This document provides an overview of lung cancer, including: - The four most common causes of lung masses are benign lesions, primary lung cancer, metastatic disease, and lung abscess. - There are two main types of lung cancer - small cell lung cancer and non-small cell lung cancer, which is most common. - Symptoms of lung cancer can include cough, breathing problems, weight loss, chest pain, and fatigue, though early-stage cancers may be asymptomatic. - Diagnostic tests include chest x-rays, CT scans, sputum cytology, bronchoscopy, and biopsies. Staging helps determine prognosis and treatment.

2. Practical Approach to Lung
Cancer
Gamal Rabie Agmy, MD, FCCP
Professor of Chest Diseases, Assiut university

3. Lung Masses

4. Common causes of a mass on a CXR
• Benign lesions
• Primary lung cancer
• Metastatic disease
• Lung abscess
There are many other causes, but these are four
important ones.
Often the history and physical examination will indicate
the likely cause.

5. Features of Benign Masses
• Small (<3 cm)
• Similar density to bone (i.e. calcified)
• Well defined margins
• Age of patient (<30 = usually benign)
• No change in size over time
…so always compare with previous CXRs if available

6. Where is the mass?

7. Where is the mass?
Here, of course.
But how would
you describe it
accurately?

8. Important points when you a see
a mass
• Where is it?
• How big is it?
• Are there any other masses?
• Are there any other features of malignancy?
– e.g. rib destruction
– e.g. pleural effusion
– e.g. mediastinal widening (implies enlarged
lymph nodes)

9. Describing this mass
“There is an ~8cm soft
tissue mass at the
right hilum. There are
no other abnormal
features.”

10. Describe this CXR

11. Describe this CXR
“There are extensive
bilateral pulmonary
masses of varying size.”

12. What is the diagnosis?
That depends on the
clinical history. In a patient
with known malignancy,
these are almost certainly
disseminated pulmonary
metastases

13. Clinical Case:
A 19 year old unemployed
male is admitted to AMAU
with breathlessless and fever.
He has venepuncture wounds
on his arms.
Look at his CXR on the next slide. Try to workout
what the diagnosisis.

15. Multiple ill-defined masses in both lungs

16. Diagnosis = Septic emboli=Multiple cavitating lung
abscesses in a intravenous drug user

17. Some masses are difficult to see…
…can you find this one?

18. Some masses are difficult to see…
…a methodical approach to looking at CXRs will reduce
the chance of missing small cancers like this one

19. Where is the mass here?

20. It is NOT in the lung. Where is it?

21. Metastasis to right 7th posterior rib
This is a rib metastasis. Look closely
to see interruption of the rib, which is
destroyed and expanded.

22. • There are many causes of lung masses
• A good clinical history will often
suggest the diagnosis
• A new lung mass in an elderly patient
is almost certainly malignant

23. Types of Lung Cancer
Two main Types of Lung Cancer:
Small Cell Lung Cancer (20-25% of all lung cancers)
Non Small Cell Lung Cancer (most common ~80%)

24. Small Cell Lung Cancer

25. Non-small cell lung cancer
• 1. Squamous cell carcinoma
• 2. Adenocarcinoma
• 3. Large cell carcinomas

26. Lung Cancer Re-cap
Small Cell Lung Cancer Non-Small-Cell Lung Cancer
Squamous cell Adenocarinoma

27. Causes and Risk factors of Lung
Cancer

28. Signs and Symptoms of Lung
Cancer
• Sometimes lung cancer does not cause any symptoms and is only
found in a routine x-ray.
• If a person with lung cancer does have symptoms, they will depend
on the location of the tumour in their lung.
• It is also imperative to note that the same symptoms can be caused
by other conditions, so may not necessarily mean cancer.
• Therefore it is important to consult a doctor when symptoms are
present.
• Signs and symptoms also depend upon the location, size of the
tumor, degree of obstruction and existence of metastases

29. Signs and Symptoms of Lung Cancer
There are 4 types of signs and symptoms of
lung cancer:
1) Localized – involving the lung.
2) Generalized – involves other areas
throughout the body if the cancer has
spread.
3) Paramalignant syndromes
4) Thoracic oncology medical emergencies

30. Localized Signs and Symptoms
Cough
Breathing Problems, SOB, stridor
Change in phlegm
Lung infection, hemoptysis
Hoarseness, Hiccups
Wt loss
Chest Pain and tightness
Pancoats Syndrome
Horner’s Syndrome
Pleural Effusion
Superior Vena Cava Syndrome
Fatigue

31. Generalized Signs and
Symptoms
• Bone pain
• Headaches, mental status changes or neurologic
findings
• Abdominal pain, elevated liver function tests,
enlarged liver, gastrointestinal disturbances
(anorexia, cachexia), jaundice, hepatomegaly r/t
liver involvement
• Weight loss
• Endocrinal , metabolic and vascular changes

