Lung Cancer 1

Lymph Node Staging EBUS, EUS, Navigational Bronchoscopy

Daniel L Miller MD

Kamal A. Mansour Professor of Surgery

Emory University School of Medicine

Chief, General Thoracic Surgery

Emory University Healthcare

Atlanta, Georgia

Lung Cancer 2

Lymph Node Staging Presentation

Stage IIIB Stage IA

Lung Cancer 3

0

200

400

600

800

1000

1200

1400

1600

IA IB IIA IIB IIIA IIIB IV

Stage Mountain CF, Chest 1997;111:1710

Lymph Node Staging Presentation

Lung Cancer 4

Lymph Node Staging Survival

0

10

20

30

40

50

60

70

80

90

100

% Alive

IA IB IIA IIB IIIA IIIB IV

Stage Mountain CF. Chest 1997; 111:1710-17

Lung Cancer 5

Lung Cancer

Lymph Node Evaluation

Lung Cancer 6

Lymph Node Staging Non-invasive staging

Sensitivity (%) Specificity (%)

CT Chest 51.9 80.3

PET Scan 74 85

Silvestri et al. Chest 2007;132:178S-201S

Integrated PET-CT: improved staging and anatomic accuracy; sensitivity: ~ 90%, specificity: ~ 94%

Lung Cancer 7

Lung Cancer Stage IA - LN Involvement

Tumor Size LN Involvement

(%)

5 yr Survival

(%)

< 1.0 cm 0 - 7 80 - 100

1.1- 2.0 cm 17-19 74 - 86

2.1 – 3.0 cm 23 - 37 51 - 68

Japan/US

Lung Cancer 8

Lymph Node Staging Invasive Staging

Mediastinoscopy

Mediastinotomy (Chamberlain procedure)

Video-assisted Thoracic Surgery (VATS)

Thoracotomy

Transthoracic needle aspiration (CT)

Endobronchial Ultrasound (EBUS)

Endoscopy Ultrasound (EUS)

Navigational Bronchoscopy (SD)

Lung Cancer 9

Lymph Node Staging Mediastinoscopy

Lung Cancer 10

Lymph Node Staging Mediastinotomy

Lung Cancer 11

Lung Cancer

American College of Surgeons Survey

In 2001, patient care survey of 729 hospitals

40,090 NSCLC pts; 11,668 pts (29%) had surgery

Surgery only – 74%; Stage I – 60%; Lobe - 75%

Mediastinoscopy (27%); LN biopsied 47%

N2 LN removed (58%); N1 with specimen (42%)

Positive surgical margin 8%; Frozen section 65%

Mortality – wedge (5%), Lobe (5%), Pneumo (9%)

Current surgical treatment of lung cancer is poor

There is no standard of care

Lung Cancer 12

Lung Cancer

Society Thoracic Surgeons Database

In 2008, GTS database (1999 – 2006)

49,029 operations; 9033 pulmonary resections

Resection: Wedge – 18%, Segment – 4%,

Lobe – 67%, Bilobe – 4%, and Pneumo – 7%

Mediastinal LN evaluate 65%; Mediastinoscopy – 21%

LN Dissection - 41%, Sampling – 21%, Biopsy – 8%

Operative mortality 2.5%

Postoperative complications 32%

Lung Cancer 13

Lymph Node Staging EBUS

Lung Cancer 14

Developed by Becker (Thorax Clinic, Germany)

Water filled balloon surrounds the crystal

» Ensures “coupling”

» 20-MHz probe

» Requires a 2.8 mm working channel

Lymph Node Staging Radial Endobronchial Ultrasound

Becker. Respiration 2006;73:583-586

Lung Cancer 15

Lymph Node Staging Mediastinal Anatomy

Lung Cancer 16

Lymph Node Staging EBUS

Lung Cancer 17

Lymph Node Staging EBUS

Lung Cancer 18

Lymph Node Staging Radial EBUS

100 patients

» Cytology needles

Group A: subcarinal LNs

» sensitivity 86% vs. 74%

Group B: paratracheal LNs

sensitivity 84% vs. 58%

Group A, Group B Chest 2004; 125: 322

Lung Cancer 19

Lymph Node Staging Clinical staging differ from pathologic staging

24% clinically over staged

20% clinically under staged

ATS/ERS: Obtain pathologic evaluation in all

patients thought to be surgical candidates

prior to VATS or thoracotomy

Lung Cancer 20

Lymph Node Staging Linear Ultrasound or “The Puncture Scope”

7.5 MHz probe

Balloon Gomez et al. Proceedings of the American thoracic Society 2009;6(2):180-186

Lung Cancer 21

Operator

end of

scope

Lymph Node Staging Linear Ultrasound or “The Puncture Scope”

Lung Cancer 22

Lymph Node Staging Real-time EBUS

Herth et al. Endoscopy 2006;38 Suppl 1:S105-109

502 patients with any size LN

Sensitivity

96%

Specificity

100%

Accuracy

97%

Linear

EBUS TBNA

Lung Cancer 23

Lymph Node Staging EBUS

100 patients with NSCLC and CT with no

mediastinal LN > 10mm EBUS-TBNA of all

identifiable nodes surgical staging with med

(15) or thoracotomy (85)

