Palliative and oncology Flashcards
Neoplastic spinal cord compression
When to suspect?
In all lower back pain in cancer
Neoplastic spinal cord compression
Which cancers is it most commonly associated with?
- Lung
- Liver
- Breast
- Prostate
- Myeloma
- Melanoma
Neoplastic spinal cord compression
Causes
- Collapse or compression of a vertebral body due to metastases (common)
- Direct extension of a tumour into the vertebral column (rare)
Neoplastic spinal cord compression
Presentation
- Back pain, may be worse on lying down/straining/coughing
- Lower limb weakness
- Sensory loss and numbness
- Lesions > L1 –> UMN signs in leg, sensory level
- Lesions < L1 –> LMN signs in legs, perianal numbness
- Tendon reflexes INCREASED BELOW, ABSENT AT LEVEL
Neoplastic spinal cord compression
Investigations
- Urgent whole spine MRI scan (within 24 hrs)
Neoplastic spinal cord compression
Management
- High-dose dexamethasone (16 mg / 24 hrs PO)
- With prophylactic GI protection (PPI) and blood glucose monitoring
- Refer urgently to oncology MDT for consideration of radiotherapy or surgery
- Radiotherapy should be given within 24 hrs of MRI diagnosis
- May need decompressive surgery depending on the prognosis
Neoplastic spinal cord compression
Prognosis
Patients with loss of motor function after 48 hrs are unlikely to recover function
Neoplastic spinal cord compression
Differentiating from cauda equina
Cauda equina presents with lower motor neuron signs (reduced tone and reduced reflexes). The nerves being compressed are lower motor neurons that have already exited the spinal cord.
- When the spinal cord is being compressed higher up (above L1) by metastatic spinal cord compression, upper motor neuron signs (increased tone, brisk reflexes and upping plantar responses) will be seen.
Neutropenic sepsis
Presentation
- Neutrophil count < 0.5 x 10^9/L
- Temp > 38 degrees OR other sign/symptom consistent with clinically significant sepsis
Neutropenic sepsis
Who should you suspect this in?
- IN all patients unwell within 6 weeks of receiving chemo (most common 7-14 days after)
- Examine indwelling catheter sites
Neutropenic sepsis
Management
- IMMEDIATE TX
- Treat post-chemo fever before WBC results
- Tazocin (Piperacillin/Tazobactam)
- If still febrile/unwell after 48 hours try meropenem +/- vancomycin
- If not responding after 4-6 days investigate for fungal disease
- Fluoroquinolone if suspect they might develop it as prophylaxis
Drugs that can cause neutropenic sepsis
- Anti-cancer chemotherapy
- Clozapine (schizophrenia)
- Hydroxychloroquine (rheumatoid arthritis)
- Methotrexate (rheumatoid arthritis)
- Sulfasalazine (rheumatoid arthritis)
- Carbimazole (hyperthyroidism)
- Quinine (malaria)
- Infliximab (monoclonal antibody use for immunosuppression)
- Rituximab (monoclonal antibody use for immunosuppression)
Superior vena cava syndrome
Pathophysiology
Reduced venous return from head, neck and upper limbs
Superior vena cava syndrome
Causes
Common = extrinsic compression from malignancy (90%):
- Lung (small cell) = most common cause
- Others: lymphoma, metastatic, lymphoma, germ cell
Less common = venous thrombosis
- If current/past central venous access
Superior vena cava syndrome
Signs and symptoms
- SOB = most common
- Swelling of face, neck, arms
- May see periorbital or conjunctival oedema
- Headache - worse in the mornings
- Visual disturbances - blurred vision
- Pulseless jugular venous distension
- Distended chest veins
Superior vena cava syndrome
What is Pemberton’s sign?
