2013-09-23 Lung Cancer Flashcards
epidemiology of lung cancer
Not the most common cancer in either men or women, but lung cancer it is clearly the leading cause of cancer mortality for both men and women in the US.
- -Incidence is 1 in 12 for men and 1 in 18 for women who ever smoked (for ref: lifetime breast cancer incidence in women is 1 in 8)
- -Mortality increased throughout the 20th century.
risk factors for lung cancer
Cigarette smoking is responsible for about 80%, majority being NSCLC
- Radon is thought to be the 2nd leading cause in U.S.
- Workplace exposure to carcinogens such as asbestos, uranium, arsenic, and certain petroleum products at the
-Concurrent exposure to one of these carcinogenic agents and cigarette smoke dramatically increases the risk for developing lung cancer
natural history of lung cancer
3/4 of the life of a lung tumor cell is is subclinical.
- -needs to gain 10^8 cells before possibly visible w/ today’s imaging (i.e. when it is >0.5cm)
- -means most lung cancers exist for years before pt becomes symptomatic with small cell before ~6 yrs up to adenocarcinoma ~15 yrs (at time of dx)
typical presenting signs and symptoms of lung cancer
Local: cough, dyspnea, obstructive pneumonitis, hemoptysis, SVC syndrome, chest pain
General sx: weight loss, fatigue
Symptoms secondary to distant metastases
diagnostic work-up for lung cancer
staging work-up for breast cancer?
Diagnosis is by pathology only! (bronchoscopy, fine needle aspiration)
Staging work-up: H&P, CXR, CBC, chemistries, CT chest/upper abd, PET, bone scan (selected cases), MRI brain (selected cases)
What is meant by “targeted therapy” for lung cancer?
Targeted therapy does not = chemo therapy
–molecules made specifically for targets of that tumor
Nibs = tyrosine kinase inhibitors Mabs = monoclonal antibodies
Example targets (drug) in lung cancer
- -VEGF (Bevacizumab)
- -HER2 (Trastuzumab=Herceptin)
- -EGFR-Tyr Kinase inhib (Erlotinib)
- -anti-EGFR antibody (Cetuximab)
- -Angiogenesis (INF-a/b)
- -Signal transduction/cell cycle inhibitors (retinoids)
- -Gene therapy (Wild type p53)
- -Vaccines
There is a linear relationship between the number of cigarettes smoked and mortality. The number of
smoking-related deaths increase significantly when more than [how many?] cigarettes are smoked a day
20 cigs/day
What is the relationship between smoking and histological subtype of lung cancer?
- all subtypes much more common in smokers
- small cell and squamous cell much more common in smokers, rare in never-smokers
- adenocarcinoma (esp. bronchioloalveolar type) are the most frequently seen types in never smokers, yet, they are still more common in smokers.
Name some paraneoplastic syndromes associated with SCLC.
- Inappropriate secretion of ADH
- Ectopic ACTH secretion
3 .Neurologic-myopathic syndromes:
–Eaton-Lambert myasthenic syndrome (3%) = anti-VGCC (voltage-gated calcium channels) antibodies, low potential at rest, incrementing response on rapid repetitive nerve stimulation
–Anti-Hu = encephalomyelitis, limbic encephalitis; actually means improved survival - Neuropathy:
–Sensory
–Autonomic - intestinal pseudo-obstruction
Name some paraneoplastic syndromes associated with NSCLC.
- Cachexia - cytokines, maladaptive metabolism, pain, chemotherapy
- Hypercalcemia (PTH-related protein) - 12.5% - squamous cell carcinoma
- Skeletal-connective tissue syndromes – hypertrophic pulmonary osteoarthropathy (HPO - clubbing and
periostosis) – adenocarcinoma - Gynecomastia (hCG in large cell carcinoma) - positive pregnancy test in a male, very rare
SCLC
- Freq in U.S.?
- How aggressive?
- Prognosis and tx generally?
- Staging basics?
- Prognostic factors?
- Incidence = 40,000 (17%) of new u.s. cases of lung cancer/yr
- most aggressive; w/o tx —> death in 2-4mos
- Tx and Prog: Chemo (many work on SCLF; usually give two at a time) incr median survival 4- to 5-fold, w/ 10% remaining dz-free for over 2 yrs
- Staging - very simple
a. Limited stage – disease confined to the chest that can be included in a radiation port (~1/3 present in this stage w/ 20% 5-yr survival)
b. Extensive stage – everything else, including malignant pleural effusion (>60% present in this stage w/ only 2% 5-year survival) - Prognostic factors include: performance status, LDH and stage
NSCLC
- Freq in U.S.
- Subtypes?
- 80% of new US lung cancer cases, w/ appx 125,000/yr
- Subtypes of NSCLC include:
a. adenocarcinoma
b. squamous carcinoma
c. large cell carcinoma
What type of cells do large cell carcinomas originate from?
transformed epithelial cells (per Wiki)
What type of cells do small cell carcinomas originate from?
Small-cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing, smaller than normal cells w/ barely room for any cytoplasm. Some researchers identify this as a failure in the mechanism that controls the size of the cells.
[Lung small cell carcinoma] is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells (named for Friedrich Feyrter). Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones… (Per Wiki)
How is NSCLC staged?
- Stage I = tumor within the lung without spread to regional lymph nodes
- Stage II = tumor within the lung with spread to regional lymph nodes (intrapulmonary and hilar only)
- Stage III = tumor with spread to mediastinal lymph nodes
- Stage IV = spread with metastases outside the chest
