Lung cancer Flashcards
What are the classifications of lung cancer?
NSCLC (85%) - adenocarinoma (40%) , squamous cell, large cell
SCLC (15%)
What are some important clinical features of NSCL subtybes?
Adenocarcinoma - peripheral, common in non -smokers and Asian women, HPOA + haem PNS, better prognosis than other subtypes
Squamous cell - centrally located, smoking assc., hypercalcaemia (PTHrP)
Large cell - peripheral, smoking assc., poor prognosis
What are some clinical features of neuroendocrine lung cancers?
SCLC - central, strong assc with smoking, PNS - neurological, rapid growth, high relapse
Carcinoid - central/peripheral, common in children, not assc with diarrhoea and flushing like gastric carcinoid, obstructive symptoms e.g. wheeze
Large cell neuroendocrine - peripheral, poor prognosis
What are stats on lung cancer prevalence and mortality?
4th most common cancer in Australian men and women
Leading cause of cancer related death worldwide
What are some RF for lung cancer?
Tobacco (polycyclic aromatic hydrocarbons)
Environmental exposures - asbestos, beryllium, radon, diesel fumes
Inflammation - pulmonary fibrosis, TB/HIV
Family history - 2-3x risk if FDR has lung cancer
What are some paraneoplastic syndromes associated with NSCLC ?
Haem: Anaemia, thrombocytosis, leukocytosis, superficial thrombophlebitis (Trousseau syndrome), VTE, DIC, Thrombotic microangiopathy
Nonbacterial thrombotic endocarditis
HPOA: Presence of clubbing, periosteal proliferation of the tubular bones symmetrical, painful arthropathy and long-bone pain that usually involves the ankles, knees, wrists, and elbows
What are some paraneoplastic syndromes associated with SCLC ?
SIADH: Anorexia, nausea, and vomiting
Neurological: Lambert-Eaton myasthenic syndrome (LEMS), cerebellar ataxia, sensory neuropathy, limbic encephalitis, encephalomyelitis, autonomic neuropathy, retinopathy, and opsomyoclonus
Cushing syndrome
Dermatomyositis
How is lung cancer diagnosed?
CT chest with contrast
Biopsy - TBNA or transcutaneous
Biopsy - histology, PDL1 score, mutations EGFR, ALK, ROS
Staging : PET/CT
MRI brain for brain mets
What is the staging of NSCLC?
Stage I: < 4 cm, limited to lung
Stage II: 3-7 cm, local lymph nodes or surrounding tissue
Stage III: 3 - > 7 cm, local lymph nodes, surrounding tissues but not distant
Stage IV: Distant mets
What is the staging for SCLC?
Limited: confined to ipsilateral hemothorax
Extensive: contralateral hilar or supraclav LN, malignant pleural effusion, distant mets
What are common sites of lung cancer mets?
Brain, bone, adrenals and liver
What is the treatment of early stage NSCLC?
Curative intent
Stages I – II Surgical resection (lobectomy + draining LN resection)
Stages II- IIIA – can consider adjuvant platinum-based chemotherapy (e.g. cisplatin) + radiotx if positive margins
If not a surgical candidate – radiotherapy (stereotactic, ablative). Can be combined with concurrent chemotherapy.
Atezolizumab PD-L1: – PBS approved for II – IIIA after surgery and platinum-based chemo, if >50% PDL-1 expression, no actionable mutation (IMPOWER)
Neoadjuvant chemoimmunotherapy – cisplatin based + nivolumab (chekmate816 ) – reduced risk of disease progression, recurrence, death - TGA approved, not PBS approved
What is the treatment of stage III NSCLC?
Only select patients are surgical candidates (N1)
Concurrent chemoradiotherapy with follow up immunotherapy
If molecular targets detected – can use TKI against EGFR, ALK,ROS 1, MET mutations
PDL1 antibody - Durvalumab - unresectable stage III NSCLC, after platinum based chemoradiotherapy (33% vs 20% BSC, regardless of PDL1 level)
What is the treatment for stage IV NSCLC?
