Lung Neoplasms

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Lung Neoplasms

• Danielle Press,MD

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Epidemiology

• Decreasing incidence in men, stable incidence in
  women
• Men 83.5 in 100,000
• Women 49.2 in 100,000
• Decline likely due to public health initiatives
  to stop smoking
• Death rates decrease to that of nonsmokers 10yrs
  after cessation

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Tumor Biology

• Many mechanisms
• Chromosomal loss of heterzygosity or allelic gain
  
• K-ras, myc, p53 mutations
• Inactivation of tumor suppressor p16INK4a (p16)
• EGF receptor mutations possibly important to
  response to chemotherapy

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Non-Small Cell Lung Cancer (NSCLC)

• Evaluate for distant mets
• Brain, contralateral lung, supraclavicular nodes,
  bone, liver, adrenals
• Labs CBC, BMP, Ca, alk phos, LDH
• CT or PET
• CT chest/upper abd to evaluate tumor lymph node
  status
• Mediastinoscopy gold standard fro tissue
  diagnosis of mediastinal lymphadenopathy

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TNM Staging Non Small Cell Lung Cancer

• T1 lt3cm, surround by lung or visceral pleura, no
  invasion of main bronchus
• T2 gt3cm, involves main bronchus but gt2cm distal
  to carina invades visercal pleura atelectasis
  or obstructive pneumonitis that extends to hilar
  region but does not involve entire lung
• T3 Any size that directly invades any of these
  chest wall, diaphragm, mediastinal pleura,
  parietal pericardium tumor in main bronchus lt2cm
  from carina but no involvement of carina
  atelectasis or obstructive pneumonitis of entire
  lung
• T4 Any size that involves any of these
  mediastinum, heart, great vessels, trachea,
  esophagus, vertebral body, carina malignant
  pleural or pericardial effusion satellite tumor
  nodule with ipsilateral primary tumor lobe

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TNM Staging

• N0 No regional lymph node mets
• N1 Mets to ipsilateral peribronchial and/or
  ipsilateral hilar lyph nodes and involvement in
  intrapulmonary nodes by direct extension of
  primary tumor
• N2 Mets to ipsilateral mediastinal and/or
  subcarinal lymph nodes
• N3 Mets to contralateral mediastinal,
  contralateral hilar, ipsilateral or contralateral
  scalene, or suprclavicular lymph nodes
• M0 No distant mets
• M1 Distant mets present (including metastatic
  tumor nodule in ipsilateral non-primary tumor
  lobe of the lung)

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TNM Staging

• Grouping TNM staging
• Stage 0 Tis N0 M0
• Stage IA T1 N0 M0
• Stage IB T2 N0 M0
• Stage IIA T1 N1 M0
• Stage IIB T2 N1 M0
• T3 N0 M0
• Stage IIIA T1 N2 M0
• T2 N2 M0
• T3 N1 M0
• T3 N2 M0
• Stage IIIB Any T N3 M0
• T4 Any N M0
• Stage IV Any T Any N M1

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• N2 nodes
• 1-4
• Regional nodes
• 5-9
• N1 nodes
• 10-14

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Risk Assessment

• Comorbidities might prohibit surgical resection
• Age alone is not a contraindication to surgery
• Preop cardiovascular risk assessment is needed
• Preop spirometry, FEV1, DLCO, ABG, quantitative
  perfusion scanning, formal or informal exercise
  testing

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Treatment of NSCLC

• Stages I/II definitive staging pulmonary
  resection with negative margins
• Enbloc resection is adjacent structures are
  involved
• Peripheral tumors can be taken with non-anatomic
  wedge resection higher risk for locoregional
  recurrence (25-50)
• Central tumors should be treated with sleeve
  lobectomy rather than pneumonectomy when possible
  
• Nodal status should be confirmed systematic
  sampling vs nodal dissection

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Survival Rates of NSCLC

• 5-Yr Survival
• Stage I 60-70
• Stage II 40-50
• Stage IIIA 15-30

• Staging
• Histology needs to be further defined
• Squamous has better survival than non-squamous
  cancer
• Does not seem to influence survival in late stage
  tumors