32. Thoracic onchology medical
emergencies
• Superior vena cava obstruction
• Tumor and pulmonary embolism
• Tumor lysis syndrome
• Hypercalcaemia
• Pericardial tamponade
• Massive pleural effusion

33. Early/late Signs and Symptoms Of
Lung Cancer
Early Signs Late signs
Cough/chronic cough Bone pain, spinal cord
compression
Dyspnea Chest pain/tightness
Hemoptysis Dysphagia
Chest/shoulder pain Head and neck edema
Recurring temperature Blurred vision, headaches
Recurring respiratory
infections
Weakness, anorexia,
weight-loss, cachexia
Pleural effusion
Liver metastasis/regional
spread

34. Diagnostic Tests
• CXR
• CT Scans
• Sputum cytology
• Fibreoptic bronchoscopy
• Transthoracic fine needle aspiration
• MRI

35. Laboratory Tests
 Blood Tests
*CBC-to check red/white blood cell & platelets
-to check bone marrow and organ function
*Blood Chemistry Test-to assess how organs
are functioning such as liver and kidney
 Biopsy-to determine if the tumor is cancer or not
-to determine the type of cancer
-to determine the grade of cancer (slow
or fast)

36. Biopsy

37. Endoscopy
• Bronchoscopy
• Mediastinoscopy
• VATS (video assisted thoracoscopic surgery)

38. Bronchoscopy

39. Mediastinoscopy

40. VATS (video assisted
thoracoscopic surgery)

41. Post-op complications for those
with lung cancer
• Airway obstruction, dyspnea, hypoxemia, respiratory failure
• Anesthesia side effects (N/V)
• Bleeding (hypotension, cardiogenic shock)
• Cardiac dysthymias, CHF, fluid overload
• Fever, sepsis
• Pneumonia
• Pneumothorax
• Pulmonary embolus
• Wound dehiscence
• Prolonged hospitalization
• Death

42. Medical Management
The three main cancer treatments
are:
*surgery (lung resections)
*radiation therapy
*chemotherapy
Other types of treatment that are
used to treat certain cancers are
hormonal therapy, biological
therapy or stem cell transplant.

43. Side effects of treatments
Surgery Radiation Chemotherapy
Pain fatigue Anemia,
thrombocytopenia
Hemotomas Decreased nutritional
intake
Fatigue
Hemmorhage Radiodermatitis Alopecia, SOB
Altered respiratory
function
Decreased hematopoietic
function
Cold, pale
Risk for atelectasis,
pneumonia, hypoxia
Risk for Pneumonitis,
esophagitis, cough
Tingling
Risk for DVT N/V Irritable
Grief Dizzy, weak

44. Lung resections
• Lobectomy: a single lobe of lung is removed
• Bilobectomy: 2 lobes of the lung are removed (only on R
side)
• Sleeve resection: cancerous lobe is removed and
segment of the main bronchus is resected
• Pneumonectomy: removal of entire lung
• Segmentectomy: a segment of the lung is removed
• Wedge resection: removal of a small, pie-shaped area of
the segment
• Chest wall resection with removal of cancerous lung
tissue: for cancers that have invaded the chest wall

45. Complimentary Therapies
• Includes acupuncture and massage and pharmacological approaches
such as vitamins and herbal medicine.
• One study showed that herbal medicine is used by approximately
48% of lung cancer patients in China.
• These herbal therapies combined with chemotherapy increases
survival in non-small-cell lung cancer by up to 42%, compared with
chemotherapy alone.

46. The new WHO classificationof lung cancer
Aims and Structure
• Introduction
• Small biopsies, immunuhistochemical and molecular testing
• Adenocarcinoma
• Squamouscell carcinoma
• Neuroendocrine tumors
• Large cell carcinoma,Adenosquamouscarcinoma, Sarcomatoid
carcinoma
• Other tumors
• Summary and outlook

47. The new WHO classification of lung cancer
The original publication (JTO 2011)
J Thorac Oncol 2011

48. The new WHO classification of lung cancer
Work flow for diagnostics of lung cancer
J Thorac Oncol 2011

49. The new WHO classificationof lung cancer
Basis for the new classification
Sica et al., Am J Surg Pathol 2010
1. Analysis of all
differentiation patterns
in 5% steps
2. Definition of the
predominant pattern
Warth et al., J Clin Oncol 2012; 30:1438-46

50. The new WHO classificationof lung cancer
Adenocarcinoma
• Lepidic adenocarcinoma
• Acinar adenocarcinoma
• Papillaryadenocarcinoma
• Micropapillaryadenocarcinoma
• Solid adenocarcinoma
• Invasive mucinousadenocarcinoma
• Colloid adenocarcinoma
• Fetal adenocarcinoma
• Enteric adenocarcinoma
• Minimal invasiveadenocarcinoma (MIA)
• Preinvasive lesions
Atypical adenomatoushyperplasia (AAH)
Adenocarcinomain situ (AIS)