- Raising the hands over the head –> facial congestion and cyanosis
Superior vena cava syndrome
Management
- Prop patient up
- High dose Dexamethasone = 16 mg OD
- Oxygen if needed
- CT to define anatomy of obstruction
- SUPERIOR VENA CAVA STENTING and balloon venoplasty
- Treat w radio/chemotherapy depending on the sensitivity of underlying cancer (e.g. SCLC, lymphoma)
Malignancy-associated hypercalcaemia
Epidemiology
- 10-20% of cancer patients
- 40% of myeloma
Malignancy-associated hypercalcaemia
Causes
PTH-related protein produced by tumour causing local osteolysis
- MYELOMA
- Bone mets (lung, breast, kidney, thyroid, prostate)
- Squamous cell lung cancer (PTHrP)
Malignancy-associated hypercalcaemia
Presentation
- BONES (painful)
- STONES (kidney)
- GROANS (GI disturbance)
- MOANS (psychiatric)
- Shortened QT interval
- HTN
- Corneal calcification
Malignancy-associated hypercalcaemia
Management
- Aggressive rehydration with normal saline
- Bisphosphonates (if eGFR > 30) -)> IV Zolendronic acid for 3 days
- Calcitonin - short-term, tolerance can develop
- Long term = control of underlying malignancy
Malignancy-associated hypercalcaemia
Prognosis
`- Poor prognostic sign
- 75% mortality within 3 months
Brain metastases
Epidemiology
Up to 40% of patients with cancer
Brain metastases
Which cancers?
- Lung = most common
- Breast
- Colorectal
- Melanoma
- Kidney
Brain metastases
Presentation
- Headache - worse in the morning, coughing, bending
- Focal neurological symptoms
- Ataxia
- Fits
- Nausea and vomiting
- Papilloedema
Brain metastases
Investigations
URGENT CT/MRI
Brain metastases
Management
- High dose dexamethasone –> reduce cerebral oedema
- Stereotactic radiotherapy
Brain metastases
Prognosis
- Poor prognosis
- Median survival = 1-2 months
- Better prognosis if single lesion or breast cancer
Tumour lysis syndrome
Pathophysiology
Chemo for rapidly proliferating tumours (leukaemia, lymphoma, myeloma) leads to:
- Cell death
- Increased urate
- Increased potassium
- Increased phosphate
- Decreased calcium
Tumour lysis syndrome
Presentation
- Increased urate
- Increased potassium
- Increased phosphate
- Decreased calcium
Tumour lysis syndrome
Associated risks
- Arrhythmias
- Renal failure
Tumour lysis syndrome
Management
- Hydration
- Uricolytics - Rasburicase, Allopurinol
- Monitor K+, Ca2+ and phosphate levels
Massive haemorrhage
Which tumours?
- Head and neck tumours
- Lung/GI tumours with Hx of bleeding
Massive haemorrhage
When to suspect?
- Suspect massive occult bleed if patient suddenly in shock
Massive haemorrhage
Management
- Stop any anticoagulation
- Palliative - remain with patient, dark towels
- Midazolam 10 mg STAT
Nausea and vomiting
Reduced gastric motility (gastric stasis)
- Domperidone
- Metoclopramide
Nausea and vomiting
Bowel obstruction WITHOUT colic
- Metoclopramide
Nausea and vomiting
Bowel obstruction WITH colic
- HYOSCINE BUTYLBROMIDE/HYDROBROMIDE
- Haloperidol
- Cyclizine
Nausea and vomiting
Chemically-mediated
- Haloperidol
- Ondansetron
Nausea and vomiting
Raised ICP
- Cyclizine
- +/- Dexamethasone
Nausea and vomiting
Vestibular
- Cyclizine
Nausea and vomiting
Cortical
- Benzodiazepine
- Cyclizine
5-HT3 antagonists
Examples
SEs
- Ondansetron, Granisetron
- SEs: constipation, headache, flushing
Anti-histamines
MoA
Examples
SEs
- Act on H1-receptors centrally and peripherally
- Cyclizine, Promethazine, Cinnarizine
- SEs: anti-muscarinic effects, palpitations & arrhythmias, sleep disturbances, EPSEs
D2 receptor antagonists
Haloperidol
MoA
SEs
- MoA: acts on D2 receptors in chemo-receptor trigger zone
- SEs: EPSEs, sedation, QT prolongation, depression
D2 receptor antagonists
Domperidone
MoA
SEs
- MoA: Act on D2 receptors PERIPHERALLY
- SEs: QT prolongation, drowsiness, dry mouth, diarrhoea, malaise
D2 receptor antagonists
Metoclopramide
MoA
SEs
- MoA: Act on D2 receptors CENTRALLY
- SEs: EPSEs, drowsiness, diarrhoea, gynaecomastia, galactorrhoea, hyperprolactinaemia
Levomepromazine, Prochlorperazine
MoA
Indications
SEs
- MoA: act on dopamine, H1 and Ach-receptors
- Used when non-specific or multi-factoral N+V cause
- SEs: EPSEs, drowsiness, anti-muscarinic SEs, postural hypotension, QT prolongation
Hyoscine butylbromide/hydrobromide, Glycopyrronium bromide
MoA
Indications
- MoA: muscarinic receptor antagonist
- Used in cases of smooth muscle spasm (bladder, GI tract), excessive secretions including sialorrhoea, drooling, death rattle and inoperable bowel obstruction)
Pain relief in palliative stomatitis/mucositis?
