Exam 2 lecture 4 (Lung)

Question 1

Risk factors for lung cancer?

Answer 1

tobacco (85-90% of cases), risk decreases after cessation, but never to baseline.
occupational/environmental exposure to asbestos
ionizing radiation (2nd leading cause)
Genetic predisposition

Question 2

What do EGFR mutations mean in lung cancer? What percent of NSCLC is it present in? Which mutation causes it to be resistant to therapies?

What do K-RAS mutations predict? what are these mutations exclusive towards in adeno carcinomas?

Answer 2

EGFR mutations can predict sensitivity to tyrosine kinase inhibitor therapy. Present in 10-15% of NSCLC. T790 mutations cause resistance to therapies.

K-RAS mutations predict resistance to TKI’s. In adenocarcinomas, mutations are exclusive to smokers,

Question 3

What are the different types of NSCLC? Where are they located in the lung? Are they related to smokers or non smokers.

Answer 3

1) Adenocarcinoma (50%)- most common in non smokers, located peripherally in lung

2) Squamous (30%)- Clearly related to smoking, located centrally

3) large cell (5%)- tend to be located peripherally

4) non-squamous

Question 4

What percent of cancer is SCLC? Is it related to smoking? How fast does it grow? Symptoms?

Answer 4

15%

Related to smoking
Fast growing and rapidly progressive
paraneoplastic syndromes

Question 5

compare SCLC and NSCLC

Answer 5

SCLC is highly sensitive to radiation and chemo, NSCLC is moderately sensitive to radiation and marginally sensitive to chemo.

NSCLC has slower growth fraction.

SCLC has clear relationship to smoking and has paraneoplastic syndromes

Question 6

How fast do SCLC and NSCLC proliferate? What percent metastasize?

Answer 6

SCLC has rapid proliferation, 2/3rds present with metastases

NSCLC is slower growing and 50% present with metastases

Question 7

What are the staging of SCLC and their 5-year survival

Answer 7

Limited stage- tumor is confined in hemothorax and contained in radiation port (20% chance if survival)

Extensive stage- tumlr is not confined to hemithorax of origin, not contained in radiation port, distant metastasis (5% chance of survival)

Question 8

use of prophylactic cranial radiation in SCLC when pt obtains complete response

Answer 8

more than 50% of pts will develop brain metastases. SO it increases survival

Question 8

How to treat limited stage disease SCLC

Answer 8

Highly sensitive to radiation so will be given concurrently with cisplatin and etoposide.

Question 9

how to treat extensive stage for SCLC

Answer 9

platinum based combination chemo without radiation preferred.

prophylactic cranial radiation should be strongly considered if a patient achieves a response in the chest

Question 10

what to do if brain metastases are present i extensive stage SCLC

Answer 10

brain radiation therapy

If patient is symptomatic, whole brain radiation should be started prior to chemotherapy.

if asymptomatic, initiate radiation therapy after chemo

Question 11

What are the 1st line regimens for extensive stage SCLC

Answer 11

Carboplatin + etoposide + Atezolizumab

Durvalumab + Carboplatin + etoposide

Cisplatin + Etoposide + Durvalumab

Question 12

complications of SCLC therapy

Answer 12

most cisplatin based regimens causes serious ototoxicity and nephro toxicity and neuropathy

Question 13

which platin causes more myelosuppression cisplatin or carboplatin

Answer 13

Carboplatin

Question 14

what is an option for metastatic SCLC in patients who have progressed on or after platinum based chemo and atleast one prior line of therapy

Answer 14

PD- inhibitor- pembrolizumab

Question 15

how sensitive is NSCLC to radiation and chemo? What is the most efficacious treatment of NSCLC? What do we use if this is not available?

Answer 15

moderately sensitive to radiation and low sensitivity to chemo

surgery is most efficacious for NSCLC

radiation therapy may be given for early stage NSCLC when surgery is not viable

Question 16

what are the three types of NSCLC

Answer 16

Resectable

unresectable

advanced/metastatic

Question 17

steps for resectable NSCLC

Answer 17

neoadjuvant
surgery
chemo followed by immunotherapy or oral agent

Question 18

how to decide which neoadjuvant to use for resectable NSCLC

Answer 18

based on histology (squamous vs non squamous)

Question 19

Non squamous NSCLC adjuvant therapy options

Answer 19

Cisplatin + pemetrexed

Question 20

Preferred squamous adjuvant therapy options? What if they dont tolerate cisplatin?

