practical approach to lung cancer

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

http://radiographics.rsnajnls.org/cgi/content/full/23/6/1521/F5B

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 original publication (JTO 2011)

J Thorac Oncol 2011


Work flow for diagnostics of lung cancer

J Thorac Oncol 2011


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


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


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


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


Radio- and histomorphologic correlations

Lederlin et al., Eur Respir J 2013; 41:943-51


Immunohistochemistry

Warth et al. Histopathology 2012; 61:1017-25


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


Molecular markers in squamous cell carcinomas


Squamous cell carcinoma

• Keratinizing squamous cell carcinoma

• Non-keratinizing squamous cell carcinoma

• Basaloid squamous cell carcinoma

• Preinvasive lesion

Squamous cell carcinoma in situ


Keratinizing squamous cell carcinoma

• Solid (strand-like) growth pattern

• Keratinization, intercellular bridges

• Immunohistochemistry: p40, p63, CK5/6 (CK14)


Basaloid squamous cell carcinoma


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)


Neuroendocrine tumors: SCLC, LCNEC, TC, DIPNECH)


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


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


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


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


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



Size >5 - 7cms T2b IIA IIB IIIA IIIB

T3 IIB IIIA IIIA IIIB

T3 IIB IIIA IIIB IIIC

Tumour Size


= change of stage grouping in 8e



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 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

Radial probe Endobronchial Ultrasound

• Utilizes radial ultrasound probe

• Mini-probe inserted through the working channel of a flexible bronchoscope

• Frequency is 20Mhz

Radial EBUS

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

practical approach to lung cancer

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