Carcinogenesis & Cancer

Question 1

True or False: Of all cancers, lung cancer causes the most deaths

Answer 1

True (25% of all cancer deaths are lung cancer)

Question 2

For lung cancer etiology, what is the most common cause? What are some other causes?

Answer 2

Tobacco smoke

Active smoking 85-87%
Passive 3-5%
Radon 3-5%
Air pollution 0-5%
Other (genetic) 0-9%

Question 3

True or False: Lung cancer risk never falls back to normal no matter how long the smoking cessation

Answer 3

True. Risk improves greatly but never returns to normal risk of never-smokers.

Question 4

What is the 5 year survival for lung cancer?

Answer 4

17%

Question 5

What is the 5 year survival for small cell lung cancer?

Answer 5

6%

Question 6

True or False: lung cancer victims often don’t present with symptoms until later stages of cancer

Answer 6

True. Over 2/3 of patients present with non-surgical disease (Stage IIIA or worse), meaning that they can’t be treated with surgery.

Question 7

Approximately ___ % of patients with lung cancer diagnosis die within two years.

Answer 7

80%

Question 8

When respiratory epithelium is damaged by smoking, what histological change happens?

Answer 8

Squamous metaplasia. Which can be followed by dysplasia and formation of cancer (carcinoma in situ).

In other words, lung cancer can form as a response to the injury that happens in the airways.

Question 9

True or False: Lung function impairment shows greater risk for lung cancer incidence

Answer 9

True

Question 10

True or False: Chronic inflammation of lungs is a common theme for lung cancer development

Answer 10

True

Question 11

If you have COPD, you have a ____ fold increased risk for developing lung cancer

Answer 11

4-5 X

Question 12

Is there familial risk for lung cancer?

Answer 12

Yes.
1st degree relatives have about 2x risk
1st degree relative with onset at age less than 60 y/o have about 3.5x risk
2nd degree relatives have about 1.3 x risk
3rd degree relatives have about 1.1 x risk

Question 13

How can sputum help in diagnosing lung cancer?

Answer 13

It’s an easy sample to obtain and you can look at dysplastic cells in their sputum (from mild dysplasia through severe dysplasia and carcinoma in situ). The more abnormal cells in someone’s sputum, the greater incidence of lung cancer.

We can also do genetic testing on sputum to find identify gene methylation that causes cancer.

Question 14

What are the risk factors for lung cancer?

Answer 14

• history of smoking
• previous history of tobacco related cancer
• age, gender
• asbestos/radon exposure
• family history
• airflow obstruction (COPD)
• sputum cytologic atypia

*in highest risk populations, yearly incidence of lung cancer approaches 2%

Question 15

What are the 2 main categories for lung cancer? Which is more prevalent?

Answer 15

Non-small cell lung cancer (87% of all lung cancers) and small cell lung cancer (13%)

Question 16

What are the 3 types of non-small cell lung cancer? Which is the most common?

Answer 16

Adenocarcinoma (40% of all lung cancers)
Squamous cell carcinoma (35% of all lung cancers)
Large cell (12% of all lung cancers)

Question 17

What markers can you stain for when looking for small cell lung carcinoma?

Answer 17

NCAM (neuroendocrine marker)

TTF-1 can be used to stain lung cancer cells in general

Question 18

How does TNM staging work?

Answer 18

T = size and location
N = number of nodes involved (higher #s also mean higher up)
M = metastasis

Question 19

What are two growth factors that we keep an eye out for when evaluating lung cancer treatment?

Answer 19

Epidermal growth factor (ERB1 or EGFR) is present in 50-80% of NSCLC (less than 5% of SCLC). Mutations in exons 18-21 in 10% (important for non-smokers or younger patients as their cancer is likely to be more genetic). There are drugs available to treat this growth factor problem but they are expensive (e.g. erlotinib/Tarceva)

Her2/neu (ERB-2)
10% NSCLC and less than 5% of SCLC. Drug available is trastuzumab (Herceptin)

Question 20

What does EGFR do? Is it increased or decreased in cancer?

