Lung cancer

Question 1

What are the classifications of lung cancer?

Answer 1

NSCLC (85%) - adenocarinoma (40%) , squamous cell, large cell
SCLC (15%)

Question 2

What are some important clinical features of NSCL subtybes?

Answer 2

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

Question 3

What are some clinical features of neuroendocrine lung cancers?

Answer 3

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

Question 4

What are stats on lung cancer prevalence and mortality?

Answer 4

4th most common cancer in Australian men and women

Leading cause of cancer related death worldwide

Question 5

What are some RF for lung cancer?

Answer 5

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

Question 6

What are some paraneoplastic syndromes associated with NSCLC ?

Answer 6

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

Question 7

What are some paraneoplastic syndromes associated with SCLC ?

Answer 7

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

Question 8

How is lung cancer diagnosed?

Answer 8

CT chest with contrast
Biopsy - TBNA or transcutaneous
Biopsy - histology, PDL1 score, mutations EGFR, ALK, ROS
Staging : PET/CT
MRI brain for brain mets

Question 9

What is the staging of NSCLC?

Answer 9

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

Question 10

What is the staging for SCLC?

Answer 10

Limited: confined to ipsilateral hemothorax

Extensive: contralateral hilar or supraclav LN, malignant pleural effusion, distant mets

Question 11

What are common sites of lung cancer mets?

Answer 11

Brain, bone, adrenals and liver

Question 12

What is the treatment of early stage NSCLC?

Answer 12

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

Question 13

What is the treatment of stage III NSCLC?

Answer 13

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)

Question 14

What is the treatment for stage IV NSCLC?

Answer 14

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

Question 15

What are some examples of targeted molecular therapies to EGFR, ALK, ROS and MET?

Answer 15

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

Question 16

What are examples of immunotherapy for lung cancer?

Answer 16

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

Question 17

What are some side effects of immunotherapy with PD1 and PDL1 inhibitors?

Answer 17

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

Question 18

What is the treatment of SCLC ?

Answer 18

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

Question 19

What are the types of mesothelioma?

Answer 19

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

Question 20

What are the RF for mesothelioma ?

Answer 20

Exclusively caused by inhalation of asbestos

Question 21

What are the clinical features of mesothelioma ?

Answer 21

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

Question 22

How is mesothelioma diagnosed?

Answer 22

CT chest with contrast
Thoracocentesis of pleural effusion OR closed pleural biopsy/ VATS biopsy
Staging via PET

Question 23

What is the management of mesothelioma?

Answer 23

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)

Question 24

What biomarkers are elevated in mesothelioma?

Answer 24

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.

Question 25

What predicts prognosis in mesothelioma?

Answer 25

Poor prognosis – median survival is 9-12 months, worse (6 months) in peritoneal mesothelioma
Epithelioid subtype has better prognosis thansarcomatoidor biphasic subtype
Factors predicting worse prognosis : advanced age, male gender andsarcomatoidsubtype

Question 26

What is the eligibility criteria for lung cancer screening in Australia ?

Answer 26

Eligibility criteria
1) Aged between 50 and 70 years and show no signs or symptoms of lung cancer
2) 30 pack year smoking hx and active smoker OR 30 pack year hx and quit <10 years ago

Question 27

What is the pathway in lung cancer screening in Australia?

Answer 27

Pathway
No abnormal findings: screen again in 2 years
Low to moderate risk of cancer: stay in the program, have another screening at 12 months or 3 months and may be referred to a specialist
High risk of cancer or suspected lung cancer: referred to a specialist linked to a multidisciplinary team (MDT).