Neoplasms

of Respiratory

System

Epidemiologic data

 Number of patients:

• 1,35 million people per year on the whole world (2003);

• Global incidence in male –

35,5/100.000, in female – 12,1/100.000.

 There were 215.020 patients in USA (114.690 male and 100.330

female). Incidence - 63,9/100.000 (79.4/100.000 for male,
52.6/100.000 for female). Surveillance Epidemiology and End Results
(http://www.seer.cancer.gov); 20 000 people in Poland.

 In 2008, 161.840 patients died due to lung cancer in USA (death rate -

72.0/100.000 for male and 41.0/100.000 for female). In USA, 75%
patients died during 5 years from cancer diagnosis, in Poland – 86%.

 The median age of diagnosis was 70 years (in 2003, in USA). 32,6%

patients was diagnosed between 65 and 74 years age.

Age-standardised death rates from Trachea, bronchus,

lung cancers by country (per 100,000 inhabitants).

no data

less than 5

5-10

10-15

15-20

20-25

25-30

30-35

35-40

40-45

45-50

50-55

more than 55

Cause of death in course of

malignant neoplasms in Poland

(1999)

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0

40,0

lar

male

0,0

2,0

4,0

6,0

8,0

10,0

12,0

14,0

16,0

llb

female

Cause of death in course of

malignant neoplasms in Poland

(2003)

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0

lar

male

0,0

2,0

4,0

6,0

8,0

10,0

12,0

14,0

female

Death rate because of malignant

neoplasm's in male in USA

1930 1940 1950 1960 1970 1980 1990

esophagus
liver
prostate
lung
stomach

Death rate because of malignant

neoplasm's in female in USA

1930 1940 1950 1960 1970 1980 1990

uterus
breast
ovary
lung
stomach

Smoking (percentage of

population)

POLAND

USA

female

27 %

30 %

male 48 %

28 %

Smoking tobacco is the major risk factor for developing lung

cancer.
Smokers have

10-25

times greater risk of lung cancer than

non-smokers.
Exposition to second-hand smoke:

1,5

times greater risk of

lung cancer.

Cigarette smoke includes more than 2000 carcinogens, e.g.

bezno[A]pirene, polyclic aromatic hydrocarbons,

nitrosamines, arsenic, hydrogen cyanide.

Additional risk factors in

smokers

 Contents of tarry substances in cigarettes.

 Manner of inhaling the smoke.

 Age of smoking beginning.

 Age of discontinuation of smoking.

 The number of cigarettes per day.

}

The
number of
pack-years

Mechanisms of smoke

pathogenic activity on

respiratory system



ciliotoxicity and impairement of
bronchial cleaning (bronchial
clearance);



disturbances in protease -
antiprotease balance;



abnormalities in immunological
response;



induction of chronic inflammation
state in airways;



bronchial hypersensitivity;



mutagenesis and oncogenesis.



1964 – Surgeon General’s
Report on Smoking and
Health:

• For the first time, this report

admitted official that smoking is
significant risk factor in
appearance of respiratory system
diseases.



CDC (Centres for Disease
Control):

• Smoking is in charge of more

than 80.000 death in year in USA
because of respiratory system
disease.

Environmental and

occupational carcinogenic

factors in lung cancer

FACTORS

Asbestos

Combustion gases from

oxidization of coal,

petroleum and soot,

diesel engine exhaust

gases

Radon

Arsenic

OCCUPATIONAL EXPOSURE

thermal insulation, plumbers
engineering;
stokers, steelworkers,
mechanics, miners and
machine operators, chimney
sweeps;

miners;
miners, welders, workers at
pesticide production.

Genetic factors in lug cancer

In lung cancer cells are accumulated
many genetic alterations, such as:

Small cell

Non-small cell

lung cancer

lung

cancer

Alterations in tumor

3p deletion

suppressor genes

mutation in RB

mutation in p6

mutation in p53

Alterations in

myc expression myc

expression oncogenes

Her-2/neu expression

mutation in ras

Bcl-2

expression Bcl-2 expression
telomerase expr. telomerase expr.