Answer 20

Proliferation, invasion, inhibition of apoptosis, metastasis, angiogenesis. EGFR is over expressed in cancer.

Question 21

True or False: There can be dramatic and rapid response to EGFR inhibitor therapy

Answer 21

True, depending on mutation. We have specific drugs for specific gene mutations and the medications can really help patients dramatically if treatment fits.

Question 22

What is immunotherapy for cancer?

Answer 22

Using the immune system to fight the cancer.

E.g. Tumor cells down-regulate T-cell effector functions by binding PD-L1 to PD-1 receptors. For immunotherapy, antibody-mediated blockage of the binding of PD-L1 protein to PD-1 receptors restores T-cell effector functions.

Question 23

What’s the difference between nodules and masses?

Answer 23

Nodules are less than or equal to 3 cm

Question 24

What are solitary pulmonary nodules?

Answer 24

Lesions that are less than or equal to 3 cm in diameter
Round or oval with smooth contour
Surrounded by aerated lung
No satellite lesions
No associated atelectasis, pneumonitis, or regional adenopathy.

Question 25

What are the goals for evaluating solitary pulmonary nodules?

Answer 25

To expedite the resection of potentially curable lung cancer. To minimize resection of benign nodules

Question 26

What is the risk of solitary pulmonary nodule evaluation?

Answer 26

5-10% morbidity and mortality of nodule evaluation. We have to take the right patients to evaluation. We can do this by assessing risk factors such as nodule size, age, prior cancer history, tobacco use, smoking, COPD, asbestos exposure, nodule characteristics.

Question 27

True or False: nodule size is associated with likelihood of malignancy

Answer 27

True

Question 28

What are the ACCP evidence-based guidelines for solitary pulmonary nodules?

Answer 28

1. All previous CXRs should be reviewed 2. Stable for greater than 2 years does not need evaluation 3. Benign, central calcification does not need further evaluation (granuloma) 4. Spiral chest CT with contrast 5. If nodule is greater than 8mm, estimate a pretest probability of cancer 6. SPN in marginal candidates, PET, if negative and repeat CT in 3 months (glucose taken up by nodules) 7. If growth on serial imaging, proceed to non-surgical biopsy and/or surgical resection 8. All resections must include a lymph node dissection 9. Lobectomy is preferred over wedge or segmentectomy.

Question 29

True or False: The bigger the solitary pulmonary nodule size, the greater the risk for malignancy and the more frequent you need to follow up with imaging and evaluation

Answer 29

True

Question 30

What if you see ground glass/hazy appearance solitary nodules?

Answer 30

You want to follow them for longer because they may be slower growing cancers. (up to 36 months)

Question 31

What are the goals of lung cancer screening?

Answer 31

Diagnosis at an early age, reduction of lung cancer mortality.

Question 32

What imaging techniques are used for lung cancer screening and which is the best?

Answer 32

CT is the best but you have to consider balancing the amount of radiation given and the quality of imaging. CXR Sputum cytology Autofluorescence bronchoscopy

Question 33

What did the NLST trial show?

Answer 33

CT screening prevented 20% more mortality than CXR screening. 6.7% all cause mortality reduction 320 persons screened with LDCT to prevent one death The difference between the two groups was nearly completely accounted by higher incidence of stage IA. This means that CT found cancers earlier so they could be treated earlier.

Question 34

What is lead time bias?

Answer 34

If two patients have lung cancer and both die at the same age, the patient who was diagnosed earlier has a longer "survival time" because survival time is from age of diagnosis until death. This bias makes it seem like the earlier you are diagnosed the longer you have to live, but you have to consider lead time bias.

Question 35

What are PET scans for?

Answer 35

PET scans should be used on nearly all NSCLC patients to evaluate for mediastinal and extra thoracic metastases. Ground glass opacities of less than 2 cm do not require PET scan for staging. Patients with peripheral stage T1A tumors do not need PET scans.