Lung - NSCLC Flashcards
When is a PET-CT indicated in lung cancer
When is MRI indicated
In all those eligible for radical treatment
If LNs > 1cm seen on staging CT -> PET-CT, EBUS & Bx
MRI - Pancoast tumour to assess involvement of brachial plexus
What brain imaging is indicated in lung cancer and when
Stage 2 - CT head with contrast
Stage 3 - MRI head with contrast
What investigations are needed to manage lung cancer
Bloods
Chest imaging & staging
Brain imaging if appropriate
Biopsy result for histology
Where is nodal station 1 and what N stage does this indicate
Highest mediastinal nodes
Ipsilateral/contralateral low cervical / supraclavicular / sternal notch nodes
=N3
How is N1 status defined
Stations 10-14 positive
10 - ipsilateral hilar
11 - peribronchial - interlobar
12 - intrapulmonary - lobar
13 - intrapulmonary - segmental
14 - intrapulmonary - subsegmental
distal to carina
How is N2 status defined
Positive stations 2-9 - ipsilateral superior mediastinal, aortic or ipsilateral mediastinal
Same side mediastinal, and aortic nodes
How is N3 nodal disease defined
Either contralateral hilar nodes (station 10) or contralateral mediastinal nodes (stations 7-9)
Which nodal stations are the ipsilateral superior mediastinal nodes
Stations 2, 3 & 4
2 = upper paratracheal
3 = pre vascular / retrotracheal
4 = lower paratracheal
Which nodal stations are the aortic nodes
Stations 5 & 6
Station 5 = sub aortic
Station 6 = para-aortic
N2 disease
Which nodal stations are the ipsilateral mediastinal nodes
Sup mediastinal
2-4
inferior mediastinal
Stations 7, 8 & 9
Station 7 = subcarinal
Station 8 = para-oesophageal
Station 9 = pulmonary ligament
Which station are the ipsilateral hilar nodes
Station 10
Which nodes are station 2 and what N stage do they indicate
2 = upper paratracheal (part of ipsilateral superior mediastinal)
N2
Which nodes are station 3 and what N stage do they indicate
3 = prevascular / retrotracheal
Part of ipsilateral superior mediastinal nodes
N2
Which nodes are station 4 and what N stage do they indicate
4 = lower para-tracheal
Part of ipsilateral superior mediastinal nodes
N2
Which nodes are station 5 and what N stage do they indicate
5 = sub-aortic
Part of aortic group
N2
Which nodes are station 6 and what N stage do they indicate
6 = para-aortic
Part of aortic group
N2
Which nodes are station 7 and what N stage do they indicate
7 = subcarinal
Part of ipsilateral mediastinal group
N2 disease
Which nodes are station 8 and what N stage do they indicate
8 = para-oesophageal
Part of ipsilateral mediastinal group
N2 disease
Which nodes are station 9 and what N stage do they indicate
9 = pulmonary ligament
Part of ipsilateral inferior mediastinal group
N2
Which nodes are station 10 and what N stage do they indicate
10 = ipsilateral hilar
N1 disease
Which nodes are station 11 and what N stage do they indicate
11 = interlobar / peribronchial nodes
N1 disease
Which nodes are station 12 and what N stage do they indicate
12 = intrapulmonary nodes - lobar
N1 disease
Which nodes are station 13 and what N stage do they indicate
13 = intrapulmonary nodes - segmental
N1 disease
Which nodes are station 14 and what N stage do they indicate
14 = intrapulmonary nodes - sub-segmental
N1 disease
Which nodal stations are the contralateral hilar /mediastinal nodes
What N stage do they indicate
As numbered according to above stations
But contralateral = N3 disease
Which nodal station are the low cervical / supraclavicular / sternal notch nodes
What N stage do they indicate
Station 1
N3 disease
How is M1 disease defined
M1a - contralateral lung nodule or malignant effusion (pleural or pericardial)
M1b - single extra-thoracic met
M1c - multiple extra-thoracic metastases
How is a T1 lung tumour defined
≤3cm
How is a T2 lung tumour defined
3-5cm
How is a T3 lung tumour defined
5-7cm or chest wall / pleural invasion
Or 2nd tumour in same lobe
How is a T4 lung tumour defined
> 7cm or direct invasion into mediastinal structures
Or second tumour on same side but different lobe
How is a stage 1A lung cancer defined
T1N0
