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Lung Cancer
Aka: Lung Cancer, Lung Carcinoma, Bronchogenic Carcinoma
- See Also
- Non-Small Cell Lung Cancer
- Small Cell Lung Cancer
- Epidemiology
- Lung Cancer is the top U.S. cause of cancer death
- Lung Cancer accounts for 27% of all U.S. cancer deaths
- Lung Cancer accounts for 33% of overall mortality in heavy smokers
- Humphrey (2013) Ann Intern Med 159(6): 411-20 [PubMed]
- Exceeds deaths from combination of 3 cancers
- Colon Cancer
- Breast Cancer
- Prostate Cancer
- Incidence: 200,000 in U.S. (2010)
- Mortality: 160,000 in U.S. (2010)
- Age at diagnosis: 68 to 70 years old on average
- Pathophysiology
- Hematogenous seeding occurs at 1-2 mm
- Earliest detection of Tumor by CT Chest: 2 mm
- Tumor 1 cm size shed 3 to 6 million cells daily
- Risk Factors
- Tobacco Abuse (Relative Risk 10-30)
- Women: Tobacco directly linked in 90% of cases
- Men: Tobacco directly linked in 79% of cases
- Passive Smoke Exposure (Relative Risk 1.3)
- Highest risk with younger age at time of exposure
- Asbestos Exposure
- Relative Risk in non-smokers: 3-6
- Relative Risk in smokers: 60
- Other associated environmental exposures
- Radon Gas (Relative Risk: 3)
- Major and emerging factor in pathophysiology of Lung Cancer
- Causes 21,000 cases of Lung Cancer per year in the United States
- Arsenic (drinking water contaminant)
- Beryllium
- Beta Carotene ingestion
- Chromium
- Nickel
- Vinyl chloride
- Soot
- Air Pollution
- History of Chemotherapy (Relative Risk: 4.2)
- Chest ionizing radiation exposure
- See Cancer Risk due to Diagnostic Radiology
- History of chest Radiotherapy (Relative Risk: 5.9)
- Comorbid conditions
- Chronic Obstructive Lung Disease (Relative Risk: 2-3.1)
- Idiopathic Pulmonary Fibrosis (Relative Risk: 7)
- Tuberculosis
- Human Immunodeficiency Virus or HIV (Relative Risk: 2-11)
- Genetic factors
- Family History of Lung Cancer (Relative Risk: 2)
- Epidermal Growth Factor Receptor (EGFR) gene mutations (20% of Lung Adenocarcinoma)
- Targeted agents for EGFR inhibition (erlotinab) and Monoclonal Antibody (cextuximab) are available
- Types
- Non-Small Cell Lung Cancer or NSCLC (75-80% of Lung Cancers)
- Adenocarcinoma (40%)
- Peripheral Lung Cancers
- Squamous Cell Carcinoma (25%)
- Central Lung Cancers most often associated with Tobacco Smoking
- Large cell carcinoma (10%)
- Peripheral Lung Cancers
- Small Cell Lung Cancer or SCLC (15-20% of Lung Cancer)
- Central, large cancers with Lymphadenopathy
- Associated with paraneoplastic syndromes
- Other types (5%)
- Symptoms
- Symptoms present in 90% of Lung Cancer patients at the time of diagnosis
- Constitutional symptoms
- Fatigue (LR+ 2.3, LR- 0.76)
- Anorexia or loss of appetite (LR+ 4.8, LR- 0.84)
- Weight loss (LR+ 6.2, LR- 0.76)
- Cardiopulmonary symptoms
- Chest Pain and rib pain (50% of cases, LR+ 3.3, LR- 0.52)
- Persistent cough, especially with multiple evaluations (75%)
- Dyspnea (60%, LR+ 3.6, LR- 0.68)
- Hemoptysis (35% of cases, LR+ 13.2, LR- 0.81)
- Digital Clubbing (LR+ 55, LR- 0.96)
- Presentations: Intrathoracic spread (40% at diagnosis)
- Nerve injury
- Recurrent laryngeal nerve paralysis
- Hoarseness
- Weak cough
- Phrenic nerve lesion
- Left diaphragm elevated
- Dyspnea
- Brachial Plexus lesion