Prevention in lung cancer

(National Cancer Institute Recommendation)

 Smoking cessation – 30-50% reduction

of death rate is noticed after 10 years
from smoking cessation.

• Zyban (bupropione hydrochloride – 150 mg) –

selective

inhibitor

neuronal

uptake

noradrenaline and dopamine.

• Chantix (verenikline) – partial agonist of nicotinic

receptors.

 Early detection of high risk of lung

cancer (genetic predisposition) and
effective diagnosis of non-invasive
forms.

 Interruption of precancerous conditions

(atypical adenomatous hyperplasia –
AAH, diffuse spontaneous proliferation of
neuroendocrine cells, progressive
dysplasia, cancer in situ).

 Secondary chemoprevention in developed

lung cancer (adjuvant chemotherapy in
patients after tumor resection).

 Primary chemoprevention (tocopherols,

beta-carotenes, retinoids, diet).

Prevention in lung cancer

(National Cancer Institute Recommendation)

Diet in lung cancer

Protective activity (antioxidative

activity)

 -carotenes;
 vitamin C;
 vitamin A.

Lung cancer

 Lung cancer is malignant neoplasm derived

from airway epithelium cells (bronchi,
bronchiole, alveoli).

 There are two types of lung cancer: small cell

lung cancer (SCLC) and non-small cell lung
cancer (NSCLC).

 88% of primary lung cancers:

• squamous cell lung cancer (cornnifying or non-cornifying);
• small cell lung cancer;
• lung adenocarcioma (with brochioloalveolar adenocarcinoma subtype);
• giant cell carcinoma (anaplastic cell carcinoma).

Frequency of lung cancer in

USA

Histological type

Frequency

5-years

survival

Lung adenocarcinoma

32% 17%

Brochioloalveolar adenocarcinoma 3%

42%

Squamous cell lung cancer

29% 15%

Microcellular lung cancer

18% 5%

Macrocellular lung cancer

11%

Carcinoid (typical or atypical)

83%

Salivary gland carcinoma 0,2% 39% - 48%

Mucoepithelioid carcinoma
Adenoid cystic carcinoma

Sarcocarcinoma

0,1% 30%

Histopathological diagnosis of lung cancer

is the basic factor, which decide of kind of

treatment. It qualifies tumor as a small cell

lung cancer (lat.

carcinoma

microcellulare

)

or one of types of non-small cell lung

cancer.

At the moment of the diagnosis and the

first symptoms occurrence, small cell lung

cancer is usually systemic disorder with

distant metastases by lymph and blood

vessel. Time of duplicate of tumor size is

only 55 days. Therefore, SCLC may be treat

by chemo- or/and radiotherapy.

Lung cancer - clinical

symptoms

Only 5-15% of patients have no

symptoms at the moment of lung

cancer diagnosis.

The symptoms connecting with

intrabronchial growth of primary

tumor

 couth (45-75%);
 shortness of breath and chronic fatigue (30-50%);
 haematoptysis (27-57%);
 unilateral whistling rales, wheezing breath, stridor;
 weight loss for no known reason (8-70%);
 lung inflammation because of bronchus occlusion

(fever, productive couth);

 chest pain.

 occlusion of a bronchus or trachea lumen;
 dysphagia;
 symptoms of lung abscess (squamous cell carcinoma and

giant cell carcinoma);

 periodic reversible nerve paralysis with hoarseness (5-20%);
 phrenoplegia with elevation of phrenic dome;
 infiltration of pericardium and heard, cardiac tamponade

(squamous cell carcinoma and small cell lung cancer);

 pleural effusion (adenocarcinoma and giant cell lung

cancer);

 hypoxemia and respiratory failure.

