Lung Cancer (2)

Question 1

What is the biggest risk factor for developing lung cancer?

Answer 1

Smoking (causes 80% of lung cancer)

Question 2

Lung cancer risk factors

Answer 2

Smoking, second hand smoke

Occupation - miners, heavy metal workers
Pollution exposure, radiation exposure

Family history

Chronic lung illnesses (COPD, TB, asthma)

Aging (more mutations, less repair)

Question 3

How does smoke exposure lead to lung cancer?

Answer 3

Smoke produces carcinogens which result in hyperplasia (more cells)
-some mechanisms will help excrete those extra cells but that only happens to a certain extent

Eventually dysplasia occurs (the cells start to look different, but still function the same)
-some cells will be repaired, others will undergo apoptosis

Eventually, cells will be miscoded and mutations will occur resulting in anaplasia (the cells look different and also do not function properly) = lung cancer
-mutations include mutations in p53 (tumor suppressor gene) and K-ras (these mutations increase tumor cell growth)

Question 4

Lung cancer prevention

Answer 4

Prevention is key

Do not smoke, or stop smoking
-risk decreases for every 5 years that you are smoke free
-and if you are smoke free for 15 years, risk decreases by 80-90%

The number of cigarettes smoked per day also has an effect… smoke less cigarettes per day to decrease risk

Question 5

What are the 3 types of lung cancer

Answer 5

1. Non small cell lung cancer (NSCLC)
   -most common
2. Small cell lung cancer (SCLC)
3. Squamous cell lung cancer aka carcinoid lung cancer (LCL)
   -rare

Question 6

Non small cell lung cancer (NSCLC)

Answer 6

This is the most common type of lung cancer

The growth rate is slow (meaning it does not have great response to traditional chemo/radiation, since that is more effective on fast growing cancer)

However, metastasis is likely because symptoms are non specific and it is not detected until later stages

EGFR, ALK, and ROS mutations may be present

Question 7

Small cell lung cancer (SCLC)

Answer 7

Not as common (10-15%)

Very aggressive, fast growing
-this means it has better response to traditional chemo/radiation

But, metastasis is likely because symptoms are non specific and it is not detected until later stages

p53 and K-ras mutations may be present

Question 8

Squamous cell lung cancer/carcinoid lung cancer (CLC)

Answer 8

This is very rare (<5%)

Slow growing (but faster than NSCLC)
-moderate sensitivity to traditional chemo/radiation

Less metastasis (than the other 2 types, because somewhat slower growing but faster so better response)

C-kit mutations

Question 9

What is the primary lung cancer metastasis site?

Answer 9

The primary metastasis site is the brain
(gets into the blood and goes to the brain)

other sites include:
Contralateral lung
Liver
Bone
Adrenal glands
Kidney
Lymph nodes

Question 10

Lung cancer symptoms/presentations

Answer 10

It is usually non-specific:
-chest, shoulder, arm pain
-fractures
-liver dysfunction
-neurologic deficits
-hypercoagulable state
patients typically do not present to the doctor with these symptoms, and so it is often an accidental finding

Or in later stages they may develop some symptoms that they would present to the doctor with including…
-hemoptysis (Coughing up blood)
-rust-streaked sputum
-dysphagia
-weight loss
these usually don’t occur until stage 3/4, which is why lung cancer is often only diagnosed in late stages

It can sometimes present as an oncologic emergency…
-hypercalcemia
-superior vena cava obstruction (due to tumor or thrombus causing obstruction)
-spinal cord compression (tumor can spread to spinal cord, presents with paresthesia)

Question 11

Curative vs palliative treatment considerations

Answer 11

In early stages we treat to cure (more aggressive treatment)

In advanced stages - palliative treatment –> improve QOL, relieve symptoms

Question 12

How is NSCLC staged?