How is a stage 1B lung cancer defined
T2a N0
How is a stage 2A lung cancer defined
T2b N0
How is a stage 2B lung cancer defined
T1-2 N1 or T3 N0
ie T3 disease or N1
How is a stage 3A lung cancer defined
T1-2 N2 or T3 N1 or T4 N0-1
ie N2 positive, T3N1 or T4 disease
How is a stage 3B lung cancer defined
T1-2 N3, T3-4 N2
How is a stage 3C lung cancer defined
T3-4 N3
How is a stage 4 lung cancer defined
M1
How does nodal positivity affect lung cancer staging
N1 = stage 2b
N2 = stage 3a at least (3b if also T3-4)
N3 = stage 3b at least (3c if also T3-4)
What three things are optimised prior to lung treatment
Smoking
PT
Dietician for nutrition
What information is required before being able to make a treatment decision
Staging CT CAP
MRI brain
PET
Histology
Pulmonary function
What is the treatment of choice for a stage 1 (T1-2N0) lung cancer
Surgery
Lobectomy - if confined to one lobe (L) or two (RML/RLL)
Sub-lobar resection - segmentectomy or wedge resection
What is the treatment of choice for a stage 2 (T2b-3 N0 / T1-2 N1) lung cancer
Presuming radical treatment:
Surgery (with NA-SACT or adj SACT)
CRT (concurrent or sequential)
When is a pneumonectomy indicated over a lobectomy
When tumour is <2.5cm from carina
What are the FEV1 requirements for surgery
FEV1 >1.5L - Lobectomy
FEV1 >2L - Pneumonectomy
What is the regimen for neoadjuvant SACT ahead of radical surgery
And what are the criteria
Neo-adjuvant chemotherapy - cisplatin/paclitaxel
Neo-adjuvant immunotherapy - nivolumab/Pt-based chemotherapy
NA nivolumab:
T2b (>4cm) or greater, or node positive (ie stage 2 or above), potentially resectable disease
Independent of PDL1 status
No actionable driver mutation - ALK/EGFR
What are the options for adjuvant treatment after surgery for a lung cancer
Adjuvant chemotherapy
Adjuvant targeted therapy
Adjuvant immunotherapy
When is adjuvant RT recommended following surgery for lung cancer
And at what dose
What is encompassed in the CTV
What is the CTV-PTV margin
R1 resection (microscopic disease) incl extracapsular spread
60Gy in 30# (or 50-55Gy/20#)
Not recommended for R0 resection as pts do worse
If R2 resection - tx as new lung cancer with CRT
CTV - tumour bed, incl clips. Resected positive nodal areas
PTV = CTV +1cm axially and 1.5cm sup/inf unless using 4D CT (use 1cm margin throughout)
What are the indications for adjuvant chemotherapy?
What is the benefit
And what regimen
Node positive
T2b (>4cm) - stage IIA or unexpected stage III
Benefit - 4-5% OS improvement at 5yrs
Cisplatin/Vinorelbine
What is the indication for adjuvant osimertinib
When does it start
Duration
What is the benefit
Completely resected EGFR mutated NSCLC (exon 19 deletion or L858R substitution)
Stage 1B (T2a) or greater, up to N2 only stage 3
ie >T2a N0, T1-2 N2, T3-4 N2
to start within 10wks if no chemotherapy or within 26wks if following chemotherapy (indicated if node positive or stage T2a (t2b - 4-5cm) or greater)
For 3yrs / disease recurrence / unacceptable toxicity
Greater benefit for greater disease stage
Adaura trial - mDFS not reached for osimertinib, vs 19mths for placebo
What are the resistance mechanisms to osimertinib
EGFR or non-EGFR mechanisms
Usually EGFR exon 20 C797X mutation or loss of T790M mutation
Alternatively MET amplification, HER2 amplification or non-EGFR pathway aberrations (RAS-MAPK, PI3K), cell cycle gene alterations, oncogenic fusions
What is the indication for adjuvant atezolizumab
Following complete resection of a NSCLC, stage 2b or greater (node positive or >T3N0)
with PDL1 >50%
For one year
and if no progression following Pt-based chemotherapy
What are the two options for radical RT for an early lung cancer
Non-SABR RT
SABR RT
When is non-SABR RT indicated for an early lung cancer
What is the dose
stage I-II (T1-2N1 or T3N0), non-resectable cancer within 1cm of the proximal bronchial tree (therefore not amenable to SABR) or overlaps critical structures
Dose:
54Gy/36# CHART - 3x/day over 12 days
Or 55Gy/20#
When is SABR RT indicated
What is the dose
Tumour up to 5cm (T2), outside of proximal bronchial tree / exclusion zone (≥2cm away).
