lung cancer Flashcards
are all lung cancer patients smokers?
no. 10-15 % of smokers have never smoked
where is cancer in rank of types of cancer death causes?
its the first
risk factors of lung cancer (age, sex and 2 others?
age - peak 75-90
sex M>F
lower socioeconomic status
smoking (biggest single factor- duration, intensity, when stopped)
causes other than smoking
Passive smoking (~15% of never smokers)
Asbestos – exposure (plumbers, ship-builders, carriage workers, carpenters, etc) – risk up to x2
Radon – e.g. silver miners in Germany late 19th century; 1950s uranium mining in Colorado
Indoor cooking fumes – wood smoke, frying fats
Chronic lung diseases (COPD, fibrosis)
Air pollution
Familial/ genetic – several loci identified
what cells can lung cancer arise form?
ALL differentiated and undifferentiated cells
describe the pathogenesis of lung cancer: (how does it arise in a cell)
1) interaction between inhaled carcinogens and the epithelium of upper AND lower airways
2) formation of DNA adducts: DNA pieces covalently bound to a cancer-causing chemical
(note: specifically oncogenes- tumour suppressor genes- key to pathogenesis of lung canc)
3) persisting DNA adducts/ misplaced lead to mutation causing
4) GENOMIC ALTERATIONS
what factor distinguishes different types of lung cancer diseases?
cell type form which cancer originates
2 broadest categories of lung cancer diseases and which is more aggressive
Non small cell lung cancer (includes: squamous cell carcinoma, adenocarcinoma, large cell lung cancer)
and
small cell lung cancer (more serious / dangerous/ highly malignant )
what is the positive thing about small cell lung cancer?
responds well to chemo
what cells does small cell lung cancer originate from
pulmonary neuroendocrine cells
what cells does large cell lung cancer originate form
heterogenous group of cells that are undifferentiated
cell origin of adenocarcinoma and location in pulmonary system
mucus producing glandular tissue - more peripherally located
squamous cell carcinoma : what part of pulm epithelium does it arise form? location in resp system ?
bronchial epithelium, centrally located
prevalence of each type of cancer cell diseases and how has this recently changed
40% adenocarcinoma most prevalent from 1980s onwards due to low tar cigarettes, inhaled more deeply / retained longer
30% squamus cell carcinoma (used to be most prevalent)
large cell lung cancer 15% = small cell lung cancer 15%
why do we care to know the relevant oncogenes?
for directed treatments
what is tyrosine kinase?
enzyme that regulates growth, proliferation and differenciation
what are some important oncogenes in non smokers
epidermal growth factor RECEPTOR (EGFR) tyrosine kinase
(women, asian)
anaplastic lymphoma KINASE (ALK) tyrosine kinase
(younger)
c-ROS oncogene 1 (ROS1) RECEPTOR to tyrosine kinase
(Younger)
oncogene for smokers
BRAF (downstream cell- cycle signalling mediator)
what type of lung cancer is each oncogene associated with
EGFR: 15-30% of adenocarcinomas
the rest are
2-7% ALK
1-2% c-ROS
1-3% BRAF
:non small lung caners
KEY SYMPOTMS OF LUNG CANCER
weight loss
cough
breathless
fatigue
chest pain
haemoptysis
common or uncommon to have asymptomatic lung canc?
common
features of advanced metastatic disease (3 categories and specifics) (features: diseases in the body)
1) neurological features a) focal weakness, b) seizures c) spinal cord compression
2) bone pain
3) paraneoplastic syndromes
a) clubbing (fingers thing) b) hypercalaemia c) hyponatraemia d) cushings
signs of lung cancer
cachexia: (loss of muscle and fat- skeleton looking)
horners syndrome : one eyelid dropped: (happens bc lung cancer compresses sympathetic nerve going up)
clubbing: fingers tips big and weird nails
pemberton’s sign (superior vena cava obstruction - red face when raise hans)
diagnostic strategy of lung cancer
1) establish mokst likely diagnosis
2) establish fitness for investigation and treatment
3) confirm diagnosis and histological type (alse genomic test it consideringn systemic treatment in nsclc- all these tests also gelp tetermine treatment)
4) confirm staging
what has changed in terms of lung cancer screening?
people at high risk (basically smokers 55-74- age group younger than actual peak of disease prevalence bc balance tryna be found with quality of life- more life for younger) invited for screening
what scan do you see lung cancer?
x ray
what scan do you stage lung cancer and what specific area?
ct- chest and abdomen
when is PET- ct used and why is it appropriate for that use
to exclude occult (hidden) metastases ex in lymph nodes ect ]
Metabolic scans, patients get fdg, glucose, glucose goes to areas of high metabolic activity – higher uptske of gluc light up – so tumours light up
what determines what type of biopsy you do?
accessibility, availability and impact on staging
what are the 3 types of biopsy and when do you do each?
bronchoscopy using a fibrotic ENDOSCOPE - useful for tumours of central and segmental airways (also useful to visualise tumour before surgery)
stage mediastinum +/- achieve tissue diagnosis
CT guided lung biopsy - to access peripheral lung tumours
3 components/ scales of IASLC (International Association for the Study of Lung Cancer) 8th edition lung cancer staging system
TNM
T1-4: size and location
N: 0-3: lymph node involvement mediastinum and beyond
M0-1c: metastases + number (= M1a, 1b, 1c)
what is M0, M1A, M1B, M1C?
