Lung Cancer Flashcards
1
Q
Notes on subtypes of lung cancers
A
Squamous cell carcinoma (20%)
- Strongly associated with tobacco smoking
- Decreasing in frequency
- More common in men
- Tend to arise centrally from segmental or subsegmental bronchi
- TP53 mutations, CDKN2A inactivation loss of RB tumour suppressor
Small Cell Carcinoma (14%)
- Strongest association with smoking - only 1% occur in non smokers
- May arise in major bronchi or periphery of lung
- No known preinvasive phase
- Most aggressive
- Most commonly associated with ectopic hormone production
- Metastasies outside the thorax late
- Genetics
- Loss of function abberation TP53 (75-90%)
- Loss of RB (nearly 100%)
- Amplification of MYC common
- High levels of BCLS (anti-apoptotic protein) on immunohistochemistry
Adenocarcinoma (38%)
- Most frequent, more common in women
- Usually more peripherally located, tend to be smaller
- Oncogenic gain of function mutations involving growth factor receptor signalling pathways - multiple genes encoding receptor tyrosine kinases
- EGFR, ALK, ROS, MET and RET
- Tumours without TK gene mutations often have mutations in the KRAS gene(downstream of receptor tyrosine kinases)
- Activating KRAS mutations - worse prognosis
Large Cell Carcinoma
- Undifferentiated, malignant
- Diagnosis of exclusion (lacks markers of other cancers)
2
Q
Distant spread of lung cancers:
A
- Any type can extend onto pleural surface and within the pleural cavity or pericardium
- Spread to bronchi, trachea, mediastinal nodes
- Distant spread - lymphatic and haematogenous
- Often spread early (exception squamous cell)
- Adrenal involved in 50% - also liver (30-50%), brain (20%), bone (20%)
3
Q
Paraneoplastic syndromes associated with lung cancer
A
- Lung cancer associated with several neoplastic syndromes
- ADH - hyponatraemia
- Adrenocorticotropic hormone - Cushing’s syndrome
- Parathormone, parathyroid hormone-related peptide, prostaglandin E - hypercalcaemia
- Calicitonin - hypocalcaemia
- Gonoadotropins - gynaecomastia
- Serotonin, bradykinin - carcinoid syndrome
- ADH, ACTH predominantly small cell
- Hypercalcaemia - squamous cell
-
Lambert-Eaton myasthenic syndrome
- Muscle weakness caused by auto-antibodies directed at the neuronal calcium channel
- Sensory peripheral neuropathy
- Dermatologic - acanthosis nigricans
- Haematologic - leukemoid reactions, hypercoaguable such as Trousseau - DVT and thromboembolism
- HPOA
- Horner’s syndrome
4
Q
Notes on carcinoid lung tumours
A
- 1-5% lung tumours
- Typically younger than 40, males and females equal
- 20-40% non smokers
-
Characteristics
- Symptoms typical of intraluminal bronchial growth
- Secretory activity - Carcinoid syndrome - occurs in 10% bronchial carcinoids
- Intermittent attacks of flushing, diarrhoea, cyanosis
- Most bronchial carcinoids do not have secretory activity and do not metastasise to distant sites - follow a relatively benign course for long periods and generally amenable to resection
5
Q
Tumours of the anterior, posterior and middle mediastinum:
A
-
Anterior mediastinum
- Thymoma
- Teratoma
- Lymphoma
- Thyroid lesions
- Parathyroid tumours
- Metastatic carcinoma
-
Posterior mediastinum
- Neurogenic tumours
- Lymphoma
- Metastatic tumour (most from lung)
- Bronchogenic cyst
- Gastroenetric hernia
-
Middle mediastinum
- Bronchogenic cyst
- Pericardial cyst
- Lymphoma
6
Q
Epidemiology, risk factors for lung cancer
A
- Leading cause of cancer related deaths worldwide
- Majority present with advanced disease
- 42% Stage 4 - 5ys 3yrs
- 20-30 year time lag between smoking prevalence and lung cancer death
- While declining in men - still rising in women due to changes in smoking patterns over the decades
- Smoking cessation after a diagnosis can improve prognosis regardless of cancer stage
Risk factors
- Tobacco smoking (cigar and pipe smoking less so) - risk will always remain in ex smokers
- Most potent carcinogens → polycyclic aromatic hydrocarbons and aromatic amines
- Industrial → asbestosis, arsenic, chromium, uranium, nickel, vinyl, chloride, mustard gas, silica
- High dose ionising radiation
- Increasing incidence with age
- Emphysema, chronic asthma, COPD, ILD
- TB, HIV
- Family history
- Lung cancer prevalence in never-smokers higher in Asian countries ?inhalation of cooking oil vapour and domestic coal use
7
Q
Presentation of lung cancer
A
- Almost always symptomatic at diagnosis
- Primary tumour - cough, haemoptysis
- Constitutional - weight loss, malaise
- Paraneoplastic syndrome - hypercalcaemia, SIADH, VTE, HPOA
- Intrathoracic spread - e.g. pleural effusion, chest wall invasion, Horner syndrome, SVC obstruction