Node negative
Or T3 only due to chest wall invasion
Not suitable for surgery or declines surgery
PS0-2
Dose:
Peripheral tumours - 54Gy in 3# over 5-8 days, prescribed to 80% isodose
Tumours in contact with chest wall - 55Gy in 5# / 10-14 days (not compromised for chest wall tolerance)
Tumours adjacent to OAR - 60Gy in 8# /10-20 days
What are the exclusion criteria for lung SABR
Pt unable to lie flat for 45min
PS >2
Tumour not definable on planning CT, ie associated with consolidation or atelectasis
Within 2cm of central exclusion zone
Previous RT within the planned treatment volume
What are the outcomes from lung SABR
Improved local control rates
2-yr local control rate >90% (similar to surgery);
5-yr local control rate 86%
Nodal recurrence 4-11% post SABR
Improved OS cf to radical RT (40% v 20% at 5yrs)
What are the OAR tolerances for lung SABR
Oesophagus - 1cc <24Gy
Lung - V20<10%
Heart - 1cc <24Gy
How is lung SABR planned
4D CT
GTV - Tumour
CTV -> ITV - Outline tumour on MIP
ITV -> PTV - 5mm
How is operable N2 disease (stage III) defined
No LN > 3cm
Must be free from major mediastinal structures: great vessels & trachea
Non-fixed, non-bulky, single zone N2
What is the regimen for radical concurrent chemoRT?
55Gy/20#, or 60Gy/30# or 66Gy/33#
Cycles 1&2 of cisplatin (40mg/m2) and vinorelbine (15mg/m2) given alongside RT
Cycles 3&4 given following completion of RT
cisplatin (80mg/m2) and vinorelbine (35mg/m2)
What is the indication for durvalumab?
No progression following concurrent chemoradiotherapy, good PS, PDL1 >1%
Given 2wkly for 12mths / disease progression / toxicity
Pacific trial (CRT +durvalumab / placebo) - Median survival benefit 47.5mths vs 29.1 months
For concurrent CRT, what GTV-ITV & PTV margin is given
GTV +5mm
PTV = CTV/ITV +1cm radically and 1.5cm if no motion management, or CTV +5mm if motion management
For sequential CRT, what GTV-ITV & PTV margin is given
GTV - post chemo lesion / tumour bed
CTV - GTV + pre-chemo LNs (no margin on primary lesions)
PTV - CTV + 10mm axially and 15mm sup/inf
What dose constraints would be acceptable for a radiotherapy plan (4 organs)
Lung: V20Gy <35%
Spinal cord: Dmax <50Gy
Heart: V40Gy <30%
Oesophagus: V35Gy <50%
What is the treatment algorithm for a pancoast tumour
If operable: Neo-adjuvant CRT - 45Gy/25# with cisplatin/etoposide, followed by surgery
If inoperable: Primary CRT - 45Gy/25# with cisplatin/etoposide
Or consider radical CRT - 60Gy/30#, followed by surgery if disease has become operable
If PDL1>1% and no progression after CRT, would be eligible for consolidation durvalumab
What targetable mutations exist for metastatic NSCLC & corresponding txs (non EGFR & ALK)
Met - exon 14 skip mutation - tepotinib
B-raf - dabrafenib/trametinib - 1st line
K-ras - sotorasib if G12C mutation 2nd line after Pt-based ChT/IO
NTRK - larotrectinib/entrectinib - 2nd line after Pt-based chemo, IO and docetaxel
Ros1 - can use crizotinib or entrectenib both 1st line
HER2 - Trastuzumab-emtansine
RET fusion - selpercatinib - approved 1st line
What are the commonest EGFR mutations in NSCLC
L858R and exon 19 deletion - confer sensitivity to osimertinib.
