1. Non Small Cell Lung Cancer Introduction
Mira Wollner
RAMBAM MEDICAL CENTER

2. Epidemiology
Most frequent cause of cancer diagnosed in the US – about 12% of all cancer
NSCLC represents ~ 80% of lung cancer
In year 2004 ~ 173,770 new cases and 160,440 deaths
Leading cause of cancer deaths in both men ( 32%) and women (25%)
75% of new cases present with non resectable disease
Overall 5 year survival < 15%
American Cancer Society, Cancer Facts & Figures 2005
SEER Cancer Statistics,

4. Newly Diagnosed NSCLC in Israel
1999 = 1338
2002 = 1450

5. Etiology Cigarette smoking responsible for > 80% cases
Use of filter
Tar content
Variation of tobacco blends
Contains ~ 300 chemicals and up to 40 potent carcinogens (nitrate)
Recent changes in histological dominant type
(due to changes in tobacco blend and use of filter)
American Cancer Society, Cancer Facts & Figures 2005
SEER Cancer Statistics,

6. Histology Adenocarcinoma ( 45%) Broncho-alveolar carcinoma
Atypical Alveolar Hyperplasia ( precursor)
Broncho-alveolar carcinoma
Squamous cell carcinoma ( 33%)
Large cell carcinoma ( 9% )
Adenosquamous carcinoma
Pleomorphic carcinoma
Carcinoma of salivary gland
Carcinoid
American Cancer Society, Cancer Facts & Figures 2005
SEER Cancer Statistics,

7. Diagnosis Medical history Physical exam Labs Imaging studies CXR
CT-scan
PET-CT scan
Bone scan

8. Diagnosis Bronchoscopy (FOB) Mediastinoscopy Histology Sputum
FNA (cytology/biopsy)
thoracotomy

9. Methods of Spread Vascular channels Lymphatic channels
Airborne or lymphatic (satellite nodules)
Lymphatic spread to regional lymph nodes: bronchopulmonary (segmental and lobar (N1), mediastinal (N2-3) ,supraclavicular (N3)
Retrograde lymphatic spread (pleural surface)
Direct invasion
Systemic dissemination

10. TNM stage grouping Stage 0 Tis NO MO Stage I T1 NO MO T2 NO MO
Stage II T1 N1 MO
T2 N1 MO
Stage III A T1 N2 MO
T2 N2 MO
T3 NO MO
T3 N1 MO
T3 N2 MO
Stage III B Any T N3 MO
T4 Any N MO
Stage IV Any T Any N M1

11. N0: No lymph node involvement
Stage I disease
> 2 cm
T1 N0 M0
T2 N0 M0
T 3 cm
T + visceral pleura
involved
T + atelectasis
T  3 cm OR
No lobar
bronchus
involvement OR
N0: No lymph node involvement

12. N1: Intrapulmonary and/or hilar nodes involved
Stage II disease
> 2 cm
T1 N1 M0
T2 N1 M0
T 3 cm
T + visceral pleura
involved
T + atelectasis
T  3 cm OR
No lobar
bronchus
involvement OR
N1: Intrapulmonary and/or hilar nodes involved

13. Stage IIIA disease OR T2 OR OR OR T1 T3 N0 M0 T1 N2 M0 T3 N1 M0
< 2 cm > 2 cm
T3 N0 M0
T3 N1 M0
T3 N2 M0
T1 N2 M0
T2 N2 M0 OR T2
T  3 cm
T + visceral pleura
involved
T + atelectasis
T  chest wall
(or diaphragm) OR OR
T  mediastinal
pleura
(or pericardium) OR T1
T  3 cm
No lobar
bronchus involvement
N1: peribronchial or ipsilateral hilar
N2: ipsilateral mediastinal and subcarinal

14. Stage IIIB disease Any T, N3, M0 Any N, T4, M0
Scalene
Supraclavicular
Any N T4
Any T
N3: lymph nodes involved T4: mediastinal involvement

