Lung, Head & neck cancers Flashcards
Lung cancer basic Epi?
80-95% of cases in Aus are smoking related
Most common cause of cancer death in Aus
Median age of Dx 70yrs
Methods of obtaining a Tissue Bx in lung cancer?
Central endobronchial lesion - broncoscopy Bx
Peripheral lung lesion - IR guided core Bx
Central nodes - EBUS
Common molecular tests for lung cancer? (ie to guide potential targeted therapies)
Non squamous NSCLC - EGFR, ALK, ROS1, MET exon 14 skipping mutation
- All adenocarcinomas, all cancers with component of adenocarcinoma (ie adenosquamous carcinoma)
- All large cell carcinomas (not large cell neruoendocrine carcinomas)
- Test these in never smoker with squamous NSCLC
Squamous NSCLC - MET exon 14 skipping mutation
- EGFR, ALK, ROS1 are extremely rare in pure lung SCC, therfore dont need to test
Classification / types of lung cancer?
Small cell lung cancer (15% of all lung cancer)
Non small cell lung cancer (85% of all lung cancer)
- Squamous (30%)
- Non squamous (70%)
-> Adenocarcinoma (90%)
-> large cell carcinoma (10%)
Initial Imaging for lung cancer?
CXR - usually raises suspicion for lung cancer
CT Chest - next test if there is abnormality noted on CXR
PET scan - used to stage mediastinum, ID any metastitic disease
- Note PET not sensitive to brain mets, therefore need dedicated MRI Brain
Treatment of NSCLC based on stage 1-4?
Stage 1:
- surgical resection if medically fit
- Stereotactic radiation if non surgical candidate
Stage 2
- surgical resection + adjuvant chemo and immunotherpy with atezolizumab (if PD-L1 high)
Stage 3
- resectable: surgical resection + adjuvant chemo and immunotherpy with atezolizumab (if PD-L1 high)
- unresectable: Concurrent chemoradiation + consolidation durvalumab (PDL 1 inh)
Stage 4
- palliative systemic therapy (chemo, targeted therapies, immunotherapy +/- palliative radiotherapy
Stage 4 NSCLC treatment?
Palliative systemic therapy (chemo, targeted therapies, immunotherapy) +/- palliative radiotherapy
- Chemo standard of care is 4 cycles of platinum containing doublet
-> ECOG 3-4 dont benefit, elderly people can benefit - Targeted therapies depends on specific mutations present
-> EGFR, ALK, ROS1, MET. Mabs can target extracellular targets (ie EGFR); TKIs can target intercellular components of this pathway
-> EGFR positive treated with second generation EGFR TKI such as Osimertanib (less resistance than 1st generation)
-> ALK fusion gene NSCLC treated with ALK TKI such as Alectinib, lorlatinib
-> ROS1 positive treated with ROS1 TKI such as Crizotinib (1st gen) or entrectinib (2nd gen)
-> MET exon 14 skipping positive treated with Tepotinib - Immunotherapy combined with chemo is better than chemo alone for wild type NSCLC regardless of PD1 status
-> therefore use in all stage IV NSCLC in addition to chemo
EGFR mutations are common in non squamous NSCLC. What are the most common EGFR activating and sensitizing mutations and in whom are these most common?
Most common EGFR activating / sensitising mutations:
- Exon 19 deletion
- Exon 21 L858R point mutation
More common in:
- non smokers
- female
- Asian ethnicity
Most common mechanism of aquired EGFR mutation in lung cancer?
Resistance after exposure to EGFR TKI is common
- resistance develops via T790M mutuation most commonly
- Histological transformation (changes into SCLC)
- On target mutations (EGFR C797S mutation)
- Off target (MET amplification ie pathway becomes indep of EGFR upstream)
ALK mutations are common in non squamous NSCLC. What are the most common ALK activation mutations and in whom are these most common?
Most common ALK activating mutation:
- AML4-ALK fusion gene formation
More common in:
- adenocarcinoma subtype
- never or light smokers
- young pts
ROS1 mutations are common in non squamous NSCLC. In whom are these most common?
Younger pts
Never or light smokers
MET exon 14 skipping mutations are common in non squamous NSCLC. In whom are these most common?
Occurs in NSCLC, squamous and non squamous types
Typically presents in pts >70 years old
What is pseudoprogresion in lung cancer and who gets this?
This is the apparent increase in size of cancer on immunotherapy, that eventually reduces in size once continues on therapy
- Can only be Dx in retrospect, may just be actually progression
What are the stages of SCLC?
Limited and extensive
- Limited disease: disease in only one hemithorax and ipsilateral mediastinal nodes, encompassed by a single radiation field
- Extensive disease: anything that isnt limited disease
Treatment of limited and extensive SCLC?
Limited:
- concurrent chemoradiotherapy + prophylactic cranial iradiation (PCI) in responders
Extensive:
- Chemertherapy (carbopatin + etopostide) + atezolizumab follow by maintainance atezolizumab
