Lung Ca-dr. Bayot

LUNG CANCER • Affects 94,000 males and 78,000 females (US), 86%die w/in 5 yrs of diagnosis • Leading cause of cancer death in both men and women in all races • Incidence peaks between 55 and 65 yrs old • Accounts for 31%of all cancer deaths in men and 25%have disease spread to regional lymph nodes & >55%have distant metastases

Lun g Can c er (UPDATED 2009)

Rommel D. Bayot, M D, FP C P , FP C C P P hilippine H eart C enter FEU- NRM F M edical C enter

LUNG CANCER

LUNG CANCER • WHO classification : 1. Squamousor epidermoid carcinoma 2. Small cell (or oat cell) carcinoma 3. Adenocarcinoma(including bronchioalveolar) 4. Large cell (or large cell anaplastic) carcinoma

• 5- year survival rate - local disease: 50% - with regional disease: 20% - overall: 14%

5. Others: Undifferentiated Carcinoma, Carcinoid, Bronchial Gland Tumors (Adenoid Cystic Carcinoma. Mucoepidermoid Tumors)

Non-small cell CA

LUNG CANCER • HistologicClassification: 1. Small cell carcinoma- at presentation, have already spread such that surgery is unlikely to be curative - usu. present as central masses w/ endobronchial growth - managed by chemotherapy with or w/o radiotherapy 2. Non-small cell varieties (Squamous, adenocarcinoma, large cell, bronchioalveolar, and mixed versions)

• Found to be localized at the time of presentationmay be cured with either surgery or radiotherapy • Do not respond as well to chemotherapy as small cell CA • 90%of patients w/ lung CA of all histologictypes are current or former smokers • ADENOCARCINOMA- most common lung CA arising in non smokers, in women, in young patients (<45 yrs) • ADENOCARCINOMA- have replaced squamouscell CA as the most frequent histologic subtype for all sexes and races combined

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Non small cell CA • In non-smokers with adenoCA, the possibility of other primary sites should be considered • Squamousand small cell CA usu present as central masses w/ endobronchial growth • Adenocarcinomasand large cell CA tend to present as peripheral nodules or masses, frequently with pleural involvement • Squamousand large cell CA cavitate in 10-20%of cases

Biology of Lung C ancer

Biology of Lung CA

Lung CA

• Lung Cancer is the leading cause of death in industrialized countries • Squamouscarcinoma: Conversion of normal bronchial epithelium by oncogenic triggering • Adenocarcinoma: development from a premalignant precursor lesion (Atypical AdenomatousHyperplasia)

• Molecular Biologic Studies – Overt cancers carry multiple genetic and epigenetic alterations

• Epidemiologic Studies – Most cases of primary lung cancer: caused by smoking – Carcinogens in smoke: induce multiple genetic alterations through DNA adducts

Chromosomal Alterations

Hallmarks of Human Cancer Cells • • • •

Chromosomal alterations Chromosomal instability Tumor suppressors Alterations in DNA methylation

• Critical molecular events – Inactivation of tumor suppressor genes – Activation of dominant oncogenes

• Lung cancers share similar chromosomal changes/ histologic type specific characteristic alterations

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Chromosomal Losses

Chromosomal Gains

• Non Small Cell Lung Ca

• Non Small Cell Lung Ca

–3p, 8p, 9p, 13q, 17p

–1q, 3q, 5p, 8q

• Small Cell Lung Ca

• Small Cell lung Ca

–3p, 4q, 5q, 8p, 10q 13q, 17p

–3q, 5p, 8q

Tumor Suppression

Knudson Hypothesis

• 2 events – Deletion of a large chromosomal DNA segment of one allele – Smaller mutation or epigenetic inactivation of the other allele

• Tumor Suppressor Gene – Genes whose reduced function can lead to neoplastic change

