강 창 현 서울대학교병원 흉부외과 서울대학교 의과대학

Staging Communication Evaluation TreatmentPrognosis Research

TNM based stage AJCC (1977) UICC (1958) Collaboration since 1982

AJCC Cancer Staging Manual editions EditionsPublicationEffective dates

References T-descriptorsJTO 2007 N-descriptorsJTO 2007 M-descriptorsJTO 2007 Stage groupingJTO 2007 ValidationJTO 2007

References SCLC (clinical staging) JTO 2007 SCLC (pathological staging) JTO 2009 Carcinoid tumorsJTO 2008 Additional prognostic factorJTO 2008 IASLC nodal mapJTO 2009

AJCC 7 th edition Based on staging project by IASLCBased on staging project by IASLC International multi-institute dataInternational multi-institute data Internal and external validationInternal and external validation

IASLC staging project 1996 IASLC workshop 1998 New staging committees 2001 Draft of data element 2005 Final submission of data

IASLC database Time Frame 1990 ~ 2000 Source of data 45 sources from 20 countries

Numbers of cases Total cases submitted100,869 Excluded from current analysis19,374 Included in analysis81,495 SCLC13,032 NSCLC68,463

Treatment modalities Surgery 42% RT 8% Chemotherapy 15% Surgery + Chemo 4% Surgery + RT 5% Chemo + RT 12% Tri- modality3 %

Distribution by continent

Validation InternalExternal By Data source Geographical regions By SEER data Literature review

Numbers analyzed T descriptors18,198 N descriptors28,371 –pN1 & pN22,876 M descriptors6,596 SCLC (clinical)8,088 SCLC (Pathologic)349 Carcinoid tumor513

T-descriptors Cutpoints of tumor size Malignant pleural effusion Separate nodules Other T2 descriptors Other T3 descriptors Other T4 descriptors

New cutpoints in size 6 th Edition7 th Edition T1≤ 3cmT1a≤ 2cm T1b≤ 3cm T2> 3cmT2a≤ 5cm T2b≤ 7cm T3> 7cm

T1 learning set (n=2,284)T2 learning set (n=2607)

Separate nodules & Malignant effusion 6 th Edition 7 th Edition Separate nodules in Same lobeT4T3 in different lobe (same lung) M1T4 in contralateral lungM1M1a Malignant pleural effusionT4M1a

N-descriptors Verification of N1, N2, & N3 Location of involved LNs Number of involved LN stations Skip metastasis Anatomical “zones”

Negative results Peripheral specific LNs Single specific LN zones Presence of skip metastasis did not had prognostic significance (except LUL with AP zone single metastasis)

Positive results? N1a single N1 zone N1b Multiple N1 zone N2a Single N2 zone N2b Multiple N2 zone

Overall disease burden, rather than anatomical location may have the most important influence on outcome

Suggestions Six Nodal zones Subdivision to 3 prognostic groups 1)N1a 2)N1b & N2a 3)N2b No change of current N-descriptors

Discrepancy in nodal maps Naruke map Naruke map (Japan Lung Cancer Society map) MD-ATS map MD-ATS map (Mountain-Dresler modification of American Thoracic Society map) vs. #1#1 & #2 #2, #3, #4R, #4L#4R, #4L #7, #10#7

M-descriptors Separate nodules –Same lobe –Same lung –Contralateral lung Malignant pleural effusion Distant metastasis –Site of interest (brain) –Single vs. multiple

Stage grouping T1a / T1b T2aT2bT3T4N0IAIBIIAIIBIIIA N1IIAIIAIIBIIIAIIIA N2IIIAIIIAIIIAIIIAIIIB N3IIIBIIIBIIIBIIIBIIIB M1a / M1b IVIVIVIVIV

AJCC the 6 th edition

AJCC the 7 th edition

Small cell lung cancer

Carcinoid tumor

Potential prognostic factors Tumor characteristics Patients characteristics Laboratory parameters Tumor biology

Potential prognostic factors

Changes in the 7 th edition Recommended for the classification of both NSCLC and SCLC and for carcinoid tumors T classification T1a (≤2cm) and T1b (>2-3cm) T2a (>3-5cm) and T2b (>5-7cm) T2 (>7cm) → T3 Multiple tumor nodules in the same lobe → T3 Multiple tumor nodules in the same lung → T4

Changes in the 7 th edition No changes in N classification But new international nodal map was proposed M classification Malignant pleural or pericardial effusion → M1a Separate tumor nodules in contralateral lung → M1a M1b designates distant metastasis MX designation has been eliminated

Limitations Lack of detailed data in each descriptors Too small numbers in specific category Different lymph node maps Biased distribution in treatment modality Effect of treatment had not been considered

New IASLC Prospective project Prospective data acquisition International multi-institute study Complete set of data Including non-anatomical prognostic factors

Timetable Data collection Follow-up 2013Data analysis Jan 2014 Submission of recommendations to UICC and AJCC Jan – July 2014 Publication in JTO 2016 Publication of 8 th edition of TNM classification by the UICC and AJCC

Future