Molecular therapy: if driver mutations detectable – PBS subsidized 1stor 2ndline is TKI for EGFR, ALK , ROS1 or MET mutations (ECOG >2)
Immunotherapy: if PD-L1 > 50% (monotherapy) or if PD-L1 <50% (combine with chemotherapy) – KEYNOTE024 and KEYNOTE 189 trial
Best supportive care and palliative radiotherapy for painful bone and cerebral metastases,haemoptysis
What are some examples of targeted molecular therapies to EGFR, ALK, ROS and MET?
EGFR mutations (10-30% NSCLC) -osimertinib, afatinib (2nd gen), gefitinib and erlotinib (1st gen) - skin toxicity and diarrhoea
ALK gene rearrangements (5% NSCLC) - alectinib, ceretinib,brigatinib,loratinib(2nd gen),crizotinib(1st gen)
ROS1 rearrangements (1-2% NSCLC) -entrectinib, crizotinib,
MET exon 14 mutation (3-4% NSCLC) – tipotinib. SE: peripheral oedema
What are examples of immunotherapy for lung cancer?
PD1
pembrolizumab - initial therapy or combined with chemotherapy for NSCLC
nivolumab - 2nd line after progression on platinum doublet chemo
nivolumab and ipilimumab (anti- CTLA4) - first line for Stage IV NSCLC
PD-L1
Atezolizumab- initial treatment fornonsquamousNSCLC with platinum doublet chemotherapy and bevacizumab, second line after progression on platinum doublet chemotherapy, first line in extensive SCLC in combination with chemotherapy.
Durvalumab - unresectable stage III NSCLC, after platinum based chemoradiotherapy
What are some side effects of immunotherapy with PD1 and PDL1 inhibitors?
Autoimmune type reactions that can affect any organ, typically skin, GI, lung thyroid and pituitary. Severe reactions may require discontinuation and treatment with immunosuppressive agents – high dose prednisone ormethyl prednisone, infliximab or vedolizumab
What is the treatment of SCLC ?
Limited disease – combined chemoradiotherapy with curative intent (including prophylactic whole brain radiotherapy as nearly 40-50% patients will go on to develop brainmets)
Extensive disease – systemic chemotherapy and immunotherapy +/- consolidation chest radiotherapy (for people who respond well to chemotherapy)
Chemotherapy agents : cisplatin- etoposide, exceptionally well responsive but high rate of relapse
Immunotherapy agent – PDL1 antibody –atezolizumab
What are the types of mesothelioma?
Invasive cancer arising from the mesothelial cells of the pleural or peritoneal cavities (and rarely pericardium or tunica vaginalis of the scrotum)
Epithelioid (commonest), sarcomatoid and biphasic/mixed
What are the RF for mesothelioma ?
Exclusively caused by inhalation of asbestos
What are the clinical features of mesothelioma ?
90% of mesotheliomas affect pleura, rarely peritoneum and tunica vaginalis of scrotum involved
Insidious onset of chest pain, dyspnea (secondary to pleural effusions) and weight loss
Abdominal involvement – abdominal distension (ascites) and pain
How is mesothelioma diagnosed?
CT chest with contrast
Thoracocentesis of pleural effusion OR closed pleural biopsy/ VATS biopsy
Staging via PET
What is the management of mesothelioma?
No cure - poor response to chemo
Management of effusions -pleural aspiration, draining with talc pleurodesis, indwelling pleural or peritoneal catheters
Radical surgery has limited benefit – no survival benefit
Chemotherapy – cisplatin/ carboplatin + pemetrexed - response rate is 40%, increases survival by 3 months
Immunotherapy – nivolumab + ipilimumab or ipilimumab alone (Checkmate 743 trial – improved survival 7 months compared to standard of care chemotherapy – better with sarcomatoid)
What biomarkers are elevated in mesothelioma?
Biomarkers are selectively elevated in patients with mesothelioma, include soluble mesothelin-related peptides, fibulin-3, andosteopontin, although they are not routinely used in the diagnosis of mesothelioma.