• An individual with an inherited predisposition to cancer inherits one normal and one mutant tumor suppressor gene • A non-predisposed individual must acquire somatic mutations in both the maternal and paternal suppressor gene alleles to initiate tumor formation

p53/ MDM2/ p14ARF Pathway

Alterations in DNA Methylation

• P53 Tumor Suppressor Gene

• Cytosine-Guanosine (CpG) dinucleotide – Contained in promoter regions – Protected from methylation in normal cells – Methylation associated with loss of expression of the particular gene; aternative mechanism for loss of tumor suppressor gene function – 9p21, 13q14, 17p13

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– Guardian of the genome; safeguard against genetic instability – Activated p53 may participate directly in DNA repair via induction of p53R2 – Activated p53 transactivatesgenes that may impose cell cycle arrest in G1 and G2 – Smoking induces p53 mutations

p53/ MDM2/ p14ARF Pathway – Correlates with poor prognosis after surgical treatment of lung cancers, especially in stage I cancers.

• p14ARF – Exerts growth inhibition by inhibiting the ubiquitin E3 ligase activity of MDM2 – Deletion may promote tumor-promoting activity of oncogenes

• MDM2 – Ubiquitin E3 ligase; oncogene – Interacts with p53 and targets the p53 protein for degradation – Paradoxically in association with a favorable prognosis

Retinoblastoma Proteins • Transforming Growth Factor - β

• p16INK4A – Maintains RB in phosphorylated state – Exerts tumor suppressor activity only in the presence of wild-type RB – p16INK4A-RB: critical regulator of cell cycle progression – Alterations in RB detected in 90%of SCLCs

– Inhibits cell proliferation of normal epithelial cells, including bronchial and peripheral lung epithelial cells, thru inductions of CDK inhibitors

• Cell Cycle Check Points – Induce arrests/ delay of cell cycle progression; provide time for DNA repair

Epidemiology of Lung CA

Epidemiology of Lung C ancer

• Most Lung CA are caused by carcinogens and tumor promoters ingested via cigarette smoking • Relative risk of developing lung CA is ↑ 13x by active smoking & 1.5x by long term passive smoking • Lung CA death rate is related to the total cigarette pack years ( risk is ↑60-70x for smoking 2 packs/day for 20 yrs compared to non smoker) • Risk of dev lung CA decreases with cessation of smoking but may never return to nonsmoker level

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*

Epidemiology of Lung CA • Increase in lung CA rate in women is associated with rise in cigarette smoking • Women have a higher relative risk per given exposure than men (↑1.5 x) likely due to higher susceptibility to tobacco carcinogens in women

Epidemiology of Lung CA

• The present pandemic of lung cancer followed the introduction of cigarettes • Role of carcinogens in disease causation • First identified occupational respiratory carcinogen: Radon

*

Epidemiology of Lung CA • Human occupational causes – Arsenic, Asbestos, Chromates, Chloromethyl ethers, Nickel, Polycyclic Aromatic hydrocarbons, Radon progeny

• Outdoor air pollutants – Combustion-related carcinogens

• Indoor air pollution

Patterns of Occurrence

Temporal Trends • Differing epidemic patterns in men and women • Epidemic among women followed that of men • Lung Cancer: most frequent cause of female cancer mortality

– Asbestos, Radon, Cigarette smoke, Fumes from cooking stoves

Epidemiology of Lung CA *• Older age groups

Race and Ethnicity

– Rates continue to increase in both sexes – Rates of increase decelerating more significantly in men

• Younger age groups – Rates decreasing; decreases more pronounced for men

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– Rates similar among African American and white women – Rates 50%higher among African American men than among white men – Mortality rates: Hispanics, Native Americans, Asians/ Pacific Islanders >African Americans and non Hispanic whites

Epidemiology of Lung CA

Occurrence by Histologic Type – Dose-response relationship (number of cigarettes smoked) steepest for Small Cell Undifferentiated Carcinoma

Geographic Patterns – Most common in developed countries – North America, Europe >Africa, South America – Rates tend to be highest in urban areas; costal areas

– Chloromethyl ethers, Radon exposure exhibit specificity for Small Cell LungCancer

