Pulmonary - Lung Cancer

7/27/2019 Pulmonary - Lung Cancer

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Lung Cancer

Kimberly M. Baker, MD

Division of Pulmonary, Critical Care, &Occupational Medicine


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Objectives

Epidemiology Screening Risk Factors Solitary Pulmonary Nodules

Pathology Presentation Diagnosis/Staging


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Lung Cancer Stats

2007 cancer deaths: Lung cancer #1: 160,000 Breast, colorectal & prostate combined: 120,000

Women Surpassed breast cancer early in last decade 1997: ~50% more women died from lung ca vs.

breast ca (66,000 vs. 44,000)

Aging pop means absolute #s will increase


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U.S. Cancer: INCIDENCE by

Leading Sites 2002

Lung and Bronchus 14 %

Prostate 30%

Colon and Rectum 11%

Bladder 7%

Lung and Bronchus 12

BREAST 31% Colon and Rectum 12%

Uterus 6%

CA Cancer J Clin 2002; 52:23-47.


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U.S. Cancer: MORTALITY

Leading Sites 2002

Lung and Bronchus 31 %

PROSTATE 11 %

Colon and Rectum 10%

Bladder 3 %

Lung and Bronchus 25%

BREAST 15 % Colon and Rectum 11 %

Uterus 2 %

CA Cancer J Clin 2002;52:23-47

All other sites 40 %

All other sites 41 %

Pancreas 6% Pancreas 5%


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Lung Cancer World-Wide (2004)

Iowa - 2192 new lung cancer cases16,620 total new cancer cases

US - 173,770 new lung cancer cases1,368,030 total new cancer cases

World-wide - 1.04 million cases (1990)12.8% of total new cancer cases,Incidence=37.5 (M) and 10.8 (F)per 100,000 population


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Lung Cancer Stage, US National

Cancer Database, 1985-94

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

Stage 1 Stage 2 Stage 3 Stage 4

Fry, 1999, Cancer; 86:1867-76


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Lung Cancer Screening

Which of the following decrease mortality in lung CA Chest X-ray

Does not decrease mortality

Sputum cytology Does not decrease mortality

Computerized Tomography Does not decrease mortality

In high risk pts referral to study may be appropriate Bottom-line no screening has been shown to

decrease mortality

ACCP Lung Cancer Guidelines 2003


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Lung Cancer: Who Gets It?

Lung Cancer is UNIQUE among allmalignancies in having a SINGLErisk factor which accounts for thehighest percentage of attributablerisk: :

TOBACCO. A preventable cause of disease

Rad Clin N Am, 2000, 38: 453-470


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Risk Factors for Lung Cancer

Cigarette Smoking, Cigarette Smoking Cause of 90% of lung cancers Increases risk - 10-20x compared to lifetime

nonsmoker Additional risk factors

Environmental (second hand smoke) Asbestos Radon Arsenic Ionizing radiation

Others (scarring, familial and dietary factors)


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Tobacco and Lung Cancer Risk

Tobacco smoke = 90% of lung cancer risk STRENGTH of relationship established by

consistency of studies clear dose-response relationship biologic plausibility

RELATIVE RISK range 5 to 29 depending on

age, race, gender, family history, concurrentexposures. Generally: male smokers: 22.1 relative risk

female smokers: 11.9


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Lung Cancer is an EnvironmentalProblem

Smoking28% of US men and 32% of US women smoke

Smoking accounts for 80-90% of pulmonary malignancies

Risk from smoking is cumulative and duration dependentproducing a dose-dependent relationshipSynergistically interacts with other risk factors

Relative Risk of Cancer due to SmokingMale Cigarette Smokers 22.4

Female Cigarette Smokers 11.9Cigar Smokers 5.6Pipe Smokers 1.6


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Passive Smoking/Sidestream Smoke Contains similar constituents, but lesser amounts

compared to mainstream smoke Risk is unknown as no unexposed control group exists Difficult to document exposure levels, responder bias

Overall OR for lung cancer among passivesmokers 1.25 (95% CI) Case control studies 1.44 (95% CI)) Prospective Studies 30% increased RR from smoking spouse

Responsible for 17% of lung cancers in non-smokers (500-5,000 deaths/yr)


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Occupational Agents Associated with LungCancer

Radon (workplace) 3.3% increased RR

(non-workplace) 1% lifetime excess risk10-15% of all lung cancers Asbestos RR=1.4-1.76x risk alone, 59x risk 2,000 mesotheliomas/yr

with smoking 4-6,000 Lung Cancers/yr

Chloromethyl Ether Cadmium Arsenic ChromateFormaldehyde Terpenes

Talc


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Lung Cancer May be a BiologicProblem

Epidemiologic data - 2.4 fold risk of lung cancer inrelatives of patients with lung cancer

Modeling of epidemiologic data suggests;Mendelian pattern of co-dominant inheritanceRare autosomal geneCarriers have an early age of lung cancer onset