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Patterns of Recurrence

• Predominant sites of relapse for all stages after
  resection are distant mets
• For all stages, brain is single most common site
  of relapse
• Other common metastatic sites
• Bone
• Ipsilateral or contralateral lung
• Liver
• Adrenal glands
• 60 recurrences in 1st 2yrs after resection
• Virtually of recurrences related to primary tumor
  occur within 5yrs of resection
• Risk of new second cancer 2-3 per year
• New, non-pulmonary cancer breast, colon,
  prostate

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Treatment of Stage III Disease

• Is locoregionally advanced disease
• Stage IIIB considered unresectable
• T4 or N3 disease has no role for resection
• Small series have shown resection with invasion
  of SVC, left atrium, or aorta after induction
  chemo to downsize has survival benefit
• Stage IIIA treatment is controversial complex

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Treatment of Stage IIIA

• Stage IIIA
• T1 N2 M0
• T2 N2 M0
• T3 N1 M0
• T3 N2 M0

• 5yr survival for N2 disease is 0-40, usually
  20-30
• Varies with mediastinal nodal involvement, size
  of primary tumor, ability to achieve complete
  resection
• Evidence suggests survival benefit for pts
  receiving preop chemo

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Stage IIIA Neoadjuvant Therapy

• Optimal treatment not yet fully defined
• Improved resectability survival with induction
  chemo vs resection or radiation alone
• Higher doses of radiation (gt5500 cGy) are
  associated with postoperative ARDS and bronchial
  stump leak

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Superior Sulcus Tumors

• Pancoast tumors
• Previously thought to be uniformly fatal
• Frequently involve brachial plexus, subclavian
  vessels, spine
• Usually T3 or T4 (Stage IIIA or IIIIB)
• Patients without N2 disease should have induction
  chemoradiation followed by resection

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Neuroendocrine Tumors

• Carcinoid
• Atypical carcinoid
• Small cell
• Large cell

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Typical Atypical Carcinoid Tumors

• Low-grade malignant potential
• About 2 of lung cancers
• From neuroendocrine stem cells of bronchial
  epithelium
• Atypical carcinoids
• Increased mitotic activity
• Increased nuclear pleomorphism
• Areas of disorganization of architecture tumor
  necrosis

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Carcinoid Tumors

• Presentation
• Hemoptysis
• Dyspnea
• Recurrent/persistent pneumonitis
• Diagnosis
• Bronchoscopy
• CXR
• Carcinoid syndrome only about 2, usually in
  pts with liver mets
• Common sites of mets lung, bone, liver,
  adrenals, brain

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Carcinoid Tumors

• Treatment is surgical resection
• Even in presence of nodal involvement
• Should include mediastinal lymph node sampling or
  dissection
• Lobectomy needed in 50
• Endoscopic resection is associated with local
  recurrence should only be palliative
• Long term surival gt90 after resection in typical
  carcinoid, 5yr survival after resection in
  atypical carcinoid 60
• Recurrence more frequent in tumors gt3cm with
  lymph node mets

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Large Cell Neuroendocrine Carcinoma

• Microscopoicly similar to neuroendocrine tumors
• Tumors are large, have high mitotic rate,
  frequently have necrosis
• High-grade tumors
• Related to smoking
• Survival w/resection 5yr 267, 10yr 9
• Management similar to NSCLC

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Small Cell Lung Cancer

• Most aggressive clinical course
• Often widely disseminated at diagnosis
• Responsive to chemotherapy
• Limited disease confined to one hemithorax and
  regional lymph nodes, ipsilateral pleural
  effusion (positive or negative cytology)
• Distant mets bone, liver, bone marrow, CNS
• lt10 SCLC is referred for surgical evaluation

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Small Cell Lung Cancer

• Response to chemoradiation
• Limited disease 85-90
• Extensive disease 75-85
• Chemo cisplatin, etoposide
• 2yr survival remains poor
• Role for resection in T1-2, N0-1 disease
• Adjuvant chemo usually given
• Relapse at primary site uncommon after resection

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Bronchial Gland Carcinomas

• About 1 of all lung neoplasms
• Also called primary salivary gland-type tumors or
  bronchial adenomas
• Centrally located tumors present with irritation,
  cough, SOB, hemoptysis, recurrent infection,
  wheezing, stridor
• Smoking not a risk factor
• Most dont metastasize
• Treatment is complete excision, preservin as much
  pulmonary tissue as possible

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Adenoid Cystic Carcinoma

• Slow growing malignant tumor arising from
  submucosal glands of the trachea main bronchi
• Tend to spread in the submucosal plane along the
  lymphatics
• Treat of choice is total resection
• Postoperative radiation is given
• Palliative treatment is endoscopic laser removal
  radiation