Epidemiology of Lung CA

Occurrence by Histologic Type – Adenocarcinoma: now the most common histologic type; most common type in females – SquamousCell: more common type in males than females – Increasing rates of Adenocarcinoma:

• Changes in cigarette characteristics – Puff volume increased • Change in deposition patterns (peripheral airways and alveoli)

– Nitrate levels in tobacco smoke increased • Nitrogen oxide production increased • Increased dose of Nitrosamine 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

• Changes in cigarette smoking behavior • Features of cigarettes

*

A Carcinogenic Pathway • AAH → small, focal BAC

Etiology of Lung Cancer

invasive AdenoCa →

• Atypical AdenomatousHyperplasia (AAH)– most common precursor to Adenocarcinoma • Bronchio-Alveolar CA (BAC) – low prevalence; includes AAH as precursor step

• Exposure to etiologic (or protective) agents • Individual susceptibility to these agents

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Environmental and Occupational Agents

Environmental and Occupational Agents

• Compared to never smokers, smokers have a 20-fold increase in lung cancer risk • Risk increases with duration of smoking and number of cigarettes smoked per day • Stronger effect of duration of smoking than amount smoked per day

• Tripling the number of cigarettes smoked per day was estimated to triple the risk; tripling the duration of smoking was estimated to increase the risk 100x • Starting at younger age have a greater likelihood of becoming heavier smokers and remaining smokers

• Smoking Cessation

– Brossand Gibson:

– Risk decreases among those who quit smoking compared to those who continue

• Filter cigarettes provided some reduction for lung cancer risk

• The Changing Cigarette

– Hammond and colleagues:

– Unfiltered → filtered cigarettes

• Lung cancer risk and tar yield of products

• Cellulose acetate, charcoal

– Low yield (<17.6 mg/ cigarette) – Intermediate – High yield (25.8 – 35.7 mg/ cigarette)

– “Light” or “mild” labels – Cigarette tar: condensable residue of cigarette smoke

• Those smoking >22 mg had the highest risk, after adjustment for smoking amount and for age of starting of smoke

• Passive smoking/ environmental tobacco smoke/ secondhand smoke

– Lee: • Risk reduction estimated for smokers of filter vs nonfilter cigarettes (decades ago)

– Changes in cigarette design and manufacturing over the last 50 years had not benefited public health

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– Nonsmoking spouses married to smokers were 30%likely to develop lung cancer – More weakly associated with lung cancer than is active smoking; lower doses of carcinogen – There is NO threshold for tobacco carcinogenesis

• Diet – Specific micronutrients may have anti carcinogenic activity – Tomatoes, cruciferous vegetables

* – Alcohol drinking • Highest consumption categories associated with increased risk

• Reduces risk

– β - carotene

– Lower BMI

• Increased risk

• Increased lung cancer risk relative to heavier persons

– Vitamin C • Protective association

– Concomitant effects of smoking (?)

– Vitamin A • Studies yield null findings

Occupational Carcinogens for Lung CA • Environmental exposures

Proven

– Occupational exposures – Asbestos – Radiation – Air pollution • Atmospheric air pollution • Indoor air pollution

Suspected

Arsenic

Acrylonitrile

Asbestos

Beryllium

Bis(chloromdethyl)ether

Vinyl chloride

Chromium

Silica

Mustard gas

Iron ore

Nickel

Wood dust

Polycyclic aromatic hydrocarbon Ionizing radiation

*

Asbestos • Fibrous, naturally occuringsilicate material • Peak incidence occur 30 -35 years after initial exposure • In combination with smoking, act synergistically to increase lung cancer risk

Radiation

• Types of Radiation

– Mechanism:

– Low Linear Energy Transfer (LET) • X-rays • γ-rays • Associated with higher risk when exposure occur at higher dose rate

– High Linear Energy Transfer (LET)

