Lung Cancer Flashcards
operative mortality of different lung surgeries
- Pneumonectomy (5-10%)
- lobectomy (2%) - lowest mortality rate but also highest rate of recurrence
- wedge resection (<1%)
- open/close thoracotomy (5%)
what is the purpose of minimally invasive lung surgery?
avoid opening the chest like in open surgery. This prevents the intercostal muscles and nerves from being stretched and damaged.
side effects of chemotherapy
* side effect and duration depends on the course of chemo
- marrow suppressed and increased risk of fatal infection
- nausea, vomiting, GI upset, mucositis (breakdown of mucous membrane taht my extend to affect the GI tract)
- fatigue and lethargy
- hair loss, nail changes
- stroke
side effects of radiotherapy
- lethargy
- pneumonitis, dysphagia (difficulty swallowing) - these are acute symptoms
- long term fibrosis, stricture, increased MI risk, secondary malignancies
side effects of immunotherapy
- colitis
- pneumonitis
- dermatitis
- endocrinopathies
what are the 3 major causes of lung cancer?
- SMOKING - the biggest (10% of smokers have lung cancer)
- second hand smoking (increases your chance of lung cancer by 50-100%)
- asbestos, radon, chemical exposure
*tobacco + asbestos have MULTIPLICATIVE effect
lung cancer stats
- causes more deaths than prostate + breast cancer combined
- 10% of smokers have lung cancer but >85% of lung cancer is linked to smoking
- average 2-3 years survival
- second hand smoking causes 25% of nonsmoking cancer
- women are more susceptible to carcinogenic factors, and they take deeper puffs
other causes of lung cancer
- addictive oncogene drivers
- inherited predisposition to nicotine addiction (the liver easily mets procarcinogens in tobacco into carcinogens)
carcinogens in tobacco and what they do
- nitrosamines: adenocarcinomas at the side of the lungs
- polycyclic aromatic hydrocarbons (PAH): squamous SCLC at the center of the lungs
describe the multihit theory of carcinogens
for lung cancer to happen, there must be numerous mutations happening in the right order in the same cell, and there must be no other mutation that will cause the cell to die before becoming cancerous. This will require accumulation and multiple hits.
Although it seems like it is impossible to get lung cancer, there would be billions of cells affected while smoking and so the chances are not that low
histological progression of lung cancer
squamous dysplasia (half of the required mutations, treatment still possible) –> carcinoma in situ (CIS) –> invasive adenocarcinoma (malignant stage, usually the symptoms show at this stage where it is already too late for treatment)
describe addictive oncogene drivers
- susceptibility from birth to have mutations that will stimulate mutations in the oncogenes for lung cancer compared to how normally you would need accumulation of mutations
- common cause of lung cancer in nonsmokers
- common in Asians
- if we can identify the oncogene, we can pharmacologically interfere with it
tobacco induced and non-tobacco induced key driver mutations
Tobacco induced:
- EGFR (15%, the most common - can cause lung cancer all by itself)
- BRAF/HER2 (1-2% each)
- ALK (2%)
- ROS1 (1%)
non-tobacco indued:
- KRAS (35%)
list the 4 main types of carcinomas of the lungs
- Small cell carcinoma (SCLC) (15%)
Non small cell carcinoma (NSCLC):
- squamous cell (40%)
- adenocarcinoma (41%)
- large cell carcinoma (4%)
what kind of tumor is likely to be caused by smoking?
squamous cell carcinomas, there are very few suitable addictive oncogenes for this and are mostly caused by smoking
SCLC vs NSCLC
SCLC: very invasive and aggressive, surgery not a suitable treatment
NSCLC: (70-80%) not as invasive and surgery is preferred at initial stages
early symptoms of lung cancer
- can be clinically silent until malignant stage
- overlaps with COPD
- CXR lumps
- haemoptysis
local effect of lung cancer
- bronchial obstruction (collapsed lung, bronchiectasis, abscess, pneumonia)
- pleural effect (inflammation, effusion, malignant spread)
- direct invasion into chest wall
- nerves
- mediastinum (affects pericardium abd SVS)
- lymph nodes (local effects, including mets, lymphagitis, carcinomatosa)
- vascular invasion (like into the vena cava)
nervous effects of lung cancer
- phrenic nerve: diaphragmatic paralysis (uneven diaphragm)
- left recurrent laryngeal nerve (hoarse voice, yell-like coughs from paralysed vocal cords)
- brachial plexus, pancostal T1 damage (tingly fingers)
- cervical sympathetic (Horner’s syndrome affecting nerves in the face and eyes)
distant effects of lung cancer
- mets (to liver, adrenal glands, bones, brain, skin)
- skeletal (finger clubbing, hypertopic osteoarthropathy HPOA in small hand joints)
- endocrine (happens in SCLC) (1. excess ACTH/SIADH resulting in excess hormone symptoms, 2. excess PTH resulting in hypercalcemia)
- neurological
- cutaneous
- harmotologic - affecting the blood
- CVS (thrombus, inflammation)
- nephrotic syndrome
when to switch to palliative care?