Symptoms connecting with tumor

spreading in the chest area

 Horner’s Syndrome – sympatic nerve paralysis

with, retraction of eyeball, tonic pupil, ptosis
of upper eyelids and hypohidrosis;

 Pancoast’s Syndrome – symptoms of the lung

apex tumor (commonly squamous cell
carcinoma) with damage of C8-Th2 spinal
nerves, generation of omalgia and destruction
of first and second costal bones;

 Superior caval vein syndrome with swelling of

the face and neck - 5% of patients.

Symptoms connecting with

tumor spreading in the chest

area

Symptoms of lung cancer

metastases

 metastases to lymph nodes – compression syndromes;
 metastases to bones – ostalgia and pathologic

fracture;

 metastases to liver – hepatocellular damage with

icterus and liver insufficiency;

 metastases to central nervous system – deficiency

signs and cephalgia;

 metastases to bone marrow – pancytopaenia and

leucoertroblastosis.

Paraneoplastic syndromes (10-

30%)

 there are no connection between

paraneoplastic syndrome and tumor size
or distant metastatic presence;

 paraneoplastic syndromes are associated

with SCLC and giant cell carcinoma;

 paraneoplastic syndrome are dependent

on production by cancer cells
polypeptide hormones, antibodies or
immunomodulators such as TNF-α,
prostaglandins.

Paraneoplastic syndromes

 neoplasm's cachexy (30% of patients) and fever

dependent on TNF-α release;

 disturbances of coagulation (profound venous

embolothrombotic disease, wandering
embolism, DIC syndrome). Tissue factor is
produced by neoplastic cells;

 hypercalcaemia and hypophosphataemia due to

ectopic production of parathormon or peptide
similar to parathormon (PTHrH);

 paraneoplastic neuro- and myopathy. Subacute

peripheral sensory neuropathy;

 hypertrophic pulmonary osteoarthropathy with

clubbed fingers.

suspicion of neoplastic disease on the

basis of full medical history of patient
(symptoms, coexistent diseases,
general condition, state of nutrition,
smoking and family history) and
physical examination;

planning of additional examination

(blood cell count, blood coagulation,
biochemistry, electrolytes, tuberculin
test, chest-X-ray examination.

The role of general practicioner

in diagnosis of lung cancer

Chest-X-ray examination

localisation of change

probability of diagnosis

 central squamous cell carcinoma small cell lung

cancer

 peripheral

giant cell carcinoma lung

adenocarcinoma

 disseminated or

brochioloalveolar

multifocal

carcinoma infiltration

 pleural effusion

lung adenocarcinoma

 hylar

lymphadenopathy

Diagnosis of lung cancer



Chest-X-ray sensitivity is 70-80%

“

Malignancy trait” in chest-X-ray examination

 weak separation of change;
 lack of central calcification;
 duplication time < 18 months;
 size > 3 cm;
 accompanying atelectasis, pneumonia and/or

lymphadenopathy

Squamous cell carcinoma shutting left main

bronchus. Trachea and main vessels are

shifted to the left

Pleural ephusion in course of

lung adenocarcinoma

Infiltration of pleura and lung inflammation

causing by neoplasm occlusion of bronchus

Pathologic mass with central necrosis in the

right lung. Enlargement of hilar and

paratracheal lymph nodes

Small cell lung cancer with invasion to mediastinum.

Infiltration of retroaortal space with superior caval

vein syndrome

Lung cancer with infiltration of

mediastinum and destruction of

oesophagus wall (broncho-

oesophageal fistula)

Lung cancer in the right main bronchus

near tracheal bifurcation. Calcification in

lymph nodes is characterised for earlier

tuberculosis

Adenocarcinoma of

the

left

lung

Adenocarcinoma

of peripheral part of

right lung with infiltration of thorax

wall and ribs

Multifocal infiltration

characterised for

rochioloalveolar

adenocarcinoma

Pancoast’s tumor in apex

of right lung

Pancoast’s tumor in MRI (infiltration

of thoracic vertebrae)

The clinical symptoms and

results of additional

examinations, which may

suggest diagnosis of lung

cancer, must be confirmed by

histopathology analysis of

tissues specimens.

