Oncology Flashcards
Diagnosis CRC
Clinical
- change in bowel habits
- > more common in left
- bleeding (haematochezia/malena)
- > more common in left
- anaemia
- > more common in right
- obstruction
- abdo pain
- > obstruction
- > peritoneal spread
- > perforation
- rectal or abdo mass
- rectal cancer
- > tenesmus
- > decreased stool caliber
- mets
- > liver
- > lungs
- > peritoneum
- > local lymph/supraclavicular nodes
Bloods:
- CBC
- LFTs
- > baseline
- > insensitive for mets
- EUCs
- > electrolytes
- > baseline
- > kidney function/contrast
- Iron studies
- Coags
- CEA
- > baseline, preop, post op decline and surveillance
Imaging
- Colonoscopy with biopsy
- CT colonography if colonoscopy unavailable
Risk factors CRC
Personal Hx (CRC or adenomatous polyps) Family Hx (CRC) Polyposis syndromes (FAP, MAP, Lynch) \+ SAAARRRCCOID -Smoking -Alcohol -Acromegaly -Androgen deprivation therapy -Radiation, pelvic (childhood cancer) -Renal transplant -Red/processed meat -Cholecystectomy -Cystic fibrosis -Obesity -IBD (UC) -Diabetes
management CRC
T1
-managed by local excision
Colon cancer
- hemicolectomy depending on site
- > 5cm proximal and distal margins
- lymphadenectomy
- > removal of mesentery to origin of named vessel
- > will contain paracolic and intermediate nodes
- neoadjuvant chemo
- > best evidence for stage III
- Surgical resection only curative option for local disease
- Decision as to presurgical radio/chemoradiation therapy. Best evidence for Stage III, disputed Stage II, certainly for rectal low lying
- post surgery chemo (oxaliplatin based) for 6 months. Treats micromets, decreases recurrence.
staging CRC
TNM system. Stage 0 = Tis. Invasion through lamina propria but not muscularis mucosae (as lamina does not contain lymph vessels) Stage 1: T1-2,N0,M0 -T1 = invasion into submucosa -T2 = invasion into muscularis propria Stage 2: T3-4,N0,M0 -T3 = invasion through muscularis -T4= locally invasive (4a= not adherent to local structures, 4b = adherent to local structures Stage 3: Tx,N1-2,M0 -N1 = 1-3 lymph nodes -N2 = 4 or more lymph nodes Stage 4: Tx,Nx,M1 M1 = distant metastases (usually liver, also lung, bone, brain)
Prognosis approx 95-90% for Stage 1 and 5% for stage 4.
pathogenesis CRC
CRC is thought to emerge from adenomatous polyps that become dysplastic. Adenomatous polyps occur when normal mechanisms regualting epithelial renewal are disrupted.
There are three broad modes of presentation, that likely represent different pathways along this adenoma-carcinoma sequence.
The first is sporadic which accounts for approx 70%. Here somatic mutations are accumulated in a stepwise manner due to environmental factors.
Truly inherited predispositions underlie approx 10% of CRC. Here, germline mutations predispose the individual to CRC, usually after acquiring further somatic mutations. There are polyposis syndromes such as FAP and MAP and non polyposis such as Lynch.
A third presentation, where there is a family history of CRC in the absence of one of the inherited conditions, is referred to as familial, which makes up about 25% of CRC. An example is Familial Colorectal Cancer Syndrome Type X. The mechanisms underlying this presentation are unclear.
pathophys CRC
There are three molecular pathways that lead to these presentations.
The first is the Chromosomal Instability Pathway, characterised by growth promoting mutations such as the oncogene RAS (kRAS; which becomes resistant to GTPase and is constitutively active as a growth signal transducer) and diminished activity of tumour suppressor genes such as APC, which regulates the Wnt pathway. Deletions in the long arm of chromosome 5, including the APC gene, underline FAP, but mutations in APC are thought to occur early in most sporadic presentations as well. Other tumor suppressor genes are p53 on chromosome 17, which occurs in the molecular sequence, and DCC on chromosome 18.
