Thoracic Oncology Flashcards
What is Tx?
Cancer cells in sputum /bronchial washing’s but not been assessed on imaging /bronchoscopy
What is T0?
No sign of cancer
What is Tis
Carcinoma in situ
Outline T1
<3cm surrounded by lung/ visceral pleura NOT involving main bronchus
T1mi- minimally invasive lung cancer , grown no more than 0.5cm into lung tissue
T1a ≤ 1cm
T1b >1cm to ≤2cm
T1c >2cm to ≤ 3cm
Outline T2
> 3cm to ≤5cm
OR
involvement of main bronchus without carina, regardless of distance from carina
OR
invading visceral pleura
OR
atelectasis
OR
post obstructive pneumonitis extending to hilum
T2a >3cm to ≤4cm
T2b >4cm to ≤ 5 cm
Outline T3
> 5 to ≤7cm
OR
Involving the Chest Wall, Pericardium, Phrenic nerve or satellite nodules in same lobe
Outline T4
> 7cm
OR
involving :Mediastinum, Diaphragm, Heart , Great vessels , Carina, Oesophagus, Trachea , Recurrent laryngeal nerve , spine or separate tumour in different lobe of ipsilateral lung
What is N1?
Ipsilateral peribronchial and /or hilar nodes and intrapulmonary nodes
What is N2?
Ipsilateral mediastinal and/or sub carinal nodes
What is N3?
Contralateral mediastinal or hilar nodes , ipsilateral/contralateral suprclavicular /scalene nodes
What is M1a?
Tumour in the contralateral lung
OR
Pericardial / Pleural Nodule
OR
Pericardial/Pleural Malignant effusion
What is M1b ?
Single extrathoracic Mets including single non regional LN
What is M1c?
Multiple extra-thoracic Mets in one or more organs
What is the incidence of brain Mets at diagnosis of lung cancer ?
10-20%
Who get a CT head with contrast ?
Stage II or Small cell
Who gets MRI brain w contrast ?
Stage 3
What staging does Mets give you?
M1a/M1b - automatically Stage IV A
M1c - automatically Stage IV B
An incidental nodule is picked up on CT , if it’s a harmatoma or typical peri fissural nodule or <5mm what action required ?
None, patient can be discharged
Incidental solid nodule picked up on CT that is 9mm, what are the next steps ?
Calculate Brock score
IF <10% follow up with CT surveillance
IF ≥ 10% then for PET scan with risk assessment using Herder
—Herder <10% CT surveillance
—Herder 10-70% Image guided biopsy or excision biopsy or CT surveillance
— Herder >70% Consider excision or non surgical treatment (+/- image guided biopsy)
Incidental solid 5-6mm nodule picked up on CT what are the next steps as per BTS guidelines ?
Follow up CT one year after baseline
— If stable on basis of 2D diameter value: CT 2 years after baseline . Then calculate VDT categories as per 1 year follow up
— Stable on basis of volumetry : discharge
— VDT >600 days : consider discharge (only if based on volumetry) or ongoing CT surveillance depending on pt preference
— VDT 400-600 days: consider biopsy or further CT surveillance depending on pt preference
- VDT <400 days or clear evidence of growth : further work up and consideration of definitive management
Incidental nodule ≥6mm or ≥80mm3 picked up on CT, talk through next steps
CT 3 months after baseline :
IF VDT ≤ 400 days / clear evidence of growth : further work up and consideration of definitive management
If VDT >400 days : repeat CT at 1 year from baseline and then
— if stable on basis of diameter then repeat CT 2 years from baseline (and VDT as per 1 year)
— if stable on basis of volumetry : discharge
— VDT > 600 days : consider discharge (only if based on volumetry) or ongoing CT surveillance depending on patient preference
— VDT 400-600 days : consider biopsy or further CT surveillance depending on patient preference
- VDT ≤ 400 days : further work up and consider definitive management
What variability in size of nodule is allowed ?