• Alter deposition pattern in the lung • Enhance retention of asbestos fibers

• Neutrons • Radon • Nonthreshold dose-response relationship

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Air Pollution

Host Factors

• Atmospheric Air Pollution

• Genetic susceptibility

• Polycyclic aromatic hydrocarbons, arsenic, nickel, chromium

– History of lung cancer predicts increased risk; mendelian codominant autosomal gene – Genetic factors may be more important at younger ages; association stronger in ages 40 – 59 years than older persons

• Indoor Air Pollution – Most important indoor air pollutants in never smokers: • Passive smoking • Radon • Others: asbestos, unprocessed solid fuels

Scheme linking nicotine addiction and lung cancer via tobacco smoke carcinogens and their induction of multiple mutations in critical genes

Cigarette smoking nicotine addiction

Metabolic activation

PAH, NNK and Other carcinogens

Excretion

– Greater than 2 fold increased risk – Predominance of non small cell lung ca

Persistence miscoding

DNA adducts

Metabolic detoxification

• HIV and Lung Cancer

Mutations and other Changes: RAS, MYC, p53, p16, RB, FHIT, And other critical genes

Lung Cancer

• Adenocarcinoma • Squamouscell

Repair

Normal DNA

– Most are males – Median age of 45 years or less

Apoptosis

• HIV and Lung Cancer

• Acquired Lung Diseases and Lung Ca*

– Potential reasons for the increased risk:

– Diseases that obstruct airflow

• HIV acting as viral carcinogen • Defective immune surveillance • Recurrent opportunistic infections and parenchymal lung inflammations leading to inflammatory foci and scar carcinomas

• COPD

– Diseases that restrict lung capacity • Pneumoconioses • Presence of silicosis is associated with an increased risk

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• Screening for Lung cancer

Bronchogenic C arcinoma

– There is no role for screening for lung cancer, even in high risk individuals American Cancer Society US Preventive Services Task Force

Presenting Symptoms of Bronchogenic Carcinoma – Sputum cytology, chest radiograph – LD - CT

Symptoms

• The thinner the slice, the more noncalcified nodules are detected • Consistently detected NSCLC as stage IA in 60 – 90%of cases; major improvement in 5-year survival

Percentage of Patients

Cough

45 – 75%

Weight loss

8 – 68%

Dyspnea

37 – 58%

Hemoptysis

27 – 57%

Chest pain

27 – 49%

Hoarseness

2 – 18%

Clinical manifestations

Chest Radiograph

• Peripheral growth of primary tumor may cause: 1. pain from pleural or chest wall involvement (malignant pleural effusion) 2. cough 3. dyspnea 4. symptoms of lung abscess resulting from tumor cavitation

• Demonstrate the size of the tumor, especially in peripheral lesions

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Clinical manifestations

Chest Radiograph

• Central or endobronchial growth of primary tumor may cause: 1. Cough 2. Hemoptysis 3. Wheeze and stridor 4. Dyspnea 5. Post-obstructive pneumonitis(fever and productive cough)

Pancoast’s(Superior SulcusTumor) Syndrome

• Central tumors may be associated with atelectasisor obstructive pneumonitis.

Paraneoplastic Syndromes In Lung CA Syndrome

• Results from local extension of a tumor (usually Squamous cell CA) growing in the apex of the lung • Involve the 8th cervical, 1st and 2nd thoracic nerves • Present with shoulder pain that cha. radiates in the ulnar distribution of the arm • Often with radiologicdestruction of the 1st and 2nd ribs • Other problems of regional spread: - Superior vena cava syndrome from vascular obstruction - Precordial and cardiac extension w/ tamponade - Arrhythmia or cardiac failure - Lymphatic obstruction with pleural effusion - Lymphangitic spread through the lungs with hypoxemia and dyspnea

HistologicType

Endocrine and Metabolic Cushing syndrome SIADH Hypercalcemia Gynecomastia

Small cell CA Small cell CA Squamouscell CA Large cell CA

Connective tissue

Clubbing & hypertrophic pulmonary osteoarthropathy

Squamouscell, adenoCA, large cell

Neuromuscular

Peripheral neuropathy Subacute cerebeller degeneration, Myasthenia (EatonLambert), Dermatomyositis

