That's cool a rossi la classificazione tnm cosa cambia 24 settembre 2010

Antonio ROSSI, MDDivision of Medical Oncology,

“S.G. MOSCATI” HOSPITAL, AVELLINO - ITALY

La classificazione TNM: cosa cambia?

Thanks to…

Component of the classification

Changes

T To subclassify T1 according to tumor size inT1a: < 2 cm andT1b: > 2 cm but < 3 cm

To subclassify T2 according to tumor size inT2a: > 3 cm but < 5 cm (or tumor with any other tumor descriptors, but < 5 cm) and T2b: > 5 cm but < 7 cm

To reclassify T2 tumors > 7 cm as T3

To reclassify T4 tumors by additional nodule/s in the same lobe of the primary tumours as T3

To reclassify M1 tumors by additional nodule/s in another ipsilateral lobe as T4

To reclassify T4 tumors by malignant pleural effusion as M1a

N No changes

M To subclassify M1 inM1a: separated tumor nodule/s in the controlateral lung; tumor with pleural nodules or malignant pleural (or pericardial) effusion; andM1b: distant metastasis

Take-home message

Changes for the 7th Edition of the TNM classification of lung cancer

Goldstraw P et al JTO, 2007

Antonio ROSSI, MDDivision of Medical Oncology,

“S.G. MOSCATI” HOSPITAL, AVELLINO - ITALY

Thank you for your kind attention

But…

Some of the aims for adopting a global standard are to:

• Aid medical staff in staging the tumour helping to plan the treatment

• Give an indication of prognosis

• Assist in the evaluation of the results of treatment

• Enable facilities around the world to collate information more productively

TNM: Uses and Aims

The history of Lung Cancer TNM

• 1968: I ed.

• 1974: II ed. (Mountain-proposal 1973)

• 1978: III ed. (minimal changes)

• 1987: IV ed. (Mountain-proposal – Chest 1986)

• 1992: IV ed. rev. (no changes)

• 1997: V ed. (last Mountain revision)

• 2002: VI ed. (no changes)

No.pts

2,155

3,753

5,319

Estimated 1.608.000 new cases of lung cancer worldwide with 1.380.000 the deaths in year 2008 (GLOBOCAN 2008)

5,319 = 0.00337% of 1.608.000 patients affected by lung cancer

TNM6: Further Limitations

Patients who had undergone surgical treatment, not representative of the entire population of patients affected by lung cancer

Patients collected in only one geographic region

…this is why we needed an updated staging system for Lung Cancer

TNM7: IASLC Lung Cancer Database

Summary of Cases Contributed to the Project

Total cases submittedTotal cases submitted 100,869 100,869

• Excluded from analysesExcluded from analyses 19,85419,854

• Outside of 1990-2000 time frameOutside of 1990-2000 time frame 5,4435,443

• Incomplete survival dataIncomplete survival data 1,5051,505

• Unknown histology Unknown histology 2,4682,468

• Incomplete stage informationIncomplete stage information 7,7207,720

• Recurrent cases and other exclusionsRecurrent cases and other exclusions 1,6031,603

• Carcinoids, sarcomas and other histologiesCarcinoids, sarcomas and other histologies 1,1151,115

Included in analysesIncluded in analyses 81,01581,015

•Small Cell Lung Cancer (and mixed SCLC/NSCLC)Small Cell Lung Cancer (and mixed SCLC/NSCLC) 13,29013,290

•Non-Small Cell Lung CancerNon-Small Cell Lung Cancer 67,72567,725

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

Europe Australia N. America Asia

59%59% 8%8% 18%18% 15%15%

TNM7: Answers to TNM6 Limitations

2009: VII ed. (forthcoming – 2007 IASLC proposal) No.pts 100,869

19,854 excluded from the analysis due to several reasons

81,015 = 5.0% of 1.608.000 patients affected by lung cancer

53% of these patients had undergone surgical treatment

Type of collection: Retrospective

Study period: 1990-2000

Internal validation: comparing results by type of data

source and geographical regions

External validation: Surveillance, Epidemiology, and

End Results Program (SEER) database

TNM7: Characteristics

IASLC Staging Project

Treatment Modalities – 67,735 NSCLC

SurgerySurgery

42%42%

ChemotherapyChemotherapy

15%15%

RTRT

8%8%

Surgery Surgery + Chemo+ Chemo

4%4%

Surgery Surgery + RT+ RT5%5%

Chemo Chemo + RT+ RT12%12%

Tri-modality Tri-modality

3%3%

No treatment details No treatment details

or best supportive or best supportive care: 10%care: 10%

When comparing overall survival between groups of patients defined by tumor size, we found that survival differences were optimized at size cutpoints of 2, 3, 5, and 7 cm. These tumor size cutpoints were chosen on the basis of pathologic measurements from completely resected cases in the learning set and were then tested in the remaining pathologic and clinical data.