Benzydamine 0.15% mouthwash (Difflam®)
First-line pain relief in palliative care
- Offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference)
- With oral immediate-release morphine for breakthrough pain
Firs-line doses of morphine
If no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain
Co-prescribing with opioids
- Laxatives should be prescribed for all patients initiating strong opioids
- Patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered.
- Drowsiness is usually transient - if it does not settle then adjustment of the dose should be considered
Breakthrough dose of morphine
1/6th of total 24 hrs dose
Opioids in renal impairment
Mild –> Moderate:
- OXYCODONE
Severe (< 10):
- BUPRENOPRHINE
- FENTANYL
(not renally excrete so less likely to cause toxicity)
When else might you consider using oxycodone?
Oxycodone generally causes less sedation, vomiting and pruritis than morphine but more constipation, so can be used in anyone complaining from these morphine SEs
Pain management in bone mets
Strong opioids
Bisphosphonates
Radiotherapy
Denosumab
Oral morphine to SC morphine
Divide by 2
How much to increase morphine dose by?
30-50%
Oral morphine to SC diamorphine
Divide by 3
Oral oxycodone to SC diamorphine
Divide by 1.5
Oral codeine to oral morphine
Divide by 10
Oral tramadol to oral morphine
Divide by 10
Management of hiccups
- Chlorpromazine
- Haloperidol
- Gabapentin
- Dexamethasone
Management of agitation and confusion
- Find cause and treat this
- Environmental factors
If require meds:
- 1st line = haloperidol
- Others: chlorpromazine, levomepromazine
In terminal phase:
- Midazolam
Management of secretions
- Avoid fluid overload
- Educate the family that they are not likely to be troubled by them
- HYOSCINE HYDROBROMIDE or HYOSCINE BUTYLBROMIDE
- Also glycopyrroinum bromide
Which HPV subtypes are most significant RFs for cancer?
- 16
- 18
- 33
Though it should be noted that the majority of healthy women will spontaneously clear HPV within 2 years without developing cervical cancer
Which HPV subtypes cause warts?
- 2
- 7
- 22
Which lung cancer is most commonly associated with smoking?
Squamous cell carcinoma
Lung cancer
Adenocarcinoma vs squamous cell carcinoma
- Squamous cell lung cancer is more commonly found near large airways, unlike adenocarcinoma which is more commonly peripheral
- Squamous cell = most common in smokers
- Adenocarcinoma = most common in non-smokers
Most common tumour causing bone metastases (in descending order)
- Prostate
- Breast
- Lung
Most common site (in descending order)
- Spine
- Pelvis
- Ribs
- Skull
- Long bones
Other than bone pain, features may include?
