practical approach to lung cancer
TRANSCRIPT
Practical Approach to Lung
Cancer
Gamal Rabie Agmy, MD, FCCP
Professor of Chest Diseases, Assiut university
Lung Masses
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.
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
Where is the mass?
Where is the mass?
Here, of course. But how would you describe it
accurately?
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)
Describing this mass
“There is an ~8cm soft tissue mass at the
right hilum. There are no other abnormal
features.”
Describe this CXR
Describe this CXR
“There are extensive bilateral pulmonary
masses of varying size.”
What is the diagnosis?
That depends on the clinical history. In a patient
with known malignancy, these are almost certainly disseminated pulmonary
metastases
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 work out what the diagnosis is.
Multiple ill-defined masses in both lungs
Diagnosis = Septic emboli=Multiple cavitating lung abscesses in a intravenous drug user
Some masses are difficult to see…
…can you find this one?
Some masses are difficult to see…
…a methodical approach to looking at CXRs will reduce the chance of missing small cancers like this one
Where is the mass here?
It is NOT in the lung. Where is it?
Metastasis to right 7th posterior rib
This is a rib metastasis. Look closely to see interruption of the rib, which is
destroyed and expanded.
• 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
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%)
Small Cell Lung Cancer
Non-small cell lung cancer
• 1. Squamous cell carcinoma
• 2. Adenocarcinoma
• 3. Large cell carcinomas
Lung Cancer Re-cap
Small Cell Lung Cancer Non-Small-Cell Lung Cancer
Squamous cell Adenocarinoma
Causes and Risk factors of Lung Cancer
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
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
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
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
Thoracic onchology medical emergencies
• Superior vena cava obstruction
• Tumor and pulmonary embolism
• Tumor lysis syndrome
• Hypercalcaemia
• Pericardial tamponade
• Massive pleural effusion
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
Diagnostic Tests
• CXR
• CT Scans
• Sputum cytology
• Fibreoptic bronchoscopy
• Transthoracic fine needle aspiration
• MRI
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)
Biopsy
Endoscopy
• Bronchoscopy
• Mediastinoscopy • VATS (video assisted thoracoscopic surgery)
Bronchoscopy
Mediastinoscopy
VATS (video assisted thoracoscopic surgery)
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
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.
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
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
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.
The new WHO classification of lung cancer
Aims and Structure
• Introduction
• Small biopsies, immunuhistochemical and molecular testing
• Adenocarcinoma
• Squamous cell carcinoma
• Neuroendocrine tumors
• Large cell carcinoma, Adenosquamous carcinoma, Sarcomatoid
carcinoma
• Other tumors
• Summary and outlook
The new WHO classification of lung cancer
The original publication (JTO 2011)
J Thorac Oncol 2011
The new WHO classification of lung cancer
Work flow for diagnostics of lung cancer
J Thorac Oncol 2011
The new WHO classification of 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
The new WHO classification of lung cancer
Adenocarcinoma
• Lepidic adenocarcinoma
• Acinar adenocarcinoma
• Papillary adenocarcinoma
• Micropapillary adenocarcinoma
• Solid adenocarcinoma
• Invasive mucinous adenocarcinoma
• Colloid adenocarcinoma
• Fetal adenocarcinoma
• Enteric adenocarcinoma
• Minimal invasive adenocarcinoma (MIA)
• Preinvasive lesions
Atypical adenomatous hyperplasia (AAH)
Adenocarcinoma in situ (AIS)
p=0.007
p=0.001 p=0.002
p=0.011
lepidic
acinar
papillary micropapillary
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
Grouping of the differentiation patterns according to prognosis in 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
The new WHO classification of lung cancer
Correlation of the differentiation patterns
with tumor size and percentage of metastases
lepid
ic
acinar
papillary
solid
mic
ropapill
ary0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
max
imal
dia
met
er (i
n cm
)
Lymph node metastases
Lepidic: 7%
Acinar: 46%
Papillary: 43%
Solid: 51%
Micropapillary: 76%
Differentiation patterns and tumor size
Impact on lymph node dissection?
