Lung Cancer Clinic (Practical) Flashcards
For illustration, what is the impact of lung cancer in today’s society?
Of all the deaths in 2019, 29% died from cancer and 22.8% of all cancers were due to lung cancer (=10,260). There were about 13,800 new lung cancer patientes in 2019 in The Netherlands (and 2.1 million worldwide).
What is the death rate compared to the incidence of lung cancer?
I presume you don’t have to know this but notice the high amount of deaths, especially compared to other types of cancer in this figure
Is the incidence of lung cancer increasing or decreasing the last years?
Increasing (lung cancer is the blue line)
(personally I’m very conflicted because in pathology we learned that there is a decrease due to the changing smoking habits)
In what ..% of the patients is smoking the cause of lung cancer?
80%
What are non-smoking related risk factors? (this is just for indication)
Occupational exposure to asbestos, chromium, arsenic, cadmium, silica and nickel, second-hand smoke, outdoor air pollutants, previous lung diseases radon exposure and dietary factors. Also please take a close look at this figure which are common risk factors of lung cancer
What are the different types of lung cancer (divided by histology)?
- Small cell lung carcinoma
- Non-small cell lung carcinoma
- Adenocarcinoma
- Squamous cell carcinoma
- Large cell carcinoma
- Other non-small cell lung carcinoma
What are the characteristics of squamous cell carcinoma? (origin cell, localization, morphology, cause, complication)
- Squamous epithelial cells
- Keratin production, tight junctions
- usually a hilar/central localization to the lungs
- Often with cavitation (central necrosis)
- strong association with smoking (incidence is decreasing due to smoking habits)
- hypercalcaemia may occur
What are the characteristics of an adenocarcinoma?
- Mucus excreting cells
- Usually peripheral localization in the lungs
- Most common, in smokers and non-smokers
- Most associated with oncogenic drivers
- E.g. EGFR mutation, ALK rearrangement
- Increasing incidence
What are the characteristics of large cell carcinoma?
- Poorly differentiated
- High volumes cytoplasm, large abnormal nucleus
- Usually peripheral localization in the lungs
- Metastasizes (relatively) quickly
What are the characteristics of small cell carcinoma?
- Often accompanied by paraneoplastic syndrome
- Usually central localization to the lungs
- Strong association with smoking
- Grows very fast
- Necrosis
- 60-70% already metastasized at diagnosis
What are the top 10 symptoms of lung cancer?
- Cough !! (#1)
- Malaise
- Weight loss
- Dyspnea
- Haemoptysis
- Pain
- Chest discomfort
- Depression
- Neurological deficit
- None
When a patient comes in with a cough, and an X-ray shows some deviations, what further steps are taken to make a diagnosis?
- Contrast enhanced CT-scan
- FDG PET/CT-scan
- MRI (mainly stage 3, mainly for brain, not lungs)
A TNM classification is made to estimate the severeness of the tumor, what does TNM stand for?
T: Tumor
N: Lymph Nodes
M: Metastases
How is a biopsy from the lungs taken?
Via a bronchoscope
Through the use of a bronchoscopy you can take a biopsy and at the same time have a virtual assesment of the lungs. Name four ways you can navigate the bronchoscope through the lungs.
- Radial EBUS
- Magnetic (not explained in the lecture)
- Fluorescence guided (not explained in the lecture)
- Virtual mapping (not explained in the lecture)
What are endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) used for?
To take a biopsy of different lymph nodes (EBUS is via the airways, the EUS is via the oesophagus)
Punctures can be guided by CT-scan or ultrasound. Where are punctures used for?
For tumor mass, pleural effusion, pericardial effusion and metastases
What are the risks of punctures?
Pneumothorax (!!!), bleeding and empysema
In this figure, different strategies are shown to to make a biopsy. What is a cell block? (don’t learn by heart)
A paraffin block, suitable for sectioning, staining, and microscopic study, prepared from any suspension of cells in fluid (that is, aspirates or washings); cells are concentrated by centrifugation or filtering, and the resulting aggregation is processed as if it were a solid specimen of tissue.
What type of tissue do you get when using a forceps biopsy?