Small cell CA Small cell CA Small cell CA All

Paraneoplastic Syndromes In Lung CA Cardiovascular

Thrombophlebitis Non-bacterial verrucous endocarditis

Adenocarcinoma

Hematologic

Anemia DIC Eosinophilia Thrombocytosis Acanthosis nigricans Erythema gyratum

All

Cutaneous

Staging of P rimary Tumor

All

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Primary Tumor

TNM Stagingfor NSCLC

Tx

Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washing but not visualized by imaging or bronchoscopy

T0

No evidence of primary tumor

T1

Tumor =3cm surrounded by lung or visceral pleura, not more proximal to the lobar bronchus Tumor =2 cm Tumor >2cm but =3cm

T1a T1b T2

T2a T2b

Primary Tumor

Tumor with any of the following features: * >3 cm but =7 cm in greatest dimension * involves main bronchus >2 cm distal to the carina * involves the visceral pleura * assoc with atelectasis or obstructive pneumonitisthat extends to the hilar region but does not involve entire lung Tumor >3 cm but =5 cm Tumor >5 cm but =7 cm

T1

TNM Staging

T3

Tumor >7 cm; or directly invading chest wall, diaphragm, phrenic nerve, mediastinal pleura, or Parietal pericardium Or tumor in the main bronchus ,< 2 cm distal to the carina; Or atelectasis, obstructive pneumonitis of entire lung; Or separate tumor nodules of same lobe

T4

Tumor of any size with invasion of the heart, gret vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; or separate tumor nodules in a different ipsilateral lobe

T2 1.8 cm.

4.2cm. spiculatedmass

T4

T3

Right apical carcinoma Negative for rib or vertebral destruction

Involvement of the carina

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Involvement of the great vessels

Chest Radiography • Inferior to CT in the detection of mediastinal lymph node metastases.

Staging of M ediastinal Lymph Nodes

*

Computed Tomography

• Use of spiral or multisection CT, thin (5-mm) sections with IV contrast material. • Normal-sized nodes may contain metastases and nodes may be enlarged due to inflammatory causes although they contain no malignant cells. • The short axis diameter is the most reliable measurement of lymph node size on CT scans. A short axis diameter of greater than 10 mm is abnormal regardless of the nodal station

*

NODAL ASSESSMENT:CT

• LYMPH NODE DIAMETER OF 1.0 CM IS USED TO DISTINGUISH NORMAL FROM ABNORMAL • SHORT AXIS DIAMETER OF NODE IS USED • SHORT AXIS MEDIASTINAL NODE CORRELATES MOST CLOSELY WITH THE ACTUAL NODE DIAMETER • UPPER LIMIT OF 1.5 CMS IS USUALLY USED FOR NODES IN THE SUBCARINAL REGION

Normal Size(Diameter) of Thoracic LNS < 6 mm •Anterior Mediastinum •AortopuimonaryWindow <15 mm <10 mm •Hilar •Subcarinal <10 mm < 7 mm •Para-aortic

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Regional Lymph Node • N0 - No lymph nodes involved • N1 - Ipsilateral bronchopulmonaryor perihilar , intrapulmonary nodes • N2 - Ipsilateral mediastinal nodes or ligament involved – – – – – – –

Upper Paratracheal & Lower Paratracheal Nodes Pretracheal and Retrotracheal Nodes Aortic and Aortic Window Nodes Para-aortic Nodes Para-esophageal Nodes Pulmonary Ligament Subcarinal Nodes

• N3 - contralateral mediastinal or hilar nodes involved (see or any scalene or supraclavicular nodes involved

Subcarinal Lymphadenopathy

Left Paratracheal Lymphadenopathy

Pre-carinal Lymphadenopathy

N3

Staging of Distant M etastases

X

Enlarged lymph nodes on both sides of the mediastinum, as well anterior to the trachea.

