Lung Volume Reduction Surgery: Reinterpreted With Longitudinal Data Analyses Methodology.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Cancer of the Esophagus and Esophagogastric Junction: An Eighth Edition Staging Primer.

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.

The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.

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.

The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming 8th Edition of the TNM Classification for Lung Cancer.

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.

The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer.

INTRODUCTION: 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. 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. 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. RESULTS: 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. CONCLUSIONS: 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.

Predicting the prognosis of lung cancer: the evolution of tumor, node and metastasis in the molecular age-challenges and opportunities.

The tumor, node and metastasis (TNM) classification of malignant tumors was proposed by Pierre Denoit in the mid-20(th) century to code the anatomic extent of tumors. Soon after, it was accepted by the Union for International Cancer Control and by the American Joint Committee on Cancer, and published in their respective staging manuals. Till 2002, the revisions of the TNM classification were based on the analyses of a database that included over 5,000 patients, and that was managed by Clifton Mountain. These patients originated from North America and almost all of them had undergone surgical treatment. To overcome these limitations, the International Association for the Study of Lung Cancer proposed the creation of an international database of lung cancer patients treated with a wider range of therapeutic modalities. The changes introduced in the 7(th) edition of the TNM classification of lung cancer, published in 2009, derived from the analysis of an international retrospective database of 81,495 patients. The revisions for the 8(th) edition, to be published in 2016, will be based on a new retrospective and prospective international database of 77,156 patients, and will mainly concern tumor size, extrathoracic metastatic disease, and stage grouping. These revisions will improve our capacity to indicate prognosis and will make the TNM classification more robust. In the future the TNM classification will be combined with non-anatomic parameters to define prognostic groups to further refine personalized prognosis.

Perspectives of novel imaging techniques for staging, therapy response assessment, and monitoring of surveillance in lung cancer: summary of the Dresden 2013 Post WCLC-IASLC State-of-the-Art Imaging Workshop.

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.

The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer.

The analyses of the retrospective database of the International Association for the Study of Lung Cancer (IASLC), consisting of more than 81,000 evaluable patients diagnosed with lung cancer between 1990 and 2000, formed the basis of recommendations to the Union for International Cancer Control and the American Joint Committee on Cancer for the revision of the sixth edition of the tumor, node, and metastasis (TNM) classification of lung cancer. However, despite the large number of patients, not all descriptors could be validated. This prompted a new collection of retrospective and prospective data to overcome the limitations of the original retrospective database. The new IASLC database has information on 94,708 new patients diagnosed of lung cancer between 1999 and 2010. They originated from 35 sources in 16 countries, and 4,667 were submitted via the online electronic data capture system. Europe contributed 46,560 patients, Asia: 41,705, North America: 4,660, Australia: 1,593, and South America: 190. After exclusions, 77,156 (70,967 with nonsmall cell lung cancer and 6,189 with small cell lung cancer) remained for analysis. This database will be analyzed according to established objectives for the T, the N, and the M components to inform the eighth edition of the TNM classification of lung cancer due to be published in 2016. The IASLC hopes for the continuing contribution of our partners around the world to improve the classification of anatomical extent of disease, but also to create prognostic groups in a parallel project of the IASLC Staging and Prognostic Factors Committee.

Surgery in 2013 and beyond.

Lung cancer is a leading cause of cancer related mortality. The role of surgery continues to evolve and in the last ten years there have been a number of significant changes in the surgical management of lung cancer. These changes extend across the entire surgical spectrum of lung cancer management including diagnosis, staging, treatment and pathology. Positron Emission Tomography (PET) scanning and ultrasound (EBUS) have redefined traditional staging paradigms, and surgical techniques, including video-assisted thoracoscopy (VATS), robotic surgery and uniportal surgery, are now accepted as standard of care in many centers. The changing pathology of lung cancer, with more peripheral tumours and an increase in adenocarcinomas has important implications for the Thoracic surgeon. Screening, using Low-Dose CT scanning, is having an impact, with not only a higher percentage of lower stage cancers detected, but also redefining the role of sublobar resection. The incidence of pneumonectomy has reduced as have the rates of "exploratory thoracotomy". In general, lung resection is considered for stage I and II patients with a selected role in more advanced stage disease as part of a multimodality approach. This paper will look at these issues and how they impact on Thoracic Surgical practice in 2013 and beyond.

Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; systematic review and comparison with a surgical cohort.

BACKGROUND AND PURPOSE: To assess the efficacy of stereotactic ablative radiotherapy (SABR) for the treatment of non-small cell lung cancer (NSCLC) through a systematic review of all relevant publications from 2006 to the present compared to controls treated with surgery. In the absence of Grade I evidence, the objective outcome data should form the basis for planning future studies and commissioning SABR services. MATERIALS AND METHODS: Standard systematic review methodology extracting patient and disease characteristics, treatment and outcome data from published articles reporting patient data from populations of 20 or more Stage I NSCLC patients treated with SABR with a median follow up of minimum of 1 year. The individual outcome measures were corrected for stage and summary weighted outcome data were compared to outcome data from a large International Association for the Study of Lung Cancer (IASLC) cohort matched for stage of disease with survival as the principal endpoint and local control (local progression free survival - local PFS) as the secondary endpoint. RESULTS: Forty-five reports containing 3771 patients treated with SABR for NSCLC were identified that fulfilled the selection criteria; both survival and staging data were reported in 3171 patients. The 2 year survival of the 3201 patients with localized stage I NSCLC treated with SABR was 70% (95% CI: 67-72%) with a 2 year local control of 91% (95% CI: 90-93%). This was compared to a 68% (95% CI: 66-70) 2 year survival of 2038 stage I patients treated with surgery. There was no survival or local PFS difference with different radiotherapy technologies used for SABR. CONCLUSIONS: Systematic review of a large cohort of patients with stage I NSCLC treated with SABR suggests that survival outcome in the short and medium term is equivalent to surgery for this population of patients regardless of co-morbidity. As selection bias cannot be assessed from the published reports and treatment related morbidity data are limited, a direct comparison between the two treatment approaches should be a priority. In the meantime, SABR can be offered to stage I patients with NSCLC as an alternative to surgery.

New staging system: how does it affect our practice?

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.

New TNM classification: achievements and hurdles.

The 7th edition of TNM for Lung Cancer represented a major advance from previous editions, in the process of revision, the size and breadth of the data base used, its international character, the intensity of the analysis and the critical nature of the internal and external validation undertaken before its launch in January 2010. This all came about by the involvement of the International Association for the Study of Lung Cancer (IASLC), which assumed the role previously performed by Dr. Mountain, of developing data-driven revisions for the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC). In taking on this task the IASLC made the global lung cancer community aware of the limitations of previous revisions and now stand accountable and subject to the same scrutiny. In this article we describe the achievements of the IASLC TNM and Prognostic Factors Committee, but also the short-comings of the 7th edition, as an essential step towards rectifying deficiencies and further improving the classification in future revisions.