when distant organs are affected by metastasis
things that prognosis of lung cancer depends on
- stage of disease
- histological classification (type of cancer - treatment will also differ)
- markers, oncogenes, gene expression profiles
- cell proliferation
- DNA aneuploidy
- immune cell infiltration
prognosis for lung cancer?
prognosis is usually bad <10% survive after 5 years (and only 10-15% gets surgery) - stage I operable >60% - stage II operable 35% 5 years survival by histology type: - NSCLC 10-25% - SCLC 4%, 9 months
target predictive biomarkers for each type of cancer
adenocarcinoma: EGFR, ALK, ROS1 (also KRAS, HER2, BRAF)
squamous cell carcinoma: no effective molecular targeted therapy, caused by accumulation of mutation from smoking
effectiveness of immunotherapy on cancer
- immunotherapy effective lung cancer that is caused by accumulation of mutations because this leads to production of abnormal proteins in which the immune system can recognize as nonself cells and attack
- nonsmoker lung cancer caused by oncogene drivers do no have enough mutation to produce enough abnormal proteins for immunotherapy to be effective.
- PD1/PDL1 and CTLA4 is another important immune checkpoints and therapeutic target. the drugs used to work against these are called immune checkpoint inhibitors
name the mutated oncogene and the chemotherapy drug used for each mutation
first line treatment
- EGFR (erlotinib, gefitinib, afatinib)
- ALK (crizotinib, ceritinib)
- BRAF (vemuratenib, dabrafenib)
- ROS1 (crozotinib)
- these drugs are kinase inhibitors
- make sure to rebiopsy after treatment because the nature of the tumor is always changing and the chemo plans would need to change as well
second line chemo treatment drugs
- docetaxel +/- nintedanib
- pemetrexed
- erlotinib
IRESSA vs carboplatin/pacitaxel
IRESSA works better in EGFR+ patients while carnoplatin/pacitaxel works well in both, but it works better than IRESSA in EGFR- patients
signs of lung cancer
- chronic coughing and other chest signs(hypercalcemia and anaemia are common causes of cough)
- haemotysis
- wheezing
- chest and bone pain
- chest infections, pericardial/pleural effusion, etc.
- nail clubbing
- unexplained weight loss
- SOB
- difficulty swallowing
- raspy, hoarse voice
- pancoast tumor
- lymphadenopathy
- skin and soft tissue nodules
- SVC obstruction
- hepatomegaly
- haematuria (blood in urine)
metastatic symptoms of lung cancer
- bone pain
- spinal cord compression (limb weakness, paralysis, bladder and bowel dysfuction)
- cerebral metastases (vomiting, headache, dizziness, focal weakness)
- thrombosis
paraneoplastic (activation of the immune system) symptoms of lung cancer
- hyponatraemia (low Na+)
- anaemia
- hypercalcemia (can be caused by PTH related protein, bone mets)
- dermatomyositis/polymyositis (proximal muscle weakness)
- Eaton-Lambert Syndrome (neuromuscular deficit due to insufficient release of neurotrasmitter acetylcholine by. nerve cells, resulting in upper limb weakness)
- Cerebellar ataxia
- Sensorimotor neuropathy
describe pancoast tumor
a type of tumor that begins in the lungs and spreads to nearby tissues and bones, common in lung cancer
doubling time in NSCLC vs SCLC
NSCLC: 129 days
SCLC: 29 days (more aggressive)
Initial investigations in primary care
- CXR (lung tumors are usually evident, but also look for pleural effusions, collapsed lungs, uneven diaphragm, chest wall invasions)
- FBC (Calcium levels, anaemia, blood enzyme level for liver function, abnormal bone profile-determines if fit for surgery)
- renal/liver functions
- spirometry
- clotting screen
further investigations (specials) for lung cancer
- CT/PET/MRI scan (CT for peripheral mets, PET for small tumors CT might miss, MRI for vascular and neurological involvements)
- bronchoscopy
- endobronchial ultrasound (EBUS) - (minimally invasive but effective procedure used to diagnosed lung cancer, infections, and other diseases causing enlarged lymph nodes in the chest)
- image guided lung/liver biopsy (check for mets)
- fine needle aspiration of neck nodes and skin mets (taking some cell samples)
- excision biopsy of cerebral mets
- bone biopsy/scan (do scan to check for mets and for damage after treatment)
