pulmonary - lung cancer
TRANSCRIPT
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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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Lung Cancer is an EnvironmentalProblem
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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Lung Cancer is an EnvironmentalProblem
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
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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.