T Descriptors

Rami Porta T et al J Thorac Oncol 2007;2: 593–602

15,234 patients with sufficient pT descriptor information (M0)

•T1 Tumour 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus)

•T1a Tumour 2 cm or less in greatest dimension •T1b Tumour more than 2 cm but not more than 3 cm in greatest dimension

TNM Clinical ClassificationT Descriptors

•T2T2 Tumour more than 3 cm but not more than 7 cm; or tumour with any of the following features:•• Involves main bronchus, 2 cm or more distal to the carina•• Invades visceral pleura•• Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung

•T2a Tumour more than 3 cm but T2a Tumour more than 3 cm but not more than 5 cm in greatest not more than 5 cm in greatest dimensiondimension

•T2b Tumour more than 5 cm but T2b Tumour more than 5 cm but not more than 7 cm in greatest not more than 7 cm in greatest dimensiondimension


•T3T3 Tumour more than 7 cm or one that directly invades any of the following: chest wall (including superior sulcus tumours), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumour in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumour nodule(s) in the same lobe as the primary.


•T4T4 Tumour of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body, carina; separate separate tumour nodule(s) in a different tumour nodule(s) in a different ipsilateral lobe to that of the ipsilateral lobe to that of the primaryprimary..


Rush V et al J Thorac Oncol 2009;4: 568–577

N Descriptors

• Reconciled “Naruke” and “Mountain-Dresler” Nodal Chart• The anatomic limits of the nodal stations are clearly

defined• The concept of “nodal zones” has been introduced

incorporating adjacent stations into larger aggregates (need to be further validated)

• Supraclavicular zone now includes the low cervical, supraclavicular and sternal notch nodes

• Identification of mediastinal line on the left paratracheal level

• Enlargement of subcarinal space

38,265 patients with sufficient pN descriptor information (M0)

N1

N2

Proposed nodal zones with their nodal stations


Survival by N statusand number of involved N zones


Three distinct prognostic groups:

Single zone N1

Multiple-zone N1 or single N2

Multiple-zone N2

(Need to be further validated)

M Descriptors

6,596 patients with sufficient cM and /or pM information

•MxMx Presence of distant metastasis cannot be assessed

•M0M0 No distant metastasis

•M1M1 Presence of distance metastasis

•M1a: separate tumor nodule(s) in a controlateral M1a: separate tumor nodule(s) in a controlateral lobe and tumor with malignant pleural lobe and tumor with malignant pleural involvement, effusion or nodule(s), or malignant involvement, effusion or nodule(s), or malignant pericardial effusionpericardial effusion

•M1b: distant metastasis outside lung/pleuraM1b: distant metastasis outside lung/pleura

T2N0 (> 5 < 7 cm)

T2N0 (> 7 cm)

T2N1 (< 5 cm)

T2N1 (> 7 cm)

T4N0 (same lobe nodules)

T4N1-2 (same lobe nodules)

T4N0-1 (extension)

T4 any N (pleural effusion)

T4N0-1M1

(ipsilateral lung)T4N2-3M1

(ipsilateral

lung)

TNM6

Stage IB T2N0 (> 5 < 7 cm)

Stage IB T2N0 (>7 cm)

Stage IIB T2N1 (< 5 cm)

Stage IIB T2N1 (> 7 cm)

Stage IIIB T4N0 (same lobe nodules)

Stage IIIB T4N1-2 (same lobe nodules)

Stage IIIB T4N0-1 (extension)

Stage IIIB T4 any N (pleural effusion)

Stage IV T4N0-1M1 (ipsilateral lung)

Stage IV T4N2-3M1 (ipsilateral lung)

TNM7

Stage IIA

Stage IIB

Stage IIA

Stage IIIA

Stage IIB (T3)

Stage IIIA

Stage IIIA

Stage IV (M1a)

Stage IIIA

Stage IIIB

Stage groups in TNM6 and TNM7

Overall survival by clinical stage

TNM6 TNM7

Goldstraw P et al J Thorac Oncol 2007; 2:706–714

Survival by clinical stage according to the sixth edition of TNM and by the newly proposed TNM stage based on the entire set of cases available for reclassification

Overall survival by pathologic stage

TNM6 TNM7


Survival by pathologic stage according to the sixth edition of TNM and by the newly proposed TNM stage based on the entire set of cases available for reclassification

Proposed stage groupings


criticism

• Database does not includes any data from Africa, South Africa, South America or Indian subcontinentAmerica or Indian subcontinent

• Under-represents cases from ChinaChina which is experiencing a rapid increase in lung cancer incidence and is the most populous country in the world

• New TNM reflects more strongly prognosis than algorithm for treatment (i.e., stage IV with oligometastases and resectable primary lesion could receive a different treatment with respect to stage IV with multiple distant metastases)

• New TNM does not offer information about biology and behaviour of the tumor; we are waiting for a better understanding of these aspects

...further Criticisms

Giroux DJ et al J Thorac Oncol 2009;24: 679–683

Lung Cancer staging: what is the next step?

TNM7 - Therapeutic implications?