- mediastinoscopy/otomy (catheter inserted through a small cut, down the trachea, and take out a lymph node)
- echocardiogram (detects pericardial effusion and determines if they are fit for surgery)
- bronchial brushings and washings (like bronchoscopy, but liquid is sprayed into a part of the lung and then sucked back up and taken to a lab)
Tumor staging - TNM staging (T)
Tx: tumor in sputum but not in detected bronchial washings or imaging
T1: no invasion, no nodules
- 1a: <2cm
- 1b: 2-3cm
T2: no invasion, no nodules, lobar atelectasis, involvement of the main bronchus, obstructive pneumonia
- 2a: 3-5cm
- 2b: 5-7cm
T3: >7cm, affects the whole lung, invades to diaphragm/chest wall/pleura/pericardium, lymph nodes and nerves, everything affected still within the same lobe
T4: invades to heart, great vessels, trachea, esophagus, spine, nodules and nerve effects found in the other lobe
TNM staging - N
N0: no regional nodal involvement
N1: ipsilateral hilar/peribronchial nodes
N2: ipsilateral mediastinal/subcranial nodes
N3: mediastinal/hilar/ipsilateral/contralateral scalene/supraclavicular nodes
*N2-3 surgery not useful, do RT or chemo
TNM staging - M
M0: no distant mets
M1: Yes distant mets
(need CT and PET to see)
progress of the cancer mets and spread
within the same lung –> lymph nodes/mediastinum of the same side –> lymph nodes on the other side and higher up –> lymph nodes in the other parts of the body
(last 2 stages surgery useless)
what are treatment decisions based on in lung cancer
- performance status
- desire of the patient
- cancer type and stage
- decision of the MDT
- whether the treatment is c radical or palliative
performance status
P0: fully active
P1: symptoms but no hospital admissions
P2: unable to work, but is up and bout more than 50% of the time
P3: has limited self care but still moving around 50% of the time
P4: bed bound
PS0-1: radical treatment
PS2: judgement
PS3-4: palliative care, will not survive toxicity of radical treatment
treatment options in lung cancer
- surgery (18%): wedge resection, lobectomy, pneumonectomy
- RT: can be radical, palliative
- chemotherapy: radical or palliative, used alone or in combination with another, adjuvant (after surgery), uses drugs that target specific agents and is effective in SCLC, adenocarcinoma, squamous carcinoma
- stereotactic ablative radiotherapy (SABR): like radiotherapy but better because it only targets cancer cells
- palliative and best supportive care in coordination with specialists for lung cancer
examples of palliative care in lung cancer (essentially treating the symptoms)
- RT/chemo
- opiates, bisphosphonates, benzodiazepines (tranquilizers)
- treat hypercalcemia, dehydration, hyperatremia
- emotional and community support
red flag signs of lung cancer
- weight loss
- night sweats
- fatigue
* these are red flag signs even if the patient does not cough or smoke
what makes metastatic diseases more dangerous?
its proximity to mediastinal structures will complicate the surgical procedure or if it involves the pleura, pericardium, and diaphragm
clinical assessment for fitness of surgery - CVS
- angina, other heart problems
- high bp (chronic high bp above 140/90 will result in thickening of the heart muscles and kidney failure)
- diabetes (slow healing post-op, kidney problems)
- peripheral vascular disease
- stroke/TIA
- carotid bruits (indicates plaque/cholesterol build up in the arteries)
- previous CABG or angioplasty (PTCA)
- heart murmurs
fitness for surgery - respiratory
- pectus carinatum - barrel chested from emphysema
- COPD
- smoking
- recent UTRI
- on oxygen
- previous thoracotomy of implantable cardioconverter-defibrillator (means that there is arrhythmia)
fitness for surgery - other systems
- mental illness, anxiety
- unsupportive social background
- chronic pain problems
- pulmonary hypertension
- rheumatoid arthritis
- bed bound (will not survive the recovery process)
- cirrhosis (liver cannot clear toxins in the blood, will die from infection and septic shock)
- had chest RT (immune system weakened from radiation, might still work in young fit people)
importance of resp testing before surgery?