Exon 20 insertions (C797X) - confer resistance
What is the response rate to osimertinib
> 60% RR for intracranial disease
80% for those with L858R mutation
What is the workup for progression on non-osimertinib EGFRi
Rebiopsy if possible:
T790M or L858R mutation - osimertinib
Otherwise - Pt-based chemotherapy doublet
What are the first line options for an ALK-positive NSCLC
What are the typical side effects
Alectinib - LFTs/anaemia/constipation/oedema/weight gain
Brigatinib - htn/rash/CPK/ILD
Good CNS penetration
What is the typical resistance mutation to first line ALK inhibition
what is the 2nd line treatment
What is the benefit
ALK G1202R
Retains sensitivity to 2nd line lorlatinib
PFS 6mths
Brain mets common in those treated with ALK inhibitors. What is the recommended treatment
Avoid WBRT if possible, consider SRS
What systemic treatment is given after progression on targeted treatement (osimertinib (EGFR mutation) or alectinib & lorlatinib (ALK mutation)), for NSCLC
Atezo, carboplatin, paclitaxel, bevacizumab
or Pt-doublet
or Pt/pemetrexed
If no actionable mutation is present, what is the first line systemic treatment for a metastatic squamous cell carcinoma?
And 2nd line
If PDL1 >50% - single agent atezolizumab or pembrolizumab, or carboplatin/paclitaxel/pembrolizumab if a rapid response is required, followed by maintenance pembrolizumab
If PDL1 <50% - carboplatin/paclitaxel/pembrolizumab +/- bevacizumab
Followed by maintenance pembrolizumab (2yrs)
Addition of bevacizumab to carbo/paclitaxel/atezo improved mOS
2nd line:
If PDL1 >50% initially - Pt-based doublet ChT
If PDL1 <50% - single agent atezolizumab, nivolumab or pembrolizumab (PDL1 >1%)
If no actionable mutation is present, what is the first line systemic treatment for a metastatic adenocarcinoma?
And 2nd line
If PDL1 >50%:
- single agent atezolizumab or pembrolizumab,
Or
-carboplatin/pemetrexed/pembrolizumab if a rapid response is required (followed by pemetrexed/pembro maintenance)
If PDL1 <50%:
- carboplatin/pemetrexed/pembrolizumab
Followed by maintenance pemetrexed/pembrolizumab (2yrs)
2nd line:
If PDL1 >50% initially - Pt-based doublet ChT or Pt/pemetrexed, followed by maintenance pemetrexed
If PDL1 <50%:
- single agent atezolizumab, nivolumab or pembrolizumab (PDL1 >1%)
- Docetaxel +/- nintedanib
What is the risk of malignancy for lung nodule/mass:
<5mm
1-2cm
2-3cm
>3cm
nodules < 5mm - 1% malignant
nodules 1-2 cm 18% malignant
nodules 2-3 cm 50% malignant
masses >3cm 90% malignant
What mass/nodule features on imaging would suggest malignancy
Size, spiculated appearance, thick walled, necrotic
What is the management of a lung nodule based on size
<8mm - CT surveillance
If <5-6mm -> CT at 1yr
>6mm - CT at 3mths
If >8mm - assess malignancy risk (Brock model)
<10% risk - CT surveillance (3mths)
>10% risk -> PET
<10% risk - CT surveillance (3mths)
10-70% risk - biopsy
>70% risk - excise
When does radiation pneumonitis typically occur
8wks post RT
treat with steroids
who is eligible for lung screening
age 55-74, hx of smoking
low dose CT
20% reduction in lung cancer related death and 6.7% in overall all cause mortality vs CXR
70% were stage I-II
what is the prognosis of NSCLC and the benefit of adj chemotherapy
5-year survival 7% men, 9% women
Adjuvant chemotherapy can increase absolute survival rates by 4%
What are the numbers for lung T staging
3-5-7
T1 <3cm
T2 3-5cm
T3 5-7cm
T4 >7cm
What is the risk of pneumothorax with RFA
40%
what is the first line treatment for a metastatic NSCLC with exon 20 egfr mutation
Pt-based chemotherapy
When is WBRT offered in lung cancer
Quartz trial - PS2 - no benefit vs BSC
WBRT is not routinely offered for brain mets in NSCLC
Except in Good PS (0-1), Age <60 & well controlled extracranial disease
when should sotorasib be taken relative to omeprazole
Sotorasib - take omeprazole 4hrs after, or 10hrs before
what treatment is indicated for a ros1+ NSCLC
crizotinib