Diagnosis of lung cancer

How to obtain pathological tissues?

 cytology of sputum;
 bronchofiberoscopy:

• intrabronchial biopsy and exfoliative biopsy (sensitivity 55-85%);
• transbronchial biopsy (forceps biopsy, sensitivity 55-85%);
• transbronchial fin-needle biopsy with EBUS-FNA (sensitivity 90-100%);
• bronchoaspirate or bronchoalveolar lavage (BAL);

 fin-needle aspiration biopsy by thorax wall (complication is pneumothorax,

which occurs in 7% of patients and in 46% patients with COPD;

 biopsy of pleura, examination of pleural effusion (paracenthesis);
 transcutaneous biopsy of lymph nodes, infiltrations of softy tissues,

metastases in liver, bones, bone marrow;

 mediastinoscopy;
 videothoracoscopy;
 exploratory thoracotomy.

Sputum cytology

Sputum cytology have to be performed

minimum 3 times

Sensitivity: 80% for central tumors

50% for peripheral tumors

Highest sensitivity for squamous cell carcinoma
Lowest sensitivity for adenocarcinoma

Imaging in lung cancer

 chest computed tomography;
 abdominal ultrasonography and ultrasonography of pleural cavity;
 abdominal computed tomography;
 computed tomography of central nervous system;
 magnetic resonance imaging of central nervous system and in the

tumor of chest wall as well as in the tumors with obturative
atelecatsis;

 scintigraphy of sceleton;
 contrast X-ray examination of oesophagus. Badania kontrastowe

przełyku jeżeli występują objawy ucisku.

 PET scan (positron emission tomography scan): A fluorodoexyglucose

is injected intra venous. The PET scanner rotates around the body

and makes a picture of where glucose is being used in the body.

Malignant tumor cells show up brighter in the picture because they

are more active and take up more glucose than normal cells do.

The role of computed

tomography in lung cancer

diagnosis

 staging in lung cancer: localisation and estimation of tumor

size, appearance of infiltration of pleura or mediastnal
organs, visualisation of enlargement lymph nodes in
mediastinum:

• qualification to surgical resection;
• planning of chemotherapy and radiotherapy (neoadivant, adiuvant

chemotherapy and chemotherapy and radiotherapy in locally advanced or
advanced non-small cell lung cancer.

 planning of chemotherapy and radiotherapy in small cell lung

cancer;

 estimation of responce on chemotherapy and radiotherapy;
 information of reccurence or progression of disease.

The main methods in lung

cancer diagnosis are:

CT and PET

bronchoscopy

Staging in lung cancer

 range of lung cancer (anatomical

staging)

• estimation of resection possibility

(computed tomography and MRI);

 estimation of general condition -

possibility of surgical treatment

• estimation of operation possibility

(performance status, pulmonary

function tests, gasometry,

electrocardiography).

International TNM

classification of lung

cancer

Stage

TNM

% of 5-years survival

I T1-T2 N0 M0

60-80

IIT1-T2 N1 M0

25-50

IIIA T3 N0-N1 M0 25-40

T1-T3 N2 M0

10-30

IIIB each T4 or

< 5

each N3 M0

each M1 < 5

Gradation in small cell

lung cancer

 Localized disease (30%) -

unilateral process, which
occupied only regional lymph
nodes, eventually with metastases
to supraclavicular lymph nodes
and pleura. There is possibility of
application of high-voltage
radiotherapy.

 Extensive disease (70%).

Solid infiltration (smaller than 3 cm) in inferior

lobe

of right lung. Probable stage I of lung cancer

(T1 N0 M0)

PET with fluorodeoxyglucose. Stage I (T1 N0

M0) of peripheral lung cancer in superior

lobe of left lung

Brochioloalveolar adenocarcinoma

in stage

I (T2 N0 M0). Tumor of 3,5 cm size

with central area of increased

translucence

Lung cancer in stage II (T2 N1 M0) in

lingula of the left lung (size of 5 cm with

dystrophic calcification and

lymphadenopathy)

PET. Primary cancer

right lung and

metastase in

mediastinium lymph

node

Small cell lung cancer infiltrating mediasti

um.