25%
An incidental sub-solid nodule is found on CT , what are the criteria that mean patient can be discharged ?
- Nodule <5mm
- Patient unfit for any treatment
- Nodule stable over 4 years
Incidental finding of sub-solid nodule >5mm , no previous imaging , talk through follow up
Repeat thin section CT at 3 months:
IF resolved : discharge
IF stable: assess risk of malignancy (Brock/ Morphology) patient fitness and preference
— Low risk of malignancy (approx <10%) repeat CT at 1, 2 and 4 years from baseline
— High risk of malignancy (approx >10%) or concerning morphology , discuss options with patient EITHER Thin section CT at 1, 2 and 4 years OR Image guided biopsy OR Favour resection /non surgical treatment
IF growth/altered morphology: favour resection / non surgical treatment
What do we mean by change in morphology of a nodule ?
Change in mass/new solid component
Patient presents with 9mm solid nodule , Brock score 40% , PET shows FDG avid, Herder score >70% risk what are the options for treatment. ? They are fit for surgery
Wedge resection with on-table frozen section - proceed to completion lobectomy during same anaesthetic
OR
Anatomical Segmentectomy if unfit for lobectomy
OR
Image guided biopsy , if malignancy confirmed - lobectomy if not confirmed can either have repeat biopsy or proceeding to excision / non surgical treatment if concern about false negative biopsy
Patient presents with 9mm solid nodule , Brock score 40% , PET shows FDG avid, Herder score >70% risk what are the options for treatment. ? They are NOT fit for surgery
Image guided lung biopsy possible and safe ?
if yes then go for this and if malignancy confirmed for SABR , RFA or conventional radical radiotherapy. If malignancy not confirmed consider repeating biopsy or proceeding to excision/ non surgical treatment if concern about false -ve biopsy ;
If not safe then for SABR, RFA or conventional radical radiotherapy
How many segments does the RUL have ?
3
How many segments does the RML have ?
2
How many segments does the RLL have ?
5
How many segments does the LUL have ?
5
(3 upper divisions and 2 lingula)
How many segments does the LLL have ?
4
How do you calculate predicted post operative value of DLCO or FEV1?
T is total segments ; ie 19- obstructed
(Don’t include non functioning segments)
R is residual segments left behind post op ; ie T - Functioning segments to be resected
So:
ppoValue = Pre-Op value/ T * R
On functional assessment pre operatively what is considered evidence of good function?
Shuttle walk test > 400m
CPET peak oxygen consumption >15ml/kg/min
What are the poor prognosis factors in SCLC?
Impaired PS
Weight loss
Increased age
Male gender
Elevated LDH
Low sodium
** In patients with locally advanced SCLC tx with CRT , hight tot gross tumour volume predicts worse outcome
Talk through treatment of limited stage SCLC which is stage 1-2 (T1-2, N0)
Surgical Resection offered
IF at resection pT1-T2 N0 R0 then for adjuvant chemo with Cisplatin and Etoposide (4 cycles)
IF at resection N2 and/or R1-2 then for concurrent CRT (*** Then evaluate , if no progression then :
PS 0-1 and ≤ 70years PCI
PS 2 and ≤ 70 years PCI
If > 70years or frail shared decision making with patient for PCI )
Talk through treatment of limited stage SCLC which is stage 1-3 (T1-2, N0-3)
If PS 0-1 : Concurrent CRT
If PS ≥ 2: Sequential CRT
**Then evaluate , if no progression then :
PS 0-1 and ≤ 70years PCI
PS 2 and ≤ 70 years PCI
If > 70years or frail shared decision making with patient for PCI
What is the preferred chemo regimen in Limited SCLC
Cisplatin and Etoposide as 3 week cycle , given as 4 cycles usually
- Cisplatin can be split over 3/7 to improve tolerability
- If Cisplatin contraindicated can give carboplatin
What is preferred Radiotherapy approach for SCLC
Standard of care if 45 Gy twice daily in 30 fractions over 3 weeks , when standard twice daily not possible can have 66Gy once daily in 33 fractions over 6 weeks
What is the role of PCI in SCLC ?