51. p=0.007
p=0.001 p=0.002
p=0.011
lepidic
acinar
papillarymicropapillary
solid
lepidic
acinar
papillary
micropapillary
solid
p=0.002
p=0.001
lepidic
acinar
papillary
micropapillary
solid
G1
G2
G3
G1
G2
G3
G1
G2
G3
Groupingof the differentiationpatternsaccordingto prognosisin 3 groups (Grading)
G1 = lepidic; G2 = acinar;
G3 = papillary, solid, micropapillary
The new WHO classification of lung cancer
Prognostic relevance of histomorphology
Warth et al., J Clin Oncol 2012
Warth et al., J Clin Oncol 2012

53. The new WHO classificationof lung cancer
Correlation of the differentiation patterns
with tumor size and percentage of metastaseslep
id
ic
acinar
p
ap
illary
solid
m
icrop
apillary
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
maximaldiameter(incm)
Lymphnode metastases
Lepidic: 7%
Acinar: 46%
Papillary: 43%
Solid: 51%
Micropapillary: 76%
Differentiationpatterns and tumorsize
Impact on lymph nodedissection?
Warth et al., J Clin Oncol 2012
Warth et al., J Clin Oncol 2012

54. The new WHO classificationof lung cancer
Radiomorphologic parameters
A B C
E F G H
D
Smooth margins Part-solid tumor Spheroid configuration Spiculated margins
Ground-glass opacity Solid tumor with pleural
tags
Necrosis Lobulated margins
Lederlin et al., Eur Respir J 2013; 41:943-51

55. A
p=0.660
C
p=0.508
GGO
solid
p=0.087
B
semi-solid
GGO
solid
semi-solid
GGO
solid
semi-solid
Survival (Stage I – IV) und CT-attenuation factors
Adenocarcinomas with 100% GGO show a 100% OS, DFS and DSS
(only few cases)
The prognosis of pure solid adenocarcinomas may be worse than that of
semi-solid adenocarcinomas
The new WHO classificationof lung cancer
Radio- and histomorphologic correlations
Lederlin et al., Eur Respir J 2013; 41:943-51

56. The new WHO classification of lung cancer
Immunohistochemistry
Warth et al. Histopathology 2012; 61:1017-25

57. The new WHO classificationof lung cancer
Selection of marker panels
1. TTF-1 (and CK 5/6)
2. p40 (and CK7)
3. NapsinA and Desmocollin-3
Initial marker panels
with
doublestaining
Warth et al. Histopathology 2012; 61:1017-25

58. The new WHO classification of lung cancer
Molecular markers in pulmonary adenocarcinomas
Kris et al., J Clin Oncol 2011

59. Perez-Moreno P et al., Clin Cancer Res 2012; 18:2443-51
The new WHO classification of lung cancer
Molecular markers in squamous cell carcinomas

60. The new WHO classificationof lung cancer
Squamous cell carcinoma
• Keratinizing squamous cell carcinoma
• Non-keratinizing squamous cell carcinoma
• Basaloid squamous cell carcinoma
• Preinvasive lesion
Squamouscell carcinoma in situ

61. The new WHO classificationof lung cancer
Keratinizing squamous cell carcinoma
• Solid (strand-like) growth pattern
• Keratinization, intercellular bridges
• Immunohistochemistry: p40, p63, CK5/6 (CK14)

62. The new WHO classificationof lung cancer
Basaloid squamous cell carcinoma

63. The new WHO classificationof lung cancer
Neuroendocrine tumors
• Small cell carcinoma (SCLC)
• Large cell neuroendocrine carcinoma (LCNEC)
• Carcinoid tumor
Typical carcinoid (TC)
Atypical carcinoid (AC)
• Preinvasive lesion
Diffuse idiopathicpulmonarycell hyperplasia (DIPNECH)

64. The new WHO classificationof lung cancer
Neuroendocrine tumors: SCLC, LCNEC, TC, DIPNECH)

65. The new WHO classificationof lung cancer
Other tumors
• Large cell carcinoma
• Adenosquamous carcinoma
• Sarcomatoid carcinoma
• Pleomorphic, spindlecell, and giant cell carcinoma
• Carcinosarcoma
• Pulmonaryblastoma
• Other and unclassified carcinomas
• Lymphoepithelioma-like carcinoma
• NUT carcinoma

66. The new WHO classificationof lung cancer
Other tumors
• Salvary gland-type tumors
• Mucoepidermoid carcinoma
• Adenoid cystic carcinoma
• Epithelial-myoepithelial carcinoma
• Pleomorphicadenoma
• Papillomas
• Squamouscell papilloma
• Glandular papilloma
• Mixed squamous cell and glandular papilloma
• Adenomas
• Sclerosing pneumocytoma
• Alveolar adenoma
• Mucinouscystadenoma
• Mucus gland adenoma