check that after you have removed some of the lung, the remaining bits can function sufficiently
goals of lung surgery
- curative resection
- removing the least we can to preserve resp function and faster recovery
- avoid thoracotomy (opening the chest, aim for minimally invasive)
- make sure it really is a tumor before the operation
cause of post-op death
- acute resp distress syndrome (main complication, caused by inflammation that prevents O2 from getting into the lungs)
- bronchopneumonia
- MI (if you already have heart issues, the heart will need to work harder now that there is less lung)
- pulmonary thromboembolism
- pneumothorax (because the pleura is punctured during surgery, put in drain and wait for recovery)
- surgical emphysema (air leak from the remaining stump of the bronchi –> subcutaneous air)
- intrathoracic bleeding
- wound infection
- empyema
- bronchopulmonary fistula (BPF) (possible infection from the air that may leak in from outside bringing bacteria with it–>empyema)
- AF (common, happens 50%)
- gastroparesis and constipation (side effect of morphine painkillers given post-op)
mis-staging of lung cancer causes
- lobar collapse so size of tumor is hard to determine
- presence of another pulmonary nodule causing confusion
- restrosternal thyroid (thyroid being in the wrong place)
operative mortality of the different types of surgery
- pneumonectomy (5-10%)
- lobectomy (2%)
- wedge resection (removal of lung mass) (<1%)
- open/close thoracotomy (5%)
tumors in the lung that are not cancer, but can confuse you in CXR
- TB, lung abscesses
- beingn tumor
- granuloma (sarcoid)
- rheumatoid nodule
- inflammatory pseudotumor
- fibrosis (organizing pulmonary infarct)
what are oat cells
the kind of cells present in SCLC histology
ECOG performace status (Eastern cooperative group)
0- symptomatic, well 1- symptomatic, able to do light work, live normally 2- rests for <50% 3- rests for >50% 4- bed bound 5- dead
units of measurement in RT
radiation dose measure in grays (Gys)
varies, but average is 45-60 Gys in 1.8-2 Gy fractions
post-operative treatment NSCLC
- chemo: increases chance of cure by 15% and 5 years survival increases by 50%, good for stages I-II
- RT: detrimental in stages I-II, use in mets
- immunotherapy: evidence of benefit when using Durvlumab for stage III
pre-operative treatment NSCLC
- chemo: no benefit in stages I-II, but benefits in stage III
- RT: beneficial in stage III for dose >55 Gy for 12 days, 5 year survival increases by 20%
- alternation between RT and chemo seems to give the best outcome, but also with toxicity, 2 year survival 27%
- SABR: 54 Gy in 3 fractions high dose for 1 week will give similar outcome as surgery and therefore sometimes used as alternative for those unfit.
what test is essential before RT
pulmonary function test
palliative care in advanced NSCLC
- 80% of NSCLC patients in this stage (stage III: 30% locally advanced, stage IV: 60% distant mets)
- RT in stage IV: improves symptoms by 70% but does not improve mortality
- chemo in stage IV: increases survival to >12 months
- 3-6 cycles of repeated chemo followed by a break to let the body recover will improve survival by 3-5 months
- single fraction RT for painful bone mets (palliative)
- resection, RT, steroids, erlotinib for brain mets
- immunotherapy for mets desiease
symptoms of SCLC
similar to NSCLC with addition of
- syndrome of inappropriate antidiuretic hormone secretion (SIADH): condition where the body makes too much antidiuretic hormone (ADH) which results in water retention
- Cushings: excess cortisol hormones
two stages of histology in SCLC
- limited disease SCLC
2. extensive disease SCLC
treatment options for limited disease SCLC
- CHEMO: treatment of choice, try to combine drugs if patient is fit enough, better if used with thoracic RT
- prophylactic cranial irradiation (PCI): for brain mets in very aggressive cancers like SCLC
treatment options for extensive disease SCLC
- PCI: standard treatment
- 4 cycles of only combination chemo
- RT: considered if not fit for chemo
- RT + steroids for brain mets
things that did not help treat limited disease SCLC
- high dose of chemo, alternating chemo, maintenance chemo (taking breaks), chemo on demand
- targeted therapies
- maintenance interferon
- although the disease is quite responsive to chemo due to its rapidly proliferating nature, it also develops resistance really fast, need to change drugs often
limited disease SCLC outcomes in lung disease
- response rate 90%
- complete remission 60%
- median survival: 8 months without treatment, 16 months with treatment
- 2 years survival 25%
extensive disease SCLC outcomes
- response rate 80%
- complete remission 3-%
- media survival: no treatment 8 weeks, with treatment 8 months