Answer 12

There are 4 stages based on tumor size and metastasis

Stage 4 is metastasis

Question 13

Stage 1 or 2 NSCLC treatment approach

Answer 13

If possible –> surgery
-then this is followed by adjuvant chemo/radiation

Adjuvant therapy for stage 1/2 is traditional chemo
(immunotherapy is only indicated for stage 3/4 as of right now)

Question 14

Traditional Chemotherapy for NSCLC (stage 1/2)

Answer 14

Platinum agent + etoposide or vinorelbine

Preferred regimen = cisplatin + etoposide ( + radiation)

Note - etoposide has better data, but vinorelbine can be used if side effects of etoposide can not be tolerated (fluid overload, metallic taste, hypotension, alopecia)

Question 15

Stage 3 or 4 NSCLC treatment approach

Answer 15

Typically: neoadjuvant chemotherapy first, then surgery, then adjuvant chemotherapy

However, some patients may not get surgery (particularly in stage 4 if there is too much spread and surgery is not an option)…
-chemo + radiation
-or chemo + immunotherapy

(so different approaches based on patient specific factors)

Question 16

Which 2 drugs are PD-L1 inhibitors?

Answer 16

Nivolumab
Pembrolizumab

(they prevent the interaction between PD-1 on t cells and PD-1L on the cancer cells, reversing t cell suppression, allowing them to kill cancer cells)

Question 17

PD-L1 inhibitor use in stage 3 cancer

Answer 17

We need to look at the amount of the ligand that the tumor expresses to see if this therapy will be effective…

For stage 3 NSCLC…
-If PD-L1 (+) with > 50% expression AND EGFR/ALK (-) … then Pembrolizumab can be used first line

-If less than 50% expression, but PD-L1 expression is 1% or higher … traditional chemotherapy first (same regimen as stage 1/2) then, follow with pembrolizumab or nivolumab

Question 18

What immunotherapy should be used for stage 3 cancer with EGFR+ mutation?

Answer 18

Erlotinib
-should be used first line, more effective than traditional chemotherapy (use before chemo)

(note EGFR mutations increase tumor cell growth)

Question 19

What immunotherapy should be used for stage 3 cancer with ALK+ mutation?

Answer 19

Crizotinib
-BUT this should be second line AFTER traditional chemo (cisplatin + etoposide)

Question 20

What immunotherapy should be used for stage 3 cancer if no other immunotherapy can be used?

Answer 20

(If negative for PD-L1, EGFR, and ALK) …
Bevacizumab
-this should be used WITH traditional chemo agents: carboplatin + paclitaxel
(different than the standard traditional chemo regimen)

Question 21

Stage 4 cancer treatment

Answer 21

If PD-L1 expression is at least 1% …
-Pembrolizumab + pemetrexed + carboplatin

If no PD-L1 expression - traditional chemotherapy (same as stage 1/2 –> cisplatin + etoposide)

Question 22

Squamous cell (carcinoid) lung cancer 2 treatment options

Answer 22

1. cisplatin + gemcitabine
2. cisplatin + vinorelbine + cetuximab

Question 23

How is small cell lung cancer staged?

Answer 23

2 classifications: limited or extensive disease
-limited disease has a 14-20 month survival rate with treatment
-extensive has a 9-11 month survival rate with treatment
(survival rate is poor even with treatment)

Question 24

Small cell lung cancer - limited disease treatment

Answer 24

Surgery - then radiation/chemo

Chemotherapy:
preferred: cisplatin + etoposide
-cisplatin is preferred, if it cannot be tolerated due to ADRs (nausea, renal toxicity, etc) then carboplatin + etoposide can be used

Patients will also undergo a PCI (prophylactic cranial irradiation) - radiation of the head to prevent spread to the brain (since this is the primary metastasis site)

Question 25

Small cell lung cancer - extensive disease treatment

Answer 25

Surgery is NOT done (too many tumors)

Chemotherapy:
cisplatin + etoposide (preferred)
-carboplatin can be used instead of cisplatin if it cannot be tolerated
-irinotecan can be used instead of etoposide if it cannot be tolerated

Patients also undergo PCI (prophylactic cranial irradiation, to prevent metastasis to the brain)