tumor growth and clinical presentation
for a single malignant cell with a doubling itme of 3-4 months to grow to a 1 cm nodule, it would take about 7-10 years
therefore, 75% of the life history of the cancer is in the undetectable stage
major pathologic cell types of lung cancer
small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma
the latter three have overlapping clinical behaviors and are often grouped into non-small cell lung cancer (NSCLC) - 80% of all lung cancers
general characteristics of small cell lung cancer
strong relationship to cigarette smoking
only about 1% occur in nonsmokers
no known preinvasive phase or carcinoma in situ
the most aggressive of lung tumors, metastasize weidely, and are virtually incurable by surgical means
genes frequently mutated in small cell lung cancer
p53 and RB1 tumor suppressor genes
high levels of anti-apoptotic protein BCL2
low frequency of expression of the pro-apoptotic protien BAX
presentation of small cell lung cancer
central mass and lymphadenopathy
highly sensitive to chemotherapy and radiation initially - patient starts to deteriorate after 6-9 months
limited stage - lymph nodes and mass encopassable in one radiographic port
extensive stage - everything else
treatment for SCLC
LS (1/3) -> radiation/chemotherapy
ES (2/3) -> chemotherapy
T component of TNM staging
The ‘T’ component reflects the tumor size and invasiveness. T values range from 0 to 4; T0 indicates no evidence of primary tumor, while T4 indicates extensive extrapulmonary extension.
N component of TNM staging
The ‘N’ component indicates the absence or presence and extent of regional lymph node metastasis. N values range from 0 to 3; N0 indicates no regional lymph node metastasis, while N3 indicates metastasis to contralateral hilar and ipsilateral and contralateral supraclavicular/scalene lymph nodes.
M component of TNM staging
The ‘M’ component defines the absence or presence of tumor spread to distant lymph nodes or organ sites. M values range from 0 to 1; M0 disease indicates no distant metastasis, while M1 indicates the presence of distant metastasis.
strategies for screening lung cancer
chest x-rays
sputum analysis
CT scans
advantages of lung cancer CT screening
increases detection of early-stage lung cancer
improves lung-cancer specific and overall mortality in a high risk population
most realistic strategy or improving lung cancer mortality
disadvantages of lung cancer CT screening
high positive rate
benefits may not extrapolate to lower risk populations
long-term risk of repetitive radiation exposure
cost
Stage I and treatment
tumor of any size is found only in the lung
treatment - surgery
Stage II and treatment
tumor has spread to lymph nodes associated with the lung
surgery/chemotherapy
Stage IIIA and treatment
tumor has spread to the lymph nodes in the tracheal area, including chest awall and diaphragm
combination of surgery, radiation, and chemotherapy
Stage IIIB and treatment
tumor has spread to the lymph nodes on the opposite lung or in the neck
combination of chemotherapy and radiation
Stage IV and treatment
tumor has spread beyond the chest
chemotharapy and/or palliative (maintenance) care
criteria for surgery in stage I/II NSCLC
predicted FEV1 after pneumonectomy is 1.2L
patient is not hypercapnic
patient does not have cor pulmonale
adjuvant therapy
treatment to keep cancer from returning
patients with resectable disease are the only group likely to be cured of their cancer
pulmonary manifestations of lung cancer
cough from endobronchial erosion and irritation
dyspnea
chest pain
hemoptysis
postobstructive pneumonia or pneumonitis
large tumors may cavitate and present as lung abscesses
pulmonary manifestatiosn of centrall located lung tumors
stridor
wheezing
hemoptysis
dyspnea
chest pain in the central location
manifestations of intrathoracic disease
hoarseness from invasion of the recurrent laryngeal nerve and resultant vocal cord paralysis
dysphagia as a result of esophageal compression
superior vena cava syndrome
shoulder arm pain from superior sulcus due to local extension of a tumor in the apex of the lung that compresses the nerves
ipsilateral Horner syndrome
superior vena cava syndrome
characterized by plethoric apperance, distension of the venous drainage of the arm and neck, edema of the face, neck and arms
collateral venous drainage may also form
dilated veins over anterior chest
ipsilateral Horner syndrome
characterized by ptosis, meiosis, and anhydrosis due to paravertebral extension and sympathetic nerve involvement of the tumors
paraneoplastic syndromes as a result of lung cancer
cytokin-mediated responses to antigens from the intrathroacic lung tumor rather than the result of distant spread of cancer
manifestations of clubbing, hypertrophic osteoarthropathy, and neurologic and hormonaal abnormalities
mainfestations of extrathoracic disease in lung cancer
most common are anorexia, weight loss, and fatigue
bone pain accompanies mets tot he bone
CNS involvement is low with cancer that has not spread to the lymph
patients with signs of mediastinal or distant involvement, the risk of occult brain mets increases
the adrenal gland is the most frequent site of distant mets of lung cancer
treatment paradigms for advanced NSCLC
2-drug platinum-based chemotherapy improves survival and quality of life in patients iwht good PS
chemo is better than supportive care
2 drugs better than 1 drug
3 drugs not better than 2 drugs
treatment should be limited to 4-6 cycles of chemo
hallmarks of cancer
self-sufficiency in growth signals
insensitiveity to antigrowth signals
tissue invasion and metastasis
limitless replicative potential
sustained angiogenesis
evading apoptosis
targeted therapy in oncology
goal is to identify anti-tumor agents that target tumor-specific molecules and spare normal cells
ideal targeted therapy drug target
drives tumor growth
turns on key mechanisms of cancer progression
reversible by inhibition
dispensable in normal cells
target is measureable in tumor tissue used for diagnosis
Erlotinib
quinazolinamine-derived small-molecule inhibitor of the EGFR kinase
inhibits the intracellular phosphorylation of the tyrosine kinase associated with EGFR
the mechanism of clinical antitumor action of erlotinib is not fully characterized
EGFR
epidermal growth factor receptor, also called ErbB1
a transmembrane receptor tyrosine kinase of human epidermal growth factor receptor (HER)
dimerizes to become activated after ligand binding
activation contributes to cell division, migration, adhesion, and survival
Gefitinib
similar to erlotinib
EGFR tyrosine kinase inhibitor
EML4-ALK fusion mutation
associated with adenocarcinoma histology
fusion results in activation of tyrosine kinase that enhances cell proliferation and survival
about 25% of all lung cancers in never-smokers
crizotinib
small molecule tyrosine inhibitor
approved in 2011 for treating tumors that possess the EML4-ALK fusion protein
bevacizumab
a monoclonal antibody to vascular endothelial growth factor (VEGF)
neutralization can inhibit tumor vascularization and block tumor growth
useful for patients with non-squamous NSCLC
Pancoast's Tumor
superior sulcus tumor
usually squamous cell
usually initial symptoms are pain, sometimes upper extremity weakness
invasion of brachial plexus, 40%
Lambert-Eaton Syndrome
a syndrome that falls under paraneoplastic syndrome
similar to myasthenia gravis clinically
proximal muscle weakness and gait disturbance
strength increased with exercise
characterized by antibodies directed against voltage-gated calcium channel and interfere with normal calcium flux necessary for release of ACh
hypertrophic osteoarhopathy
thoracic malignancy is the most common cause
pain is often present
more common with adenocarcinoma
clubbing is often the first clue