- Presents as Horner Syndrome (Ptosis, myosis, facial Anhidrosis)
- Associated with Pancoast's tumor (Shoulder Pain and muscle wasting C8-T3)
- Chest wall invasion
- Pleuritic Chest Pain
- Malignant Pleural Effusion
- Decreased breath sounds
- Dyspnea
- Malignant Pericardial Effusion
- Decreased heart sounds
- Cardiomegaly on Chest XRay
- Esophageal invasion or obstruction
- Dysphagia
- Superior Vena Cava Obstruction
- Facial swelling
- Upper extremity edema
- Plethora
- Presentations: Extrathoracic spread (33% at diagnosis)
- Long bone or Vertebral pathologic Fractures (up to 25% of cases)
- Bone Pain
- Includes spinal column
- Increased Alkaline Phosphatase
- Liver metastases (up to 60% of cases)
- Weakness
- Weight loss
- Anorexia
- Hepatomegaly
- Liver transaminases are paradoxically, rarely increased
- Brain metastases (up to 10% of cases)
- Headache
- Seizures
- Nausea or Vomiting
- Mental status change
- Lymph nodes
- Supraclavicular Lymphadenopathy
- Adrenal Glands (rare)
- Adrenal Insufficiency
- Skin (rare)
- Subcutaneous Nodules
- Presentation: Paraneoplastic Syndromes (10% at diagnosis, especially SCLC)
- Digital Clubbing (29% of cases, esp. NSCLC)
- Hypercalcemia (10-20% of cases)
- Parathyroid Hormone-related peptide production
- Hyponatremia (1-5% of cases)
- Syndrome of Inappropriate Antidiuretic Hormone or
- Atrial natriuretic peptide ectopic production
- Other uncommon to rare syndromes
- Cushing's Syndrome
- Adrenocorticotropic hormone (ACTH) ectopic production
- Hypertrophic pulmonary Osteoarthropathy (triad)
- Digital Clubbing
- Arthralgias
- Ossifying periostitis
- Lambert-Eaton myasthenia syndrome
- Muscle Weakness
- Paraneoplastic Encephalitis
- Mental status changes
- Diagnosis
- Precautions
- Molecular testing requires a significant amount of tissue
- Targeted therapies (advanced disease)
- Patients without prior smoking
- Squamous Cell Lung Cancer
- Findings that most significantly increase Lung Cancer likelihood
- Hemoptysis or Digital Clubbing
- Two or more symptoms present in combination
- Age over 40 years old
- Risk factors as above
- Bronchoscopy based procedures
- Bronchoscopy with Bronchial samples and biopsy
- Indicated for central tumors
- Test Sensitivity for central lesions: 88%
- Test Sensitivity for peripheral lesions: 70%
- Transbronchial needle aspiration
- Indicated in central lesions
- Electromagnetic navigation bronchoscopy
- Allows for bronchoscopy of peripheral lesions
- Endobronchial Ultrasound-guided transbronchial aspiration
- Indicated in paratracheal, subcarinal or perihilar lymph nodes
- Other non-invasive and less invasive measures
- Sputum Cytology
- Test Sensitivity for central tumors: 71%
- Test Sensitivity for peripheral tumors: 50%
- Lymph node or accessible metastasis biopsy or fine needle aspiration
- Indicated in palpable lymph node or metastasis
- CT-Guided Transthoracic needle aspiration
- Indicated in larger peripheral lesions seen on CT
- Test Sensitivity for peripheral lesions: 90%
- Pleural EffusionThoracentesis
- Send for Pleural Fluid cytology
- Pleural biposy may be considered when pleural cytology is non-diagnostic
- Surgery
- Video-assisted thoracic surgery
- Indicated in small, single, high-risk Nodules
- Thoracotomy
- Indicated for non-small cell carcinoma
- Lesion amenable to surgery
- Staging