PCI decreases risk of symptomatic brain Mets and increases survival I. Patient with complete remission
What does is prophylactic cranial irradiation given at in SCLC?
25 Gy over 10 fractions
Who is offered PCI in SCLC?
PS 0-1 , response to CRT , <70 years
Can be considered in PS 2
What is the treatment option for extensive SCLC (Stage IV or Stage III not eligible for tx with curative intent) and PS ≥ 2 due to co- morbidities
Best Supportive Care
What is the treatment option for extensive SCLC (Stage IV or Stage III not eligible for tx with curative intent) and PS 0-1 with no c/i for ICI?
Carboplatin + Etoposide + Atezolizumab and maintenance Atezolizumab
Or
Platinum - Etoposide - Durvalumab and maintenance Durvalumab
What is the treatment option for extensive SCLC (Stage IV or Stage III not eligible for tx with curative intent) and PS 0-1 with c/i for ICI?
Carboplatin + Etoposide
Or
Carboplatin + Oral Topotecan
Or
Cisplatin - Irinotecan
If response PS 0-2
Then :
- Consolidation thoracic RT is an option
- if <75 years then for PCI or MRI surveillance
What is the treatment option for extensive SCLC (Stage IV or Stage III not eligible for tx with curative intent) and PS ≥ 2
Carboplatin + Etoposide (4-6 cycles)
Or
Carboplatin + Gemcitabine (4-6 cycles)
If response PS 0-2
Then :
- Consolidation thoracic RT is an option
- if <75 years then for PCI or MRI surveillance
How do you manage recurrence of SCLC?
Platinum Resistant Relapse (<3 months treatment free interval) :
IF Refractory &/ or PS> 2 for BAC and LURBINECTEDIN
IF PS 0-2 for Oral or IV Topotecan OR Cyclophosphamide -Doxorubicin- Vinicristine OR LURBINECTEDIN
—————————-
Platinum Sensitive Relapse (≥ 3 months treatment free interval)
Rechallenge with Platinum and Etoposide
Or
Oral or IV Topotecan
Or
Cyclophosphamide - Doxorubicin - Vinicristine
What are the ESMO follow up suggestions for SCLC patients ?
Limited stage who receive potentially curative tx should have CT every 3-6 months for 2 years with lengthening intervals after
Extensive stage disease potentially qualifying for further treatments should have CT every 2-3 months
Regular MRIs every 3/12 for the first year then every 6 months advised in those not undergoing PCI
Screening for NSCLC with LDCT has been shown to reduce cancer related mortality in which high risk subjects ?
55-74 years with ≥ 30 pack years or ≤ 15 years since quit
What is the treatment of unresectsble Stage III NSCLC?
Chemotherapy and Radiotherapy
IF no progression
Then for Durvalumab in PDL 1 ≥ 1%
What is the treatment for stage IB -IIIA NSCLC ?
RESECTION
If R1 resection THEN for post operative radiotherapy and then adjuvant chemotherapy
IF R0 resection THEN for adjuvant chemo , Cisplatin in combo with Vinorelbine/Gemcitabine/Docetaxel / Pemtrexed (non squamous , adenocarcinomas) if resected primary tumour ≥ 4cm for Carboplatin and Paclataxel. If completed resection EGFR exon 19 del or exon 21 , L858R substitution»_space; Osimertinib (NB data not entirely there as trial looked at T> 5 cm so < 5cm will be at clinician discretion
List the biomarkers for metastatic NSCLC
EGFR
ALK
ROS1
BRAF
NTRK
PD-L1
Which pts should have molecular testing ?
All patients w advanced /possible/ probably /definite adenocarcinoma should be tested
Molecular testing not recommended in Squamous Cell carcinoma except in never / long time ex /light (<15 pack years) smokers
Who gets offered systemic therapy in NSCLC?
