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Lung Cancer: Diagnosis, Staging, and Treatment

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Title: Lung Cancer: Diagnosis, Staging, and Treatment


1
Lung CancerDiagnosis, Staging, and Treatment
  • Eric D. Anderson, MD, FCCP
  • Director, Interventional Pulmonology
  • Associate Professor of Medicine
  • Division of Pulmonary, Critical Care, Sleep
    Medicine

2
Question 1
  • Which of the following statements about lung
    cancer in the United States is correct?

3
Question 1
  • A) There are more new cases of lung cancer each
    year than breast or prostate CA.
  • B) Survival of patients diagnosed with lung
    cancer has improved significantly in the past 20
    years.
  • C) There are more deaths each year from lung
    cancer than colorectal, breast, prostate
    pancreatic cancers combined.
  • D) More women die from breast cancer than lung
    cancer.

4
Answer 1
  • A) There are more new cases of lung cancer each
    year than breast or prostate CA.
  • B) Survival of patients diagnosed with lung
    cancer has improved significantly in the past 20
    years.
  • C) There are more deaths each year from lung
    cancer than colorectal, breast, prostate
    pancreatic cancers combined.
  • D) More women die from breast cancer than lung
    cancer.

5
Lung Cancer
  • Most common cause of cancer death in US
  • Overall 5 year survival of 15
  • More deaths by lung cancer than the next four
    most common cancers combined (Colorectal, Breast,
    Prostate, Pancreas)

6
Cancer Deaths in U.S.2007
7
Lung Cancer in the U.S.
  • Number of patients in the U.S. with lung cancer
    continues to rise
  • In 2007 estimated
  • 213,380 new cases
  • 160,390 deaths
  • American Cancer Society 2007.

8
Lung Cancer Risk Factors
  • Gender
  • Smoking history
  • Older age
  • Presence of airflow obstruction
  • Genetic predisposition
  • Occupational exposures

9
Lung Cancer and Gender
  • Male predilection, but changing rapidly
  • Increase in women smokers
  • In 2007
  • 55 Men
  • 45 Women

10
Age-Adjusted Cancer Death Rates (1930
-1988)Males Females
11
LUNG CANCER
Relationship to Smoking
Etiology
Tobacco Percent active 85-87 passive
3-5
12
Lung Cancer and Smoking
  • 90 of lung cancers attributed to smoking
  • However, only 20 smokers will develop lung
    cancer in their lifetime.
  • ? Death from other causes ie. CAD, COPD
  • Genetic predisposition
  • Risk decreases when stop smoking
  • Yet, 50 of new cases are former smokers

13
Occupational Exposures Linked to 3 - 15 of Lung
CancersProven Suspected
  • Arsenic
  • Asbestos
  • Bischloromethyl ether
  • Chromium
  • Mustard gas
  • Nickel
  • Polycyclic aromatic hydrocarbons
  • Ionizing radiation
  • Acrylonitrile
  • Beryllium
  • Vinyl chloride
  • Silica
  • Iron ore
  • Wood dust

14
Asbestosis Lung Cancer
  • Prolonged heavy exposure has relative risk
    between 2 - 10 of causing lung cancer.
  • Peak incidence 15 - 24 years after exposure.
  • Fiber type is important
  • Crocidolite amosite gt chrysotile
    anthophyllite.

15
Asbestosis Lung Cancer
  • Risk of smoking asbestos exposure is
    multiplied.
  • Mortality ratio
  • Nonsmoking asbestos worker 5.17
  • Smoker 10.85
  • Smoker asbestos worker 53.24

16
Relative Risk of Developing Lung Cancer
17
Lung CancerSymptoms at Presentation
  • Due to primary tumor
  • Cough, hemoptysis, chest pain, wheezing, dyspnea,
    fever.
  • Thoracic extension of tumor
  • Chest pain, SVC syndrome, hoarseness, dysphagia.

18
Lung CancerSymptoms at Presentation
  • Metastases
  • Lymph node enlargement, bone pain, neurologic
    deficits, skin subcutaneous lesions.
  • Systemic symptoms
  • Anorexia, weight loss, weakness, paraneoplastic
    syndromes
  • Patients often present with advanced disease due
    to lack of symptoms at early stages.

