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49 Outcomes in Surgically Resected T3N0 NSCLC in the Dutch population Introduction The TNM classification has been developed to predict survival outcome in patients with cancer76. The T, N, and M descriptors for NSCLC have evolved over time, with the recent transition from the seventh edition of the TNM staging classification (TNM-7)77,78 to the eight edition of the TNM staging classification (TNM-8) (2017)79, based on analyses of the International Association for the Study of Lung Cancer (IASLC) database. The T3 category for lung cancer represents a heterogeneous subgroup as shown in Table 1. In the sixth edition of the TNM staging classification (TNM-6)15, tumors with a diameter larger than 7 cm were classified as T2, whereas tumors with a separate nodule in the same lobe were classified as T4 tumors. In the TNM-7, both these categories were designated as T3, consisting of tumors with (1) a diameter larger than 7cm, (2) a second nodule or multiple lesions in the same lobe (two or more nodules), (3) parietal pleural invasion, (4) less than a 2-cm margin from the main carina, and/or (5) atelectasis or obstructive pneumonitis of the entire lung. The Staging and Prognostic Factors Committee of the IASLC published proposals to revise the lung cancer staging criteria for the TNM-8 in 201578. Changes to the T3 component included reclassifying tumors larger than 5 cm from T2 to T3, with tumors larger than 7 cm moved to T4. Diaphragm invasion became a T4 descriptor, but lung atelectasis, both partial and total, and all cases of main bronchus invasion, regardless of the distance from the carina were defined as T2. The IASLC recommendations to revise the T3 category in TNM-8 were largely based on information derived from centers in Asia79, as were the vast majority of all data in the IASLC database. As survival outcome and prognostic factors may differ between various countries/ regions, we aimed to validate the recent TNM-8 T3 recommendations in a large series from the Netherlands, using clinical data from the Netherlands Comprehensive Cancer Organization (IKNL) and pathology data from the Nationwide Network and Registry of Histopathology and Cytopathology in the Netherlands (PALGA)80. Table 1. Changes in NSCLC T3 descriptors between the 6th, 7th and 8th edition of the staging manual77, 78, 79 TNM-6 TNM-7 T-descriptor TNM-8 T2 T2b diameter 5-7 cm T3 T3 T3 < 2 cm carina T2 T3 T3 complete atelectasis T2 T4 T3 separate nodules T3 T3 T3 pleural/chest wall invasion T3 T2 T3 diameter > 7 cm T4 T3 T3 diaphragm invasion T4 TNM-6, sixth edition of the TNM classification; TNM-7, seventh edition of the TNM classification; TNM-8 eight edition of the TNM classification 4

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