Stage IV NSCLC w PS 0-2
What is the treatment for SCC?
Platinum based doublets with addition of third generation cytotoxic agent (Gemcitabine, Vinorelbine and taxanes) in those without major comorbidities and PS 0-2
What is the 30 day mortality for lobectomy and pneumonectomy ?
Lobectomy - <2%
Pneumonectomy 5.8%
At what dose does lidocaine toxicity develop in flexible bronch?
Levels >9.6mg/kg
What size of tumour would make patient suitable for SABR?
<5cm
Describe Horner’s Syndrome
Miosis, Ptosis, Enophthalmos, Anhydrosis
What is hypertrophic pulmonary osteoarthropathy?
Often associated with clubbing (any cell type, more common in squamous and adenocarcinoma). Periosteal bone proliferation with symmetrical painful arthropathy , predominantly large joints but hands and feet are involved
What is Lambert Eaton Myasthenic Syndrome?
-Associated with SCLC
- Symptoms may pre-date diagnosis of lung cancer by 4 years
- Proximal limbs and trunk with autonomic involvement (dry mouth, constipation, erectile dysfunction) and hyporeflexia , although reflexes return on exercising affected muscle group
- VGCC Antibodies cause it due to reduced acetylcholine release at motor nerve terminal
- Tx of underlying SCLC may improve neurology. If weakness severe can trial IVIG/ plasmapharesis with short term benefits. 3-4 diaminopyridine may increase muscle strength
What is limbic encephalitis ?
Associated with SCLC (also breast , testicular, other cancers)
Occurs within 4 years of diagnosis
Personality change , seizures, depression, subacute confusion and short term memory loss
Anti Hu Antibodies positive in 50% if associated with lung cancer
What is lymphangitis carcinomatosis ?
Infiltration of pulmonary lymphatics by tumour , may be due to lung cancer (or breast, prostate, stomach, pancreas)
Causes SOB and cough. Often sign of advanced malignancy
Oral steroids/ Diuretics can give symptomatic relief but usually part of rapid decline
What are current NHS stipulations re 2 WW referral times ?
TREAT within 31 days of decision to treat
TREAT within 62 days of urgent referral
DIAGNOSTICS requested by 28 days
Who should have a PET scan?
- All patients considered for radical therapy
- Patients with apparent N2-N3 on CT of uncertain significance who are otherwise surgical candidates
- Limited stage SCLC
NB any FDG avid node that would exclude patient from surgery if malignant should be confirmed with biopsy
Who gets false negative results with PET ?
Tumours with reduced metabolic activity (typically carcinoids), small ground glass nodules and hyperglycemic patients
Who gets false positive results with PET?
Benign pulmonary nodules with high metabolic rate such as infective granulomata/rheumatoid nodules
With bronchoscopic samples what makes them more likely to be histologically positive ?
- An endobronchial component to the tumour
- Tumour < 4cm from the origin of the nearest lobar bronchus
- A segmental or larger airway leading to the mass
Who do we undertake TBNA-EBUS in ?
PET avid and >10mm in the short axis on CT
NB nodes that are enlarged (>10mm on short axis) should be sampled prior to surgery for definitive nodal staging whether PET avid or not
For radiological guided lung biopsy what is seen as more favourable lung function?
FEv1> 1L (or >35% predicted)
*no absolute cut off
What is the median survival of limited SCLC treated and untreated ?
Treated : 15-20 months
Untreated 12 weeks
What is the median survival of extensive SCLC treated and untreated ?