19
Question 2
  • A 65 year old male presents with a complaint of
    fevers, chills, a productive cough and scant
    hemoptysis. A CXR is obtained. What diagnostic
    test do you order next?

20
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21
Question 2
  • A) CT scan of the thorax with IV contrast.
  • B) Sputum cytology.
  • C) Flexible bronchoscopy.
  • D) CT-guided transthoracic needle biopsy.
  • E) Surgical resection.

22
Answer 2
  • A) CT scan of the thorax with IV contrast.
  • B) Sputum cytology.
  • C) Flexible bronchoscopy.
  • D) CT-guided transthoracic needle biopsy.
  • E) Surgical resection.

23
Lung CancerFindings on Chest X-ray
  • Nodule (lt 3cm) vs. Mass (gt 3cm).
  • Location
  • Peripheral (Adenocarcinoma) vs.
  • Central (Squamous).
  • Single or multiple (metastases).
  • Endobronchial obstruction.
  • Atelectasis of lobe or lung.
  • Pneumonia.

24
Lung CancerThe Chest X-ray
  • Hilar and mediastinal adenopathy.
  • Pleural effusions.
  • Elevated hemidiaphragm.

25
Lung CancerCT Scan of Thorax
  • Nodule details
  • Calcification, spiculation etc..
  • Evaluate extension into adjacent structures
  • Endobronchial, great vessels, pericardium etc..
  • Evaluation of adenopathy.
  • Upper abdominal pathology
  • Metastatic lesions in liver, adrenals, kidneys.

26
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27
Lung CancerSputum Cytology
  • Helpful for central lesions.
  • With three samples
  • 80 detection rate of centrally located tumors.
  • 50 detection rate of peripheral lesions.

28
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29
Lung CancerVideo Flexible Bronchoscopy
  • Excellent to evaluate endobronchial disease.
  • Brushings and bronchial biopsies are high yield
    for visible lesions.
  • Transbronchial biopsies of large peripheral
    lesions /- fluoroscopic guidance.
  • Evaluation of obstruction for stent placement
    brachytherapy.

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31
Lung CancerTransbronchial Needle Aspiration
(TBNA)
  • Allows biopsy of subcarinal paratracheal lymph
    nodes during flexible bronchoscopy.
  • Helpful for staging.
  • Minimal risk to patient.

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33
Lung CancerCT - Guided Transthoracic Needle
Biopsy
  • Peripheral lesions away from diaphragm.
  • 25 pneumothorax risk.
  • May be beneficial for poor operative candidates.
  • Remember
  • Negative needle biopsy result may be false
    negative.

34
Question 3
  • Patient is a 65 year old smoker with following
    CXR and CT scan of chest

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37
Question 3
  • What test do we order next?
  • A. CT-guided lung biopsy.
  • B. Video Assisted Thoracic Surgical open lung
    biopsy with possible lobectomy.
  • C. PET scan.
  • D. PFTs.
  • E. CT scan of head.

38
Answer 3
  • What test do we order next?
  • A. CT-guided lung biopsy.
  • B. Video Assisted Thoracic Surgical open lung
    biopsy.
  • C. PET scan.
  • D. PFTs.
  • E. CT scan of head.

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40
Answer 3
  • Mediastinoscopy or Transbronchial Needle
    Aspiration (TBNA)
  • would also have been an appropriate method of
    staging mediastinum.

41
Lung CancerPET Scan
  • Marker of active glucose metabolism.
  • Can detect lesions to 0.8cm.
  • 90 sensitivity 85 specificity.
  • Indications
  • Staging lung cancer.
  • Solitary pulmonary nodule.

42
PET Case
  • 85 yo male with h/o COPD and s/p LLL lobectomy in
    2003 for stage IA adenocarcinoma.
  • Follow up CT chest

43
PET/CT
44
Lung CancerOther Diagnostic Tests
  • Thoracentesis.
  • Surgical resection
  • Thoracotomy vs. VATS.

45
Staging of the Mediastinum
  • Mediastinoscopy
  • Mediastinal lymphadenopathy staging.
  • Central lesions.
  • Large peripheral lesions.
  • Gold Standard.