The second pathway is via defects in MMR. Though this can occur in sporadic disease, it is typical of Lynch syndrome in which there are mutations in hMSH 2 on chromosome 2 or hMLH1 on chromosome 3 that codes for the MMR enzyme. The resultant genetic signature has multiple stretches of incorrect nucleotide base pairs known as microsatelite instability.
The third pathway is largely epigenetic, which hypermethylation of CpG islands, including the promotor region for MMR enzymes such as hMLH1.
Familial Adenomatous Polyposis
Inheritance
- autosomal dominant condition
- 30% have no family hx
- > de novo mutations
- deletion in long arm of chromosome 5
- > including adenomatous polyposis coli gene (APC) which ->tumor suppressor gene
Associated with
- > 100 (usually thousands) of adenomatous colonic polyps
- almost 100% get CRC
- represents only 1% of CRC
- mesenteric desmoid tumours and congenital retinal pigment hypertrophy
- > Gardners
- CNS tumours
- > Turcots
- Attenuated FAP
- > fewer polyps
Management
- surveillance (sigmoidoscopy) from 10-15
- require colectomy after first polyp
MUTYH Associated Polyposis
Inheritance
- autosomal recessive
- mutation in base excision repair gene MUT-4H
- > predisposes to APC mutations giving polyposis phenotype
Management
- 2 yearly colonoscopy from 18 years old
- yearly after first polyp
- if polyps cannot be adequately controlled
- > require colectomy
Lynch syndrome (Hereditary Nonpolyposis Colon Cancer)
Inheritance
- defined by amsterdam criteria (replaced by bethesda)
- > 3 family members with CRC
- > at least one under 50
- > across two generations
- mutations in mismatch repair genes
- > hMSH2 on chromosome 2
- > hMLH1 on chromosome 3
- generally have one germline mutation and a second somatic
Associated with
- CRC
- > approx 30% risk
- > mostly right sided
- polyps are rare
- > those that occur have high cancer risk
- other cancers
- > endometrial
- > ovarian
- > gastric
- > urothelial
- > small bowel
Management
- annual surveilence from age 25
- high rate of metachronous cancer
- risk reduced by
- > subtotal with ileosigmoidal anastamosis
- > total with ileorectal anastamosis
Screening for CRC
Average risk
- faecal occult
- every 2 years
- > from 50-74
- if positive
- > colonoscopy as soon as possible
Risk categories
- category 1
- > 2x risk
- > 1 family member above age 55
- category 2
- > 3-6x risk
- > first degree younger than 55
- > two first degrees of any age
- > 1 first and two second degree
- category 3
- > 7-10x risk
- > two second degree with one before 55
- > three first degree
Surveillance of categories
- category 1
- > doesn’t benefit from colonoscopy screening
- > faecal occult every 2 years from 45
- category 2
- > faecal occult every 2 from 40-50
- > colonscopy every 5 from 50-74
- > low dose aspirin
- category 3
- > faecal occult every 2 years from 35-45
- > colonoscopy every 5 years from 45-74
- > consider low dose aspirin
- > consider genetic counselling
Staging approach CRC
Colonoscopy
- visualise lesion
- > distance from anal verge
- > grossly more T2 or more?
