NSCLC Flashcards
What is the treatment paradigm for Stage I-II node negative lung cancer?
(T1-2bN0M0 disease)
Medically operable:
Lobectomy + Mediastinal Lymph node dissection
Chemotherapy for Stage II, debatable in IB cases (LACE)
PORT if + margin and not re-resectable
Medically inoperable:
SBRT- perferred over conventional EBRT
Phase III TROG CHISEL study demonstrated superior outcomes in patients randomised to stereotactic radiotherapy versus those receiving standard external beam radiotherapy
Concurrent chemoRT 60GY/30# if not SABR candidate
For treatment purposes NSCLC can be divided into Early and Late based on:
1) Early = <Stage III
2) Late Stage III
Stage III is node +veor T4 disease,
with the exception that T1-2 w/ +ve N1 node (i.e. Ipsilateral peribronchial and/or ipsilateral hilar LNs = stations 10–14) is stage II (i.e early).
Define stage III NSLC
1) Either T4 = >7cm OR Satellite nodules in different lobes ipsilateral lung, or invasion: thoracic structures beyond pericardium, phrenic n. or chest wall (these are T3)
2) Any nodal disease, except N1 with only T1 (<=3cm) or T 2 (>3cm, <=5cm - without invasion)
In NSCLC contrast the definition of T3 and T4 disease:
In T3 disease, any satellite nodule needs to be within the same lobe
In T4 in different lobes same lung
Invasion in T3 is parietal pericardium, chest wall, or phrenic nerve. T4 is any other structure.
Size: T4 is >7cm, T3 is >5cm to =7cm.
In NSCLC define “peripheral tumour”
“peripheral tumour” = more than 2cm from bronchial bifurcation.
Define the “N1 nodes”
Ipsilateral peribronchial and/or ipsilateral hilar LNs (stations 10–14)
Poor prognostic factors for NSCLC:
Stage,
weight loss >5% in 3 months,
KPS <90,
age >70,
+LVSI,
Marital status (single)
Indications for PORT in NSCLC
+ve micro margins or gross residual disease
1) stage I-II patients PORT not indicated in completely resected as per meta-analysis.
2) Stage III - Lung ART RCT study looked at completely resected N2 disease - found no benefit (DFS or OS) to PORT 54/30 in completely resected N2 disease.
PORT-C study confirms this. OS at 3yrs is about 80%
What histology subtype of NSCLC is least associated with smoking?
Adenocarcinoma
What are the paraneoplastic syndromes associated with lung cancers?
Hypercalcemia of malignancy - PTHrP
SIADH - leads to hyponatremia
Cushing - increased ACTH
Lambert-Eaton syndrome
Hypercoagulability (adenocarcinoma)
Gynecomastia (large cell)
Carcinoid (vasoactive intestinal peptide), diarrhea
Hypertrophic osteoarthropathy (adenocarcinoma)
What is the cause of Lambert-Eaton syndrome? Clinically how do you distinguish L-E syndrome from myasthenia gravis?
Circulating antibodies against against presynaptic P/Q calcium channel. With repeat motion, patients with L-E have improved strength whereas MG patients fatigue with repitition
What histologic subtypes of lung cancer are associated with peripheral and central lesions?
Peripheral: adenocarcinoma, large cell
Central: SCC, carcinoid
With which histologic subtypes of lung cancer is Thyroid Transcription Factor-1 (TTF-1) staining associated?
Adenocarcinoma, nonmucinous bronchioalveolar carcinoma (adenocarcinoma in situ) and neuroendocrine tumors
TTF-1 is rare in squamous cell
In NSCLC what is the role of CXR or CT screening for high risk patients?
CXR is not recommended.
The USPSTF recommends annual screening with LDCT in people between ages 55 and 80 with a greater than 30 pack-year smoking history in current smokers and those who quit <15 yrs ago
What RCT reported low dose CT screening for lung cancer?
The national lung cancer screening trial - prospective RCT comparing LDCT vs. annual CXR for 3 years
LDCT reduced RR of lung cancer death by 20%
To prevent 1 death: 320 high risk pts need to be screened
What is lead-time bias and how could it affect the results of a screening trial?
Lead time in diagnosis is the time between detecting the cancer from screening and when the diagnosis would have otherwise occurred due to symptoms or imaging studies. This can lead to an apparent increase in survival.
What is length-time bias and how could it affect the results of a screening trial?
Length-time bias occurs when a screening test detects cancers that take longer to become symptomatic due to the detection of slower growing or indolent cancers. This leads to an apparent increase in survival.
What is the single most clinically significant acquired genetic abnormality in NSCLC?
EGFR mutation in exon 19 and exon 21
Is EGFR overexpression more common in SCC or adenocarcinoma?
EGFR may be overexpressed in 80-90% of SCCs vs. 30% of adenocarcinomas
What are common mechanisms associated with TKI resistance?
T790M is a point mutation that accounts for 60% of TKI resistence, usually devlop after 9-13 months of therapy
Other mechanisms: KRAS, ALK, ROS1, exon 20 insertion, small cell transformation, epithelial-mesenchymal transition phenotype
What are the most common presenting symptoms of NSCLC?