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Metastatic Involvement • M0 - No metastases • M1a – separate tumor nodules in a contralateral lobe;tumor w/ pleural nodules; malignant pleural dissemination • M1b- distant metastasis

Sonogram shows a 6 cm. right adrenal metastasis of lung cancer

Computed Tomography

1

Magnetic Resonance Imaging

3

2 *Contrast-enhanced MRI of the brain in a patient with known small-cell lung cancer (SCLC). Axial section at the level of lateral ventricles shows at least 2 ring-enhancing metastatic lesions in the periventricular region. The brain is one of the predominant sites for SCLC metastasis. *notes ni doc 

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Pulmonary metastases are usually more numerous in the lower zones than in the upper zones.

Hot spots due to bony metastases in the right second and ninth ribs.

TNM Staging of Non-small Cell CA STAGE

TNM subset

IA IB

T1a,b, N0 M0 T2a N0 M0

IIA

IIB

IIIA

T1a,b N1 M0 T2a N1 M0 T2b N0 M0 T2b N1 M0 T3 N0 M0 T3 N1 M0 T1-3 N2 M0 T4 N0,1 M0

IIIB

T4 N2 M0 T1-4 N3 M0

IV

Any T, any N, M1a,b

*

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

T4

T4

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Staging of Small Cell CA • Limited Stage - confined to one hemithoraxand regional lymph nodes (including mediastinal contralateral hilar, and ipsilateral supraclavicular nodes - Advanced stage - with involvement of contralateral hemithorax

CT Criteria for Resectability • Contact between mass and mediastinumof less than 3 cm • Circumferential contact between the mass and aorta of less than 90° • Presence of a fat plane between the mass and mediastinum

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CT Criteria for Non-Resectability • Involvement of the carina • Tumor surrounding, encasing, or abutting the aorta. Main or proximal portions of the right or left pulmonary arteries, or esophagusby more than 180°

The left hilar tumor extends to the carina, invades the left pulmonary artery, and is contiguous with the descending aorta over an arc of greater than 180°the stage is T4. The primary tumor is difficult to separate from the mediastinal lymphadenopathy (stage Nx) and from the distal atelectasis and pneumonitis. *notes ni Doc

Major contraindications to Curative surgery: • • • • • • • • •

Extrathoracic metastases Superior vena cava syndrome Vocal cord and phrenicnerve paralysis Malignant pleural effusion Cardiac tamponade Tumor w/in 2 cm from the carina Metastasis to supraclavicular lymph node Contralateral mediastinal node metastasis Involvement of main pulmonary artery

Summary of Treatment Approach to Patients with Lung Cancer

Treatment modalities

Stages IA, IB, IIA, IIB, and some IIIA NSCCA -Surgical resection for stages IA, IB, IIA, and IIB -Surgical resection with complete-mediastinal lymph node dissection and consideration of neoadjuvant CRxfor stage IIIA disease with "minimal N2 involvement" (discovered at thoracotomyor mediastinoscopy) -Postoperative RT for patients found to have N2 disease if no neoadjuvant CRxgiven -Discussion of risks/benefits of adjuvant CRxwith individual patients -Curative potential RT for "nonoperable" patients

Stage IIIA with selected types of stage T3 tumors: • Tumors with chest wall invasion (T3): en bloc resection of tumor with involved chest wall and consideration of postoperative RT • Superior sulcus(Pancoast's) (T3) tumors: preoperative RT (30-45 Gy) followed by en bloc resection of involved lung and chest wall with consideration of postoperative RT or intraoperative brachytherapy • Proximal airway involvement (<2 cm from carina) without mediastinal nodes: sleeve resection if possible preserving distal normal lung or pneumonectomy

Treatment modalities

Treatment modalities

StagesIIIA "advanced, bulky, clinically evident N2 disease" (discovered preoperatively) and IIIBdisease that can be included in a tolerable RT port: • Curative potential RT +CRxif performance status and general medical condition are reasonable; otherwise, RT alone • Consider neoadjuvant CRxand surgical resection for IIIA disease with advanced N2 involvement