15. Mediastinal lymph node map Mountain CF, Dresler CM
Mediastinal lymph node map Mountain CF, Dresler CM. Chest 1997; 111:

16. Involvement of lymphatic metastatic spread in non-small cell lung cancer accordingly to the primary cancer location
Skip metastases to level 10 (hilar) ~ 5%
Skip metastases to mediastinal LN ~ 19%
Mediastinal LN dissection must be the standard procedure
Kotoulas CS et al 2004 Lung Cancer;44:

22. Patterns of failure after resection of NSCLC
CHRIS R. KELSEY,., KIM L. LIGHT, AND LAWRENCE B. MARKS, 2006
Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 4, pp. 1097–1105

27. Treatment algorithm Glotocan, Epidemiology Lung Cancer, 2002

28. Survival and Frequency Mountain Chest 1997; 111:1718-1723
Stage
Frequency (%)
5-year survival %
Clinical Pathological IA
~ 10 IB
IIA
~ 13
IIB
IIIA
~ 22
IIIB
~ 5 IV
~ 32
<1

29. Surgery Lobectomy = gold standard for early stage
Limited recection showed higher local recurrence rate
(15%) then lobectomies (5%) for T1N0 tumors
Ginsberg RJ et al. Ann Thorac Surg 1995;60:615

30. Sites of Recurrence Following Complete Surgical Resection
Mountain CF, McMurtrey MJ, Frazier OH. Current results of surgical treatment for lung cancer. Cancer Bull 1980;32:105–108

31. Resected LN-negative Failure
Author
Stage
Pts No
Chest %
Distant %
Feld et all
T1N0
162 9 17
T2N0
196 11 30
Pairolero et all
170 6 15
158 23
Thomas et all
T1N0 Sq
226 5 7
non-Sq
346

32. Resected LN-positive Failure
Author
Stage
Pts No
Chest %
Distant %
Feld et all
T1N1 32 9 22
Pairolero et all 18 28 39
Martini et all
T1-2N1sq 93 16 31
T1-2N1
adeno
114 8 54
T2-3N2sq 46 13 52
T2-3N2 adeno
103 17 61

33. Completely Resected Stage II or IIIA With Postoperative Adjuvant Therapy (ECOG)
Keller SM, Adak S, Wagner H, Herscovic A, et al. New Engl J Med 2000,343;17:

34. Completely Resected Stage II or IIIA With Postoperative Adjuvant Therapy (continuing)
Keller SM, Adak S, Wagner H, Herscovic A, et al. New Engl J Med 2000,343;17:

35. Patterns of Failure
S. Lee et al. Postoperative adjuvant chemotherapy and radiotherapy for stage II and III non-small cell lung cancer (NSCLC) Lung Cancer 37 (2002) 65/71

36. Prognostic Factors
S. Lee et al. Postoperative adjuvant chemotherapy and radiotherapy for stage II and III non-small cell lung cancer (NSCLC) Lung Cancer 37 (2002) 65/71

37. Are All T1-2 Tumors the Same. Mulligan CR et al
Are All T1-2 Tumors the Same? Mulligan CR et al. Ann Thorac Surg 2006;81(1):
Tumor size (cm)
5 year survival (%) ≤1
48,6
1-2
45,9
2-3
25,6
3-4 27
4-5
14,4
>5
11,6

38. Outcome After Surgical Resection in Operable NSCLC
Stage
5 year survival
(%)
Relapse
Local
Distant IA
T1N0M0 67 10 15 IB
T2N0M0 57 30
IIA
T1N1M0 55
IIB
T2N1M0 39 12 40
T3N0M0 38
IIIA
T3N1M0 25 60
T1N2M0 23
Pisters and Le Chevalier. J Clin Oncol 2005;23:

39. Prognostic factors TNM Stage Tumor size Pathological N2
Extend of LN involvement (single vs multiple)
Occult vs Bulky
Type of surgery
wedge/segmentectomy vs lobectomy
LN sampling vs dissection
Positive surgical margins
age > 60 years
PS/QoL