46
Newer Technologies
  • Endobronchial Ultrasound (EBUS)
  • Endoscopic Ultrasound (EUS)

47
Histology of Lung Cancers in U.S.
48
Adenocarcinoma
  • Most common cell type in US.
  • Peripheral location.
  • Glandular formation.
  • Mucin production.

49
Bronchoalveolar Cell Carcinoma
  • Subtype of adenocarcinoma.
  • Preservation of alveolar architecture.
  • Spread through the airways.
  • May present as unresolving pneumonia.

50
Squamous Cell Carcinoma
  • Cavitation.
  • Centrally located along airways.
  • Intravascular invasion.
  • Intercellular bridging.
  • Keratinization.

51
Squamous Cell Carcinoma
  • Keratin pearls.
  • Nests of cells.

52
Large Cell Carcinoma
  • A poorly differentiated carcinoma.
  • Diagnosis of exclusion.
  • Large cells.
  • Abundant cytoplasm.
  • Large nuclei with prominent or vesicular nucleoli.

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54
NonSmall Cell CancerT Stage
  • T1 lt 3cm in diameter, contained within
    visceral pleura.
  • T2 gt 3cm in diameter, gt 2cm away from carina,
    invading into visceral pleura, or lobar
    atelectasis
  • T3 any size, extension into chest wall,
    diaphragm, mediastinum, (but not great vessels)
    or lt2cm from carina or atelectasis of entire lung

55
NonSmall Cell CancerT Stage
  • T4 any size invading into great vessels, heart,
    trachea, esophagus, vertebrae, main carina or
    malignant pleural effusion.

56
NonSmall Cell CancerN Stage
  • N0 No nodes.
  • N1 Ipsilateral hilar or peribronchial.
  • N2 Ipsilateral mediastinal, subcarinal.
  • N3 Contralateral hilar, contralateral
    mediastinal or supraclavicular/scalene.

57
Non Small Cell Carcinoma Staging
58
Non Small Cell CASurvival Months after Treatment
CF Mountain. Chest. 1997 111(6).
59
Non Small Cell CASurvival Months after Treatment
CF Mountain. Chest. 1997 111(6).
60
Upcoming Changes
  • Satellite nodules ?T3
  • Malignant effusions. ?stageIV
  • Nodules in same lung but different lobe. StageIV?

61
Neuroendocrine Lung Tumors
  • Small cell carcinoma.
  • Atypical carcinoid.
  • Typical carcinoid.
  • Malignant
  • Intermediate
  • Benign

62
Small Cell Carcinoma
  • Aggressive tumor.
  • Smokers.
  • Centrally located.
  • Bulky adenopathy is common.
  • Distant metastases common on presentation.

63
Small Cell Carcinoma
  • Small cells.
  • Fine chromatin pattern.
  • Abundant mitosis.
  • Scant cytoplasm.
  • Tends to smudge on microscopy.
  • Synaptophysin chromogranin.

64
Carcinoid
  • Typical carcinoid
  • Usually endobrochial.
  • Present with postobstructive pneumonia.
  • Surgical resection is curative.
  • Atypical carcinoid
  • More aggressive.
  • May require surgery with chemotherapy.

65
Small Cell Lung CancerStaging
  • Limited
  • 30-40 of small cell lung cancers.
  • Confined to the hemithorax, mediastinum, and
    ipsilateral supraclavicular lymph node.
  • Within the confines of radiation port.
  • Extensive
  • 60-70 of small cell lung cancers.
  • Any distant spread.

