6 lungcancer

Bronchogenic Carcinoma （ Lung Cancer ）

Guo Yubiao, M.D & Ph.D

Pulmonary & Critical Care Medicine The first Affiliated Hospital of Sun-Yat Set University

Outline Epidemiology/Classification

Clinical manifestations

Symptoms

Signs

Diagnostic workup & Differential Diagnosis

Diagnosis

Differential Diagnosis

Treatment & Prevention

Summary

Bronchogenic

Carcinoma

（ Lung Cancer ）— tumor cell o

riginates from the mucosa or gland

of bronchus.

Definition

Epidemiology

Global Incidence of Lung Cancer(2001)

Global Mortality OF Lung Cancer(2001)

Females Males80

60

40

20

01930 1940 1950 1960 1970 1980 1990 1997

80

60

40

20

01930 1940 1950 1960 1970 1980 1990 1997

UterusBreastPancreasOvaryStomachLung and bronchusColon and rectum

PancreasLiverProstateStomachLung and bronchus Colon and rectumLeukemia

Rat

e pe

r 10

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0

Rat

e pe

r 10

0,00

0

Year Year

美国癌症死亡率 :无论男性还是女性，肺癌均为头号致死肿瘤

Lung cancer - US incidence and mortality rates (1973-1996)

10

50

100

Incidence - malesMortality - malesIncidence - femalesMortality - females

Rate per 100,000 people(log scale)

1974 76 78 80 82 84 86 88 90 92 94 96

Year of diagnosis/death

Ries et al 1999

Epidemiological Characteristic of Lung Cancer

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5

10

15

20

25

30

35

40

45

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72--7490--92

Anatomy and Pathology

Thyroid cartilage

Cricothyroid ligament

Cricoid cartilage

Connective tissuesheath (cut away)

Intercartilaginousligaments

Mucosa showinglongitudual folds formedby dense collectionsof elastic fibres

Tracheal cartilages

Toupperlobe

Eparterialbronchus

Tomiddlelobe

Tolowerlobe

R. mainbronchus

L. mainbronchus

Intrapulmonary Extrapulmonary Intrapulmonary

Tolowerlobe

Tolingula

Toupperlobe

Trachealis muscle

Oesophageal muscle

Epithelium

Lymph vesselsElastic fibres

Gland

Small arteries

Nerve

Posterior wall

Cross sectionthrough trachea

Anterior wall

Epithelium

Nerve

Lymph vessels

Small artery

Gland

Elastic fibres

Cartilage

Connective tissue sheath

Structure of trachea and major bronchi

© Novartis

Classifications of Lung Cancer

Classification by Anatomic Site

– Central Lung Cancer

– Peripheral Lung Cancer

Classification by Histopathology

– Small Cell Lung Cancer (SCLC ,15-20%)

– Non-Small Cell Lung Cancer (NSCLC ,80-85%)

Squamous epithelial cell cancer , Adenocarcinoma , Large Cell Cancer

adrnosquamous lung cancer etc.

Histological Types of Lung CancerRelative Incidence

Symptoms and Signs

Clinical Manifestations Development of Lung Cancer Symptoms

– Formation of Lung Cancer Asymptomatic

– Bronchia involved Cough

– Mucosa capillary involved Hemoptysis

– Pleura and chest wall involved Dyspnea, chest pain

– Obstruction of bronchus Short breath, fever

– Pleura spreading Pleural effusions

Non-special symptoms: Anorexia, weight loss

Clinical Manifestations

Symptoms Caused by Tumor Spreading and Metastasis

– Superior Vena Cava Obstruction Syndrome

– Horner’s Syndrome

– Pancoast’s Syndrome

Extra-pulmonary Manifestations

– Hypertrophic Pulmonary Osteoarthropathy

– Carcinoid Syndrome

– Gynaecomastia

Major signs and symptoms of lung cancer

Baseline major presenting symptoms

0

20

40

60

80

100

HemoptysisLoss of appetite

PainCoughDyspnea

Patients(%)

Hollen et al 1999

Para-neoplastic syndromes Not fully understood patterns of organ dysfunction

related to immune-mediated or secretary effects of neoplasm.