Accounts for 69%, 47%, and 22% of the cumulativeincidence of lung cancer up to 50, 60, and 70 yo


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Gender, Family and Lung Cancer

Women and Lung Cancer younger, less likely to be current or former

smokers, consumed fewer cigarettes, have moreadenocarcinoma, and survived longer

risk significantly increased regardless of smoking history if there is a positive family

history Genetic Risk of Lung Cancer

Multiple studies have demonstrated a familialclustering of lung cancer. RR 2.4

Ambrosone, 1993; Sellers, 1990; Ferguson 1990;Perrot 2000


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Solitary Pulmonary Nodule

Coin lesion Intraparenchymal lesion < 3cm

Lung lesion > 3cm = masses

1:500 radiographs contains nodule 90% are asymptomatic 150,000 per year Differential = neoplastic, infectious,

inflammatory, vascular, rheumatoid


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Solitary Pulmonary Nodule

Low risk follow q3-6 months on CT for 24 months If grows - resection

High risk surgical resection Intermediate individualize Referral to nodule expert if uncertain

Pulmonologist, thoracic surgeon

Variable Low Intermediate High

Diameter (cm) 20 cig/dayCessation 7 yrs < 7 years Never quit

Characteristics of nodule Smooth Scalloped Spiculated


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Types of Lung Cancer Non-Small Cell - 81.8%

Adenocarcinoma - 30.7%, most common, non-smoker , peripheral ,metastasizes early, histologically look for gland formation,

Bronchioloalveolar (adenocarcinoma subset)

Squamous Cell Carcinoma - 30%, central , smoker , bronchogenic, canachieve very large size, hemoptysis, frequently cavitate, commonlyassociated with hypercalcemia, histologically look for keratin,

Large Cell Carcinoma - 9.4% Carcinoid - 1%, Typical and Atypical

Small Cell - 18.2% Arises submucosally in the airways, quickly metastasizes to

mediastinal nodes and systemically, histologically look for monotonoustumor histology

Mesothelioma - < 1%


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Clinical Presentation of Lung

Cancer Only about 6-10% are asymptomatic at

time of diagnosis

Symptoms: Primary lesion Intrathoracic spread

Distant metastases Paraneoplastic syndrome


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Diagnosis of Lung Cancer History and Physical Exam

Asymptomatic 6% Symptoms from primary tumor 27%

Fatigue, lethargy 80-85% Cough 8-61% Dyspnea 7-40%

Chest Pain 20-33% Hemoptysis 6-31% Anorexia, weight loss 55-88% Hoarseness 3-13%

Dysphagia 1-5% Wheezing 2%

Signs Clubbing, HPO 6-13%

Pleural Effusion 12-33% Neurologic Changes 4-21%


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Lung Cancer Common MetastaticSites

Site SqCCa AdenoCaPleura 34 60Other Lung 21 60Heart 25 36Liver 25 41

Adrenals 25 50Bone 20 36Kidney 21 23Chest Wall 20 20CNS 18 37Esophagus 13 8

Sputum 3 6


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Symptoms Due to IntrathoracicSpread

Pleural effusion: dyspnea Pericardial effusion: dyspnea Hoarseness (2-18%)(left sided)

Superior Vena Cava (SVC) Syndrome (4%) Headache or fullness; physical findings Small cell ca most common cause

Brachial Plexis (Pancoast) Horners syndrome, rib destruction, atrophy of hand muscles, pain in C8, T1, & T2 nerve roots


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Distant Metastases Symptoms

Bone mets: pain Usually spine, also ribs, pelvis

Hepatic mets: weakness, wt loss

Poor prognosis Brain mets: lung is initial site (>70%)

symptomatic brain tumors Headache, N/V, focal neurologic signs, personality

change, confusion, seizures

Adrenal mets: asymptomatic 2/3 of adrenal masses are benign


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Clinical Syndromes in LungCancer

PARANEOPLASTIC SYNDROMES Systemic - cachexia, weight loss

Endocrine - Hypercalcemia, SIADH, CushingsSyndrome Neurologic - Eaton Lambert, Cerebellar

Degeneration, Peripheral neuropathy

Cutaneous - clubbing, HypertrophicOsteoarthropathy

Hematologic - Hypercoagulability, Anemia

Am J Resp Crit Care Med, 1997, 156:320-332.


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Diagnosis of Lung Cancer

Initial Evaluation: GOAL - DETERMINE LOCAL vs. METASTATIC

Disease COMPLETE History and Physical POSITIVE Findings - direct further evaluation

If initial comprehensive clinical evaluation isnegative, the likelihood of finding metastaticdisease on exhaustive imaging and testingwork-up is low


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Diagnostic Biopsy in Lung

Cancer Why Biopsy?

