Keynote lecture Lung cancer Flashcards
Which percentage of lung cancer is caused by smoking?
90%
What does NSCLC stand for?
For non-small cell lung cancer
What is the most common NSCLC?
An adenocarcinoma
Where can thoracic tumors also be located?
In the pleura, mediastinum and other organs in the thorax
How is the staging of tumors done?
According to tumor size, nodal and distant metastasis
In which stage are the majority of the patients diagnosed?
Stage IV
What treatment is given in stage I NSCLC?
A surgical resection or radiotherapy, systemic treatment is not needed
Does the stage I treatment given have a good outcome?
Yes
What treatment is given in stage II/III NSCLC?
A combination of local and systemic treatment (eg resection + neo-adjuvant immunotherapy, chemo + adjuvant immunotherapy, osimertinib for EGFR)
What is done to determine the treatment given in stage II/III NSCLC?
A molecular analysis and PD-L1 testing
What are the cure rates for stage II/III?
Stage II: 60%, stage III: 40%
What treatment is given in stage IV NSCLC?
A systemic treatment (same methods used as in stage II/III to determine the treatment)
What caused a major improvement in stage IV curing and what was it?
Immunotherapy and targeted therapy. Cure rate became 15%, 5 year survival 25%. However 45% is not fit for treatment
Why is DNA or RNA sequencing done?
To identify the achilles heel of cancer and match a treatment to it
What can DNA or RNA sequencing get information on?
On oncogenic/TSG mutation, TMB, PD-L1 expression levels
What is mutation positive lung cancer?
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)
What is common lung cancer?
Found in smokers, immunotherapy is effective, targeted therapy is not effective, there is a high mutational load
How can common lung cancer be treated?
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
What is the treatment if there is a high PDL1 expression?
Immunotherapy only
Which percentage of the patients shows a major response when being treated with a PDL1-PD1 inhibitor?
About 25%
What happens in patients that do not respond to a PDL1-PD1 inhibitor?
They either have primary or secondary resistance
What is alternative treatment in patients that do not respond to the PDL1-PD1 inhibitor?
Engaging other immune checkpoints eg TIL, CAR-T, tumor vaccine
How does the treatment TIL work?
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
How does the treatment CAR-T work?
Creates a new T-cell receptor
Is a tumor vaccine used on its own?
No, it is used in combination with other immunotherapies
Which mutation is not necessarily found in mutation positive patients?
KRAS mutation, is commonly induced in smokers as well (so it is sensitive to immuno and targeted therapy)
What are characteristics of targeted therapy?
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
What are characteristics of immunotherapy?
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
Can immunotherapy and targeted therapy be combined?
No, this is too toxic in general
Why is targeted therapy not a cure?
As the tumors create all different types of mutations that the drug cannot adapt to
What are benefits of biopsy to identify a resistance mutation?
It has a high sensitivity and specificity
What are downsides of using a biopsy to identify a resistance mutation?
Is not always possible, need longer assessment and only provides info about the biopsied lesion
What are the benefits of a blood sample to identify a resistance mutation?
It has high specificity, gives information about all lesions, a short assessment time
What are the downsides of a blood sample to identify a resistance mutation?
It has low sensitivity
What do you look at to identify the resistance mutation?
Both the biopsy and the blood sample