Occur in 10%-20% of lung cancer patients. 15% of patients with small cell carcinoma will dev

elop SIADH; 10% of patients with squamous cell carcinoma will

develop hypercalcemia. Digital clubbing is seen in up to 20% of patients at

diagnosis. Other common para-neoplastic syndromes include:

increased ACTH production, anemia, hypercoagulability, peripheral neuropathy

Achropachy (clubbed finger )

Laboratory Findings

Cytology (tissue samples, Sputum, pleural effusions)

Thoracoscopy

Fine needle aspiration of palpable lymph nodes

Fibrotic bronchoscopy - fluorescence bronchoscopy - endoscopic ultrasound - eBUS-TBNA

Mediastinoscopy, video-assisled thoracoscopic surgery (VATS), and thoracotomy

Serum tumor markers are neither sensitive nor specific enough to aid in diagnosis

IMAGING X-ray

NSCLC CT scans

Transthoracic needle aspiration (TTNA) of a non-small cell Pancoast tumor

荧光支气管镜(Auto fluorescence bronchoscope, AFB)

隆突前可见一淋巴结Enlarged Lymph node of Inferior Tracheal Protuberance (Spiral CT Scan )

支气管镜下粘膜表面光滑Smooth mucosa appearanceunder bronchoscope

(BF-UC160F-OL8; Olympus Medical Systems, Tokyo,

Japan)

(BF-UC160F-OL8; Olympus Medical Systems, Tokyo,

Japan)

Linear Real-time Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Scope

支气管内超声可见一异常回声区

超声引导下穿刺针刺入粘膜

超声实时引导下穿刺针刺入病灶

Bronchoscopic View of a Transbronchial Needle Aspiration of a Subcarinal Node

Herth FJ. Eur Respir J 2006

涂片可见癌细胞cancer cells found in the TBNA tissue samples

Mediastinoscopy

Positive Electron Tomography (P

ET) -CT———— 或许是肺癌，甚至是全身实体肿瘤最好的早期诊断方或许是肺癌，甚至是全身实体肿瘤最好的早期诊断方

法，但要用于筛查，还有待经济的发展。法，但要用于筛查，还有待经济的发展。

Diagnosis of Lung Cancer

Principles– Pay attention to the respiratory symptoms ineffectiv

e to treatment

– Pay attention to the extrapulmonary manifestations

– From routine to complicated

From non-invasive to invasive

– Highlight the pathological diagnosis

Cytology , histology

NSCLC diagnosis

Physical examination Detect signs

Visualize and sample mediasturial lymph nodes

Detect position, size, number of tumors

Detect chest wall invasion mediastinal lymphodenopathy distant metastases

Lymph node staging

Detect changes in hormone production, and hematological manifestations of lung cancer

Precise location of tumor obtain biopsy

Chest X-ray

CT scan

PET scan

Laboratory analysis

Bronchoscopy

Mediastinoscopy

FNA Cytology

NCCN Guidelines 2000

Staging and Prognostication

Mountain 1997

NSCLC stages - an overview

Disease

Early

Localized

Advanced

Stage

0IAIB

IIAIIB

IIIA

IIIB

IV

TNM

TIS N0 M0 (carcinoma in situ)T1 N0 M0T2 N0 M0

T1 N1 M0T2 N1 M0T3 N0 M0T3 N1 M0

T1-3 N2 M0

T4, Any N, M0Any T, N3, M0

Any T, Any N, M1

NSCLC stages

Stage 0

Stage IA

Stage IIB

Stage IIIB

Stage IV

Lymph nodes

Main bronchus

Contralateral lymph node

Metastasis to distant

organs

Invasion of chest wall

NSCLC: clinical stage as a prognostic factor

1 year

3 years

5 years

0

10

20

30

40

50

60

70

80

90

100

IA IB IIA

T2N1M0

IVIIB IIIA IIIBClinical stage at presentation

Survival (%)

Mountain 1997

T3N0M0T3N1M0

T1-3N2M0T4

N3

Probability of survival according to clinical stage

Treatment

Strategy of Lung Cancer Treatment

According to the pathological type

– Small Cell Lung Cancer (SCLC)