- biopsy
- > tis or T1
- synchronous lesions
CT chest abdo pelvis
- M and N status
- T4 status can be determined
- MRI of liver more sensitive
PET CT
- only used when mets are found
- > to more accurately detect small distal mets
MRI pelvis
-more accurately examines locoregional involvement for rectal cancers
pancreatic cancer background
epidemiology
-age >65
risk factors
- modifiable
- > smoking
- > obesity
- genetic
- > lynch syndrome and FAP
- > peutz jeghers
- > BRCA1/2
- > hereditary pancreatitis
histology
- majority arise in head
- exocrine (>95%)
- > adenocarcinoma (most are ductal)
- > from epithelial cells
- endocrine (<5%)
- > neuroendocrine
pancreatic cancer stages and treatment options
staging
- stage 1
- > limited to pancreas
- > whipples with chemo
- stage 2
- > beyond pancreas
- > not involving coeliac or superior mesenteric
- > whipples with chemo
- stage 3
- > involves coeliac/superior mesenteric
- > inoperable
- > palliative chemo and radiation
- stage 4
- > mets
- > palliative chemo and radiation
pancreatic cancer prognosis
prognosis
- 80% have stage 3/4 at diagnosis
- > early metastasis
- no screening program
- adeno
- > stage 1 = 30% 5 year survival
- > stage 2 = 10% 5 year survival
- > stage 3/4 = median survival 6 months
- neuroendocrine
- > much more favourable
pancreatic cancer investigations
FBC -thrombocytopenia in DIC -anaemia LFTs -obstructive pattern Coags -DIC -Trousseau's syndrome Cancer antigen 19-9
non-invasive imaging
- abdominal ultrasound
- > mass/dilated ducts/liver mets
- > lower sensitivity for tail
- CT with contrast
- > mass and spread
consider
- biopsy
- > only necessary for decision to palliate, not for surgery
- > ultrasound guided endoscopic biopsy
- > ERCP
- ERCP or MRCP
- > when CT equivocal
- > better visualisation with ERCP and option for biopsy
GTD background
types (CHIPE)
- choriocarcinoma
- hydatiform mole
- > partial
- > complete
- invasive mole
- placental site trophoblastic tumour
- epithelioid trophoblastic tumour
choriocarcinoma
- occurs with
- > complete molar pregnancy
- > within 1 year of non molar abortion
- > after term pregnancy
- presentation
- > PV bleeding
- > pelvic mass
- > mets symptoms
- > HCH always elevated
hydatiform mole
- complete
- > fertilisation of chromosomally empty egg
- > 46XX or 46XY of only paternal DNA
- partial
- > fertilisation of normal ovum by two sperms
- > 69XXY or 69XXX
- presentation
- > fetal parts, circulation, RBCs in partial
- > higher HCG in complete
- > hyperemesis gravidarum, hyperthyroid, HTN
placental site trophoblastic tumour
- many years after
- > molar pregnancy
- > non molar abortion
- > term pregnancy
- presentation
- > mets less common
- > gynaecological symptoms
- > low HCG
epithelioid trophoblast tumour
- follows
- > long after normal pregnancy
- presentation
- > HCG low
- > mets less likely
investigations, management and complications GTD
INVESTIGATIONS beta hCG -elevated FBC -anaemia from bleeding EUCs -chemo LFTS -chemo Coags -increased risk of bleeding with treatment Blood type with antibody screen TSH -hyperthyroidism
ultrasound -snowstorm appearance -absence of fetal cardiac activity CXR -mets
MANAGEMENT
- suction dilatation and evacuation
- hysterectomy
- all patients require contraception
COMPLICATIONS
- chorciocarcinoma
- invasive gestational trophoblastic neoplasia
- pre-eclampsia
- ashermans syndrome
types of lung cancer
Small cell (15%)
- neuroendocrine
- arising from major bronchi or lung periphery
- strongest association with smoking
- highly aggressive
- morphology
- > small
- > scant cytoplasm and nuceoli
- > granular chromatin
- immunophenotyping
- > CD56
- > neural cell adhesin molecule (NCAM)
- > synaptophysin
NSCC
- squamous and non squamous
- > squamous = p40 or 63 and mucin stains