- Pathological fractures
- Hypercalcaemia
- Raised ALP
Cytotoxic agents
Cyclophosphamide
MoA
- Alkylating agent
- Causes cross-linking in DNA
Cytotoxic agents
Cyclophosphamide
Adverse effects
- Haemorrhagic cystitis
- Myelosuppression
- Transitional cell carcinoma
Cytotoxic agents
Bleomycin
MoA
- Degrades performed DNA
Cytotoxic agents
Bleomycin
Adverse effects
- Lung fibrosis
Cytotoxic agents
Anthracyclines, e.g. Doxorubicin
MoA
- Stabilizes DNA-topoisomerase II complex inhibits DNA and RNA synthesis
Cytotoxic agents
Anthracyclines, e.g. Doxorubicin
Adverse effects
- Cardiomyopathy
Cytotoxic agents
Methotrexate
MoA
- Inhibitis dehydrofolate reductase and thymidylate synthesis
Cytotoxic agents
Methotrexate
Adverse effects
- Myelosuppression
- Mucositis
- Liver fibrosis
- Lung fibrosis
Cytotoxic agents
Fluorouracil (5-FU)
MoA
Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)
Cytotoxic agents
Fluorouracil (5-FU)
Adverse effects
- Myelosuppression
- Mucositis
- Dermatitis
Cytotoxic agents
6-mercaptopurine
MoA
Purine analogue that is activated by HGPRTase, decreasing purine synthesis
Cytotoxic agents
6-mercaptopurine
Adverse effects
- Myelosuppression
Cytotoxic agents
Cytarabine
MoA
Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase
Cytotoxic agents
Cytarabine
Adverse effects
- Myelosuppression
- Ataxia
Cytotoxic agents
Vincristine/blastine
MoA
Inhibits formation of microtubules
Cytotoxic agents
Vincristine/blastine
Adverse effects
- Vincristine: peripheral neuropathy (reversible), paralytic ileus
- Vinblastine: myelosuppression
Cytotoxic agents
Docetaxel
MoA
Prevents microtubule depolymerisation & disassembly, decreasing free tubulin
Cytotoxic agents
Docetaxel
Adverse effects
- Neutropenia
Cytotoxic agents
Irinotecan
MoA
Inhibits topoisomerase I which prevents relaxation of supercoiled DNA
Cytotoxic agents
Irinotecan
Adverse effects
- Myelosuppression
Cytotoxic agents
Cisplatin
MoA
Causes cross-linking in DNA
Cytotoxic agents
Cisplatin
Adverse effects
- Ototoxicity
- Peripheral neuropathy
- Hypomagnesaemia
Cytotoxic agents
Hydroxyurea
MoA
Inhibits ribonucleotide reductase, decreasing DNA synthesis
Cytotoxic agents
Hydroxyurea
Adverse effects
- Myelosuppression
PET Scan
- Form of nuclear imaging which uses fluorodeoxyglucose (FDG) as the radiotracer
- Allows a 3D image of metabolic activity to be generated using glucose uptake as a proxy marker
- The images obtained are then combined with a conventional imaging technique such as CT to decide whether lesions are metabolically active
- Used to evaluate primary and possible metastatic disease
Tumour markers
CA 19-9
Pancreatic cancer
Tumour markers
CA 125
Ovarian cancer
Tumour markers
CA 15-3
Breast cancer
Tumour markers
PSA
Prostate carcinoma
Tumour markers
alpha-feto protein (AFP)
- Hepatocellular carcinoma
- Teratoma
Tumour markers
Carcinoembryonic antigen (CEA)
Colorectal cancer
Tumour markers
S-100
- Melanoma
- Schwannoma
Tumour markers
Bombesin
- Small cell lung carcinoma
- Gastric cancer
- Neuroblastoma
BRCA 1 and 2
- Carried on chromosome 17 (BRCA 1) and Chromosome 13 (BRCA 2)
- Linked to developing breast cancer (60%) risk.
- Associated risk of developing ovarian cancer (55% with BRCA 1 and 25% with BRCA 2).
- BRCA2 mutation is associated with prostate cancer in men
Gardners Syndrome
- Autosomal dominant familial colorectal polyposis
- Multiple colonic polyps
- Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts
- Desmoid tumours are seen in 15%
- Mutation of APC gene located on chromosome 5
- Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer
- Now considered a variant of familial adenomatous polyposis coli
Amsterdam criteria
- Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two.
- Two successive affected generations.
- One or more colon cancers diagnosed under age 50 years.
- Familial adenomatous polyposis (FAP) has been excluded.
Lynch Syndrome
- Autosomal dominant
- Develop colonic cancer and endometrial cancer at young age
- 80% of affected individuals will get colonic and/ or endometrial cancer
- High risk individuals may be identified using the Amsterdam criteria
Li-Fraumeni Syndrome
- Autosomal dominant
- Consists of germline mutations to p53 tumour suppressor gene
- High incidence of malignancies particularly sarcomas and leukaemias
Diagnosed when:
- Individual develops sarcoma under 45 years
- First-degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age
What sort of bone lesions would be seen in metastases?
focal sclerotic bony lesions