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67
Lung CancerWhy the Poor Prognosis?
  • Survival statistics reveal the advanced stage at
    time of diagnosis
  • Presentation is often after the patient becomes
    symptomatic
  • Usually Stages IIIA/B or IV
  • These stages have poor long term survival
    lt 10 at 5 years

68
Lung CancerWhy the Poor Prognosis?
  • Successful surgical resection and cure are only
    possible at early stages
  • In U.S. only 20-25 of newly detected lung cancer
    is Stage I

69
Question 4
  • 60 yo male smoker with 4.1 cm solitary
    adenocarcinoma. What is the best option for
    treatment/survival?
  • Wedge resection.
  • Lobectomy.
  • Lobectomy with adjuvant chemotherapy.
  • Lobectomy with adjuvant radiation.
  • Lobectomy with adjuvant chemotherapy and
    radiation.

70
Answer 4
  • 60 yo male smoker with 4.1 cm solitary
    adenocarcinoma. What is the best option for
    treatment/survival?
  • Wedge resection.
  • Lobectomy.
  • Lobectomy with adjuvant chemotherapy.
  • Lobectomy with adjuvant radiation.
  • Lobectomy with adjuvant chemotherapy and
    radiation.

71
Non Small Cell Lung CancerTreatment
  • Stage IA
  • Lobectomy is treatment of choice.
  • T1N0, lobectomy has 70 5 year recurrence free
    survival.
  • If inoperable
  • 30 cure rate with XRT alone.
  • Stereotactic radiosurgery (CyberKnife).
  • Radiofrequency ablation.

72
Non Small Cell Lung CancerTreatment
  • Stage 1B
  • Lobectomy.
  • Adjuvant chemotherapy adds a 4-12 survival
    benefit. Best in tumors gt 4 cm.
  • NEJM 2004.
  • ASCO 2004.

73
Non Small Cell Lung CancerTreatment
  • Stage II
  • Lobectomy is treatment of choice.
  • Adjuvant chemotherapy now standard.
  • Consider adjuvant XRT to mediastinum

74
Non Small Cell Lung CancerTreatment
  • Stage III
  • Combination chemotherapy with XRT is treatment of
    choice.
  • Surgery has yet to be established consistently as
    benefit in randomized trials.
  • Neoadjuvant therapy followed by surgical
    resection is option in IIIA.

75
Non Small Cell Lung CancerTreatment
  • Stage IV
  • Chemotherapy.

76
Non Small Cell Lung CancerContraindications to
Surgical Resection
  • Stage IIIB or IV.
  • Extensive invasion into surrounding structures
  • Vena cava or atrium involvement.
  • Recurrent laryngeal or phrenic nerve involvement.
  • SVC obstruction, malignant effusion, pericardial
    tamponade.
  • Contralateral lymph nodes.

77
Non Small Cell Lung CancerContraindications to
Surgical Resection
  • Medically unfit
  • Poor cardiac or pulmonary status.
  • Predicted postoperative FEV1 lt 40.
  • Predicted postoperative DLCO lt 40.
  • Exercise studies for marginal candidates.

78
Chemotherapy Drugs
  • Non small cell
  • Two drug regimen.
  • Cis/Carbo platin 1 other (Taxol/Taxotere/Gemcita
    bine)
  • Small cell
  • Cisplatin / Etoposide

79
Biologic Agents
  • Avastin
  • Angiogenesis inhibitor.
  • Added to chemo.
  • Bleeding risk.
  • Contraindicated in squamous cell carcinoma.

80
Biologic Agents
  • Tarceva
  • Epidermal growth factor inhibitor.
  • Second line therapy.
  • Asian, never smoking, women, adenocarcinoma /
    bronchoalveolar cell CA.
  • PO.
  • Rash, diarrhea.

81
Small Cell Lung Cancer Treatment
  • Untreated 1.5 - 3 month median survival
  • Limited Chemotherapy with XRT.
  • 10-20 month median survival.
  • 5 year survival 10
  • Extensive Chemotherapy.
  • 7-11 month median survival.
  • 5 year survival lt 1.

82
Small Cell Lung Cancer Brain Irradiation
  • For known metastatic lesions.
  • Prophylaxis in both Limited Extensive disease.
  • Decreases the risk of developing brain
    metastases.
  • Improved survival.

