12- Acute presentations in cancer (secondary to treatment) Flashcards
acute presentations secondary to cancer therapy e.g. chemotherapy/radiotherapy
- Neutropenic sepsis
- Tumour lysis syndrome
- Immune related colitis
- Radiation mucositis
- Thrombocytopenia
Neutropenic sepsis
background
Definition
- Patient undergoing systemic anticancer treatment (SACT)
- Temp >38 or over 37.5 degrees over 1 hour
- Neutrophil count < 0.5 x 10 9 per litre or <1.0 and falling
- Patient can have infection and no fever
Remember
Suspect in all chemo patients who become unwell as some chemo patients cannot mount a fever (corticosteroids)
what is neutrophil nadir
Neutrophil levels reach a low point about 7 to 14 days after treatment. This is called the nadir. At this point, you are most likely to develop an infection. Your neutrophil count then starts to rise again.
when does neutrophil nadir typically occur
day 10
- Haematological malig Rx; deeper nadir, greater duration of neutropenia
newer biological/targeted therapies and neutropenic sepsis
less propensity to cause neutropenia
causes of neutropenic sepsis
Gram-negatives: can all produce extended-spectrum beta-lactams
* E.coli
* Klebsiella
* Enterobacter spp. - can get carbapenem-resistant strains (CRE)
* Pseudomonas aeruginosa
* Acinetobacter
* Gram-positives:
Coagulase-negative staphylococci (e.g. staph epidermidis)
* Staphylococcus aureus (including MRSA)
* Enterococcus (including VRE)
* Viridans group strep
* Strep pneumoniae
* Group A streptococci
Fungal:
* Candida
* Aspergillus
Risk of infection increased with
- Prolonged neutropenia (>7 days)
- Severity of neutropenia
- Significant comorbidities (COPD, DM, renal/hepatic impairment)
- Aggressive cancer
- Central lines
- Mucosal disruption
- Hospital inpatient
presentation of neutropenic sepsis
- Fever >38 or over 37.5 degrees over 1 hour
- Tachycardia >90
- HYPOTENSION < 90 systolic= URGENT
- RR > 20
- Symptoms related to a specific system e.g. cough, SOB, line, mucositis
- Drowsy
- Confused
investigations for neutropenic sepsis
Investigations
Blood tests
- FBC (with differential)
- U&Es
- LFTs
- Lactate/ABG
- CRP
Cultures/swabs
Urine
Sputum
Wound swabs
CXR
initial management of suspected neutropenic sepsis
DO NOT WAIT TO DO TESTS OR GET TEST RESULTS
GIVE STAT DOSE: IV TAZOCIN +- PIPERACILLIN (TAZOBACTAM)
full management of neutropenic sepsis
- Prompt assessment by HCPs who are familiar with NS
- Don’t wait for the FBC
- Empiric IV broad spectrum antibiotics within the
- hour (NICE guidelines)
o Tazocin
o Meropenem +/- Vancomycin if no improvement after 48h - Fluid resuscitation
- Oxygen
- Consider catheterisation
- Involve senior members of the team – SpR/Consultant
- Consider need for escalation of care
- Usually need 5/7 broad spectrum ABx, may switch to oral ABx after 48 hours if risk low
- GCSF (Granulocyte colony stimulating factor) can reduce severity and duration of neutropenia (sub cut injection)
o Side effects: bone pain, headache, fatigue and nausea - NOT used routinely, may be considered in patients who are profoundly septic/neutropenic
When the neutrophil count is normal, has been afebrile for 48 hours and blood tests have normalized, antibiotics can be stopped.
Neutropenic sepsis and GCSF
Granulocyte colony stimulating factor can reduce severity and duration of neutropenia (sub cut injection)
o Side effects: bone pain, headache, fatigue and nausea
- NOT used routinely, may be considered in patients who are profoundly septic/neutropenic
Prophylaxis for neutropenic sepsis
- A neutrophil count of < 0.5 x 109 as a consequence of their treatment they should be offered a fluoroquinolone
- All patients should be issued with an alert card with 24hr contact numbers
what can be used to risk assess neutropenic sepsis
MASCC risk index
Antifungal management for neutropenic sepsis
give IV voriconazole
Tumour lysis syndrome background
- Generally triggered by the initiation of cytotoxic therapy – mortality 15%
- Metabolic emergency that presents as severe electrolyte abnormality
- Massive tumour cell lysis -> release of large amounts of potassium, phosphate and uric acid into the systemic circulation
- Requires appropriate prophylaxis and early recognition and treatment
blood test findings for tumour lysis syndrome
3 High
- Hyperuricemia
- Hyperkalaemia
- Hyperphosphatemia
1Low
- Hypocalcaemia
AKI from uric acid and/or calcium phosphate crystals in renal tubules
tumour lysis syndrome susceptible tumour types
Susceptible tumour types
Risk greatest for haematological malignancies
- High grade lymphoma
- Leukaemia
- Myeloma
Bulky chemo-responsive tumour
- Less common in solid tumour
Patient specific risk factors for TLS
- High volume/bulky disease
- Pre-treatment LDH high
- High circulating WCC
- Pre-existing renal dysfunction/nephropathy
- Pre-treatment hyperuricaemia
- Hypovolemia
- Pre-treatment diuretic use
- Urinary tract obstruction from tumour
presentation of TLS
- Normally day 3-7 post chemotherapy
- N and V
- Diarrhoea
- Anorexia
- Lethargy
- Haematuria-> oliguria -> anuric
- Fluid overload
- Cardiac arrhythmia/arrest (peaked T waves, QTc derangement)
- Muscle cramps/ tetany/ seizures
what kills patients with tumour lysis syndrome
