oncology Flashcards
describe the stage of the WHO performance status and the relevance to cancer patients
0 - no symptoms, normal activity
1 - symptomatic, able perform daily activities
2 - symptomatic, bedbound <50% day, needs some assistance
3 - symptomatic, bedbound >50% day
4 - bedridden
5 - dead
only consider treating people between 0-2
treatment intents:
- neo-adjuvant
- radical
- adjuvant
- palliative
neo-adjuvant - given before curative (surgery) to shrink it or remove micro metastases that may cause re-occurance
- radical - curative (mainly surgery) and long term control
- adjuvant - after curative intent treatment eg chemo/radio - reduce micro-metastases
- palliative - shrink + control but not get rid - preserve QoL + prolong
how does chemotherapy work
broadly by damaging DNA:
- directly by binding
- indirectly - affecting replication/miosis
what is radiotherapy
is the use of high energy x-rays in carfully measured doses to damage
- ionising - energetic enough to displace an electiron from its orbit around a nucleus. this electron can go on and interact with other atoms
how is radiotherapy used?
- brachytherapy ?
what is immunotherapy
systemic agents that aim to stimulate a patient own immune system to attack cancer cells
- good for melanoma
s/e of immunotheraopy
autoimmune toxicities
- colitis most common eg lots of diarrhoea
what are and name some targeted agents
inhibit specif
important things to consider with palliative patients
ask them what else they are putting themselves on at the minute - ensure not interacting with actual treatments eg weird diets/pills from internet
treatment related oncological emergencies
cytopenias - neutropenic sepsis electrolyte disturbance tumour lysis syndrome diarrhoea vomiting anaphylaxis extravasation radiotherapy s/e
in what day of the 3 week cycle are they neutropenic
7/8
tumour related oncological emergencies
spinal cord compression SVCO upper airway obstruction brain mets bowel obstruction
most appropriate treatment for cancer associated thrombosis?
dalteparin first
or rivaroxaban
what do you always pair with dexa when prescribing
antiemetic
when does spinal cord end
L1
define hypertrophy
Increase in size of cells -> increase in size of organ
Physiological (response to functional demand) e.g. cardiac at athletes, pathological (response to abnormal increase demand) e.g. cardiac at hypertension
define hyperplasia
Increase in number of cells, may be associated with hypertrophy
Physiological e.g. breast at puberty, pathological e.g. psoriasis
define atrophy
Decrease in size of cell/organ due to cessation of growth. Atrophy is an adaptive response (use it or lose it)
Pathological: disuse (post fracture), loss of innervation (nerve transection), loss of blood supply (due to hypoxia e.g. skin at varicose veins), pressure atrophy (tissue compression e.g. bed sore), lack of nutrition, hormone induced (@skin following corticosteroids)
define dysplasia
Abnormal increased cell growth with 1) cellular atypia 2) decreased differentiation (pre-malignant, but reversible at early stage)
define metaplasia
Transdifferentiation: transformation of one terminally differentiated cell into another e.g. Barrett’s = squamous -> glandular, cigarettes = respiratory to squamous
necrosis vs apoptosis
apop
Programmed cell death (individual cell deletion in physiological growth control and in disease.
necro
Death of cells/tissue from ischaemic, metabolic or traumatic cause.
Failure of membrane integrity.