67. The new WHO classificationof lung cancer
Other tumors
• Mesenchymal tumors
• Pulmonaryhamartoma
• Chondroma
• PEComatous tumors
• Congenital peribronchial myofibroblastic tumor
• Diffuse pulmonarylymphangiomatosis
• Inflammatorymyofibroblastic tumor
• Epitheloid haemangioendothelioma
• Pleuropulmonary blastoma
• Synovial sarcoma
• Pulmonaryartery intimal sarcoma
• Pulmonarymyxoid sarcoma with EWSR1-CREB1 translocation
• Myoepithelial tumors / myoepithelial carcinoma
• Other mesenchymal tumors

68. The new WHO classificationof lung cancer
Other tumors
• Lymphohistiocytotic tumors
• Extranodal marginal zone lymphoma of mucosa-associated lymphoid
tissue (MALT lymphoma)
• Diffuse large B-cell lymphoma
• Lymphomatoid granulomatosis
• Intravascular large B-cell lymphoma
• PulmonaryLangerhanscell histiocytosis
• Erdheim-Chester disease
• Tumors of ectopic origin
• Germ cell tumors
• Intrapulmonarythymoma
• Melanoma
• Meningioma
• Metastases to the lung

69. The new WHO classificationof lung cancer
Summary and outlook
• The new WHO classification is applicable on resection specimens,
small biopsiesand cytologic materials.
• It provides pathways / algorithms for the diagnosis of the relevant
types of lung cancer.
• It is based on histopathology, immunohistochemistry, and molecular
pathologywith regards to prognosis and treatment.
• The most obvious progress has been achieved for the classification of
pulmonary adenocarcinoma, which shows relevant correlationsof
clinical, radiological and pathological (including genetic) findings.
• For squamous cell carcinoma, the new WHO classification is clearer. It
reveals different genetic alterations compared with adenocarcinoma.
• Neuroendocrine tumors of the lungs are better visiblein one single
chapter, for the first time. There are more precise diagnosticcriteria.
• Taken together, the new WHO classification provides the basis for all
disciplines dealing with lung cancer not only in interdisciplinarytumor
boards and thus achieves better diagnostics and treatment of lung
cancer for the sake of our patients.

70. New Guidelines for the Classification of
Lung Cancer:
TNM and Classification
changes in the 8th Edition.

71. Lung Cancer
 A new data base was created following the
successful conclusion of the previous revision.
 94,708 cases (4,667 EDC) collected from 35
centres in 16 countries recruited 1999-2010.
 JTO publications to date:
 Database, 2014; 9: 1618 - 1624.
 T descriptors, 2015; 10: 990 - 1003.
 M descriptors, 2015; 10: 1515 - 1522.
 N descriptors, 2015: 10: 1675 - 1684.
 Stage groupings, 2016; 11: 39 - 51.
 Proposals submitted to UICC/AJCC mid 2015.

72. cT1-cT2 by size only, 1-cm increments
by Size Only
cT1-2 N0 M0 NSCLC
0%
20%
40%
60%
80%
100%
0 2 4 6 8 10
Years After Diagnosis
CT1A: 0.1-1 cm
CT1A: 1.1-2 cm
CT1B: 2.1-3 cm
CT2A: 3.1-4 cm
CT2A: 4.1-5 cm
CT2B: 5.1-6 cm
CT2B: 6.1-7 cm
Deaths / N
69 / 802
541 / 3161
601 / 2480
464 / 1534
213 / 563
107 / 245
62 / 121
5-Year
Estimate
92% (90, 94)
83% (81, 84)
75% (74, 77)
68% (65, 70)
59% (55, 64)
52% (45, 59)
43% (33, 53)
Similar graphs for
any N

73. Lung Cancer - T category Proposals (1).
 Retain 7e size cut points.
 Create new cut points at 1cm and 4 cm.
 Subdivide T1:
 T1a: ≤ 1 cm; T1b: >1 & ≤ 2 cm; T1c: < 2cm & ≤ 3 cm.
 Redefine T2a as >3- ≤ 4 cm.
 Redefine T2b as >4- ≤ 5 cm.
 Reclassify tumours >5 cms but =/< 7cms
as T3.
 Reclassify tumours > 7cms as T4.

74. Lung Cancer - T category Proposals (2).
 Size now a descriptor in all T categories.
 Reclassify tumours invading diaphragm as
T4.
 Reclassify tumours < 2cms from carina or
collapse/consolidation of whole lung as T2.
 Remove rarely used descriptor, i.e.
Mediastinal invasion.

75. Size of solid component
• Size of solid component in part-solid tumors as a T
descriptor
Travis W et al. J Thorac Oncol 2016;
in press.