– Non-Small Cell Lung Cancer (NSCLC)

According to the TNM Clinical Stage

Choose the optimal therapeutic protocols

Follow-up regularly

NSCLC: an overview of treatment options

Localized tumor

surgery

Regional tumor

chemotherapy, radiotherapy (surgery)

Advanced tumor

chemotherapy

PDQ Guidelines

Treatment of NSCLC stage 0

Lobectomy, segmentectomy, or wedge resection

Curative radiotherapy if surgery is contra-indicated

Endoscopic photodynamic therapy (under evaluation in selected patients)

PDQ Guidelines

Treatment of NSCLC stage I and stage II

Lobectomy or pneumonectomy

Curative radiotherapy if surgery is contra-indicated

Adjuvant chemotherapy

Adjuvant radiotherapy

Neoadjuvant chemotherapy

PDQ Guidelines

NSCLC stage I: surgeryLocoregionalrecurrencerate(per person-year)

Locoregionalrecurrencerate(% of patients)

0

10

20

30

40

50

Segmen-tectomy(n=68)

Lobectomy(n=105)

00.0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.10

Limitedresection

(n=122)

Lobectomy(n=125)

p=0.008

Warren and Faber 1994Ginsberg and Rubinstein1995

p<0.05

Treatment of NSCLC stage III

Surgery alone (selected patients in stage IIIA only)

Postoperative radiotherapy

Chemotherapy + radiotherapy

Radiotherapy alone

Chemotherapy alone (stage IIIB with malignant pleural effusions)

PDQ Guidelines

NSCLC stage III: surgery combination regimens

Study

Pass et al 1992

Roth et al 1994

Rosell et al 1994

Regimens

Surgery plus chemotherapy (n=13)

Surgery plus radiotherapy (n=14)

Surgery plus chemotherapy (n=28)

Surgery alone (n=32)

Surgery plus radiotherapy plus chemotherapy (n=30)

Surgery plus radiotherapy (n=30)

Median survival (months)

28.7

15.6

64

11

26

8

p value

0.095

<0.008

<0.001

NSCLC stage III: combination radiotherapy and chemotherapy

NSCLC Collaborative Group 1995

0.0 0.5 1.0 1.5 2.0Radiotherapy plus

chemotherapy betterRadiotherapy (control)

better

Buenos AiresBrusselsFLCSG 2EssenSLCSGCEBI 138WSLCRG/FIPerugiaCALGB 8433EORTC 08842SWOG 8300aSWOG 8300b

Subtotal

p=0.005

Treatment of NSCLC stage IV

Chemotherapy (platinum-based), modest survival benefits

New chemotherapy agents

External beam radiotherapy (palliative relief)

Endobronchial laser or endobrochial therapy for obstruction

PDQ Guidelines

NSCLC recurrence after chemotherapy

Surgery (selected patients with isolated brain metastases)

Palliative radiotherapy

Palliative chemotherapy

Endobronchial laser therapy or interstitial radiotherapy

PDQ Guidelines

Future Developments

NSCLC: future developments

Current treatment remains unsatisfactory

Prevention

Earlier diagnosis

Improved treatment

PDQ Guidelines

Prevention

Education

– avoidance of environmental carcinogens such as tobacco smoke

Chemoprevention?

– vitamin A

– isotretinoin

Earlier diagnosis

Obstructive lung disease

Genetic risk factors

Sputum cytology

Molecular tumor markers

Computed tomography

Positron emission tomography (PET)

Edell 1997

Treatment

NSCLC

Novel biological

targets

Immunology:- interleukins- interferons- vaccines

Newchemotherapy

drugs

Gene therapy:- interleukins- K-ras

Novel biological approaches- molecular target therapy

Epidermal growth factor (EGF) tyrosine kinase inhibitors (TKI)

Anti-vascular therapy

Metalloproteinase inhibitors

Immunotherapy and gene therapy

Immunomodulators

– interferons, interleukins

Vaccination

– passive immunisation

– active immunisation

Gene therapy?

– oncogenes eg K-ras

– immunomodulators eg interleukins

Thank You!