Exclude Nonmalignant Disease Differentiate Small Cell vs. Non-small Cell Staging Direct Palliative Therapy

What Lesion To Biopsy? Lesion which will result in most advanced stage


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How To Get Tissue for Diagnosis

Sputum Cytology

Transthoracic Needle Biopsy

Fiberoptic Bronchoscopy

Mediastinoscopy

Video-Assisted Thoracotomy / Wedge Resection


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Sputum Cytology

Diagnostic in 75% of

symptomatic central tumo No Staging Data


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Transthoracic Needle BiopsyDiagnosticRate:

60-95%Small LesionsDifficult

Diagnostic Rate:

40-70%

T4 if positivefor tumor cells

Thoracentesis


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Fiberoptic BronchoscopyEndobronchial view of normal LLL (left) and obstructing

tumor of lateral/posterior basal segments (right).Dx = squamous cell


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Cervical Mediastinoscopy and

VATS

Samples paratracheal and sub-carinalnodes. Used primarily for NODAL STAGING.

Overall safe, total complication rate 1-2%.


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Staging Lung Cancer, WHY?

Patient Prognostication

Guide Therapy

Standardize Communication

Multidisciplinary and Inter-disciplinarytreatment clinics

Research


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Staging NSC Lung Cancer -

The T factor T1 - < 3.0 cm, surrounded by lung T2 - >3.0 cm, or with atelectasis, pneumonitis, or

pleural involvement T3 - Invades chest wall, diaphragm, mediastinal

pleura, main bronchus within 2 cm carina. T4 - Mediastinal invasion, heart/great vessels,

malignant effusion. Satellite nodule.

Mountain. Chest 1997, 111:1710-17


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Staging - N and M factors

N0 - No node mets. N1 - Ipsilateral hilar N2 - Ipsilateral mediastinal or subcarinal

N3 - Contralateral mediastinal, hilar. Scalene or supraclavicular nodes.

M0 - no metastasis M1 - Distant metastasis including contralateral lung

Mountain. Chest 1997, 111:1710-17


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STAGE PARADIGM - Putting Itall Together

IA - T1 NOMO IB - T2 NOMO

IIA - T1 N1 MO IIB - T2 N1 MO, T3 NOMO IIIA - T3N1MO, T1-3

N2 MO IIIB - T4 NOMO, T1-

4N3 MO

IV - AnyT AnyN M1

FinalStage

T N

M

CommunicationTreatmentPrognosis

Mountain. Chest 1997, 111:1710-17


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Staging System

Small Cell Lung Cancer Limited - Confined to one hemithorax and

regional lymph nodes Extensive - Everything else


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Diagnostic Evaluation

Confirmation of tumor Type of tumor

Staging for surgical resection Nonsmall cell:

T= tumor characteristics (size, location, etc) N=nodes hilum, mediastinum

M= presence or absence of distant mets Small cell:

Disease limited to hemithorax or outside hemithorax

Functional evaluation: tolerate surgery?


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0

20

40

60

80

100

0 12 24 36 48 60

cIA (n=687)cIB (n=1,189)

cIIA (n=29)cIIB (n=357)cIIIA (n=511)cIIIB (n=1,030)cIV (n=1,427)

Survival Based on ClinicalStaging

S u r v

i v a

l ( % )

Time (Months)


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Treating Small Cell Lung Cancer

Limited Disease - Combined Chemotherapyand Radiation therapy

Goal : Cure Prognosis if treated 20-30% 5 year survival

Extensive Disease (majority of patients) - Palliative Chemotherapy +/- XRT Median Survival


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Non-Invasive Staging Chest X-Ray Tumor Size, Nodal Involvement

Computed Tomography Tumor Size, Nodal Involvement,Other nodules, Liver, Adrenals

Magnetic Resonance Suspected cord or Thoracic OutletImaging (Chest) Involvement

Blood Tests CBCLiver Function (AST, ALT, LDH)Chemistry (Alk Phos, Ca+)

Bone Scan Bone Metastasis Head CT/MRI If Suspected Brain Metastasis PET Scan Metabolic Assessment


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Diagnostic Procedures Sputum Cytology 66% sens 99% specific Bronchoscopy 60-80%

>2cm, central, 90%


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General Approach to Treatment

Small cell: chemotherapy/radiation Nonsmall cell:

Stage I: resection Stage II: resection +/- RadRx or chemo. Stage IIIa: resection and investigational protocol Stage IIIb or IV: unresectable; chemo; palliative Rx

Unresectable tumors compromising theairway: Laser bronchoscopy, cryotherapy, stents


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Conclusions

Lung cancer is the most deadly of cancers 160,000 deaths per year

Two general types of lung cancer Non-small cell - surgical - possible cure Small cell - chemotherapy - poor prognosis

Solitary pulmonary nodule Very common and found incidentally Risks to be assess and nodule followed.


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Questions?

Kim Baker

[email protected]


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References

Diagnosis and Management of Lung Cancer: ACCP Evidence-Based

Guidelines Chest 2003;Jan (123) suppl1s-337s

Solitary Pulmonary Nodule NEJM 2003

348:25 2535-42.

Documents

Pulmonary - Lung Cancer