging of lymph node involvement is a critical aspect of the initial management of nonmetastatic non-small cell lung cancer (NSCLC). We sought to determine whether the current N descriptors should be maintained or revised for the next edition of the international lung cancer staging system.MethodsA retrospective international lung cancer database was developed and analyzed. Anatomical location of lymph node involvement was defined by the Naruke (for Japanese data) and American Thoracic Society (for non-Japanese data) nodal maps. Survival was calculated by the Kaplan-Meier method, and prognostic groups were assessed by Cox regression analysis.ResultsCurrent N0 to N3 descriptors defined distinct prognostic groups for both clinical and pathologic staging. Exploratory analyses indicated that lymph node stations could be grouped together into six “zones―: peripheral or hilar for N1, and upper or lower mediastinal, aortopulmonary, and subcarinal for N2 nodes. Among patients undergoing resection without induction therapy, there were three distinct prognostic groups: single-zone N1, multiple-zone N1 or single N2, and multiple-zone N2 disease. Nevertheless, there were insufficient data to determine whether the N descriptors should be subdivided (e.g., N1a, N1b, N2a, N2b).ConclusionsCurrent N descriptors should be maintained in the NSCLC staging system. Prospective studies are needed to validate amalgamating lymph node stations into zones and subdividing N descriptors.

Background Although surgery offers the best chance of cure for patients with non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and improvements are urgently needed. In the 1990s, much interest was generated from two small trials that reported striking results with neo-adjuvant chemotherapy, and therefore our intergroup randomised trial was designed to investigate whether, in patients with operable non-small cell lung cancer of any stage, outcomes could be improved by giving platinum-based chemotherapy before surgery.Methods Patients were randomised to receive either surgery alone (S), or three cycles of platinum-based chemotherapy followed by surgery (CT-S). Before randomisation, clinicians chose the chemotherapy that would be given from a list of six standard regimens. The primary outcome measure was overall survival, which was analysed on an intention-to-treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN25582437.Results 519 patients were randomised (S: 261, CT-S: 258) from 70 centres in the UK, Netherlands, Germany, and Belgium. Most (61%) were clinical stage I, with 31% stage II, and 7% stage III. Neo-adjuvant chemotherapy was feasible (75% of patients received all three cycles of chemotherapy), resulted in a good response rate (49% [95% CI 43%-55%]) and down-staging in 31% (25%-37%) of patients, and did not alter the type or completeness of the surgery (lobectomy: S: 56%, CT-S: 60%, complete resection: S: 80%, CT-S: 82%). Post-operative complications were not increased in the CT-S group, and no impairment of quality of life was observed. However, there was no evidence of a benefit in terms of overall survival (hazard ratio [HR] 1.02, 95% Cl 0.80-1.31, p=0.86). Updating the systematic review by addition of the present result suggests a 12% relative survival benefit with the addition of neoadjuvant chemotherapy (1507 patients, HR 0.88, 95% CI 0.76-1.01, p=0.07), equivalent to an absolute improvement in survival of 5% at 5 yearsInterpretation Although there was no evidence of a difference in overall survival with neo-adjuvant chemotherapy, the result is statistically consistent with previous trials, and therefore adds considerable weight to the current evidence.

AIM: To highlight the variation in clinical manifestations, imaging and management of four cases of unilateral pulmonary artery agenesis presenting in adulthood. METHOD: Four patients with unilateral pulmonary artery agenesis were referred to our institution between 1995 and 2005. They underwent a series of investigations, including chest radiography, echocardiography, ventilation perfusion scintigraphy, angiography, computed tomography (CT) and magnetic resonance imaging (MRI). RESULTS: Two of the four patients had absence of the right main pulmonary artery, whilst the remaining two patients had absence of the left main pulmonary artery. One patient showed a restrictive defect on pulmonary function tests. Two patients who had ventilation perfusion scintigraphy showed absent perfusion and reduced ventilation on the affected side. Angiography (where performed), CT and MRI confirmed the anatomy and the presence of multiple collaterals. Bronchiectasis was demonstrated on CT in two patients, with one also demonstrating a mosaic attenuation pattern. One patient had an incidental lung tumour on the side of the agenesis, which was diagnosed as a chondroid hamartoma on histology. Three of the four patients eventually underwent resection of the affected lung. CONCLUSION: Isolated unilateral pulmonary artery agenesis has a non-specific presentation. Awareness of this condition can lead to earlier diagnosis, with cross-sectional imaging making an important contribution.

The aim of this study is to analyze all metastatic (M) categories of the current tumor, node, and metastasis (TNM) classification of lung cancer with the objective of providing suggestions for modifications of the M component in the next edition of the TNM classification for lung cancer.The new International Association for the Study of Lung Cancer lung cancer database was created from 94,708 patients diagnosed as having lung cancer between 1999 and 2010. Including further patients submitted through the electronic data capture system to Cancer Research and Biostatistics until 2012, all together 1059 non-small-cell lung cancer cases were available for a detailed analysis of the clinical M categories. Overall survival was calculated using the Kaplan-Meier method, and prognosis was assessed using a Cox proportional hazards regression analysis.No significant differences were found among the M1a (metastases within the chest cavity) descriptors. However, when M1b (distant metastases outside the chest cavity) were assessed according to the number of metastases, tumors with a single metastasis in a single organ had significantly better prognosis than those with multiple metastases in one or several organs.In this revision of the TNM classification, cases with pleural/pericardial effusions, contralateral/bilateral lung nodules, contralateral/bilateral pleural nodules, or a combination of multiple of these parameters should continue to be grouped as M1a category. Single metastatic lesions in a single distant organ should be newly designated to the M1b category. Multiple lesions in a single organ or multiple lesions in multiple organs should be reclassified as M1c category. This new division can serve as a first step into providing rational definitions for an oligometastatic disease stage in non-small-cell lung cancer in the future.