Warth et al., J Clin Oncol 2012 Warth et al., J Clin Oncol 2012
The new WHO classification of 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
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 classification of lung cancer
Radio- and histomorphologic correlations
Lederlin et al., Eur Respir J 2013; 41:943-51
The new WHO classification of lung cancer
Immunohistochemistry
Warth et al. Histopathology 2012; 61:1017-25
The new WHO classification of 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
double staining
Warth et al. Histopathology 2012; 61:1017-25
The new WHO classification of lung cancer Molecular markers in pulmonary adenocarcinomas
Kris et al., J Clin Oncol 2011
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
The new WHO classification of lung cancer
Squamous cell carcinoma
• Keratinizing squamous cell carcinoma
• Non-keratinizing squamous cell carcinoma
• Basaloid squamous cell carcinoma
• Preinvasive lesion
Squamous cell carcinoma in situ
The new WHO classification of lung cancer
Keratinizing squamous cell carcinoma
• Solid (strand-like) growth pattern
• Keratinization, intercellular bridges
• Immunohistochemistry: p40, p63, CK5/6 (CK14)
The new WHO classification of lung cancer
Basaloid squamous cell carcinoma
The new WHO classification of lung cancer
Neuroendocrine tumors
• Small cell carcinoma (SCLC)
• Large cell neuroendocrine carcinoma (LCNEC)
• Carcinoid tumor
Typical carcinoid (TC)
Atypical carcinoid (AC)
• Preinvasive lesion
Diffuse idiopathic pulmonary cell hyperplasia (DIPNECH)
The new WHO classification of lung cancer
Neuroendocrine tumors: SCLC, LCNEC, TC, DIPNECH)
The new WHO classification of lung cancer
Other tumors
• Large cell carcinoma
• Adenosquamous carcinoma
• Sarcomatoid carcinoma
• Pleomorphic, spindle cell, and giant cell carcinoma
• Carcinosarcoma
• Pulmonary blastoma
• Other and unclassified carcinomas
• Lymphoepithelioma-like carcinoma
• NUT carcinoma
The new WHO classification of lung cancer
Other tumors
• Salvary gland-type tumors
• Mucoepidermoid carcinoma
• Adenoid cystic carcinoma
• Epithelial-myoepithelial carcinoma
• Pleomorphic adenoma
• Papillomas
• Squamous cell papilloma
• Glandular papilloma
• Mixed squamous cell and glandular papilloma
• Adenomas
• Sclerosing pneumocytoma
• Alveolar adenoma
• Mucinous cystadenoma
• Mucus gland adenoma
The new WHO classification of lung cancer
Other tumors
• Mesenchymal tumors
• Pulmonary hamartoma
• Chondroma
• PEComatous tumors
• Congenital peribronchial myofibroblastic tumor
• Diffuse pulmonary lymphangiomatosis
• Inflammatory myofibroblastic tumor
• Epitheloid haemangioendothelioma
• Pleuropulmonary blastoma
• Synovial sarcoma
• Pulmonary artery intimal sarcoma
• Pulmonary myxoid sarcoma with EWSR1-CREB1 translocation
• Myoepithelial tumors / myoepithelial carcinoma
• Other mesenchymal tumors
The new WHO classification of 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
• Pulmonary Langerhans cell histiocytosis
• Erdheim-Chester disease
• Tumors of ectopic origin
• Germ cell tumors
• Intrapulmonary thymoma
• Melanoma
• Meningioma
• Metastases to the lung
The new WHO classification of lung cancer
Summary and outlook
• The new WHO classification is applicable on resection specimens,
small biopsies and cytologic materials.
• It provides pathways / algorithms for the diagnosis of the relevant
types of lung cancer.
• It is based on histopathology, immunohistochemistry, and molecular
pathology with regards to prognosis and treatment.
• The most obvious progress has been achieved for the classification of
pulmonary adenocarcinoma, which shows relevant correlations of
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 visible in one single
chapter, for the first time. There are more precise diagnostic criteria.
• Taken together, the new WHO classification provides the basis for all
disciplines dealing with lung cancer not only in interdisciplinary tumor
boards and thus achieves better diagnostics and treatment of lung
cancer for the sake of our patients.
New Guidelines for the Classification of Lung Cancer:
TNM and Classification changes in the 8th Edition.
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.
cT1-cT2 by size only, 1-cm increments
by Size OnlycT1-2 N0 M0 NSCLC
0%
20%
40%
60%
80%
100%
0 2 4 6 8 10Years After Diagnosis
CT1A: 0.1-1 cmCT1A: 1.1-2 cmCT1B: 2.1-3 cmCT2A: 3.1-4 cmCT2A: 4.1-5 cmCT2B: 5.1-6 cmCT2B: 6.1-7 cm
Deaths / N69 / 802
541 / 3161601 / 2480464 / 1534213 / 563107 / 24562 / 121
5-YearEstimate
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
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.
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.
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.
• 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.