Stage IIIBdisease with carinal invasion (T4) but without N2 involvement: • Consider pneumonectomywith tracheal sleeve resection with direct reanastomosis to contralateral mainstembronchus

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Treatment modalities

Treatment modalities

Stage IV and more advanced IIIBdisease: • RT to symptomatic local sites • CRxfor ambulatory patients • Chest tube drainage of large malignant pleural effusions • Consider resection of primary tumor and metastasis for isolated brain or adrenal metastases

SMALLCELLLUNG CANCER • RT for brain metastases, spinal cord compression, weight-bearing lytic bony lesions, symptomatic local lesions (nerve paralyses, obstructed airway, hemoptysis, intrathoracic large venous obstruction, in non-small cell lung cancer and in small cell cancer not responding to CRx) • Appropriate diagnosis and treatment of other medical problems and supportive care during CRx • Encouragement to stop smoking • Entrance into clinical trial, if eligible

Non-small Cell CA

Staging for Small Cell Lung Ca

• Early stage Lung Cancer

• Limited Disease (LD)

– Stage I and II

– Limited to one hemithorax

• surgical disease

• Supraclavicular and mediastinal lymphadenopathy

• Locally Advanced Lung Cancer – Stage IIIA and B

– Chemotherapy +radiotherapy

• Chemotherapy +radiotherapy

• Extensive Disease (ED)

• Metastatic Disease

– Any disease outside of the hemithorax – Chemotherapy

– Stage IV • chemotherapy

Solitary Pulmonary Nodule

Solitary Pulmonary Nodule

• An X-ray density completely surrounded by normal aerated lung, with circumscribed margins of any shape, ususually1-6 cm in greatest diameter • Approx 35%in adults are malignant (primary lung CA) • <1%are malignant in non-smokers under 35 years old

• Risk factors in favor of malignancy: 1. History of cigarette smoking 2. age =35 yrs, relatively large lesion 3. lack of calcification 4. chest symptoms- asso. atelectasis, pneumonitis, or adenopathy 5. growth of the lesion revealed by comparison with old CXR

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Solitary Pulmonary Nodule • Radiographic criteria which reliably predict a benign nature of solitary pulmonary nodule: 1. lack of growth over a period of >2 yrs 2. characteristic patterns of calcification: a. dense nidus b. multiple punctate foci c. “bull’s-eye” calcification- (granuloma) d. “popcorn ball” calcification(hamartoma)

Th e En d God Bless!

KDE, 2009

TNM Staging of Non-small Cell CA STAGE

TNM subset

IA IB

T1a,b, N0 M0 T2a N0 M0 T1a,b N1 M0 T2a N1 M0 T2b N0 M0

IIA

T2b N1 M0 T3 N0 M0

IIB

T3 N1 M0 T1-3 N2 M0 T4 N0,1 M0

IIIA

IIIB

T4 N2 M0 T1-4 N3 M0

IV

Any T, any N, M1a,b

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Primary Tumor

TNM Stagingfor NSCLC

Tx

Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washing but not visualized by imaging or bronchoscopy

T0

No evidence of primary tumor

T1

Tumor =3cm surrounded by lung or visceral pleura, not more proximal to the lobar bronchus Tumor =2 cm Tumor >2cm but =3cm

T1a T1b T2

T2a T2b

Primary Tumor

Tumor with any of the following features: * >3 cm but =7 cm in greatest dimension * involves main bronchus >2 cm distal to the carina * involves the visceral pleura * assoc with atelectasis or obstructive pneumonitisthat extends to the hilar region but does not involve entire lung Tumor >3 cm but =5 cm Tumor >5 cm but =7 cm

TNM Staging

T3

Tumor >7 cm; or directly invading chest wall, diaphragm, phrenic nerve, mediastinal pleura, or Parietal pericardium Or tumor in the main bronchus ,< 2 cm distal to the carina; Or atelectasis, obstructive pneumonitis of entire lung; Or separate tumor nodules of same lobe

T4

Tumor of any size with invasion of the heart, gret vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; or separate tumor nodules in a different ipsilateral lobe

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