Keynote lecture Lung cancer

Question 1

Which percentage of lung cancer is caused by smoking?

Answer 1

90%

Question 2

What does NSCLC stand for?

Answer 2

For non-small cell lung cancer

Question 3

What is the most common NSCLC?

Answer 3

An adenocarcinoma

Question 4

Where can thoracic tumors also be located?

Answer 4

In the pleura, mediastinum and other organs in the thorax

Question 5

How is the staging of tumors done?

Answer 5

According to tumor size, nodal and distant metastasis

Question 6

In which stage are the majority of the patients diagnosed?

Answer 6

Stage IV

Question 7

What treatment is given in stage I NSCLC?

Answer 7

A surgical resection or radiotherapy, systemic treatment is not needed

Question 8

Does the stage I treatment given have a good outcome?

Answer 8

Yes

Question 9

What treatment is given in stage II/III NSCLC?

Answer 9

A combination of local and systemic treatment (eg resection + neo-adjuvant immunotherapy, chemo + adjuvant immunotherapy, osimertinib for EGFR)

Question 10

What is done to determine the treatment given in stage II/III NSCLC?

Answer 10

A molecular analysis and PD-L1 testing

Question 11

What are the cure rates for stage II/III?

Answer 11

Stage II: 60%, stage III: 40%

Question 12

What treatment is given in stage IV NSCLC?

Answer 12

A systemic treatment (same methods used as in stage II/III to determine the treatment)

Question 13

What caused a major improvement in stage IV curing and what was it?

Answer 13

Immunotherapy and targeted therapy. Cure rate became 15%, 5 year survival 25%. However 45% is not fit for treatment

Question 14

Why is DNA or RNA sequencing done?

Answer 14

To identify the achilles heel of cancer and match a treatment to it

Question 15

What can DNA or RNA sequencing get information on?

Answer 15

On oncogenic/TSG mutation, TMB, PD-L1 expression levels

Question 16

What is mutation positive lung cancer?

Answer 16

Usually found in someone who has not smoked, targeted therapy is effective, immunotherapy is not effective, and there is a low mutational load (not a lot of variants)

Question 17

What is common lung cancer?

Answer 17

Found in smokers, immunotherapy is effective, targeted therapy is not effective, there is a high mutational load

Question 18

How can common lung cancer be treated?

Answer 18

There is a PDL1-PD1 interaction which represses T cell activation. Thus if the interaction is blocked with a molecule the immune response can be upregulated

Question 19

What is the treatment if there is a high PDL1 expression?

Answer 19

Immunotherapy only

Question 20

Which percentage of the patients shows a major response when being treated with a PDL1-PD1 inhibitor?

Answer 20

About 25%

Question 21

What happens in patients that do not respond to a PDL1-PD1 inhibitor?

Answer 21

They either have primary or secondary resistance

Question 22

What is alternative treatment in patients that do not respond to the PDL1-PD1 inhibitor?

Answer 22

Engaging other immune checkpoints eg TIL, CAR-T, tumor vaccine

Question 23

How does the treatment TIL work?

Answer 23

There is a resection done of a small part of metastasis, this is stimulated and T cells are expanded ex vivo. Then the patient is treated with chemo, after that the cells are put back and stimulated with IL2. This is also used when TMB is low or in patients who are mutation positive

Question 24

How does the treatment CAR-T work?

Answer 24

Creates a new T-cell receptor

Question 25

Is a tumor vaccine used on its own?

Answer 25

No, it is used in combination with other immunotherapies

Question 26

Which mutation is not necessarily found in mutation positive patients?

Answer 26

KRAS mutation, is commonly induced in smokers as well (so it is sensitive to immuno and targeted therapy)

Question 27

What are characteristics of targeted therapy?

Answer 27

A high response rate, works fast, has a low toxicity and can be used in unfit patients as it has little side effects. It is fixed (1 drug), eventually there is always resistance and it never cures patients

Question 28

What are characteristics of immunotherapy?

Answer 28

There is a varying response, it takes weeks to work, it has a higher toxicity, you need fit patients, its adaptive, resistance can occur and the patients can cure

Question 29

Can immunotherapy and targeted therapy be combined?

Answer 29

No, this is too toxic in general

Question 30

Why is targeted therapy not a cure?

Answer 30

As the tumors create all different types of mutations that the drug cannot adapt to

Question 31

What are benefits of biopsy to identify a resistance mutation?

Answer 31

It has a high sensitivity and specificity

Question 32

What are downsides of using a biopsy to identify a resistance mutation?

Answer 32

Is not always possible, need longer assessment and only provides info about the biopsied lesion

Question 33

What are the benefits of a blood sample to identify a resistance mutation?

Answer 33

It has high specificity, gives information about all lesions, a short assessment time

Question 34

What are the downsides of a blood sample to identify a resistance mutation?

Answer 34

It has low sensitivity

Question 35

What do you look at to identify the resistance mutation?

Answer 35

Both the biopsy and the blood sample