Enlargement of paravertebral lymph nodes.

Stage IIIB (T4 N2 M0)

Lung cancer with infiltration of

mediastinum and destruction of

oesophagus wall (broncho-oesophageal

fistula). Stage IIIB (T4 N2 M0)

Adenocarcinoma of superior lobe of left lung.

Infiltration of paratracheal lymph nodes, main

vessels and mediastinum lymph nodes on the

right side. Stage IIIB (T4 N3 M0)

Lung cancer metastases –

necrotic masses in left

suprarenal gland and in

pancreas. Stage IV (M1)

ung cancer

etastases

liver. Stage IV (T4 N3 M1)

Adenocarcionoma metastases into brain

and their complete regression after

erlotinib treatment

Mezothelioma

 malignant neoplasm of pleura causing by exposition to

asbestos fibre (crocidolite) – occupational disease;

 mezothelioma appears in two different forms: tumor

form or diffuse form;

 rare metastases formation;
 diagnosis:

• symptoms;
• chest X-ray and computed tomography;
• pleural biopsy and examination of pleural effusion;

 treatment: surgical, radio- and brachytherapy,

chemotherapy (cisplatin + pemetrexed (Alimta

Mezothelioma

Pleural condensation and lack of

invasion in the chest wall typical for

mezothelioma

Benign noeplasms of

the lung

 adenoma of bronchi:

• carcinoid from APUD cells and

carcinoid syndrome;

• cystadenoma;
• mucoepidermal tumor;

 hammartoma, choristoma.

Hamartoma in „clavicular

shadow”

anteroposterior projection

oblique projection

Metastases to the lung

in chest X-ray

examination:

 breast round shadings
 brain

reticulo-nodular shading

 colon

nodular shading

with or

without disintegration

 genitourinary system

adenopathy in

mediastinum and pleural effusion

Surgical treatment of non-small cell lung

cancer

 I and II stages, and some IIIA stages:

 surgical resection in stages I and II – lobectomy or pulmonectomy

(segmentectomy or wedge resection only in patients with bad condition);

 survival time is more than 5 years for 50% of patients treated with radical

resection and more than 10 years for 15% of patients. Post-lobectomy mortality is
3%;

 surgical resection with total removal of lymph nodes from mediastinum and

consideration for adjuvant chemotherapy in IIIA stage with N2 feature;

 tumors with infiltration of chest wall (stage IIIB) - en block surgical

resection tumor and chest wall;

 Pancoast’s tumor (T3 and stage IIIA) - en block resection of tumor

and chest wall, especially with intra-operation brachytherapy;

 proximal infiltration of airway and N0 or N1 (stage IIIB) – cuff

resection or pulmonectomy with reanastomosis with opposite main
bronchus;

 surgical resection of single metastases in central nervous system or

suprarenal glands and pulmonectomy of small primary tumors (stage
IV).

 palliative surgical treatment (e.g. brain metastases).

respiratory and/or circulatory failure

connecting with COPD and other lung
diseases:

• total respiratory efficiency less than 40% of

normal value (FEV1 < 1 l);

• retention of carbon dioxide;
• pulmonary hypertension;

myocardial infarction in last 3 months;
arrhythmia;
poor performance status (PS = 3 or 4

points).

Contraindications to radical resection in lung

cancer - examination of patients’ general

condition

 smoking;
 patients older than 35 years;
 tumor size larger than 6 cm;
 lack of calcification;
 symptoms suggested malignant neoplasm in chest;
 attelectasis, pneumonia and/or hilar

lymphadenopathy in chest X-rays;

 enlargement of tumor size in comparison with

previously chest X-rays.