carcinogenesis
Transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
benign v malignant
Benign: Localised Non-invasive Closely resemble normal structure Circumscribed/encapsulated Nuclear morphology = normal Necrosis and ulceration rare Growth exophytic (up and out) Morbidity/mortality - pressure on adjacent structures, flow obstruction, hormone production, transformation to malignant
malignant: Invasive Metastatic Rapid growth Variable resemblance to normal structure Poorly defined border (crablike) Increased mitotic activity Necrosis and ulceration common Growth endophytic (down and in) Morbidity/mortality - destroy surrounding tissue, metastases, blood loss ulcers, flow obstruction, hormone production, paraneoplastic syndrome
names for benign epithelial lesion
papilloma
adenoma
names for malignant epithelial lesion
carcinoma
adenocarcinoma
connective tissue benign lesions
the OMAs
lipoma, osteoma, angioma, rhabdomyoma (striated), leiomyoma (smooth)
connective tissue malignant lesion
sarcoma
what does poor differentiation mean
high grade
what does well differentiated mean
low grade
what would you expect from these grades of cancers 1 2 4 X
Grade 1: cancer cells look like normal cells and are growing slowly
Grade 2: cells look less like normal cells and grow more quickly
Grade 3: cells look abnormal and are growing quickly
Grade X: grade can’t be assessed
what is radiotherapy
High energy beam of X-rays delivered to precise area using linear accelerator - causes DNA damage. Dose in Grays (1 Gray = 1 J/kg)
May be used as sole treatment or with surgery (before - neoadjuvant, post resection - adjuvant)
types of radiotherapy
External beam radiation therapy - using CT/MRI to target tumour
Internal radiation therapy - brachytherapy - radiation source placed near target tumour
Stereotactic radiotherapy - involves very accurate treatment, may be good for small discrete lesions
complications of radiotherapy
Acute (during treatment or <2-3 weeks):
Fatigue (80%)
Skin - Erythema, dry and moist desquamation, irritation
GI - loss of taste, oral mucositis (complicated by yeast/bacterial superinfection), diarrhoea, nausea, vomiting
BM - cytopenias
Lungs - pneumonitis, fever, cough, dyspnoea
Chronic Infertility Lymphoedema Delayed healing Loss of salivary flow Transverse myelitis, Lhermitte’s Increased risk CV events/stroke Hypothyroidism
chemotherapy how given its target types routes
Chemotherapy does not tend to be curative (except in leukaemias, lymphomas)
It may be neo-adjuvant (before surgery) or done in combination with surgery if patient is younger/curative cancer
Given in cycles (3 weekly) to allow normal cells to recover
Tends to target fast replicating cells e.g. gut mucosa, hair and bone marrow
types Alkylating agents - Chlorambucil, carmustine, darcarbazine Cytotoxic antibiotics - Doxorubicin, bleomycin Antimetabolites - 5-fluorouracil, methotrexate (NEVER INTRATHECAL) Topoisomerase inhibitors - etoposide Mitotic inhibitors - Vincristine (vinca alkaloid), paclitaxel (taxane) Platinum compounds e.g. cisplatin
route
Oral, IM, IV, intrathecal, topical
s/e of chemo
side effects: Myelosuppression - anaemia, infection, bleeding One week after, FBC prior to admission Alopecia Infertility Nausea, vomiting and diarrhoea Major cause of distress - use domperidone or metoclopramide Fatigue Teratogenicity Mouth ulcers
what is extravasation
mgmt
Is a problem with chemotherapy
Associated with pain, redness and inflammation -> may lead to skin necrosis + amputation (dissolving soft tissue). May see brown demarcation of veins
Maintain high index of suspicion with blotching/blistering
Reduce risk by administration by trained personnel
Rx: Topical agents e.g. dimethyl sulfoxide, heat, cold, debridement and grafting may be required
biological therapies
how do they work
types
Designed to boost body’s defences by:
- Stop/slow growth cancer
- Stop spread of cancer
- Help immune system
types
Monoclonal antibodies
Non-specific immunotherapies - interferons and interleukins
Oncolytic virus therapy - melanoma (T-VEC)
T-cell therapy
Cancer vaccines
what do you need to know to consent
Logistics Benefits (pros) SE (cons) Alternatives Prognosis
anaphylaxis
what type of reaction
mgmt
t1 hypersensitivity
Stop the drug
Perform ABCDE assessment - if anything is deranged consider anaphylactic reaction rather than strong allergic reaction - airway management, fluid resuscitation, IM adrenaline (0.5mg), IV hydrocortisone + IV chlophenamine/piriton
may recur 4-12 hours so beware
neutropenic sepsis why @ risk suspect when def ix mgmt
why @ risk
Is a risk due to myelosuppression
Suspect with fever in anyone who has had chemotherapy in the last 6W
Defined as neutrophil count of less than 1 per high power field or severe neutropenia = NP < 0.5 x 10^9/L (mod = 0.5-1)
Pyrexia or temp > 37.5 taken at >1 site >1 hour apart
BUT may not get a temperature
Ix