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Mucoepidermoid Carcinoma

• Low or high-grade malignancy
• Have same microscopic appearance as the salivary
  gland tumor
• Present as submucosal lesions
• Treatment is similar to carcinoid
• High-grade tumors have the same prognosis as
  bronchogenic carcinoma
• Complete surgical resection is the mainstay of
  treatment

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Mucous Gland Adenoma

• Rare, submucosal tumors arising from mucous
  glands
• Also known as bronchial cysts or papillary
  cystadenomas
• Benign tumor behavior
• Treated with endoscopic excision
• Surgical resection if endoscopic excision is
  contraindicated or incomplete or if distal lung
  is damaged by chronic infection

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Surgical Resection of Pulmonary Metastases

• First reported in 1926
• Historically done in pts w/complete resection of
  primary tumor, no evidence of recurrence or other
  metastatic disease, general good health
• Indications for resection of metastases have
  become more liberal

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Clinical Presentation Diagnosis

• Asymptomatic in 85
• CXR well-circumscribed spherical, solid mass
  with well-defined borders
• Usually arise from parenchyma
• Endobronchial mets from renal cell, colon, breast
• Hilar or mediastinal nodal involvement with
  pulmonary mets poor prognostic indicator
• Solitary lesion metastatic or new primary?
• More likely to be metastatic if primary lesion is
  sarcoma or melanoma
• More likely new primary if original tumor was
  head neck or breast

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Criteria for Surgical Resection

• Disease-free interval time from resection of
  primary tumor to diagnosis of mestastases
• Tumor doubling time measure of aggressiveness
  of tumor growth
• Number of metastatic nodules considered
  predictive of survival
• Resection should only be undertaken if complete
  resection is considered feasible
• Not every metastatic lesion should be resected
  some nodules indicate disseminated disease even
  if pulmonary nodule is solitary (breast)

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Metastatectomy Primary Disease/Recurrence

• Metastatic lesion recurrence at primary site
• Resect recurrent primary first
• Primary tumor metastatic disease diagnosed
  simultaneously
• Resect metastatic disease first if primary tumor
  might not be completely resectable

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Preoperative Evaluation

• Similar to that for pulmonary resection for
  primary cancer
• Pulmonary function post-chemotherapy may be
  substantially reduced
• Bleomycin mitomycin diminish DLCO cause
  ARDS-like picture postop (prevent by using lt35
  FiO2 intraop)
• Preop cardiac evaluation necessary, especially in
  pts receiving doxorubicin
• Avoid surgery while pt is neutropenic or
  thrombocytopenic

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Surgical Technique

• Two priniciples
• Complete resection of disease
• Maximal sparing of functioning lung tissue
• Anterolateral or posterolateral thoracotomy for
  unilateral disease
• Bilateral disease should be resected
  simultaneously if possible
• Median sternotomy or clamshell incision
• VATS doesnt allow palpation of lung its role
  is questioned in resection of metastatic disease
• Repeat metastatectomy for recurrent disease is
  beneficial

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Results
Primary Cancer 5-Year Survival
Renal Cell 54
Head Neck Cancer Squamous cell Glandular tumors Overall 34 64 50
Colorectal Cancer 44
Soft Tissue Sarcoma Incomplete resection No resection Unknown Overall 46 23 17 25
Testicular Germ Cell Tumors 68
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Benign Tumors of the Lung
Epithelial Mesen-chymal Muscle Misc Other Inflam-matory
Polyps Sclerosing hemangioma Leiomyoma Hamartoma Lipoma Plasma cell granuloma
Papilloma Lymphagioma Teratoma Chondroma Pulmonary hyalinizing granuloma
Mucous gland adenoma Granular cell tumor Clear cell tumor Fibroma
Neurilemoma
Neurofibroma
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Hamartoma

• Most frequent benign tumor
• 75 of benign lesions
• Most frequent component is cartilage
• Extremely slow growth
• Do not require excision unless centrally located
  cause symptoms of obstruction, etc or carcinoma
  cant be ruled out

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Other Benign Tumors

• May present as endobronchial lesions
• May be removed endoscopically
• Surgical excision when diagnosis is in doubt or
  when endoscopic excision has been incomplete
• Peripheral tumors are often removed for diagnosis