Dyspnea, cough, weight loss, chest pain, hemoptysis
What is the sensitivity and specificity of sputum cytology for diagnosis of lung cancer?
Sensitivity <70%, specificity >90%
Accuracy increases with more # of specimens, at least 3 are recommended
What is the sensitivity and specificity of FDG-PET compared to CT for staging of lung cancers?
PET: sensitivity 83%, specificity 91%
CT: sensitivity 64%, specificity 74%
What is the estimated % of patients who will have false + N2 nodes on PET/CT?
10-20%. N2 nodes by PET/CT need pathologic confirmation before deferring to potentially curative surgery
N2 = ipsilateral mediastinal or subcarinal
What is the estimated % of patients who will have false - N2 nodes based on PET/CT?
5-16%.
Describe the N staging of NSCLC
N1: ipsi hilar or pulmonary nodes
N2: ipsi mediastinal or subcarinal nodes
N3: any SCV/scalene nodes or contralat mediastinal/hilar nodes
If re-resection is not possible, what RT dose is used for a +margin after surgery?
Microscopic +margin: 54-60Gy
Gross +margin: 60-70 Gy
Risk factors
- Tobacco smoking - pack/year
- Asbestos exposure
- Air pollution
- Occupational hazard- silica, cadmium, arsenic, beryllium, diesel exhaust, coal soot
- Fam Hx
- Genetic mutations
- Pulmonary fibrosis, COPD
Epidemiology of NSCLC
- most common non cutaneous cancer in world
- Most common cause of cancer death world wide
- Approx 80% lung cancer are NSCLC
- 15-20% NSCL present with early stage disease
Compare and contrast Adeno vs SCC NSCLC
Adeno- 40% NSCLC
- Most common NSCLC
- 40% of all lung cancer
- not as strongly related to smoking
*younger - peripheral location
SCC- 20% NSCLC
- 20% of all lung cancers
- Most closely linked to smoking
- Older
*Seen with interstitial lung disease (chronic inflammation is carcinogenic) - Central/bronchogenic location
*arise from bronchial tree metaplasia
Microscopic features of Adeno NSCLC
Malignant epithelial tumour with glandular differentiation, mucin production, or pneumocyte marker expression
Histological Subtypes of Adeno NSCLC
Non-Mucinous:
LAMPS
- Lepidic
- Acinar
- Micropapillary
- Papillary
- Solid
Mucinous
Subtypes of SCC NSCLC
- Basaloid
- Clear cell (containing glycogen)
- Small cell (small tumour cells with focal
keratinisation)
*Papillary
Microscopic features of SCC NSCLC
Malignant epithelial tumour that shows either keratinization (including cells of keratin pearls) and intercellular bridges , or expresses IHC markers of squamous differentiation
May be keratinizing or non keratinising.
Macroscopic appearance of Adeno NSCLC
- Tan white cut surface
- May have central area of scar (necrosis/
haemorrhage not so common)
usually well-defined but not encapsulated
Macroscopic appearance of SCC NSCLC
Central tumour
* usually central portion of lung, affecting central bronchi; invade peribronchial soft tissue/ lung parenchyma; with atelectasis
Peripheral tumour
* nodular growth with central necrosis and cavitation
IHC markers of NSCLC adeno
Positive: CK7+, TTF1+, Napsin A+
Negative: p40-, p63-, p53-, CK20-
IHC markers of NSCLC SCC
Positive: CK5/6+, p63+, p40+, p63
Negative: TTF1-, Napsin-A-
Subtypes of NSCLC
Adenocarcinoma
SCC
Large cell
What is a carcinoid tumour vs atypical carcinoid?
Carcinoid = A low grade neuro endocrine tumour
Atypical carcinoid = ntermediate grade neuro-endocrine tumour
How common is carcinoid lung tumour?
1-5% of all lung cancer; but lung second most common site of carcinoid tumours (second most common site)
what differentiates carcinoid from atypical carcinoid microscopically?
Looks like carcinoid except:
- Higher mitotic activity
- With necrosis
- Increased cellularity
- Nuclear pleomorphism, hyperchromasia, high N/C ratio
What is the most common NSCLC type to have clinically relevant mutations?
> 95% clinically relevant genetic mutations found in adenocarcinoma
Epidemiology of EGFR mutation
- 10-15% of adenocarcinoma in Caucasian, and 50% of adenocarcinoma in Asian
- Often in non-smoker, women
- Mutually exclusive with ALK re-arrangement
- Significantly associ with Non-mucinous adeno with lepidic component
What is the lung function criteria which = medically inoperable?
baseline FEV1<40%,
DLCO<40%
What common chemotherapy regimes are used in concurrent chemo RT?
Weekly Cisplatin (50mg/m2 D1) + Q4W Etoposide (50mg/m2 D1-5, and D29-33)
Weekly Carboplatin (2AUC) and weekly Paclitaxel (45mg/m2)
What type of drug is ipilumimab?
Anti-CTLA-4 antibody
