Non Small Cell Lung Cancer Introduction

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Non Small Cell Lung CancerIntroduction

• Mira Wollner
• RAMBAM MEDICAL CENTER

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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 lt 15
• American Cancer Society, Cancer Facts Figures
  2005
• SEER Cancer Statistics, 1998-2002.
  http//seer.cancer.gov

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Newly Diagnosed NSCLC in Israel

• 1999 1338
• 2002 1450

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Etiology

• Cigarette smoking responsible for gt 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, 1998-2002.
  http//seer.cancer.gov

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Histology

• Adenocarcinoma ( 45)
• 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, 1998-2002.
  http//seer.cancer.gov

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Diagnosis

• Medical history
• Physical exam
• Labs
• Imaging studies
• CXR
• CT-scan
• PET-CT scan
• Bone scan

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Diagnosis

• Bronchoscopy (FOB)
• Mediastinoscopy
• Histology
• Sputum
• FNA (cytology/biopsy)
• thoracotomy

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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

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TNM stage grouping
Stage 0 Tis NO MO Stage I T1 NO MO T2 NO MO Sta
ge 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
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Stage I disease
gt 2 cm
T2 N0 M0
T1 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
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Stage II disease
gt 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
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Stage IIIA disease
lt 2 cm gt 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
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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
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Mediastinal lymph node map Mountain CF, Dresler
CM. Chest 1997 1111718-1723
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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 Cancer44183-191

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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. 10971105

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Treatment algorithmGlotocan, Epidemiology Lung
Cancer, 2002
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Survival and FrequencyMountain Chest 1997
1111718-1723
Stage Frequency () 5-year survival
Clinical Pathological
IA 10 61 67
IB 38 57
IIA 13 34 55
IIB 24 39
IIIA 22 13 25
IIIB 22 5
IV 32 lt1
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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 199560615

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Sites of Recurrence Following Complete Surgical
Resection

• Mountain CF, McMurtrey MJ, Frazier OH. Current
  results of surgical treatment for lung cancer.
  Cancer Bull 198032105108

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Resected LN-negative Failure
Author Stage Pts No Chest Distant
Feld et all T1N0 162 9 17
T2N0 196 11 30
Pairolero et all T1N0 170 6 15
T2N0 158 6 23
Thomas et all T1N0 Sq 226 5 7
T1N0 non-Sq 346 9 17
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Resected LN-positive Failure
Author Stage Pts No Chest Distant
Feld et all T1N1 32 9 22
Pairolero et all T1N1 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
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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 2000,343171217-1222

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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 2000,343171217-1222

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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

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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

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Are All T1-2 Tumors the Same?Mulligan CR et al.
Ann Thorac Surg 200681(1)220-226
Tumor size (cm) 5 year survival ()
1 48,6
1-2 45,9
2-3 25,6
3-4 27
4-5 14,4
gt5 11,6
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Outcome After Surgical Resection in Operable NSCLC
Stage 5 year survival () Relapse ()
Local Distant
IA T1N0M0 67 10 15
IB T2N0M0 57 10 30
IIA T1N1M0 55
IIB T2N1M0 39 12 40
T3N0M0 38
IIIA T3N1M0 25 15 60
T1N2M0 23

• Pisters and Le Chevalier. J Clin Oncol
  2005233270-3278

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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 gt 60 years
• PS/QoL