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A Pictorial Guide to the Revised Staging System for Non-Small Cell Lung Cancer Through the Use of PET/CT Bruno P. Soares, MD; Katherine Zukotynski, MD; Mizuki Nishino, MD; Annick Van Den Abbeele, MD Department of Imaging Dana-Farber Cancer Institute Disclosure of Commercial Interest The authors do not have a financial relationship with a commercial organization that may have direct or indirect interest in the content of this exhibit. OBJECTIVE To illustrate the changes to the staging system for non-small cell lung cancer through the use of PET/CT and to discuss the rationale behind these changes. Contents • Epidemiology of lung cancer • PET/CT in lung cancer staging • Changes in the TNM classification system Epidemiology of Lung Cancer • Second most common malignancy and the leading cause of cancer death for both men and women • In 2009, there were an estimated 219,440 new cases of lung cancer and an estimated 159,390 deaths from lung cancer in the US • Direct medical cost for treatment of lung cancer is approximately $5 billion annually • Smoking is responsible for 87% of lung cancer deaths Reference: American Cancer Society, Surveillance and Health Policy Research, 2009. Contents • Epidemiology of lung cancer • PET/CT in lung cancer staging • Changes in the TNM classification system What is the TNM staging system? What is the TNM staging system? • T: extent of primary tumor (size and involvement of contiguous structures) • N: extent of involvement of regional lymph nodes • M: extent of spread to distant sites Why use TNM staging? Why use TNM staging? – Survival is heavily dependent on TNM tumor stage – Stages IA - IIIB are dependant on T and N classification – Stage IV disease is defined by metastatic disease Role of PET/CT in T Staging • Defining extent of invasion of adjacent structures • Distinguishing tumor from atelectasis • Evaluating additional pulmonary nodules • Identification of malignant pleural effusions Role of PET/CT in N Staging • Evaluates the entire mediastinum (unlike mediastinoscopy) • Relies on metabolic activity (unlike CT) • Changes N staging in ~ 20% of cases, due to its ability to: – Detect tumor in anatomically normal lymph nodes – Exclude tumor involvement in enlarged lymph nodes Limitations of PET/CT in N Staging • Micrometastases in normal-sized lymph nodes may not be detected • Negative predictive value decreases depending on: – Size of metastatic deposits – Avidity of the primary tumor Role of PET/CT in M Staging The strength of FDG-PET is M staging! – Improved detection of metastasis – May reduce futile intervention Contents • Epidemiology of lung cancer • PET/CT in lung cancer staging • Changes in the TNM classification system Background • Limitations of the AJCC Cancer Staging Manual 6th ed: • Based essentially on a single institution series • Limited number of patients (small subgroups) • Weighted toward surgically treated patients • Since the 6th edition in 2002, there have been refinements to the techniques available for clinical staging, especially computed tomography (CT) and positron emission tomography (PET) Rationale for Changes (1) Expansion of database of patients treated for lung cancer: • 81,015 cases from 46 sources in over 19 countries diagnosed between 1990 and 2000 • Treated by all modalities of care • 41% surgery only • 23% chemotherapy only • 11% radiotherapy only • 25% combined modalities Rationale for Changes (2) • The major determinant for development of subgroups of T, N and M descriptors was the outcome measure of overall survival • Proposed changes to the TNM staging system were externally validated against the Surveillance, Epidemiology and End Results (SEER) database from the same time period Histologic Classification of Lung Tumors –Non-small cell carcinoma (NSCLC) » Squamous cell carcinoma Unlike the prior edition, which was » Adenocarcinoma validated only for NSCLC... » Large cell carcinoma The new TNM staging system includes cell carcinoma small –Small cell carcinoma and carcinoid tumors –Carcinoid tumor –Other rare types TNM Staging 7th Edition: Summary of Changes • TNM staging system now also includes small cell carcinomas and carcinoid tumors of the lung • T classifications have been redefined: • T1 has been divided into T1a (≤2 cm in size) and T1b (>2-3 cm in size) • T2 has been divided into T2a (>3-5 cm in size) and T2b (>5-7 cm in size) • T2 (>7 cm in size) has been reclassified as T3 • Multiple tumor nodules in the same lobe have been reclassified from T4 to T3 • Multiple tumor nodules in the same lung but in a different lobe have been reclassified from M1 to T4 • No changes in the N classification • M classifications have been redefined: • M1 has been divided into M1a and M1b • Malignant pleural and pericardial effusions have been reclassified from T4 to M1a • Separate tumor nodules in the contralateral lung are considered M1a • Distant metastases are considered M1b Looks confusing? So let’s describe and illustrate the changes step by step... TNM Staging 7th Edition: Changes in T Staging • T1: Smaller than 3cm • T1a: less than or equal to 2cm; The size threshold of •3 cm was confirmed beor a significant T1b: >2cm and less to than to 3cm There was a