cardiac arrythmia due to electrolyte problems e.g. high pottassium, low calcium
investigations for TLS
Important investigations include: U&E (potassium and phosphate are typically raised), calcium (low), uric acid (raised), and ECG (metabolic abnormalities e.g. hyperkalaemia may precipitate life-threatening arrhythmias)
management of tumour lysis syndrome
1) Hydration
- Pre-hydration and vigorous hydration throughout treatment
- maintain urine output
2) Monitoring of electrolytes and fluid balance
3) Lowering of uric acid levels
- Allopurinol (xanthine oxidase inhibitor –> less hyperuricaemia)
- Rasburicase -> synthesic uricase -> degraded uri acid to allantoin (water soluble)
what is given prophylactically to prevent TLS
allopurinol
Immune related colitis
background
- Increased used of immunotherapy e.g. immune check point inhibitors in cancer treatment has increased prevalence of immune related adverse events such as immune related colitis
- Causes inflammation of the large intestine
- Examples of cancers which use immunotherapy
o Melanoma
o NSCLC
o RCC - Example drugs
o Ipilimumab
o Pembrolizumab
Pathophysiology of immune related colitis
- Immune checkpoint proteins reduce the bodies immune response preventing autoimmunity
- Cancer cells use these immune checkpoints to evade the immune system
- Inhibiting immune checkpoint proteins, therefore enhancing the immunes system (T cell) ability to destroy cancer cells
- However other cells such as those found in the GI tract can be affected by off-target inflammation and autoimmunity
presentation of immune colitis
Immune colitis can develop at any time during therapy
- Diarrhoea
- Abdominal pain
- N and V
- Haematochezia
- Weight loss
- Fever
presentation of immune colitis
Immune colitis can develop at any time during therapy
- Diarrhoea
- Abdominal pain
- N and V
- Haematochezia
- Weight loss
- Fever
Investigation for immune related colitis
- Bloods
o FBC, UE, LFTs, TFTs, CRP - Stool sample
o Rule out infective causes e.g. clostridium difficile, Ova and parasites - Imaging to rule out bowel perforations
- Endoscopic investigations
o Rule out metastasis
management of immune mediated colitis
depends on grade of symtoms
- Supportive measures for mild (grade 1 symptoms such as diarrhoea)
o Loperamide
o Encourage oral fluids
o Electrolyte replacement - Grade 2 or severe grade 3 symptoms
o Stop immunotherapy
o Prednisolone
–> Bone protection and PPI cover and co-trimoxazole
o Or IV methylprednisolone - If no response to steroid
o Infliximab – providing no contraindications
Radiation mucositis background
- Acute inflammation of mucosa
- Oral mucosa most affected
- Debilitating complication – can lead to nutritional problems and increased risk of infection
- Signif impact on QoL
- Occurs in 91% of patient with H and N cancer receiving radiotherapy
o Dose limiting toxicity since can lead to early discontinuation
Pathophysiology of radiation induced mucositis
- Mucositis occurs because cancer treatments such as radiotherapy break down rapidly dividing epithelial cells lining the GI tract
o From mouth to anus - Leaves lining open to ulceration and infection
Risk factors of radiation induced mucositis
- Most cancer patients receiving chemotherapy in combination with radiotherapy will experience mucositis
- Poor oral health
- Smoking
- Alcohol
- Females
- Dehydration
- Low BMI
- Methotrexate and fluorouracil
radiation mucositis presentation
Presentation
Generally begins 5-10 days following initiation of treatment
- Bleeding mouth
- Red, shiny or swollen mouth and gum
- Ulcers
- Soreness
- Painful swallowing and talking
- Dryness
- Increased mucus and thicker saliva
management of radiation induced mucositis
Prevention
* Good oral hygiene
* Stop smoking and avoid alcohol
* Ice chip therapy
* Mucoadhesive hydrogel rinses and calcium phosphate rinses
* Modify diet to limit trauma to mouth
E.g. avoid spicy, rough food
Prophylactic placement of PEG
- Prevent dehydration and weight loss
Managing
* Topical anaesthetics e.g. lidocaine swish and spit
* Low level laser therapy applied to mucositis lesions
* Morphine mouthwash
* Consider admission to hospital for systemic analgesic
Thrombocytopenia
- Common problem which limits chemotherapy dose and frequency
- Why is it a problem?
o Platelet count of <10,000/ uL increases risk of spontaneous bleeding
o <50,000 surgical procedures complicated - Other causes
o Immune thrombocytopenia
o Coagulopathy
o Infection
o Post-transfusion pupura
o Leukaemia and lymphomas due to pancytopenia - Major cause of chemotherapy disruption and delay
causes of thrombocytopenia in cancer patients
RF for thrombocytopenia
Risk factors
- Chemotherapy
o Gemcitabine
o Platinum based regimes
- Pancytopenia due to blood cancers
Pathophysiology of thrombocytopenia
- Chemotherapy destroys rapidly growing cells, including those in the bone marrow that produce platelets
Presentation of thrombocytopenia
Occurs 6-10 days following administration of chemo
- bleeding gums, blood in stool, easy bruising etc
Management of thrombocytopenia
Preventing bleeding
- Use soft-bristle toothbrush
- Wear proper fitting shoes
- Blow nose carefully
Treating thrombocytopenia
- Platelet transfusion
- However associated with complications
–> Anaphylaxis
–> Infections
