Lung Cancer Flashcards
Prevalence of lung cancers
3rd most common cancer
Leading cause of cancer death
Age around 75-90
Males more likely to get
10-15% of pt never smoked
Causes of lung cancer other than smoking
Asbestos-exposure to plumbers carpenters for example which increases risk by 2-
Radon-eg silver miners
Indoor cooking fumes eg wood,smoke
Chronic lung disease eg COPD/fibrosis
Air pollution
Familial/genetic
Pathogenesis
May arise from differentiated and undifferentiated cells
Interaction between inhaled carcinogens and epithelium of upper and lower airways causes DNA adducts to form (pieces of dna covalently bound to a cancer causing chemical)
Persisting dna adducts causes mutation and genomic alterations
Types of lung cancer
Squamous cell carcinoma-oginiates from bronchial epithelium,centrally located
Adenocarcinoma-originates rom mucus producing glandular tissue so more peripherally located. From low tar cigarette which are more deeply inhaled and retained
Large cell lung cancer-heterogeneous group,undifferentiated
Small cell lung cancer-originate from pulmonary neuroendocrine cells and is highly malignant
1-3 are non small cell lung cancer (NSCLC)
Oncogenes involved
EGFR tyrosine kinase-causes adenocarcinoma more so in women of Asian ethnicity and never smokers
Anaplastic lymphoma kinase (ALK) tyrosine kinase-non small cell lung cancer in younger patients and never smokers
c-ROS oncogene 1 (ROS1) receptor tyrosine kinase-non small lung cancer in younger patients and never smoked
BRAF (downstream xell cycle signal mediators)-non small cell lung cancer esp in smokers
Symptoms
Cough
Weight loss
Breathlessness
Fatigue
Chest pain
Haemoptysis
Or asymptomatic
Features of metastatic disease
Neurologist features:focal weakness,seizures,spinal chord compression
Bone pain
Paraneoplastic syndromes eg clubbing,hypercalcaemia,hyponaetraemia,cushings
Signs
Clubbing
Horners syndrome (drooping on one side of face)
Superior vena cava obstruction (pembertons sign)
Cachexia (muscle wasting disorder)
Diagnostic strategy
Establish most likely diagnosis
Establish fitness for investigation and treatment
Confirm diagnosis and histology’s
Confirm stage
Lung cancer screening
Current or ex smokers aged 55-74 invited
What imaging is most useful to exclude occult metastasis
PET-CT
Biopsy
Bronchoscopy-for tumours of central and segmental airways
Endobronchial ultrasound and transbronchial needle aspiration of mediastinal lymph nodes-to stage mediastinum
Navigational bronchoscopy and robotic sronchoscopy-for peripheral lesions/nodules that aren’t amenable to
conventional bronchoscopy or ct
Ct guided lung biopsy-to access peripheral lung tumours
Staging
T1-4 tumour size and location
N0-3 lymph node involvement mediastinum and beyond
M0-1c metastasis and number
Determinant of treatment
Patient fitness
Cancer histology
Cancer stage
Patient preference
Health servuce
Patient fitness
0-asymptomatic (fully active to carry on all pre disease activity)
1-symptomatic but complete ambulatory (restricted in physical strenuous activity but able to do light or sedentary work
2-symptomatic and about >50% of waking hours (ambulatory and able to self care but can’t do work activities)
3-symptomatic confined to bed or chair >50% waking hour (limited self care)
4-completely disabled (can’t do self care,confined to bed)
5-death
Radical treatment restricted to PS0-2
Surgery
Standard for early stage disease
Lobectomy and lymphadenoctom
Sublobar resection if stage 1 <3cm
Radical radiotherapy and
Alternative to surgery for early disease particularly if comorbidity
Stereotactic ablative body radiotherapy (SABR)
Technique of choice
High precision targeting multiple convergence beams
Systemic treatments oncogene directed
First line treatment for non small cell cancer with mutation
EGFR-erlotinib,gefitinib,afatinib,dacomitiniv,osimertinib
ALK-critonizib,ceritinib,alectinib,brigatinib,lorlatinjb,
ROS-
Critozinjb,entrectinib
Cause little side effects but can get diarrhea,rash or pneuomoitis (rare)
2b immunotherapy’s
First line for metastatic NSCLC with no mutation and PDL1>50%
Pemprolizumab,atezolizumab,nivolumab
Efficacy-improvement in progression free survival and overall survival
Side effects are well tolerated ,immune related usually (thyroid,skin,bowel,lung and liver)
Is an anti pdl-1 drug which reactivates the immune system
3 cytotoxic chemo
First line for metastatic NSCLC with no mutation and PDL1<50% (in combo with immunotherapy)
long established-targets rapidly dividing cells,platiunum based regiments eg carboplatin,cisplatin,paclitaxel,pemetrexed
Modest improvement in survival
Side effects-frequent causes fatigue,nausea,bone marrow suppression,nephrotoxicty
Quality of life poorly evaluated/no improvement
Palliative and supportive care
Should be offered to all patients with advanced stage disease
At 12 weeks see improved quality of life and lower depression scores
Summary of treatment
Early stage use surgery or radiotherapy with curative intent
Locally advanced stage involving thoracic lymph nodes do surgery and adjuvants chemo or radiotherapy and chemo with or without immunotherapy
Metastatic disease use tyrosine kinase inhibitors if there is a targetable mutation No mutation PDL-1 positive DI immunotherapy alone but if PDL-1 negative do standard chemo and immunotherapy
PDL-1
Binds to PD-1 receptor on the t cell to turn it off so can’t destroy cancer cells
Tumour staging in detail
T0 means no primary tumour
Tis is carcinoma jn situ
T1 tumour <3cm
t1a minimally invasive adenocarcinoma and tumour <1cm
T1b tumour >1 but <2cm
T1c tumor >2 but <3
T2 3-5cm
T2a >3 <4
T2b>4 <5
T3 5-7 or invades chest wall pericardium,phrenic nerve or separate nodule jn same lobe
T4 tumour >7cm or invades mediastinum diaphragm heart great vessels recurrent laryngeal nerve carina trachea esophagus spine
N0 means nk metastasis
N1 metastasis jn ipsilateral pulmonary or hilar nodes
N2 metastasis jn ipsilateral mediatstinal/subcarina, nodes
N3 metastasis in contralateral mediatsinal or hilar or supraclavicular lymph nodes
M0 no distant metastasis
M1a malignant pleural/pericardial effusion or separate nodule jn contralateral lobe
M1b single extrathoracic metastasis
M1b multiple extrathoraic metastasis
Systemic treatment 2a immunotherapy
Block PD-LQ or PD-1 fl allow T cell to kill tumour cell
Order for IVX
Chest X ray
Ct abdominal and chest
PET CT
Biopsy