Want to take FBC, LFT, U + Cr, CRP, lactate, blood cultures (multiple sites), urine culture, NOT LP (may introduce infx), swabs and cultures from central line (each part)
mgmt
IV ABX according to local policy -> Beta lactam monotherapy piperacillin and tazobactam (Tazocin), or gentamycin (sometimes) ± G-CSF ± fluconazole (thrush), ± aciclovir (VZV)
spinal cord compression epi pres where ix mgmt
epi
Occurs in 3-5% of those with known cancer
Occurs in 10% of those with known spinal metastasis (bronchus, breast, prostate, mm)
Presents with PAIN ± sensory loss at level ± weakness below level ± loss of continence
where
70% are thoracic, 20% are lumbosacral, 10% are cervical, below L1/L2 think cauda equina
ix
Perform a peripheral nerve exam + percuss spine
MRI whole spine, refer to neurosurgery/spinal surgery
mgmt
IV DEXAMETHASONE + prevention VTE
painful spine mets mgmt
Analgesia (NSAID/non-opiate/opiate)
Bisphosphonates if myeloma/breast cancer (lytic lesions)
Palliative radiotherapy
Vertebroplasty
DVT/PE in cancer patients
why high risk
Both the cancer and its treatment (higher number of platelets and clotting factors)
Surgery and chemotherapy may damage vessel walls (increased clots)
Patients tend to be less active
why haemorrhage risk in cancer patients
Both chemotherapy and disease process may lead to low platelets
Cancer may cause direct erosion of blood vessels (n.b. major blood vessel = fatal)
Decreased clotting factors with liver metastasis or chemotherapy
Consider NSAIDs for pain, topical tranexamic acids/adrenaline soaks, oral tranexamic acid
hypercalcaemia of malignancy mechs def causes types symps ix mgmt
mechs
- Secretion of PTH related peptide by tumour (humoral hypercalcaemia)
- Local release of factors increasing osteoclast proliferation (local osteolytic hypercalcaemia) - including PTH-rP
- Autonomous production of calcitriol by lymphoma
def 10% of malignancies assoc hypercalcaemia, 20% hypercalcaemias due to malignancy
causes
Humoral - renal, ovarian, breast, endometrial, squamous cell carcinoma
Local osteolytic - breast, multiple myeloma
Calcitriol mediated - lymphoma and granulomatous disease
Ectopic PTH (small cell lung Ca)
20% due to unrelated hyperparathyroidism
types
humoral
local osteolytic hypercalcaemia
calcitriol mediated
symps
Dehydration + bones, stones, abdominal moans, thrones, psychic overtones
Poor skin turgor/dry mucous membranes (DEHYDRATION)
Bone pain (BONES)
Abdominal pain (STONES)
Constipation, loss of appetite, nausea (ABDOMINAL MOANS)
Polyuria + polydipsia (THRONES)
Confusion + fatigue (PSYCHIC OVERTONES)
ix total calc serum ionised calc serum albumin resting ECG serum PTH serum PTHrP serum phos serum calcitiriol skeletal survery
mgmt avoid meds that worsen: Thiazide diuretics Calcitriol Calcium supplementation Antacids Lithium if mild/asymp - supportive if mod/severe IV normal saline (reverses dehydration secondary to hypercalcaemia induced nephrogenic diabetes insipidus) IV bisphosphonates/denosumab (pamidronate, zoledronic acid) - block osteoclastic bone resorption Furosemide to avoid fluid overload
SVC obstruction where what surrounded by patho symps ix mgmt
where
SVC from junction of L + R brachiocephalic to RA
surrounding stuff
Located in middle mediastinum
Surrounded by trachea, right bronchus, aorta, pulmonary artery, perihilar LNs
patho
SVC obstruction initiates collateral venous return to heart - most important is azygous system (azygous, hemiazygous, intercostals), second is internal mammary venous system
symps
Oedema of face and upper extremities (80%)
Dyspnoea (60%) - worse leaning forward
Facial plethora (venous engorgement)
Cough
Distended neck veins + chest veins - worse leaning forward
Hoarse voice
? Blurred vision + sev = laryngeal oedema, cyanosis, mental changes
FIXED (non-pulsatile) + RAISED JVP
ix
Chest x-ray (widened mediastinum or mass in lung),
CT thorax with contrast (collat vess, loc, sev, path),
USS upper extremities (dilated SVC, thrombus)
mgmt
Acute airway obstruction?
1. Secure airway (intubate/surgical) + local radiotherapy + corticosteroids (dexamethasone 10mg IV bolus + 4mg every 6 hours) OR
2. Secure airway + percutaneous endovascular stent (bleeding risk, patency)
Malignant (usually gradual)
Treat malignancy - often cancers are radiosensitive (thymoma = radio/chemo resistant)
+ palliative radiotherapy/ dexamethasone (for thymoma/lymphoma)
tumour lysis syndrome def common when pres patho ix mgmt
def Combination of metabolic and electrolyte abnormalities occurring spontaneously following initiation of cytotoxic treatment in patients with cancer. Characterised by excessive cell lysis.
common when
In highly prolif, chemosensitive malignancies e.g. lymphoma and leukaemia esp NHL/ALL
pres
in lab:
- 2 of hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia
Lab + increased serum creatinine, arrhythmia (K+, PO4, hypoCa), seizure (hypoCa + muscle cramps + tetany)
patho
Malignant cells have high turnover. Produce high nucleic acid products (-> uric acid) + phosphate.
