Dorothy J. Giroux

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

Introduction: The seventh edition of the TNM Classification of Malignant Tumors is due to be published early in 2009. In preparation for this, the International Association for the Study of Lung Cancer established its Lung Cancer Staging Project in 1998. The recommendations of this committee for changes to the T, N, and M descriptors have been published. This report contains the proposals for the new stage groupings. Methods: Data were contributed from 46 sources in more than 19 countries. Adequate data were available on 67,725 cases of non-small cell lung cancer treated by all modalities of care between 1990 and 2000. The recommendations for changes to the T, N, and M descriptors were incorporated into TNM subsets. Candidate stage groupings were developed on a training subset and tested in a validation subset. Results: The suggestions include additional cutoffs for tumor size, with tumors >7 cm moving from T2 to T3; reassigning the category given to additional pulmonary nodules in some locations; and reclassifying pleural effusion as an M descriptor. In addition, it is suggested that T2b N0 M0 cases be moved from stage IB to stage IIA, T2a N1 M0 cases from stage IIB to stage IIA, and T4 N0–1 M0 cases from stage IIIB to stage IIIA. Conclusions: Such changes, if accepted, will involve a reassessment of existing treatment algorithms. However, they are based on an intensive and validated analysis of the largest database to date. The proposed changes would improve the alignment of TNM stage with prognosis and, in certain subsets, with treatment.

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.

Induction Chemoradiation and Surgical Resection for Superior Sulcus Non–Small-Cell Lung Carcinomas: Long-Term Results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160)

PURPOSE Traditional treatment for superior sulcus non-small-cell lung cancers (SS NSCLC), radiation plus surgery, yields a 50% rate of complete resection and a 30% 5-year survival. On the basis of improved outcomes in other subsets of stage III NSCLC, this trial tested the feasibility of induction chemoradiotherapy for SS NSCLC. PATIENTS AND METHODS Patients with T3-4, N0-1 SS NSCLC received two cycles of cisplatin and etoposide concurrently with radiation (45 Gy). Patients with stable or responding disease underwent thoracotomy. All patients received two more cycles of chemotherapy. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed by Cox regression analysis. RESULTS From April 1995 to November 1999, 110 eligible patients (76 men, 34 women) were entered onto the study (78 T3, 32 T4 tumors). Induction therapy was completed by 104 (95%) patients. Of 95 patients eligible for surgery, 88 (80%) underwent thoracotomy, two (1.8%) died postoperatively, and 83 (76%) had complete resection. Pathologic complete response (CR) or minimal microscopic disease was seen in 61 (56%) resection specimens. Five-year survival was 44% for all patients and 54% after complete resection, with no difference between T3 and T4 tumors. Pathologic CR led to better survival than when any residual disease was present (P = .02). Disease progression occurred mainly in distant sites. CONCLUSION This combined-modality approach is feasible and is associated with high rates of complete resection and pathologic CR in both T3 and T4 tumors. Local control and overall survival seem markedly improved relative to previous studies of radiation plus resection.

The IASLC lung cancer staging project: Proposals for the inclusion of broncho-pulmonary carcinoid tumors in the forthcoming (seventh) edition of the TNM classification for lung cancer

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.

Initial analysis of the international association for the study of lung cancer mesothelioma database

Background: The current staging system for malignant pleural mesothelioma (MPM) is controversial. To plan revisions of this system, the International Association for the Study of Lung Cancer Staging Committee developed an international database. Initial analyses focus on patients managed surgically. Methods: Participation was solicited from centers known to have MPM registries. Common data elements were analyzed by the International Association for the Study of Lung Cancer Staging Committee Statistical Center. Survival was analyzed by the Kaplan–Meier method, prognostic factors by log rank and Cox regression model. p Value less than 0.05 was significant. Results: Data included 3101 patients (15 centers, 4 continents). Demographics: median age 63 years, 79% men, 62.3% epithelioid tumor. Best tumor, node, metastasis (bTNM) stages were: I (11%), II, (21%), III (48%), and IV (20%). Curative-intent surgery was performed in 1494 patients (64.5%). Median survivals by clinical TNM and pathological TNM were similar: stage I, 21 months; stage II, 19 months; stage III, 16 months; and stage IV, 12 months. Median survival by histology: epithelioid 19 months, biphasic 13 months, and sarcomatoid 8 months. By multivariable analyses, significant differences in overall survival were seen for: T4 versus T3 and T3 versus T2 but not T2 versus T1; N0 versus N1 and N2 but not N1 versus N2; stages III and IV versus I but not II versus I; epithelioid histology versus other; age of female versus age of male; and palliative versus curative-intent surgery. Conclusions: This is the largest international database examining outcomes in surgically managed MPM patients. Survival differences reported from smaller databases are confirmed but suggest the need to revise tumor and node staging.