76. • Tis (AIS), Tis (SQC): Stage 0
• T1a(mi) or T1mi: Stage 1A1
New T categories
Travis W et al. J Thorac Oncol 2016; in press.

77. N-Category
Pathologic- R0 Clinical
Pathologic- all Clinical,nonsurgicalcases
R 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
0 2 4 6
Y E A R S A F T E R R E S E C T IO N
N 0
N 1
N 2
N 3
E v e n t s / N
2 3 2 1 / 1 1 5 2 9
6 0 3 / 1 4 9 5
1 0 6 0 / 2 0 5 5
1 8 / 5 0
M S T
N R
N R
4 6 .0
N R
6 0 M o s
7 9 %
5 6 %
4 3 %
5 4 %
A n y R
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
0 2 4 6
Y E A R S A F T E R R E S E C T IO N
N 0
N 1
N 2
N 3
E v e n t s / N
2 4 1 3 / 1 1 7 1 2
6 3 8 / 1 5 6 9
1 2 0 6 / 2 2 6 5
3 3 / 6 6
M S T
N R
7 1 .9
4 3 .0
3 9 .0
6 0 M o s
7 9 %
5 6 %
4 1 %
3 9 %
7777
C lin ic a l N S t a g e
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
0 2 4 6
Y E A R S A F T E R E N T R Y
N 0
N 1
N 2
N 3
E v e n t s / N
5 3 5 / 1 8 4 6
9 8 / 2 0 8
2 4 9 / 4 7 1
9 7 / 1 7 6
M S T
N R
3 2 .2
2 6 .5
1 3 .8
6 0 M o s
5 9 %
3 8 %
3 3 %
2 4 %
C lin ic a l N S t a g e - M 0
N o n s u r g ic a l
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
0 1 2 3 4 5
Y E A R S A F T E R E N T R Y
N 0
N 1
N 2
N 3
E v e n t s / N
9 3 / 1 4 9
8 / 1 5
8 5 / 1 3 6
9 0 / 1 5 3
M S T
1 7 .0
1 5 .2
1 4 .8
1 2 .9
6 0 M o s
1 8 %
3 1 %
0 %
1 9 %

78. Number of Positive Levels
N1 Single vs N1 Multiple vs
N2 Single N2 Stations vs N2 Single N2+N1 vs N2 Multiple N2 Stations
“N2 single” = 1 N2 station and no N1 stations
“N2 single + N1” = 1 N2 stationplus at least 1 N1 station
“N2 multiple N2” must have multiple N2 stations
Split out N2 single vs N2 single N2+N1
0%
20%
40%
60%
80%
100%
0 2 4 6 8 10
YEARS AFTER RESECTION
1. N1 Single
2. N1 Multiple
3. N2 Single
4. N2 Single+N1
5. N2 Multiple N2
Events / N
448 / 1156
153 / 322
271 / 628
324 / 615
474 / 805
MST
79.3
60.9
68.9
43.9
38.0
12 Mos
88%
84%
87%
86%
83%
Logrank P-value < .0001
Combination of pNanatomy and
pNn indicates prognosis well.

79. Lung Cancer - N category Proposals.
 Retain 7th edition N categories.
 pN data showing the number of stations/nodes
combined with anatomical location may better
indicate prognosis than anatomical location alone did
not conform to validation process but may be a
“Proposal for Testing”.
 pN1a single N1 station involvement.
 pN1b multiple N1 station involvement.
 pN2a1 single “skip” N2 station involvement.
 pN2a2 single N2 station with N1 positive station(s).
 pN2b multiple N2 station involvement.

80. Prognostic Impact of
M1a Descriptors
Survival By M1a Descriptor
M1a Cases from EDC Only
0%
20%
40%
60%
80%
100%
0 2 4 6
Survival, Years
Pleural/Pericardial Nodule(s)
Contra/Bilateral Tumor Nodule(s)
Pleural/Pericardial Effusion
Multiple M1a Descriptors
Events / N
35 / 52
59 / 93
52 / 80
57 / 92
Median
in Months
14.3 (10.6, 18.8)
12.0 (9.8, 15.4)
11.3 (7.5, 15.9)
9.7 (6.6, 15.1)
Prognosis for the different M1a descriptors is similar.