- > adeno = thyroid transcription factor 1
- squamous
- > highly associated with smoking
- > resp epithelium of bronchi
- adenocarcinoma
- > glandular diff or mucin production
- > more peripheral than squamous
- > becoming most common
- > common in non smokers
- > adeno in situ, minimally invasive, invasive
- large cell carcinoma
- > least common of main
- > diagnosis of exclusion
- > lacks glandular or squamous or neuoendocrine differentiation (by light microscopy and immunophenotyping)
risk factors lung cancer
older age
COPD
family hx
smoking
- cigarrette
- > strong link
- > 30% in heavy user
- > risk proportional to use
- > declines but doesnt reach never smoker with cessation
- > cigars and pipes also
- > marijuana and ecigs less certain
- second hand
- air pollution
- indoor cooking
radon
- gaseous decay of uranium
- > miners
- > soil and housing
asbestos
-mainly occupational
diesel exhaust
paraneoplastic syndromes lung cancer
HAMCAN
- haematologic
- > anaemia
- > thrombocytopaenia
- > leukocytosis
- ADH (syndrome of inappropriate ADH secretion)
- > hyponatraemia
- musculoskeletal
- > hypertrophic osteoarthropathy
- > poly/dermatomyositis
- calcium (hyper)
- > lytic bone lesions
- > PTHrP
- Neurologic
- > Lambert Eaton syndrome (neuromuscular ACh release)
- > limbic encephalitis
- > ataxia
hx and exam lung cancer
Risk factors
Intrathoracic disease
- cough
- haemoptysis
- > represents cancer in up to 30% gen pop
- > bronchitis most common cause
- > pneumonia during red hepatization
- chest pain
- > dull and aching
- hoarseness
- > involvement of recurrent laryngeal
- pancoast syndrome
- > apical tumour
- > pain in C8, T1/2
- > hand and finger weakness
- > horners
- SVC syndrome
- > facial pleth
- > chest veins
- > widening mediastinum
- pleural effusion
Extrathoracic (mets)
- liver
- > al phos
- bone
- > pain
- > lytic lesions
- brain
- > headache, confusion, seizures etc
- adrenals
- > balot
Paraneoplastic (HAMCAN)
- fever
- anorexia
- fatigue, weakness
- weight loss
- nausea/vomitting
lung cancer complications of spread
Local spread:
- pleura
- > effusion
- chest wall
- > compression of intercostal nerves (neuropathic pain)
- brachial plexus (C8, T1,2)
- > pain in dermatomes and hand weakness
- pancoast syndrome
- > brachial plexus + inferior cervical ganglion/sympathetic chain
- SVC invasion
- > SVC syndrome
- recurrent laryngeal
- > hoarseness
Regional mets (lymphatic)
- hilar, mediastinal, supraclavicular nodes
- > oesophagus compression (dysphagia)
Distant mets (haematogenous)
- liver
- bone
- > pain
- > fractures
- > radiculopathy
- brain
- > seizures, confusion, headache
- adrenals
- > rarely symptomatic
small cell staging
Small cell
- limited
- > confined to ipsilateral hemithorax
- > disease within single radiation port
- extensive
- > bilateral involvement
- > mets
- > malignant effusion (can’t be encompassed within one port)
non small cell staging
Stage 1
-focal tumour
Stage II
- local spread
- > parietal pleura
- > chest wall
- > up to 2cm from carina
- nodes
- > hilar
- > mediastinum
Stage 3
- local spread with lymph nodes (hilar/mediastinal)
- local spread
- > great vessels
- > mediastinum
- > oesophagus
- > trachea
- nodes
- > contralateral
- > ipsilateral supraclavicular
Stage 4
-distant mets
bronchoscopy for lung cancer
flexible versus rigid
- flexible
- > conscious sedation
- > can visualise tertiary bronchi
- > diagnostic and therapeutic options
- rigid
- > larger
- > can only access proximal airways
- > requires general anaesthesia
- > used for interventions not available with flexible
flexible, conventional white light
- endobronchial brushing, washing or lavage
- > cytology
- > obvious lesions in airway
- transbronchial biopsy with forceps
- > peripheral, parenchyma lesions
- > not directly visualised