» Mean LN diameter: 8.1mm

» 2 aspirates / node

» Cancer seen in 19 LN, missed in 2 LN

» Sensitivity 92.3%, Specificity 100%, NPV 96.3%

» Could avoid surgery in 17% of patients with no CT

evidence of disease

Herth et al, Eur Respir J 2006; 28: 910

Lung Cancer 24

Lymph Node Staging EBUS Upstaged

97 patients with known/suspected NSCLC and

negative PET-CT in the mediastinum

EBUS-TBNA followed by surgical staging

» Mean diameter 7.9 mm

» Cancer found in 8 patients: N3 in 1, N2 in 5, N1 in 2

» 1 additional patient found with N1 disease on surgical

staging

» 5% upstage Herth et al, Chest 2008; 133:887

Lung Cancer 25

Lymph Node Staging Invasive staging of the mediastinum

Sensitivity

(%)

Specificity

(%)

Cervical Mediastinoscopy (stations 1-2-4-7)

78 100

Anterior Mediastinoscopy (stations 5-6)

75 100

VATS (only ipsilateral) 75 100

De Leyn. Eur L Cardiothrac Surg 2007;32:1-8

Lemaire et al. Ann Thorac Surg 2006;82:1185-1189

Yasufuku et al. Respirology 2007;12:173-183

Lung Cancer 26

Lymph Node Staging EBUS vs. Mediastinoscopy

Ernst A. et al. Journal of Thoracic Oncology: 3(6):577-82, 2008 Jun

66 patients with know cancer in a cross over study

Sensitivity

68%

Specificity

100% NPV 59%

Mediastinoscopy

Sensitivity

87% Specificity

100%

NPV 78%

Linear

EBUS-TBNA

Lung Cancer 27

Lymph Node Staging EUS

Lung Cancer 28

Lymph Node Staging EUS

Lung Cancer 29

Lymph Node Staging EUS

Lung Cancer 30

Lymph Node Staging EUS

Superior to CT in the detection of mediastinal lymph nodes in patients with NSCLC

EUS-Guided FNA reported for mediastinal masses and lymph nodes » Sensitivity 83-90%

» Specificity 92-97%

Micames et al CHEST 2007

Ann Int Med 1997; 127:604, Ann Thor Surg 1996; 61:1441

Lung Cancer 31

Lymph Node Staging EBUS and EUS

138 patients (surgically proven)

Sensitivity

90%

NPV 97% Sensitivity

89%

Linear

EBUS-

TBNA

Linear

EBUS/

EUS

Linear

EUS-

TBNA

Linear

EBUS/

EUS

Sensitivity

93% Wallace et al. JAMA, 2008

Lung Cancer 32

Lymph Node Staging Combination of EBUS and EUS

150 patients with 619 LN (surgically proven)

Sensitivity

92%

NPV

95%

Sensitivity

89%

Linear

EBUS-

TBNA

Linear

EBUS/

EUS

Linear

EUS-

TBNA

Linear

EBUS/

EUS

Sensitivity

96%

Herth et al, CHEST 2010; 138(4). 790-794

Lung Cancer 33

Lymph Node Staging EUS

- Only modality #8 LN

- Can stage adrenal

L seen in 97%

R seen in 20%

Lung Cancer 34

Lymph Node Staging Is Ultrasound-guided TBNA replacing Surgery ?

Learning process to master

anatomy and interpretation

50 supervised procedure, and 10/yr

(25 in Europe) to maintain

competency !!

No technical reimbursement

Easy scope damage

Standard of care

Already taught in residency

Requires general anesthesia

Costly

Results not impressive in non-

adequate hands

Lung Cancer 35

Lymph Node Staging Ultrathin Bronchoscopy

Standard bronchoscope with an external diameter of 6.1

mm and a working channel of 2.0 mm ; right: an ultrathin

bronchoscope with an external diameter of 2.8 mm and a

working channel of 1.2 mm (BF-XP40; Olympus)

Lung Cancer 36

Lymph Node Staging Ultrathin Bronchoscopy

Lung Cancer 37

Lymph Node Staging Ultrathin Bronchoscopy

Lung Cancer 38

Lymph Node Staging EBUS-TBBX - Fluoroscopically-invisible

N=54 (Lesions seen on CT, not Fluoro)

Peripheral

radial EBUS

Lesions

identified in 89% 70% diagnosis

Prevented

surgery in 17%

Herth et al. Chest 2006;129:147-150

Lung Cancer 39

Lymph Node Staging Navigational Bronchoscopy

Lung Cancer 40

Lymph Node Staging Navigational Bronchoscopy

Lung Cancer 41

Sensors on patient account for inspiration, expiration & patient movement

Lymph Node Staging Navigational Bronchoscopy

Lung Cancer 42

Lymph Node Staging Navigational Bronchoscopy

Lung Cancer 43

Lymph Node Staging Navigational Bronchoscopy

N=60 (LN and peripheral lesions)

75% yield from

peripheral lesions

100% yield from

lymph node

Final diagnosis obtained in

80% of cases (75% cancer)

Mehta et al. Am J of Resp and Crit Care Med 2007 No Rhythm issues or Fluoro required

Lung Cancer 44

Lymph Node Staging Conclusions

Lymph node metastasis can occur in any size NSCLC

tumor

Accurate clinical staging is essential to provide the

best treatment for patients with NSCLC

Endoscopic staging (EBUS, EUS, SD) methods are

proving to be reliable for staging of the mediastinum

Lung Cancer 45

Lung Cancer

Smoking Cessation