A fragmented, very thin, tissue
Why is needle core biopsy the favorite biopsy of pathologists? (don’t learn by heart)
The advantages of core needle biopsy (over e.g. fine needle biopsy) include obtaining a more definitive histologic diagnosis, providing the distinction between invasive and in situ cancer, and usually providing adequate sampling for immunohistochemistry evaluation.
From the three steps of pathologic diagnostics (: morphology, immunohistochemistry), what type of technique is shown here?
Morphology testing (Hematoxylin Eosin, PAS)
Don’t learn these markers, maybe recognize them?
From the three steps of pathologic diagnostics (: morphology, immunohistochemistry), what type of technique is shown here?
Immunohistochemistry (p40, p63, TTF-1, PD-L1, ALK, NTRK, ROS1, MET, Her2)
Don’t learn these markers, maybe recognize them?
Another diagnostic technique is Fluorescence in situ hybridization (FISH). How does this method work?
Fluorescence in situ hybridization (FISH) is a laboratory technique for detecting and locating a specific DNA sequence on a chromosome. The technique relies on exposing chromosomes to a small DNA sequence called a probe that has a fluorescent molecule attached to it. In the lung cancer diagnostics, translocations are investigated, as shown by this figure (: ALK, ROS1, RET, NTRK)
Another diagnostic technique is Next Generation Sequencing (NGS). How does this method work?
The basic next-generation sequencing process involves fragmenting DNA/RNA into multiple pieces, adding adapters, sequencing the libraries, and reassembling them to form a genomic sequence. In principle, the concept is similar to capillary electrophoresis. In this picture you see that they have chosen a spot with a high number of tumor cells, scraped it off and sequenced it (markers: EGFR, KRAS, BRAF, MET, Her2, …)
Please take a look at this diagnostic algorithm and notice how e.g. adenocarcinoma has many markers such as EGFR, KRAS, BRAF and MET that determines the subtype of this category
Although the teacher focused a lot on this slide, I don’t presume you have to know all these markers, but maybe familiarize yourself with them?
Explain in NSCLC (non-small cell lung carcinoma) if there’s primarily local or systemic therapy in an early stage or a metastasized stage
In the early stages, the focus is on local therapy (surgery/radiotherapy), in the later stages, the focus is on systemic therapy (chemo-, immune and targeted therapy)
Look at this figure of the different stages of NSCLC. Can you fill the black boxes in with the type of treatment that would be given?
Choose from:
- Chemoradiotherapy and immune oncology drugs
- Resection or radiotherapy (SABR)
- Resection or radiotherapy (SABR) and adjecent chemotherapy
- Systemic therapy
- Systemic therapy (followed by radiotherapy)
Explain what concurrent and sequential treatment looks like
Concurrent starts with (3 rounds of) chemotherapy, where eventually radiotherapy is added. It always ends with immunotherapy. Sequential therapy is 3 rounds of chemotherapy, followed by radiotherapy and then immunotherapy
For illustration: This patient had stage IIIa lung cancer and was treated with chemoradiotherapy about 10 years ago. As you can see the tumor shrunk tremendously
She is still alive today
Explain some characteristics of chemotherapy, targeted therapy and immunotherapy (all systemic therapy)
Important to remember from this picture: Targeted therapy has the highest response and is only effective in patients with an oncogenic driver, immunotherapy is only useful in patients with increased PD-L1 expression and is very expensive
What does this IPASS trial (2009) show?
On the right you see patients who are EGFR positive, on the left you see EGFR negative. The green line is an TK-i (tyrosine kinase inhibitor) and the orange line is chemotherapy. You see that when patients are positive to the mutation they react much much better to the TK-i than those who don’t have this mutation (and these patients are better treated with chemotherapy)
In the FLAURA trial (2020), a third-generation TK-i was compared to the first-generation TK-i. What were the results?
Good, as you can see the median survival time is about 7 months longer than the first-generation TK-i (blue = third-, red = first-generation).
In another study (called Keynote24) a PD-L1 inhibitor was compared to chemotherapy in a population where >50% had PDL1 over expression. What were the results?
Also good, as you can see the Pembrolizumab performed better than chemotherapy, shown by both the progression-free survival and overal survival curve.
A note to the graphs: there was probably a crossover, so patients with chemo also received pembrolizumab, making the overall survival of chemotherapy higher than reality
Here we see another example of a patient who was treated on NSCLC with high PD-L1 expression
Lovely results :)