N-Category Pathologic- R0 Clinical
Pathologic- all Clinical, nonsurgical cases
R 0
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
0 2 4 6Y E A R S A F T E R R E S E C T I O N
N 0N 1N 2N 3
E v e n t s / N2 3 2 1 / 1 1 5 2 9
6 0 3 / 1 4 9 51 0 6 0 / 2 0 5 5
1 8 / 5 0
M S TN RN R
4 6 . 0N 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 6Y E A R S A F T E R R E S E C T I O N
N 0N 1N 2N 3
E v e n t s / N2 4 1 3 / 1 1 7 1 2
6 3 8 / 1 5 6 91 2 0 6 / 2 2 6 5
3 3 / 6 6
M S TN R
7 1 . 94 3 . 03 9 . 0
6 0 M o s 7 9 % 5 6 % 4 1 % 3 9 %
77 77
C l i n i c a l N S t a g e
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
0 2 4 6Y E A R S A F T E R E N T R Y
N 0N 1N 2N 3
E v e n t s / N5 3 5 / 1 8 4 6
9 8 / 2 0 82 4 9 / 4 7 1
9 7 / 1 7 6
M S TN R
3 2 . 22 6 . 51 3 . 8
6 0 M o s 5 9 % 3 8 % 3 3 % 2 4 %
C l i n i c a l N S t a g e - M 0N o n s u r g i c a l
0 %
2 0 %
4 0 %
6 0 %
8 0 %
1 0 0 %
0 1 2 3 4 5Y E A R S A F T E R E N T R Y
N 0N 1N 2N 3
E v e n t s / N9 3 / 1 4 9
8 / 1 58 5 / 1 3 69 0 / 1 5 3
M S T1 7 . 01 5 . 21 4 . 81 2 . 9
6 0 M o s 1 8 % 3 1 % 0 %
1 9 %
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 station plus 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 10YEARS AFTER RESECTION
1. N1 Single2. N1 Multiple3. N2 Single4. N2 Single+N15. N2 Multiple N2
Events / N448 / 1156153 / 322271 / 628324 / 615474 / 805
MST79.360.968.943.938.0
12 Mos 88% 84% 87% 86% 83%
Logrank P-value < .0001
Combination of pNanatomy and
pNn indicates prognosis well.
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.
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.
Prognostic Impact of Single & Multiple Metastatic Lesions in a Single Organ vs Multiple Metastatic Sites
The data we have suggest the number of metastatic lesions may be more prognostic than the site of metastasis. Additionally, prognosis based on a single distant metastatic lesion may be more similar to M1a.
M1 DetailsBy Number of Lesions
EDC Data Only
0%
20%
40%
60%
80%
100%
0 2 4 6 8Survival, Years
M1aM1b, Single Organ/LesionM1b, Single Organ/Mult. LesionsM1b, Multiple Organs
Events / N220 / 324159 / 225180 / 229202 / 247
Medianin Months
11.5 (10, 13.4)11.4 (9.6, 13.2)7.0 (5.6, 7.8)4.8 (4.3, 6.6)
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
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)N0 T2(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 N2 T1-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
stage
Branches based on best
splits, STRATIFIED on
type of database
submission. (Registry vs.
Not)
Red = Terminal node groups
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
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
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
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
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
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
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
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
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
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.
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.
Practical approach to Lung cancer diagnosis, staging and molecular
testing
• Define the role of radial probe ultrasound and navigation bronchoscopy for the diagnosis of the lung cancer
• Outline a cost effective approach to the diagnosis of primary tumor and
mediastinal staging based on patient-and imaging-related variables • Summarize the published evidence and guidelines pertinent to the diagnosis,
staging and molecular testing for NSCLC
Practical Approach to Lung Cancer diagnosis, staging and molecular testing
Case 1
• 55 y/o male
• Smoker
• Poor lung function
• PET indeterminate
1. Observation with follow-up chest CT 1. Bronchoscopy with electromagnetic navigation
2. CT-guided needle aspiration
3. Conventional Bronchoscopic biopsy using fluoroscopy
What should be done next?
1. Observation with follow-up chest CT
2. Bronchoscopy with electromagnetic
navigation
3. CT-guided needle aspiration
4. Conventional Bronchoscopic biopsy using
fluoroscopy
What should be done next?
A. Volume doubling time
B. Nodule Size A. Nodule Location
B. Enhancement
Which of the Following is Not a Predictor of Malignancy?
