Summary
Summary clinical immunology (AM_470655)
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A summary of the powerpoints and lecture recordings of the last 4 lectures of the course
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HC20 Immunotherapy in daily practiceLung cancer very prevalent and has a high mortality.
Etiology:
- 80-90% cause by SMOKING
- Pre-existing factors: lung fibrosis, HIV and Genetic predisposition
- Environmental factors: Radon radiation exposure: Asbestos, Polycyclic aromatic
carbs, Ionizing radiation, Exposure to: arsenic, chromium, nickel.
Diagnosis: what is the disease?
Staging: how extensive (uitgebreid) is the disease present?
Staging:
Top 10 symptoms:
- Cough!!
- Malaise, Weight loss, Dyspnea, Haemoptysis, Pain - Chest discomfort, Depression,
Neurological deficit or None sympoms.
→ Metastasis
Diagnosis: X-ray
Staging: CT scan, PET scan and MRI
PET scan: FDG = fluorodeoxyglucose gets injected in the patient and it accumulate in
different tissues that have a high metabolism of glucose. Once it gets in the cell it does not
come out → ideal tracer to see witch tissues have a high metabolism.
- For patients with stage 1, 2 and 3
MRI: to be sure there is no disease in the brain
These scans lead to TNM classification:
- T (tumor) → size, number of lesions, ingrowth in organs
- N (lymph node) → higher lymp node, side of the body
- M (metastases) → how many lesions, in the same lung, further organs
→ All three factors are giving a number and this ‘code’ forms the stage.
Diagnosis:
Tumor biopsy: the tube/scope goes through the nose to the lungs
- Visual assessment
- Navigation options
o Radial EBUS (endobronchial ultrasound) → this is an echo machine; you can
see through the wall of the trachea, to see the Mediastinal Lymph Nodes that
are close to the trachea. Endoscopic ultrasound (EUS) is for the esophagus.
o Magnetic
o Fluorescence guided
o Virtual mapping
o → Not widespread
, Transthoracic punctures (when the tissue is too far for a biopsy): CT or US guided
- Very small biopsy → may miss
- Risks → pneumothorax: the air escapes and the lungs come loose from the chest and
the lungs collapse
For classification of diagnosis use:
- NSCLC (non-small cell long cancer)
- SCLC (small cell long cancer)
Therapy:
Early stage of the disease: local therapy
Locally advanced stage: use both local and
systemic therapies
Advanced stage: systemic therapy
Systemic therapy modalities:
- Chemotherapy
- Targeted therapy: a specific target has to be identified as the driver of the tumor,
start targeted therapy against this specific target (kinase inhibitors)
- Immunotherapy: if it works it works really well, but if it does not work it does not
work → select the right patients for this therapy (PD-L1)
o Pathological diagnostic algorithm: morphology, NGS, HE, IHC, FISH.
Approach to systemic treatment:
First line therapy (1L)
- First look for → oncogenic driver mutations (non-squamous)
o EGFR, ALK, BRAF, ROS1
o NTRK, RET
- If no oncogenic driver found → look at tumor PD-L1 expression
o If ≥50% → anti-PD-1 monotherapy (+/- chemo)
o If <50% → combination of chemotherapy and immunotherapy
Immunotherapy:
Mainly Immune Checkpoint Inhibitors
- PD-1 inhibitors: nivolumab, pembrolizumab
- PD-L1 inhibitors: durvalumab, atezolizumab
- CTLA4 inhibitors: ipilimumab
- LAG3 inhibitors, TIM3 inhibitors and Immune modulating agents: trials ongoing
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