- > typically image guided (fluoscopy or ultrasound)
- > histology
- transbronchial needle aspirate
- > lesions and lymph nodes close to airways
- > guided by CT images in conventional
endobronchial ultrasound
- flexible bronchoscopy with hybrid scope
- > ultrasound probe attached
- real time ultrasound guidance
- > visualise anatomy
- > localise lymph nodes and peripheral lesions
- endobronchial needle aspirate or biopsy
- > cytology with aspirate
complications
- common
- > hypotension and hypoxia from sedation
- > bleeding
- > pneumothorax
- > nasal/throat pain
- > haemoptysis
- rarer but serious
- > broncho/laryngospasm
- > infection
- > cardiac arrthymias
lung cancer investigations
FBC -anaemia -leuko/thrombocytosis EUC -hyponatraemia -hypokalaemia (cushing/ACTH) CMP -hypercalcaemia LFTs -al phos Coags
CXR
-nodules, effusion, atelectasis, mediastinal mass
CT chest, neck, upper abdo with contrast
-tumour spread
-poor sensitivity for mediastinal staging
PET CT
-adjunct to CT (combination improves staging accuracy)
-more accurate evaluation of mediastinum and extrathoracic disease
-sometimes detects occult mets
-can guide biopsy
-not required if mets is already confirmed
Confirm diagnosis
- sputum cytology
- > high specificity, low sensitivity
- bronchoscopy
- > transbronchial needle aspirate most common
- > conventional or EBUS
- transthoracic needle aspiration
- > peripheral lesions unaccessible by bronchoscopy
- other lymph nodes
- > supraclavicular or neck
- thoracocentesis
- > if pleural effusion
- > presence of malignant cells
Pretreatment
- ECG
- pulmonary function tests
- staging scan (eg. MRI brain)
- genes (primary or metastatic lesion)
- > EGFR
- > ALK
- > ROS1
tumour genes lung cancer
epidermal growth factor receptor (EGFR)
- encoded by tyrosine kinase gene
- mainly adenocarcinoma
- never smokers
- detected by PCR
- benefit from EGFR kinase inhibitor therapy over chemo
anaplastic lymphoma kinase (ALK)
- rearrangements in gene
- adenocarcinoma in young non smokers
- detected by FISH
- benefit from ALK inhibitor therapy over chemo
ROS1
- receptor tyrosine kinase
- driver oncogene
- young, never smokers or light smokers
- adenocarcinoma
treatment workup lung cancer
division between surgical resection and inoperable (chemo/radiation)
- anatomic staging
- physiologic staging
- > patient’s ability to withstand treatment
- principally for NSCLC
- > small cell assumed to be systemic at time of diagnosis
anatomic staging
- inoperable
- > any criteria of stage 3 or 4
- > malignant pleural effusion
- > tamponade
- > within 2cm carina
- > phrenic and laryngeal nerve involvement
physiologic staging
- screen for comorbidities
- > basic bloods, ECG etc
- pulmonary function tests (COPD common)
- > FEV1 >2L or 80% predicted = pneumonectomy
- > FEV1 >1.5L = lobectomy
- cardiopulmonary exercise testing
- > for borderline lung function
- > maximal O2 consumption <15mL/kg = high post op complication risk
- secondary surgical options
- > wedge or anatomic segmental resection
- > higher rate of recurrence
- MI
- > within past 3 months = contraindication to thoracic surgery
- other major contraindications
- > uncontrolled arrhythmias
- > FEV1 <1L
- > PCO2 >45
- > DLco<40%
- > severe PHTN
treatment options lung cancer
NSCLC
- Stage 1A
- > surgery alone
- Stage 1B
- > surgery + adjuvant chemo
- Stage II or III with hilar or mediastinum nodes only
- > surgery + adjuvant chemo
- supraclavicular or contralateral nodes
- > no surgery
- > chemoradiation
- Stage 4
- > systemic therapy (chemo, immunotherapy)
- > pain management
- > radiotherapy
SCLC
- limited
- > surgically resection not usually recommended
- > can be performed with adjuvant chemo
- extensive
- > combined chemo + radiation preferable
- > alternate chemo/radiation if intolerable