m0: No distant metastases
m1a: malignant pleural pericardial effusion or nodules
m1b: single extrathoracic metastasis
m1c: multiple extrathoracic metastasis
what are N0, N1, N2, N3
0: no regional node metastasis
n1: ipsilateral pulmonary or hilar nodes
n2: ipsilateral mediastinal/ subcranial nodes
n3: contralateral mediastinal/ hilar or supraclavicular nodes
what is t1 t2 t3 t4
t1: </= 3 cm
t2 is either: 5 >/= t2: > 3
OR involves visceral pleura / main bronchus
t3: either 7>/=tumor >5
OR invading chest wall, pericardium, phrenic nerve
OR if theres separate tumor nodule in same lobe
t4: >7 cm
OR invading MEDIASTINUM, diaphragm, heart, great vessels, reccurent larengeal nerve, carina, trachea, oesophagus, spine
what are the T1a T1b T1C and T2a T2b
is you remember the large range, they are the splits of each cm so
t1a</= 1
1<b</=2
c: 2-3(=)
t2a 3-4(=)
t2b 4-5(=)
what dimension of the tumour counts or tumour size?
the biggest dimension
check slife 22 with images
detemrinants of treatment
disease related:
cancer stage, histology
patient related:
patient fitness, patient preference
resource related:
health service factors
0-5 scale of patient fitnes based on who - perofrmance status
0: asymptomatic, completely capable of pre-disease activities
1: symptomatic but completely ambulatory, only thing they cant do is strenus exercise
2: sumpotmatic but more than 50% of the time mobile, can do all self care but not some extra work
3: sympotmatic more than 50% chair or bed bound, difficulty in self care
4: totally disabled and completely confined to bed or chair
5: death
is surgery resection standard care approach for any stage in disease?
yes, for early stage
what is the usual parts rmeoved in surgery of early stage?
lymphadenectomy and lobectomy or sublobar resection if stage 1
what is an alternative that patients can choose other than surgery for early disease? when is it particularly prefered? explain that method a bit
radical radiotherapy - stereotactic (σκέψου τον κρατάμε στερεό και ατακ) ablative body radiotherapy
when there are comorbidities
high percision targeting with multiple convergent beams (v high radioactive dose)
why is surgery still more effective than radical radiotherapy?
because you also remove lymph nodes whereas in radiotherapy u dont adress lymph nodes that may have microcancer
what are the types of systemic treatment?
immunotherapy, oncogene directed treatment, cytotoxic chemotherapy
when are oncogene directed treatments given?
when there is
1) no SCLC
2) theres metastasis
3) theres mutation
when do you give immunotherapy?
when there is
1) NO SCLC
2) theres metastasis
3) no mutation
4) PDL1>/= 50% (you stain for this)
when do you give cytotoxic chemotherapy?
same criteria as immunotherapy and you give it along with immunotherapy
NICE approved medications for EGFR mutation?
erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK approved meds
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ros-1 targeted meds
ROS-1: crizotinib, entrectinib
What is the effect of oncogene targeted treatment compared to chemotherapy in terms of progression free survival and overall survival?
oncogene targeted therapy is more effective in terms of progression free survival but less in overall survival (trials for erlotinib and crizotinib showed same trend)
side effects of oncogene targeted therapy
rash, diarrhoea and uncommonly pneumonitis
generally tablet is well tolerated though
NICE approved immunotherapy drugs
Pembrolizumab, atezolizumab, nivolumab
efficacy compared to chemotherapy ?
better progression free survival AND overall survival
side effects of immunotherapy
generally well tolerated
immune related side effects in 10-15 % 9THYROID, SKIN, BOWEL, lung, liver)
what is the mechanism of immunotherapy?
- theres the PD-L1 receptor in tumour cells that binds PD-1 on T cells and inhibits t cell from killing tumor cell
- treatment is anti-PD-1 and anti PD-L1 so antibodies bind on both sides of this interaction and the t cell is now allowed to kill the tumour cell
what chemical element are cytotoxic chemotherapies all based on? give drug examples
platinium- based regiments
eg carboplatin, cisplatin, paclitaxel, pemetrexed
which immunotherpay drug have there been trials about/ evidence
pembrolizumab
efficacy of chemotherapy
when sued alone MODEST imporvements in ONE YEAR survival compared to best SUPPORTIVE CARE
however much worse than pembrolizumab which has 23% surv rate for 2 yrs vs 5% chemo
side effects of chemo
fatigue
nausea
bone marrow supression
nephrotoxicity
quality of life poorly rate din trials…
palliative supportive care when is it given and what it involves?
Should be offered as standard to all patients with advanced stage disease
Symptom control, psychological support, education, practical and financial support, planning for end of life
key group of specialists in palliative care
lung cancer nurses
efficacy of palliative care?
1) survuval rates improved
2) quality of life imporved (less depression
3)
what is the difference between chemo given in early stage disease vs locally advanced?
first is curative intent instead of surgery, second is ADJUVANT, meaning given along with surgery (after)
what is another treatment plan for locally adv dis other than surg and chemo
radiotherapy and chemotherapy and maybe also immuno
categories of metastatic disease based on treatment
with targetable mutation (tyrosine kinase inhibitor)
no mutations and PDL-1 positive or negative
palliative care alone or with the above (patient wishes)