T and M descriptorsT and M descriptors N0N0 N1N1 N2N2 N3N3

66thth edition edition77thth

editionedition StadioStadio StadioStadio StadioStadio StadioStadioT1 (< 2 cm)T1 (< 2 cm) T1aT1a IAIA IIAIIA IIIAIIIA IIIBIIIBT1 (> 2-3 cm)T1 (> 2-3 cm) T1bT1b IAIA IIAIIA IIIAIIIA IIIBIIIBT2 (< 5 cm)T2 (< 5 cm) T2aT2a IBIB IIA (ex IIB)IIA (ex IIB) IIIAIIIA IIIBIIIBT2 (> 5 < 7 cm)T2 (> 5 < 7 cm) T2bT2b IIA (ex IB)IIA (ex IB) IIBIIB IIIAIIIA IIIBIIIBT2 (> 7 cm)T2 (> 7 cm)

T3T3

IIB (ex IB)IIB (ex IB) IIIA (ex IIB)IIIA (ex IIB) IIIAIIIA IIIBIIIBT3 invasionT3 invasion IIBIIB IIIAIIIA IIIAIIIA IIIBIIIB

T4 (same lobe nodules)T4 (same lobe nodules) IIB (ex IIIB)IIB (ex IIIB)IIIA (ex IIIA (ex

IIIB)IIIB) IIIA (ex IIIB)IIIA (ex IIIB) IIIBIIIB

T4 (extension)T4 (extension) T4T4 IIIA (ex IIIB)IIIA (ex IIIB)IIIA (ex IIIA (ex

IIIB)IIIB) IIIBIIIB IIIBIIIBM1 (ipsilateral lung)M1 (ipsilateral lung) IIIA (ex IV)IIIA (ex IV) IIIA (ex IV)IIIA (ex IV) IIIB (ex IV)IIIB (ex IV) IIIB (ex IV)IIIB (ex IV)T4 (pleural effusion)T4 (pleural effusion)

M1aM1a IV (ex IIIB)IV (ex IIIB) IV (ex IIIB)IV (ex IIIB) IV (ex IIIB)IV (ex IIIB) IV (ex IIIB)IV (ex IIIB)M1 (controlateral lung)M1 (controlateral lung) IVIV IVIV IVIV IVIVM1 (distant)M1 (distant) M1bM1b IVIV IVIV IVIV IVIVIn yellow changing in classificationIn yellow changing in classification

No treatment changes





T3T3







Adjuvant CT is already being

considered





T3T3







Same lobe nodules are being already

considered for surgery





T3T3







T4N0-1 was being already considered for

surgery





T3T3







The ipsilateral/other lobe disease was already being considered for surgery if

less than N2





T3T3







As always been treated has stage IV

TNM7 & Adjuvant therapy

Complete resection and N0

IB (new): T2a (3-5 cm) = 5-y Survival 58%

IIA (new): T2b (5-7 cm) = 5-y Survival 49%

IIB (new): T3 (> 7 cm) = 5-y Survival 35%

IIB (new): T3 (invasion) = 5-y Survival 41%

IIB (new): T3 (same lobe) = 5-y Survival 45%

*Strauss GM et al JCO 2008 **Winton et al NEJM 2005

[should we evaluate post- or pre-operative chemotherapy in selected patients?]

CALGB9633 (4 cm)* = 5-y Survival 62%

JBR.10 (N1 disease)** = 5-y Survival 68%

0

500

1000

1500

2000

2500

3000

3500

4000

Europe Australia N.America

Asia

Limited

Extensive

TNM Only

IASLC Lung Cancer Database: SCLC

Small Cell Lung Cancer: Stage Distribution by Continent, 13,290 Cases

(58%)(58%) (6%)(6%) (34%)(34%) (2%)(2%)Percent of total small Percent of total small cell cases contributedcell cases contributed

Shepherd F et al J Thorac Oncol 2007; 2:1067–1077

TNM7: Small Cell Lung Cancer

TNM6 TNM7

Survival by clinical sixth edition of TNM, and IASLC proposed TNM stage

TNM7: To date application in clinical practice

• Effective January 2010, the 7th editions of the American Joint Commission (AJCC) on Cancer and the International Union Against Cancer (UICC) Staging Manuals were published*

• Since January 2010, 3 clinical trials concerning NSCLC therapy have been activated in our Division:

• All trials were activated in the second half of 2009 • 1 Trial addressed to locally-advanced NSCLC (stage IIIA-IIIB)

• 2 Trials addressed to advanced NSCLC (stage IIIB-IV)

• No trials use TNM7*Rusch VW et al J Thorac Cardiovasc Surg 2010

TNM7: Final Comments• The IASLC Lung Cancer Staging System is the largest, validated,

internationally recognized system to date (over 100.000 patients registered in 46 databases)

• Challenges are mainly seen with T size stratification, multiple nodule recharacterization, and pleural effusion impact

• These changes may define new strategies for surgical approaches as well as the use of adjuvant or neoadjuvant therapies

• This classification is also reccomended for small cell lung cancer

• Prospective database collection for the forthcoming 8th Edition to correct TNM7 biases

• Trials will be needed to clarify appropriate treatment strategies

Thank you

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That's cool a rossi la classificazione tnm cosa cambia 24 settembre 2010

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