The main risk factor supporting lung

resection in the suspicion of lung

cancer without confirmation in

histopathological diagnosis

Chemotherapy and radiotherapy

in non-small cell lung cancer

 neoadiuvant chemotherapy in patients with stage IIIA, if

surgical resection could be performed based on

mediastinoscopy results.

 adjuvant chemotherapy in patients with stage IB, II and

IIIA after radical resection. Adjuvant radiotherapy may

be applied only in limited number of patients with stage

IIIA and N2 feature;

 sequential or concurrent chemotherapy and radiotherapy

in patients with locally advanced NSCLC (stage IIIB);

 first-line chemotherapy in patients with advanced NSCLC

(stage IIIB or IV);

 second-line chemotherapy in patients with advanced

NSCLC and progression after first-line treatment;

 third-line chemotherapy in patients with advanced

NSCLC and progression after first- and second-line

treatment;

Cytostatics and scheme of

treatment in non-small cell lung

cancer

 First-line chemotherapy:

• Chemotherapeutic scheme involving two drugs based on

cisplatin or carboplatin and one of the following:
vinorelbine (Navelbine), gemcytabine (Gemzar), etoposid
(Vepesid), pemetrexed (Alimta) or docetaxel. These
scheme may be supplemented by bevacizumab (Avastin).
21-day cycles are used for various combination
chemotherapy regiments. The cycles are repeated twice
in neoadiuvant chemotherapy, 2-4 times in adiuvant
chemotherapy and up to 6 times in patients with
advanced NSCLC.

 second-line chemotherapy:

• repeat of chemotherapy scheme if remission occured;
• monotherapy with pemetrexed, docetaxel or erlotinib.

 third-line therapy with erlotinib.

Small cell lung cancer treatment

 sequential or concurrent multidrug chemotherapy and chest radiotherapy in patients with

localised disease and in good general condition;

 multidrug chemotherapy in patients with extensive disease and in good general condition;
 radiotherapy of central nervous system in the cases of metastases in brain or spinal cord in

limited or extensive disease;

 palliative radiotherapy of distant metastases;



21-day cycles are used for various combination chemotherapy regiments. The cycles are repeated up to 6
times. Chemotherapeutic scheme involving following drugs

•

cisplatin or karboplatin with etoposide (Vepeside);

•

CAV scheme (endoxan, vinblastine, adriamycine);

 in second-line chemotherapy, the scheme from first-line treatment should be used if remission

duration was more than 3 months. Topotecan (hycamtin) in monotherapy or another scheme
of chemotherapy should be used if early progression after first-line chemotherapy is noted

 treatment effect:

•

clinical remission is noted in 30-50% of patients, disease progression in 10% of patients,

•

complete recovery is observed in 15-25% of patients with LD and in 1-5% of patients with ED;

•

survival time is 14-18 months for patients with limited disease and 10-12 for patients with extensive disease.
Survival time for untreated patients is 2-4 months.

 relief of pain:

• nonsteroids anti-inflammatory drugs (NSAIDs);

• weak narcotic drugs with NSAIDs (codeine, tramal);

• narcotic drugs (Durogesic, morphine) with NSAIDs;

 corticosteroids in limited number of patients;

 counteraction of anorexia and effect of emaciation (Megace, hydration);

 counteraction of infection due to granulocytopenic fever after

chemotherapy (rhG-CSF – Neupogen);

 anemia controlling (erytropoietin – NeoRecormon, Darbopoietin);

 vomiting controlling (Zofran, Atossa);

 treatment of venous thromboembolic disease (low molecular weight

heparine - clexane);

 treatment of bony pain and pathologic fracture (bisphosphonian - aredia);

 antidepressive agents and psychotherapy;

 brachytherapy;

 palliative radiotherapy of metastases and infiltration of spine, bones,

central nervous system;

 resection of life-threatening metastases (e.g. in central nervous system).

Symptomatic treatment in lung

cancer

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