- Non-Small Cell Lung Cancer
- See Non-Small Cell Lung Cancer for staging
- Small Cell Lung Cancer
- Limited: Lesion confined to ipsilateral chest
- Extensive: Metastases beyond ipsilateral chest
- Labs: Evaluation for metastases
- Complete Blood Count
- Basic metabolic panel
- Serum Electrolytes
- Serum Calcium
- Serum Creatinine
- Blood Urea Nitrogen (BUN)
- Liver Function Tests
- Alkaline Phosphatase
- Aspartate Aminotransferase (AST)
- Alanine Aminotransferase (ALT)
- Imaging
- Chest XRay
- Does not exclude Lung Cancer if normal
- Obtain chest CT with contrast if high level of suspicion
- Evaluation for metastases
- Chest CT and Abdominal CT
- PET Scan (enhances staging by Chest CT)
- MRI Brain
- Indicated in all cases except Stage IA NSCLC
- Diagnostics: Functional Capacity
- Background
- Evaluation for lung resection
- Predictor of Chemotherapy tolerance
- Pulmonary Function Tests
- Initial Testing (FEV1, DLCO)
- Second-line testing (indicated for DLCO or FEV1 <80%)
- Cardiopulmonary Exercise testing
- Arterial Blood Gas sampling
- Eastern Cooperative Oncology Group Performance Status
- Grade 0
- Fully active and at predisease functional status without restriction
- Grade 1
- Ambulatory and able to perform light activity or sedentary work
- Restricted in physically strenuous activity
- Grade 2
- Ambulatory and able to perform self care
- Ambulatory >50% of working hours
- Unable to perform work activity of any kind
- Grade 3
- Able to perform self-care
- Confined to bed or chair >50% of waking hours
- Grade 4
- Completely disabled
- Unable to perform self-care
- Confined to bed or chair
- Prevention
- Prevention
- Tobacco Cessation
- Tobacco exposure is the predominant cause of Lung Cancer
- Never smoking is the best way to prevent Lung Cancer
- Consider Radon Gas testing in the home
- Screening
- Indicated in age 55 to 80 years old with 30 py Tobacco use (ongoing or quit in last 15 years)
- Screen with annual low dose CT chest
- Advantages
- Number Needed to Screen in 5 years to prevent one death: 312
- All cause mortality Relative Risk Reduction: 6.7%
- Disadvantages
- Cummulative radiation and cost ($12 billion/year) with annual screening will be substantial
- High False Positive Rate with screening (96%) will require significant resources to evaluate
- Despite USPTF recommendation for screening, other organizations, such as AAFP do not recommend
- References
- Aberle (2011) N Engl J Med 365(5): 395-409 [PubMed]
- Gates (2014) Am Fam Physician 90(9): 625-31 [PubMed]
- Kovalchik (2013) N Engl J Med 369(3): 245-54 [PubMed]
- USPTF Lung Cancer screening guidelines
- http://www.uspreventiveservicestaskforce.org/uspstf/uspslung.htm
- Prognosis
- Five year survival >50% for localized Non-Small Cell Lung Cancer
- Five year survival survival <5% for distant metastases
- See staging and prognosis calculator link below
- Resources
- Harvard Lung Cancer risk calculator
- http://www.diseaseriskindex.harvard.edu/update/
- Staging and Prognosis Calculator
- http://staginglungcancer.org/calculator
- NCI Adult Cancer Treatment
- http://www.cancer.gov/cancertopics/pdq/adulttreatment
- References
- Beckles (2003) Chest 123(1 suppl): 97S-104S [PubMed]
- Hamilton (2005) Thorax 60(12): 1059-65 [PubMed]
- Latimer (2015) Am Fam Physician 91(4): 250-6 [PubMed]