Treated: 8-13 months
Untreated : 6 weeks
Describe treatments available for EGFR-TK mutations
17% NSCLC
Non smoking , Asian women
Treat with Tyrosine Kinase Inhibitor (TKI) : Afatinib, Dacomitinib , Erlotinib, Gefitinib
Toxicities: GI, Liver derrangements, Pneumonitis , Dry eyes , Corneal erosions
Describe treatments available for ALK gene rearrangements
- Fusion oncogene created when EML4-ALK are fused
- Younger patients with light / no smoking history
- Treat with Tyrosine Kinase Inhibitors : Alectinib, Crizotinib, Ceritinib
Describe treatment for ROS-1 gene rearrangement
TKI - Crizotinib
What treatments can we give to NSCLC advanced disease with PS0-2 who have no mutations but PD-L1>50%?
Pembrolizumab (Anti PD-1)
What treatments can we give to NSCLC advanced disease with PS0-2 who have no mutations but PD-L1 <50%?
Atezolizumab (Anti PD-L1 antibody) + Bevacizumab (VEGF inhibitor) + Carboplatin + Paclitaxel
OR
Pembrolizumab + Pemetrexed + (carbo/cisplatin)
OR
Pemetrexed + Carboplatin
OR
Other platinum doublet chemotherapy
What is the initial therapy for Squamous NSCLC ?
PD-L1 Expression ≥ 50% : Pembrolizumab
PD-L1 Expression <50%: Pembrolizumab + Paclitaxel + Carboplatin (if tolerated)
otherwise
(Gemcitabine /Vinorelbine) + (Carbo/Cisplatin)
Combined chemoradiotherapy may be given to some patients with stage III disease and this is Cisplatin and Etoposide if so
What are the side effects of chemotherapy ?
Nausea, myelosuprresion, ototoxicity , peripheral neuropathy, nephropathy if dehydrated , alopecia
What is the LFT cut off for radical radiotherapy?
FEV1 ≥ 1.5L
(RFA, FEV1 >1L)
What is SVCO?
Superior Vena Cava Obstruction , obstructs blood flow in SVC caused by external compression of the SVC by tumour extending from Right lung (4x more common than left) , LN or other mediastinal structure OR thrombosis within the vein.
Most common cause is malignancy and of the malignancies lung and lymphoma . 10% lung are SCLC
Usually a clinical diagnosis but can have CT . Stents gold standard , radiotherapy takes time to work (10/7)
Prognosis depends on underlying disease, not related to duration of SVCO
Why do patients with lung cancer get hypercalcemia?
Increased Osteoclast activity from boney Mets or production of PTH related protein
In malignant hypercalcemia PTH is suppressed
Causes of SIADH
Drugs (Fluoxetine, Carbamazepine, high dose cyclophosphamide)
Post major surgery
Pneumonia
HIV infection
CNS disorders (stroke, infection, psychosis)
SCLC (ectopic ADH secretion or stimulation of normal ADH secretion - poor prognostic factor)
What is pulmonary carcinoid?
- Uncommon primary lung tumour
- More common in women 40-50
- Form of neuroendocrine tumour , can have similar histology to SCLC , occasionally associated with MEN1
- Common endobronchially but can be peripheral
- Typically slow growing benign but may be more agressive
What are the symptoms of carcinoid?
Isolated wheeze , dyspnoea, infection, haemoptysis or persistent lobar collapse
Carcinoid syndrome with flushing , tachycardia , sweats , diarrhoea , wheeze and hypotension 2-5% predominantly with liver Mets
Can also cause Cushing syndrome due to ectopic ACTH
What scan is useful for carcinoid?
Octreotide scan or Ga68-DOTA-Octreotate PET have a role in staging
Normal PET has reduced sensitivity
What bloods / ix useful for carcinoid?
Standard + Plasma Chromogranin A
For carcinoid - 24 hour urinary 5HIAA
For Cushings- Cortisol + ACTH & 24 hour urinary cortisol
What do you see on bronch for carcinoid?
Cherry red covered with intact epithelium
Brushings may be adequate for diagnosis
Biopsy- significant concerns with bleeding
What are the histological types of carcinoid?