81. Prognostic Impact of Single & MultipleMetastaticLesions
in a Single Organ vs MultipleMetastaticSites
The datawe have suggest the number of metastaticlesions may be more prognostic than the
site of metastasis. Additionally,prognosisbased on a single distantmetastatic lesion may be
more similar to M1a.
M1 Details
ByNumber of Lesions
EDC Data Only
0%
20%
40%
60%
80%
100%
0 2 4 6 8
Survival, Years
M1a
M1b, Single Organ/Lesion
M1b, Single Organ/Mult. Lesions
M1b, Multiple Organs
Events / N
220 / 324
159 / 225
180 / 229
202 / 247
Median
in Months
11.5 (10, 13.4)
11.4 (9.6, 13.2)
7.0 (5.6, 7.8)
4.8 (4.3, 6.6)

82. Lung Cancer - M category Proposals.
 Retain M1a category for intrathoracic
metastases.
 Reclassify M1b as single distant
metastasis in one organ.
 Create M1c for multiple metastases in a
single or multiple organs.
 Consequent changes for Stage IVA and B

83. N0-N1
N2-N3
T2b(5-7cm)-T4
T1-T2(4-5cm)
N0
N1
All T1
T2 (3-4cm)-T2(4-
5cm)
T1a/T1b T1C
T1aN0 T1b2N0
T1A
T1b
T1cN0 T2(4-5)N0T2(3-4)N0
T2(5-7cm)-
T3
T2(5-7)-T3
N1
N0 N1
T3(>7)-T4 N0-1
T1-T2(4-5cm) T2(5-7)-T4
N2
N3
N2
N3
T2(5-7)-T4 N3
T2(5-7)-T4 N2T1-T2(4-5) N2
T1-T2(4-5) N3
T3(>7cm)-
T4
T2 (3-
4cm)
T2 (4-5cm)
T2(5-7)-T3 N0
T1 - T2 (4-5cm)
N1
Tree based on 25,911 M0 Training Cases, best
stageBranches based on best
splits, STRATIFIED on
type of database
submission. (Registry vs.
Not)
Red = Terminal node groups

84. 0 24 48 72
Months
0%
20%
40%
60%
80%
100% Events / N MST
24
Month
60
Month
IA1 46 / 544 NR 97% 92%
IA2 357 / 2079 NR 94% 83%
IA3 362 / 1616 NR 90% 77%
IB 360 / 1274 NR 87% 70%
IIA 145 / 403 NR 78% 60%
IIB 400 / 973 66.0 73% 53%
IIIA 1379 / 2141 29.0 55% 36%
IIIB 1051 / 1441 18.2 44% 25%
IIIC 554 / 650 12.7 25% 14%
IVA 256 / 357 12.1 22% 8%
IVB 222 / 266 4.8 10% 0%
Proposal 6
Clinical Stage

85. Events / N MST
24
Month
60
Month
IA1 105 / 985 NR 96% 90%
IA2 568 / 3821 NR 94% 84%
IA3 579 / 2960 NR 92% 80%
IB 1094 / 4144 NR 89% 73%
IIA 373 / 1098 NR 83% 65%
IIB 1445 / 3518 NR 77% 56%
IIIA 2143 / 3862 42.0 65% 41%
IIIB 815 / 1172 22.0 47% 24%
IIIC 38 / 47 10.5 31% 12%
0 24 48 72
Months
0%
20%
40%
60%
80%
100%
Proposal 6
Pathologic Stage

86. 0 24 48 72
Months
0%
20%
40%
60%
80%
100%
Events / N MST
24
Month
60
Month
IA1 126 / 1223 NR 96% 90%
IA2 636 / 4135 NR 93% 82%
IA3 623 / 3097 NR 90% 78%
IB 1157 / 4308 NR 88% 72%
IIA 392 / 1133 NR 82% 64%
IIB 1532 / 3715 NR 76% 55%
IIIA 3126 / 5184 36.0 61% 38%
IIIB 1719 / 2339 19.7 43% 22%
IIIC 581 / 677 11.2 25% 11%
IVA 256 / 357 12.1 22% 8%
IVB 222 / 266 4.8 10% 0%
Validation
Set
Proposal 6; Best
Stage

87. Proposed Stage Groups (1).
 Stage 0 Tis(AIS, SCIS)
 Stage IA (1-3) T1mi, a-c, N0 M0
 Stage IB T2a, N0 M0
 Stage IIA T2b, N0 M0
 Stage IIB T3, N0 M0
T1-2, N1 M0
 Stage IIIA T3, N1 M0
T4, N0-1 M0
T1-2, N2 M0

88. Proposed Stage Groups (2).
 Stage IIIB T1-2, N3 M0
T3-4, N2 M0
 Stage IIIC T3-4, N3 M0
 Stage IVA T any, N any M1a-b
 Stage IVB T any, N any M1c

89. Proposed Stage Groupings for 8e
N0 N1 N2 N3
v7 New v7 New v7 New v7 New
T1a IA IA1 IIA IIB IIIA IIIA IIIB IIIB
T1b IA IA2 IIA IIB IIIA IIIA IIIB IIIB
T1c IA IA3 IIA IIB IIIA IIIA IIIB IIIB
T2a 1B IB IIA IIB IIIA IIIA IIIB IIIB
T2b IIA IIA IIB IIB IIIA IIIA IIIB IIIB
T3 IIB IIB IIIA IIIA IIIA IIIB IIIB IIIC
T4 IIIA IIIA IIIA IIIA IIIB IIIB IIIB IIIC
M1a IV IVA IV IVA IV IVA IV IVA
M1b IV IVA IV IVA IV IVA IV IVA
M1c IV IVB IV IVB IV IVB IV IVB