- Distant metastases - bone, headache, cord compression, Addisson’s
- Increasing incidental detection of lung nodules on CT scans for other reasons
8
Q
Diagnostic work-up for lung cancer
A
- CT CAP (including neck)
- 75% sensitivity, 66% specificity for mediastinal lymph nodes
- PET if potential for radial treatment (high sensitivity for distant metastases)
- 91% sensitivity, 86% specificity for mediastinal LNs
-
Tissue evaluation
- Bronchoscopy +/- endobronchial ultrasound
- CT guided lung biopsy
- Biopsy of mets
- Less common - mediastinscopy, sputum cytology
- Liquid biopsy (e.g. blood urine)
- May benefit those who are medically unfit for invasive procedures
- Tissue diagnosis still considered gold standard
9
Q
Notes on lung cancer staging
A
- Lymph node staging
- 1 → ipsilateral peribronchial and/or hilar lymph nodes
- 2 → ipsilateral mediastinal and/or subcarinal lymph nodes
- 3 → contralateral mediastinum and hilar nodes, I/L or C/L scalene or supraclavicular lymph nodes
- Lymph node involvement changes survival significantly
- Pleural effusion = metastatic (IV)
10
Q
Management of early stage non-small cell lung cancer
A
- 20% patients
- Surgical resection with curative intent recommended if medically fit and early stage - Stage I, II +/- Stage IIIa if N2 lymph nodes identified during procedure) - lobectomy with mediastinal lymph node dissection standard
- Thoracotomy
- VATs - less pain, fewer hospital complications and shorter hospital stays
- Adjuvant platinum based chemotherapy recommended for stages II-IIIA - absolute decreased risk of death of 5% at 5 years - substantial toxicities
- Molecularly targeted therapies - not demonstrated an overall survival benefit in early-stage patients
Non-surgical candidates:
- Stage I - stereotactic (ablative) body radiotherapy for Stage I-IIA disease
- Better survival than conventional radiotherapy
- Other options conventional fractionated radiotherapy
- Stage II - radiotherapy with curative intent with or without concomitant chemotherapy
11
Q
Management of locally advanced non-small cell lung cancer:
A
- 30% patients - T3-T4, N2-N3
- Most non-surgical candidates
- Concurrent chemo-radiotherapy followed by immunotherapy
- Cisplatin-etoposide or cisplatin-vinerelbine
- Durvalumab improves PFS after CRT (PDL-1 inhibitor) regardless of PDL-1 status
- TKIs targeting EGFR, ALK, ROS1
- Unclear whether patients with oncogene driven lung cancer respond to immunotherapy
- If no targetable alterations - immunotherapy may be given after platinum based chemo-radiation
12
Q
Management of metastatic non-small cell lung cancer
A
- Median survival 4-5 months with best supportive care
- TKIs
- Chemo-immunotherapy
- Immunotherapy - integral part as 1st/2nd line in patients without target mutations
- Chemotherapy followed by immunotherapy
- Best supportive care
- Palliative radiotherapy (painful bone mets, cerebral mets)
13
Q
Examples of molecularly targeted therapies in lung cancer:
A
- EGFR mutations - 10-30% NSCL tumours - up to 60% in Asians
- First generation TKIs - gefitinib, erlotinib
- Second generation - afatinib, osimertinib
- ALK gene rearrangements - 5% NSCLC
- First generation - crizotinib
- Second generation - certinib, alectinib, lorlatinib, brigatinib
- ROS1 rearrangements - 1-2% NSCLS
- Crizotinib, entrectinib
14
Q
Notes on immunotherapy in lung cancer
A
- Immune checkpoints keep immune responses from being too strong and enable self-tolerance
- PD-L1 can be upregulated on tumour cells as a means of immune escape by providing a negative immune regulatory signal
- When the checkpoint and ligand proteins bind together then send off a signal to the T cells preventing them from killing cancer cells
- Immune checkpoint inhibitors are monoclonal antibodies that target PD L1 and PD 1
- When checkpoints are blocked - T cells can kill cancer cells better
-
PD 1
- Pembrolizumab - initial treatment of NSCLC
- Nivolumab
-
PDL1
- Atezolizumab
- Durvalumab
15
Q
Notes on management of small cell lung cancer
A
- Exceptionally high proliferative rate, early mets, poor prognosis
- One third has earlier stage disease - potentially curable with multimodality therapy
- CT screening does not detect at earlier stages - does not effect survival
- Localised disease - chemoradiotherapy and prophylactic cranial irradiation reduces brain metastases
- Metastatic - chemotherapy +/- immunotherapy, plus consolidation chest radiotherapy for patient who respond to chemotherapy
- Initially very responvie to cytotoxic therapies
- Standard therapy is cisplatin-etoposide (has not changed in past three decades)
- Subset derive durable benefit from immunotherapy - majority do not