TYPICAL: no necrosis , occasional nuclear pleomorphisms and <2 mitoses , distant Mets rare
5 year survival 87-100% and 10 year survival 82-87%
ATYPICAL : focal necrosis, often multiple pleomorphisms , increased levels of Ki-67 expression , distant Mets 20%
5 year survival 30-95% , 10 year survival 35-56%
What is management of pulmonary carcinoid tumour ?
Isolated pulmonary carcinoid :
Surgical resection- lobectomy with nodal dissection
Endobronchial resection - may rarely be possible with intraluminal polyploid tumour with no CT evidence of extra liminal compression
IF METASTATIC
- isolated liver Mets - resection, RFA, arterial embolisation
- Hotmonal overproduction SSA (Octreotide )
- if heavy bulk can have SSA then local ablation or peptide receptor radionuclide therapy
- if advanced and unresectable then can have chemo - no standard regimen
What is the 5 year survival for Stage IA lung cancer ?
77-92%
What is the 5 year survival for Stage IB lung cancer ?
68%
What is the 5 year survival for Stage IIA lung cancer ?
60%
What is the 5 year survival for Stage IIB lung cancer ?
53%
What is the 5 year survival for Stage IIIA lung cancer ?
36%
What is the 5 year survival for Stage IIIB lung cancer ?
26%
What is the 5 year survival for Stage IIIC lung cancer ?
13%
What is the 5 year survival for Stage IVA lung cancer ?
10%
What is the 5 year survival for Stage IVB lung cancer ?
0%
What is ECOG PS 0
Fully active, able to carry on all pre-disease performance without restriction
What is ECOG PS 1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
What is ECOG PS 2
Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
What is ECOG PS 3
Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
What is ECOG PS 4?
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
What is ECOG PS 5?
Dead
Summarise the tumour markers of Adenocarcinoma
TTF1 positive
CK7 positive
Napsin A positive
Summarise the tumour markers of Squamous Cell Carcinoma
P63 positive
CK5 positive
CK6 positive
TTF1 negative
Summarise the tumour markers of Small Cell Carcinoma
TTF1 Positive
Neuroendocrine markers positive (CD56, synaptophysin, chromogranin)
Immunohistochemistry (IHC) testing reveals the sample is positive for calretinin, CK5, CK6, GLUT-1, and is negative for TTF-1, CK7, p63, and BerEP4.
Mesothelioma can be difficult to differentiate from pleural-based adenocarcinoma and the diagnosis can often rely on immunohistochemistry from a pleural biopsy. To confirm a diagnosis of mesothelioma, immunohistochemistry must show 2 positive mesothelial markers and 2 negative adenocarcinoma markers. Mesothelial markers include calretinin, CK5/6, Wilms’ tumour 1, D2-40, thrombomodulin, GLUT-1, and p53. Adenocarcinoma markers include TTF-1, CEA, Ber-EP4, Leu1, and CD15
What is included in the Brock Score ?
Age
Sex
Family history of lung cancer
Emphysema
No of nodule
Size of nodule
Type of nodule
UL nodule
Spiculated nodule
Why do a Brock?
Because if >10% alters nodule mx
What is the Herder score ?
Probability of malignancy based on PET
What is Brock score ?
Probability of Malignancy based on CT
What is included in the Herder Score?
Age
Smoking history
Hx of extra thoracic cancer
Nodule size
Nodule in UL
Nodule spiculated
Nodule PET avid
What is a <5mm ground glass nodule?
Atypical adenomatous hyperplasia
What is a > 5mm ground glass nodule?
Adenocarcinoma in situ
What is a <5mm part solid nodule?
Minimally invasive adenocarcinoma
What is >5mm part solid nodule ?
Invasive adenocarcinoma
What is the histology features for adenocarcinoma ?
Mucin, gland formation
(In lepidic, alveolar structure is preserved)
What is the histology features in squamous ?
Bridges, keratin pearls
What are the histology features in small cell?
Almost all nucleus , crowding
What are the features of benign nodules?
Perifissural or subpleural location
Lentiform or Triangular shape, macroscopic fat and calcification