significant difference in prognosis forequal lesions cutpoint retained in the of T1than vs. T2 tumor. less thanand 2 cm compared to definition lesions larger 2 cm • T2: >3cm or Involves the main bronchus, 2 cm or more distal (cutpoint), generating subgroups T1a and T1b. to the carina or invades the visceral pleura, or with atelectasis extending to the hilum TNM Staging 7th Edition: Changes in T Staging • T1a: less than or equal to 2 cm • T1b: >2cm and less than or equal to 3 cm • T2a: >3cm and less than or equal to 5 cm • T2b: >5cm and less than or equal to 7 cm • T3: >7 cm Significant cutpoints were identified at 5 and 7 cm, generating new subgroups. Example: 9 mm nodule T1a: less than or equal to 2cm (previously T1) Example: 2,2 cm nodule T1b: >2cm and less than or equal to 3cm (previously T1) Example: 6,4 cm mass T2a: >3cm and less than or equal to 5 cm T2b: >5cm and less than or equal to 7cm T3: >7cm (previously any tumor larger than 3 cm was considered T2 if there was no invasion of adjacent structures) Example: 7,2 cm necrotic mass T3: >7cm Large mass with FDG-avid rim and central photopenia consistent with necrosis Example: Chest wall invasion T3: > 7 cm or tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus < 2cm distal to the carina, but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung. Tumors > 7 cm are T3, irrespective of features mentioned above. TNM Staging 7th Edition: Additional Lung Nodules Additional nodules in the same lobe as the primary tumor are now T3 (previously T4) Additional nodules in another ipsilateral lobe are now T4 (previously M1) Contralateral lung nodules are now M1a (previously M1) Example: Additional nodules in the same lobe Additional nodules in the same lobe as the primary tumor are now T3 (previously T4) TNM Staging System: Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes involved by direct extension of the primary tumor N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s) N3 Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) No Changes in N Staging! Example: Ipsilateral hilar lymph nodes N1: Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes involved by direct extension of the primary tumor Example: Subcarinal lymphadenopathy N2: Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s) Example: Contralateral hilar nodes N3: Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) TNM Staging 7th Edition: Changes in M Staging MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 M1a M1a Distant metastasis present Contralateral nodules (previously M1) Pleural dissemination (previously T4) M1b Distant metastasis Additional nodules in another ipsilateral lobe are now T4 (previously M1) Example: Pleural dissemination Pleural dissemination is now M1a (previously T4) Example: Distant metastasis in the adrenal Distant metastasis is now M1b (previously M1) Example: Distant metastases in liver and adrenal Distant metastasis is now M1b (previously M1) Example: Distant metastasis in bone Distant metastases in the bones are now M1b (previously M1) So now that we have gone step by step through all the changes… Let’s put it all together in one table! 6th vs. 7th ed: Summary of changes 6th edition T and M descriptors 7th edition T and M descriptors N0 N1 N2 N3 T1 (<=2 cm) T1a IA IIA IIIA IIIB T1 (>2-3 cm) T1b IA IIA IIIA IIIB T2 (<= 5 cm) T2a IB IIA IIIA IIIB T2 (>5-7 cm) T2b IIA IIB IIIA IIIB T2 (>7 cm) T3 IIB IIIA IIIA IIIB T3 invasion T3 IIB IIIA IIIA IIIB T4 same lobe nodules T3 IIB IIIA IIIA IIIB T4 invasion T4 IIIA IIIA IIIB IIIB M1 ipsilateral lung T4 IIIA IIIA IIIB IIIB T4 pleural effusion M1a IV IV IV IV M1 contralateral lung M1a IV IV IV IV M1 distant M1b IV IV IV IV * Changes to the staging groups are in red So after all these changes, here’s what the new TNM staging system looks like: The New TNM Staging System Stage Groups T N M Ia T1a,b N0 M0 Ib T2a N0 M0 IIa T1a,b T2a T2b N1 N1 N0 M0 M0 M0 IIb T2b T3 N1 N0 M0 M0 IIIa T1-3 T3 T4 N2 N1 N0,1 M0 M0 M0 IIIb T4 T1-4 N2 N3 M0 M0 IV any any M1a,b Conclusions • Staging is critical to selecting patient appropriately for surgery and multimodality therapy. • PET/CT is important in staging patients with lung cancer and is becoming increasingly popular. • Our presentation provides practical insights into the changes to the TNM staging system for lung cancer. Thank you … We hope you enjoy ECR 2010! References AJCC Cancer Staging Manual, 7th edition; 2010. American Cancer Society, Surveillance and Health Policy Research, 2009. Katz S, Ferrara T, Alavi A,Torigian D. PET, CT, and MR imaging for assessment of thoracic malignancy: structure meets function. PET Clinics 2009; 3: 395-410. Kligerman S, Digumarthy S. Staging of non-small cell lung cancer using integrated PET/CT. AJR Am J Roentgenol 2009;193: 1203-1211. Patz EF, Jr., Connolly J, Herndon J. Prognostic value of thoracic FDG PET imaging after treatment for non-small cell lung cancer. AJR Am J Roentgenol 2000; 174(3):769-74. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. Jama 2001; 285(7):914-24. Demura Y. 18F-FDG accumulation with PET for differentiation between benign and malignant lesions in the thorax. J Nucl Med. 2003; 44(4):540-8. Wahl, RL, Buchanan, JW, editors. 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