90. Stage shifts due to T changes in the 8e.
Descriptor T 7e T 8e N0 N1 N2 N3
Size >4 - 5cms T2a IB IIA IIIA IIIB
T2b IIA IIB IIIA IIIB
T2b IIA IIB IIIA IIIB
Tumour Size
= change of stage due to change of T descriptor

91. Stage shifts due to T changes in the 8e.
Descriptor T 7e T 8e N0 N1 N2 N3
Size >5 - 7cms T2b IIA IIB IIIA IIIB
T3 IIB IIIA IIIA IIIB
T3 IIB IIIA IIIB IIIC
Tumour Size
= change of stage due to change of T descriptor
= change of stage grouping in 8e

92. Stage shifts due to T changes in the 8e.
Descriptor T 7e T 8e N0 N1 N2 N3
Size >7cms T3 IIB IIIA IIIA IIIB
T4 IIIA IIIA IIIB IIIB
T4 IIIA IIIA IIIB IIIC
Tumour Size (and diaphragm invasion)
= change of stage due to change of T descriptor
= change of stage grouping in 8e

93. 1. Multiple primary tumours:
– One TNM for each tumour
2. Separate tumour nodules:
– T3, T4, M1a
3. Multiple adenos with GGO/lepidic features:
– Highest T (#/m) N M
4. Pneumonic type adenocarcinoma:
– T3, T4, M1a
Cancers with multiple lesions
Detterbeck F et al. J Thorac Oncol 2016;
4 papers in press.

94. 8th Edition of TNM
 All proposals have been published in JTO
 Free to non-members of IASLC.
 IASLC has submitted proposals to UICC/AJCC
on Lung Cancer, Thymic malignancies and
Mesothelioma July/August 2015.
 Publication presently scheduled for late 2016
(WCLC 2016 in Vienna).
 IASLC educational products available at
WCLC Vienna, free/discounted for members.
 To be enacted January 2017.

95. Practical approach to Lung cancer
diagnosis, staging and molecular
testing

96. • Define the role of radial probe ultrasound and navigationbronchoscopy for
the diagnosis of the lung cancer
• Outline a cost effectiveapproachto the diagnosis of primary tumor and
mediastinalstaging based on patient-andimaging-related variables
• Summarizethe publishedevidenceand guidelines pertinentto the diagnosis,
staging and molecular testingfor NSCLC
Practical Approach to Lung Cancer
diagnosis, staging and molecular testing

97. Case 1
• 55 y/o male
• Smoker
• Poor lung function
• PET indeterminate

98. 1. Observation with follow-up chestCT
1. Bronchoscopy with electromagneticnavigation
2. CT-guided needle aspiration
3. ConventionalBronchoscopicbiopsyusing fluoroscopy
What should be done next?

99. 1. Observation with follow-up chestCT
2. Bronchoscopy with electromagnetic
navigation
3. CT-guided needle aspiration
4. ConventionalBronchoscopicbiopsyusing
fluoroscopy
What should be done next?

100. A. Volume doublingtime
B. NoduleSize
A. NoduleLocation
B. Enhancement
Which of the Following is Not a Predictor of Malignancy?

101. 4% A. Volume doublingtime
0% B. NoduleSize
74% C. NoduleLocation
22% D. Enhancement
Which of the Following is Not a Predictor of Malignancy?

102. 1. VDT of 25-400 days is highly suggestiveof malignancy
2. Larger size and enhancementby dynamicCT also predictmalignancy
3. Location has not been reliably shownto predictmalignancy
Predictors of Malignancy

103. Structured Approach to the Managementof
Pulmonary Nodules
High probability
• Surgeryif able
• Biopsy and SBRT if not surgical candidate
Intermediate probability
• What is the likelihood of cancer?
 Clinical suspicion
 Predictioncalculators
Low probability
• Observation
• Biopsy?