4% A. Volume doubling time
0% B. Nodule Size
74% C. Nodule Location
22% D. Enhancement
Which of the Following is Not a Predictor of Malignancy?
1. VDT of 25-400 days is highly suggestive of malignancy
2. Larger size and enhancement by dynamic CT also predict malignancy
3. Location has not been reliably shown to predict malignancy
Predictors of Malignancy
Structured Approach to the Management of Pulmonary Nodules
High probability • Surgery if able • Biopsy and SBRT if not surgical candidate
Intermediate probability • What is the likelihood of cancer?
Clinical suspicion Prediction calculators
Low probability • Observation • Biopsy?
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
Which of the Following is Most Influential in Predicting a Successful Biopsy?
A. Radial ultrasound view (concentric vs eccentric) B. Air bronchus sign C. Lesion size D. Distance from the pleura
Which of the Following is Most Influential in Predicting a Successful Biopsy?
18% A. Radial ultrasound view (concentric vs eccentric)
47% B. Air bronchus sign
29% C. Lesion size
6% D. Distance from the pleura
Radial Ultrasound View
Radial probe Endobronchial ultrasound provides information regarding airway position relative to the target lesion
Radial EBUS Position
• Diagnostic yield with a concentric view is 84%
• Diagnostic yield with a eccentric view is 48%
• concentric view obtained in 63% of cases
• Eccentric view obtained 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
Air Bronchus Sign
• More data for ENB with conflicting results
• Prospective study of 51 patients showed a significant difference in yield using ENB when a bronchus sign was present (79% vs 31%)
• Retrospective review of 55 patients showed no significant difference
Seijo LM et al. Chest 2010; 138: 1316-1321 Brownback KR et al. J Bronchology Interv Pulmonol 2012; 19: 91-97
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
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
Which of the Following Instruments Has the Highest Diagnostic Yield?
A. Forceps
B. Brush
C. Needle
D. Bronchial washing
Which of the Following Instruments Has the Highest Diagnostic Yield?
42% A. Forceps
17% B. Brush
42% C. Needle
0% D. Bronchial washing
Prospective study of 182 patients randomized to radial EBUS +CDP (forceps and brush) vs radial EBUS+TBNA+CDP Diagnostic yield of TBNA+CDP was 78.4% vs 60.6% in the CDP only arm TBNA alone was diagnostic in 62.5% of cases vs 48.9 (forceps ) and 19.8% (washing) Pneumothorax rate between groups did not differ (2.2%) Chao TY, et al. Chest 2009; 136: 229-236
Diagnostic Yield by Instrument
Which of the Following techniques Has the Highest Diagnostic Yield?
A. Radial probe Endobronchial ultrasound
B. Electromagnetic navigation
C. Virtual bronchoscopy
D. CT guided needle aspiration
Which of the Following techniques Has the Highest Diagnostic Yield?
28% A. Radial probe Endobronchial ultrasound
9% B. Electromagnetic navigation
0% C. Virtual bronchoscopy
63% D. CT guided needle aspiration
CT Guided Needle Aspiration
Diagnostic yield 75-90% Rate of complication 8-64% Chest tube Hospitalizations Prolonged air leak Dependent upon location of nodule and caliber of needle
Geraghty P, et al. Radiology 2003; 229(2):475-481 Baaklini WA, et al. Chest 2000; 117: 1049-1954
Virtual Bronchoscopy
Any platform in which three dimensional reconstructions of endoscopic views are created based on imaging modalities such as CT
Virtual Bronchoscopy
• Provides a pathway to the target lesion
• No sensor tracked during procedure
Virtual Bronchoscopy Diagnostic vield
Wang – Memoli JS et al. Chest 2012; 142: 385 - 393
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
Electromagnetic Navigation
Pathway and location provided
Virtual Bronchoscopy Diagnostic vield
Wang – Memoli JS et al. Chest 2012; 142: 385 - 393
Radial probe Endobronchial Ultrasound
• Utilizes radial ultrasound probe
• Mini-probe inserted through the working channel of a flexible bronchoscope
• Frequency is 20Mhz
Radial EBUS
Virtual Bronchoscopy Diagnostic vield
Wang – Memoli JS et al. Chest 2012; 142: 385 - 393
Which of the Following is True Regarding Advanced Diagnostic Procedures?
A. Radial probe EBUS is a navigational tool B. Electromagnetic navigation provides real-time tracking of target lesions C. Combining modalities has resulted in improved diagnostic yields over individual modalities D. Virtual bronchoscopy was recommended by the ACCP for the diagnosis of early stage lung cancer