Lung Cancer (2) Flashcards
What is the biggest risk factor for developing lung cancer?
Smoking (causes 80% of lung cancer)
Lung cancer risk factors
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)
How does smoke exposure lead to lung cancer?
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)
Lung cancer prevention
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
What are the 3 types of lung cancer
- Non small cell lung cancer (NSCLC)
-most common - Small cell lung cancer (SCLC)
- Squamous cell lung cancer aka carcinoid lung cancer (LCL)
-rare
Non small cell lung cancer (NSCLC)
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
Small cell lung cancer (SCLC)
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
Squamous cell lung cancer/carcinoid lung cancer (CLC)
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
What is the primary lung cancer metastasis site?
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
Lung cancer symptoms/presentations
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)
Curative vs palliative treatment considerations
In early stages we treat to cure (more aggressive treatment)
In advanced stages - palliative treatment –> improve QOL, relieve symptoms
How is NSCLC staged?
There are 4 stages based on tumor size and metastasis
Stage 4 is metastasis
Stage 1 or 2 NSCLC treatment approach
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)
Traditional Chemotherapy for NSCLC (stage 1/2)
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)
Stage 3 or 4 NSCLC treatment approach
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)
Which 2 drugs are PD-L1 inhibitors?
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)
PD-L1 inhibitor use in stage 3 cancer
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
What immunotherapy should be used for stage 3 cancer with EGFR+ mutation?
Erlotinib
-should be used first line, more effective than traditional chemotherapy (use before chemo)
(note EGFR mutations increase tumor cell growth)
What immunotherapy should be used for stage 3 cancer with ALK+ mutation?
Crizotinib
-BUT this should be second line AFTER traditional chemo (cisplatin + etoposide)
What immunotherapy should be used for stage 3 cancer if no other immunotherapy can be used?
(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)
Stage 4 cancer treatment
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)
Squamous cell (carcinoid) lung cancer 2 treatment options
- cisplatin + gemcitabine
- cisplatin + vinorelbine + cetuximab
How is small cell lung cancer staged?
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)
Small cell lung cancer - limited disease treatment
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)
Small cell lung cancer - extensive disease treatment
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)