104. Surgery for Non-Malignant disease
• 39% of patients screened with low-dose chest CT had at least one
abnormal finding in NLST which required additional evaluation
• A benign diagnosis was found in 24% of patients undergoing
surgery
Aberle DR et al. N. Engl J Med 2011; 365:395-409

105. Which of the Following is Most Influential in Predicting a
Successful Biopsy?
A. Radial ultrasoundview(concentricvs eccentric)
B. Air bronchus sign
C. Lesion size
D. Distance from the pleura

106. Which of the Following is Most Influential in Predicting a
Successful Biopsy?
18% A. Radial ultrasoundview(concentricvs eccentric)
47% B. Air bronchus sign
29% C. Lesion size
6% D. Distance from the pleura

107. Radial Ultrasound View
Radial probeEndobronchialultrasoundprovides informationregardingairway
positionrelative to the targetlesion

108. Radial EBUS Position
• Diagnosticyield with a concentricviewis 84%
• Diagnosticyield with a eccentricviewis 48%
• concentricviewobtainedin 63% of cases
• Eccentricviewobtained in 31% of cases
Chen A, et al. Ann Am Thorac Soc 2014; 11: 578-528
Yamada N, et al. Chest 2007; 132: 603-608

109. Air Bronchus Sign
• More data for ENB with conflicting results
• Prospective study of 51 patients showed a
significantdifference in yield usingENB when
a bronchus sign was present(79% vs 31%)
• Retrospective reviewof 55 patients showed
no significantdifference
Seijo LM et al. Chest 2010; 138: 1316-1321
Brownback KR et al. J Bronchology Interv Pulmonol 2012; 19: 91-97

110. Lesion Size
Meta-analysis including 20 studies using
different advanced diagnostic
bronchoscopy showed a diagnostic yield
of
60.9% for nodules <20 mm vs. 82.5% for
nodules >20 mm
Wang- Memoli JS et al. Chest 2012; 142: 385-393

111. Distance From the Pleura
• No reliable data commenting on relative location of the nodule
in relation to how peripheral it is
• Some data suggests little difference in yield by anatomic lobe
Yamada N et al. Chest 2007; 132: 603-608

112. Which of the Following Instruments Has the Highest
Diagnostic Yield?
A. Forceps
B. Brush
C. Needle
D. Bronchial washing

113. Which of the Following Instruments Has the Highest
Diagnostic Yield?
42% A. Forceps
17% B. Brush
42% C. Needle
0% D. Bronchial washing

114. Prospective study of 182 patients randomized to radial EBUS +CDP (forceps
and brush)vs radial EBUS+TBNA+CDP
Diagnosticyield of TBNA+CDP was 78.4% vs 60.6% in the CDP only arm
TBNA alone was diagnosticin 62.5% of cases vs 48.9 (forceps ) and 19.8%
(washing)
Pneumothoraxrate betweengroups did notdiffer(2.2%)
Chao TY, et al. Chest 2009; 136: 229-236
Diagnostic Yield by Instrument

115. Which of the Following techniques Has the Highest
Diagnostic Yield?
A. Radial probeEndobronchialultrasound
B. Electromagneticnavigation
C. Virtual bronchoscopy
D. CT guided needle aspiration

116. Which of the Following techniques Has the Highest
Diagnostic Yield?
28% A. Radial probe Endobronchial ultrasound
9% B. Electromagneticnavigation
0% C. Virtual bronchoscopy
63% D. CT guidedneedleaspiration

117. CT Guided Needle Aspiration
Diagnosticyield 75-90%
Rate of complication 8-64%
Chest tube
Hospitalizations
Prolongedair leak
Dependentupon locationof nodule
and caliber of needle
Geraghty P, et al. Radiology 2003; 229(2):475-481
Baaklini WA, et al. Chest 2000; 117: 1049-1954

118. Virtual Bronchoscopy
Any platformin which three dimensionalreconstructionsof
endoscopicviewsare createdbased on imaging modalitiessuch as CT

119. Virtual Bronchoscopy
• Providesa pathway to the target
lesion
• No sensor tracked during
procedure

120. Virtual Bronchoscopy
Diagnosticvield
Wang – Memoli JS et al. Chest 2012; 142: 385 - 393

121. Electromagnetic Navigation
 Virtual Bronchoscopic images generated from a CT scan
 Electromagnetic sensor is tracked during procedure
 Sensor position is superimposed on virtual airway
reconstruction using various forms of registration

122. Electromagnetic Navigation
Pathway and location provided

123. Virtual Bronchoscopy
Diagnosticvield
Wang – Memoli JS et al. Chest 2012; 142: 385 - 393

124. Radial probe Endobronchial Ultrasound
• Utilizesradial ultrasoundprobe
• Mini-probe inserted throughthe working
channel of a flexible bronchoscope
• Frequency is 20Mhz

125. Radial EBUS

126. Virtual Bronchoscopy
Diagnosticvield
Wang – Memoli JS et al. Chest 2012; 142: 385 - 393

127. Which of the Following is True Regarding
Advanced Diagnostic Procedures?
A. Radial probe EBUS is a navigational tool
B. Electromagneticnavigation providesreal-time tracking of targetlesions
C. Combining modalitieshas resulted in improved diagnosticyieldsover
individual modalities
D. Virtual bronchoscopywas recommendedby the ACCP for the diagnosisof
early stage lung cancer