Answer 20

cisplatin + gemcitabine
cisplatin + docetaxek

other recommended regimens- cisplatin + vinorelbine
cisplatin + etoposide

if not able to tolerate cisplatin- Carboplatin + Pacitaxel
carboplatin + gemcitabine

Question 21

What are additional adjuvant therapies used in ALK mutations? eGFR mutations (exon 19 deletion, exon 21 L858R)? PDL-1>1%?

Answer 21

1. ALK mutation positive- alectinib
2. positive for EGFR mutations (exon 19, exon 21 deletion L858R)- osimertinib
3. PD-L1 >1%- Atezolizumab

Question 22

treatment of unresectable NSCLC

Answer 22

chemo and radiation

Question 23

stage III unresectable treatement for patients that can not get definitive chemo with radiation

Answer 23

pembrolizumab

Question 24

what drug can we give for unresectable stage III NSCLC with disease that has not progressed following concurrent chemotherapy and radiation therapy

Answer 24

durvalumab

Question 25

optimal regimen for stage IIIB and IV disease NSCLC unresectable

Answer 25

cisplatin/paclitaxel cisplatin/ gemcitabine Cisplatin/ docetaxel carboplatin/paclitaxel absolutely no difference in survival among groups carboplatin/paclitaxel had fewer toxicities

Question 26

treatment of advanced/metastatic NSCLC

Answer 26

chemotherapy targeted therapy (1st line) Chemotherapy targeted therapy (2nd line)

Question 27

If a patient has a targetable mutation and is PD-L1 (+) for advanced/metastatic adenocarcinoma lung cancers what do we use

Answer 27

It is preferred to use the oral therapies first and then move on to immuno therapies later

Question 28

What are the most common EGFR mutations in advanced/metastatic unresectable NSCLC? How to treat them? What percent of adeno carcinomas is it present in?

Answer 28

exon 19 deletion and exon 21 L858R mutation Osimertinib is 1st line if T790 mutation is present present in 10-15% of adenocarcinomas

Question 29

WHat drugs are used in non resectable advanced/metastatic NSCLC in BRAF mutations? Side effects associated with these drugs?

Answer 29

Dabrafenib plus trametinib dabrafenib- fevers, secondary skin cancers trametinib- fevers, rash, visual changes retinal detachment

Question 30

What are K-RAS mutations associated with in unresectable advanced/metastatic NSCLC? When are KRAS inhibitors used? What drug is it?

Answer 30

Associated with cigarette smoking use as subsequent therapy after platinum based chemotherapy sotorasib is drug name

Question 31

What to do for metastatic NSCLC unresectable if no mutation or if targeted oral chemo options have been exhausted

Answer 31

Check PD-L1 status. PD-L1 positivity of >1% will allow use of pembrolizumab

Question 32

treatment of mutation positive metastatic NSCLC non squamous

Answer 32

Oral chemo | PD-L1 status 1-49%= pembrolizumab (preferred) Also look at PS to determine if single agent or pembrolizuman + chemo is best for patient PD-L1 status >50%- 1. pembrolizumab or pembrolizumab + chemo 2. atezolizumab or 4. cemiplimab- rwlc +/- chemo PD=L1 negative- a) pembrolizumab or atezolizumab + chemo (preferred) b) platinum based chemo alone if immunotherapy is contraindicated

Question 33

first line tx for metastatic mutation negative NSCLC non squamous

Answer 33

Carboplatin + pemetrexed + pembrolizumab

Question 34

treatment of metastatic NSCLC squamous

Answer 34

if no contraindication to immunotherapy 1. pembrolizumab 2. pembrolizumab + cehmo 3. Atezolizumab or nivolumab or cemiplimab- rwlc if contraindication to immunotherapy Platinum doublet regardless of PD-L1 status

Question 35

first line for squamous metastatic NSCLC

Answer 35

platinum based doublet has been standard ( carboplatn with paclitaxel) pembrolizumab + carboplatin + paclitaxel or albumin bound paclitaxel