Ability of kidney to eliminate large amounts is saturated
Hyperuricaemia + reduced urinary flow -> uric acid crystals, renal tubule obstruction and decline in renal func (AKI)
Hyperphosphataemia -> calcium phosphate crystals -> nephrocalcinosis and urinary obstruction
Secondary hypocalcaemia due to hyperphosphataemia
Hyperkalaemia from cell degradation
AKI -> fluid overload and pulmonary oedema
Main mechanism of AKI is uric acid nephropathy + calcium phosphate deposition
rfs
Haematological malignancy, large tumour burden (*high lactate dehydrogenase, WBC and uric acid pre-treatment), chemosensitive, renal impairment, dehydration
pres Syncope/chest pain/dyspnoea Seizure Nausea/vomiting/diarrhoea Muscle weakness/cramps
ix
Serum uric acid (25% increase), phosphate (25%), potassium (25%), calcium (25%) decrease
FBC - elevated WCC, serum creatinine (x 1.5 upper limit), lactate dehydrogenase (elevated), serum urea (high at AKI), ECG
mgmt
low risk - monitor + avoid nephrotoxic drugs
inter - prechemo IV hydration, reg monitor, aluminium hydroxide as phosphate binder, allopurinol
high risk - prechemo IV hydration, reg monitor, phosphate binder, rasburicase
acute - Treat hyperkalaemia
Intense fluid resuscitation
Phosphate binder
Rasburicase
Sodium bicarbonate
paraneoplastic syndromes
what is it
mediators
common which with cancers?
A syndrome that is the consequence of cancer in the body, but unlike mass effect is not due to local presence of cancer cells.
Mediated by humoral factors - hormones/cytokines secreted by cancer cells, or by immune response to tumour
Common with breast, lung, ovarian or lymphoma
lambert-eaton myasthenic syndrome def mech pres ix mgmt
def Rare AI disorder of NM junction associated with SCLC (50%) + smoking + AI disease
mech
Circulating antibodies against VGCaC, impair NM transmission by inhibiting calcium current and release of Ach to synaptic cleft.
SCLC cells contain high concentrations of VGCaC (induce production of VGCaC antibodies)
pres Limb weakness (proximal legs + arms) Dry mouth (xerostomia + metallic taste) - autonomic Weakness (Limb girdle + waddling gait) Dysarthria, ptosis, diplopia, impotence
ix Nerve conduction studies - doubling of compound muscle action potential post exercise Anti VGCaC - positive Anti AChR - negative Chest CT - ? malignancy Serial LuFT - low FVC - ? resp crisis
mgmt
No resp/bulbar weakness -> treat cause + amifampridine ± pred
Severe resp/bulbar weakness -> intubation and ventilation + plasma exchange/IVIG
carcinoid syndrome pres patho dx mgmt comps
Commonly presents with flushing/diarrhoea (± wheeze, palpitations, telangiectasia, abdo pain)
Symptoms due to secretion of serotonin and kinins (vasoactive peptides) from neuroendocrine tumours (gastric carcinoma, bronchial adenoma - carcinoid type, pancreatic carcinoma). Often seen in pts with liver mets
Diagnose by elevated urinary-5-hydroxyindoleacetic acid (24 hr)
Treatment - medical therapies (octreotide - somatostatin analogue) + surgical resection
Complications - carcinoid heart disease (fibrosis on R valves) and crisis at times of stress (surgery = hypotension and wheeze)
which cancers to bone?
reast - lytic or sclerotic Prostate - sclerotic Bronchus - lytic Myeloma - lytic Thyroid - lytic
familial cancer syndromes
MEN - see endocrine
NF - see endocrine
Retinoblastoma - associated with sarcoma (Rb1, Ch13)
Ataxia telangiectasia - AR - assoc lymphoma and leukaemia
HBOC (hereditary breast/ovarian cancer) - AD by BRCA
HNPCC/Lynch syndrome - AD - endometrial, stomach, ovarian, small bowel, pancreas
FAP - AD - 100% penetrance
Li Fraumeni - AD (Tp53 gene) - soft tissue sarcoma, osteosarcoma, breast, brain, leukaemia
VHL - Von Hippel Lindau - AD - benign and malignant. CNS and retinal hemangioblastoma, clear cell renal, phaeo, pancreatic
places where chemo doesnt reach well? what are these called
A sanctuary site is an area that chemotherapy does not reach well e.g. brain and scrotum in ALL