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.

The IASLC Lung Cancer Staging Project: data elements for the prospective project.

The International Association for the Study of Lung Cancer Retrospective Staging Project culminated in a series of recommendations to the International Union Against Cancer and to the American Joint Committee on Cancer regarding the seventh edition of the tumor, node, metastasis (TNM) classification for lung cancer. The International Staging Committee of the International Association for the Study of Lung Cancer now issues this call for participation in the Prospective Project designed to assess the validity of each component of T, N, and M, and other factors relevant to lung cancer staging and prognosis. In the Retrospective Project, the original data acquisition was typically motivated by interests other than staging. In contrast, the Prospective Project offers online data entry. Alternatively, participants may transfer existing data, provided core objectives are addressed. Cancer Research and Biostatistics will coordinate data management and analysis. The study population is newly diagnosed lung cancer patients. Data elements include patient characteristics, baseline laboratory values, first-line treatment, TNM plus supporting evidence, and survival. Pretreatment TNM will be collected for all cases; postsurgical TNM, if resection is attempted. T descriptors include size and degree of tumor extension, with further description of extent of visceral pleural invasion, venous invasion, carcinomatous lymphangitis, and pleural lavage cytology. M descriptors characterize the newly proposed M1a category and sites of distant metastases. Nodal station involvement is described by means of a newly proposed nodal map, facilitating international participation, and allowing further investigation of nodal zones. Successful collection and analysis of these data can be expected to yield unprecedented improvements in the utility and validity of lung cancer staging.

The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer

ABSTRACT This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part‐solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.

The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal for an Evidence-Based Stage Classification System for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors

A universal and consistent stage classification system, which describes the anatomic extent of a cancer, provides a foundation for communication and collaboration. Thymic epithelial malignancies have seen little progress, in part because of the lack of an official system. The International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group assembled a large retrospective database, a multispecialty international committee and carried out extensive analysis to develop proposals for the 8th edition of the stage classification manuals. This tumor, node, metastasis (TNM)-based system is applicable to all types of thymic epithelial malignancies. This article summarizes the proposed definitions of the T, N, and M components and describes how these are combined into stage groups. This represents a major step forward for thymic malignancies.

The ITMIG/IASLC thymic epithelial tumors staging project: A proposed lymph node map for thymic epithelial tumors in the forthcoming 8th edition of the TNM classification of malignant tumors

Although the presence of nodal disease is prognostic in thymic malignancy, the significance of the extent of nodal disease has yet to be defined. Lymph node dissection has not been routinely performed, and there is currently no node map defined for thymic malignancy. To establish a universal language for reporting as well as characterize the staging of this disease more accurately, an empiric node map is proposed here. This was developed using prior classification systems, series reporting specifics of nodal involvement, anatomical studies of lymphatic drainage, and preexisting node maps of the chest as defined by the International Association for the Study of Lung Cancer and the neck as defined by the American Academy of Otolaryngology—Head and Neck Surgery and the American Society for Head and Neck Surgery. The development of this node map was a joint effort by the International Thymic Malignancy Interest Group and the Thymic Domain of the IASLC Staging and Prognostic Factors Committee. It was reviewed and subsequently approved by the members of ITMIG. This map will be used as an adjunct to define node staging as part of a universal stage classification for thymic malignancy. As more data are gathered using definitions set forth by this node map, a revision may be undertaken in the future.