83
Question 5
  • A 60 year old white male smoker without symptoms
    presents for a routine annual physical and a CXR
    is performed. What test do you order next?

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Question 5
  • A) CT chest with IV contrast.
  • B) CT-guided transthoracic needle biopsy.
  • C) Review prior chest X-rays.
  • D) Full body PET scan.
  • E) Surgical resection.

86
Answer 5
  • A) CT chest with IV contrast.
  • B) CT-guided transthoracic needle biopsy.
  • C) Review prior chest X-rays.
  • D) Full body PET scan.
  • E) Surgical resection.

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89
Evaluation of the Solitary Pulmonary Nodule
  • 25 have symptoms of cough, chest pain, or
    hemoptysis.
  • 75 asymptomatic.
  • Benign nodules
  • 23 Tubercular lesions
  • 14 Benign tumors (Hamartoma, neurogenic
    tumors, bronchial adenoma, mesothelioma)
  • 13 Others (Chronic pneumonia, echinoccoccal
    cyst, bronchogenic cyst, aspergilloma etc.)

90
Evaluation of the Solitary Pulmonary Nodule
  • Malignant nodules 49 of all SPNs
  • Primary lung cancer 38, metastatic cancer 9
  • Incidence of malignancy increases with age
  • Ages 35-39 3 are malignant.
  • Ages 40-49 15
  • Ages 50-59 42
  • Ages 60 50

91
Evaluation of the Solitary Pulmonary Nodule
  • Malignant Characteristics
  • Spiculations.
  • Irregular contour.
  • Eccentric calcifications.
  • gt 3 cm.
  • Benign Characteristics
  • Smooth round.
  • Well circumscribed.
  • Central, densely calcified, laminated, or
    popcorn.
  • lt 3 cm.

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94
Evaluation of the Solitary Pulmonary Nodule
  • Comparison to prior films
  • New? Enlarging? Change in shape?
  • Likely benign if no change in 2 years.
  • CT scan for better detail.
  • Removal if new, bigger, or changing.
  • CT-guided biopsy if not surgical candidate.
  • Sampling error may require surgical biopsy.

95
Evaluation of the Solitary Pulmonary Nodule
  • Close follow up (3 months) if benign appearance
    may be an option.
  • Consider PET scan.
  • Risk of waiting - may spread if malignant
    decrease survival.
  • Future? Superdimension 3D electromagnetic
    tracking/ virtual bronch

96
Solitary Nodule
  • Follow up CTs
  • 3, 6, 12, 24 months.
  • If stable at 2 years, no further follow up.

97
Common Paraneoplastic SyndromesSyndrome Freque
nt Histology
  • Hypercalcemia
  • SIADH
  • Cushings Syndrome
  • Eaton-Lambert
  • Squamous Cell
  • Small Cell
  • Small Cell
  • Small Cell

98
Question 6
  • A 55 year old former smoker is concerned about
    his risk for lung cancer and seeks your advice.
    Which of the following screening tests is
    recommended?

99
Question 6
  • A) Annual chest x-ray.
  • B) Sputum for cytology.
  • C) Spiral CT scan.
  • D) Flexible bronchoscopy /- flourescence.
  • E) None of the above.

100
Answer 6
  • A) Annual chest x-ray.
  • B) Sputum for cytology.
  • C) Spiral CT scan.
  • D) Flexible bronchoscopy /- flourescence.
  • E) None of the above.

101
NCI Cooperative StudyResults Mortality
Rates/1,000/year
  • No significant change in mortality was noted
  • Screening should not be offered to general
    population
  • However, CXR may be of benefit in an individual
    high risk patient

102
Lung Cancer ScreeningSpiral CT Scan
  • In preliminary studies, spiral CT detected higher
    numbers of Stage I lung cancers in patients at
    high risk.
  • However, many benign nodules were also discovered
    and required close follow up.
  • Some patients had surgery for benign disease as a
    result.
  • Three large studies look promising!

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Lung Cancer and Smoking
  • In North America
  • 50 million current tobacco smokers
  • 50 million former smokers
  • Primary prevention is key especially among the
    youth

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