Oncology Emergencies Presentation and Management Clinical Training Information

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Oncology EmergenciesPresentation and
ManagementClinical Training Information

• Imperial Hospitals NHS Trust
• and
• North West London Cancer Network

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Aims for todays talk

• Briefly cover the evidence that defines the need
  for an Acute Oncology service
• Review the common cancer emergencies and their
  management
• Details of the structure of the acute oncology
  service and contact information are on the
  handout

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(No Transcript)
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NCEPOD

• 85 re-admitted, 15 to different
• hospital
• 51 under care of haem/oncologist
• 49 under care of acute physicians
• Advice before admission telephone triage 19,
• GP 30, A E 43, OPD 8
• 17 with G 3 or 4 toxicity delayed gt24 hrs
• 83 admissions with neutropenic sepsis delays in
• admission, lack of policies in A E and DGHs,
• failure to make diagnosis, lack of assessment by
• senior staff, delays in prescribing admin of
  antibiotics

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A key recommendation

• Development of an Acute Oncology Service
• Management of patients who develop severe
  complications following chemotherapy or as a
  consequence of their cancer
• Management of patients who present as
  emergencies with previously undiagnosed cancer

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Key Features of an Acute Oncology Service

• Access to information on individual patients
  across the Trust
• Early review by an oncologist or oncology nurse
  specialist (within 24 hours)
• 24/7 access to telephone advice from an
  oncologist
• Fast track clinic access from AE
• Protocols for the management of oncological
  emergencies and training for AE staff
• Training for physicians on management of
  acutely unwell cancer patients

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A Growing Problem

• Increasing incidence of cancer
• 250,000 people diagnosed annually in UK
• Estimated that an additional 100,000 cases will
  be diagnosed each year by 2025
• Improved survival
• More complex therapies

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Emergency admissions in cancer patients

• Patients with advanced malignancies can have
  acute problems as a result of their illness or
  treatment
• Patients having standard outpatient adjuvant
  treatment can have life threatening side effects
  from chemotherapy treatment
• Patients with undiagnosed advanced malignancies
  can present as emergencies to A and E or
  medical/surgical specialities

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Some general points

• Oncology emergencies have considerable morbidity
  and mortality
• Patients frequently present to clinicians other
  than their oncologists, often at hospitals other
  than their cancer treatment centre
• High clinical suspicion and early detection,
  combined with a low threshold to initiate
  investigations and the optimal treatment,
  undoubtedly results in improved outcomes
• Patients die needlessly die every year because
  of a failure to recognise and appropriately treat
  these conditions

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The most common oncology emergencies

• Neutropenic sepsis
• Malignant hypercalcaemia
• Spinal cord compression
• Tumour lysis syndrome
• Superior vena cava obstruction
• Others Acute renal failure
• Pulmonary embolus
• Hyponatraemia

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Neutropenic Sepsis

• Temperature gt38 deg or single reading of 38.3 deg
• Neutrophils lt1.5
• Typically day 7-10 post chemotherapy
• Chemo effect on bone marrow therefore anaemia,
  thrombocytopenia also.
• Incidence neutropenic sepsis 5-10

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Neutropenic sepsis

• Febrile neutropenia / neutropenic sepsis is a
  common, expected complication of chemotherapy
• If untreated, it has extremely high morbidity and
  mortality
• Every year a number of patients die from their
  cancer treatment
• How can we minimise this risk?

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Neutropenic SepsisBackground Information

• Neutrophils are the most abundant of the
  leukocytes, normally accounting for 54-75 of the
  WBCs
• An adult typically has 3,000-7,500
  neutrophils/mm3 of blood. They are called
  neutrophils because their granules stain poorly -
  they have a neutral color
• What is the life span of a neutrophil in health?
  A day or two
• What about a Red cell? 100 days
• How many neutrophils do we make a day?
• The bone marrow makes about 80,000,000 new
  neutrophils per minute!

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Neutropenic sepsis

• Normal Neutrophil count 3.0-7.5 (that is thousand
  per cubic mm)
• Nadir the low point
• Grade 1 1.5-2.0
• Grade 2 1.0-1.5
• Grade 3 0.5-1.0
• Grade 4 lt 0.5

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What is the likely risk of neutropenia and
neutropenic sepsis?
? The risk of serious grade 3 or 4 neutropenia
Overall risk of neutropenic sepsis -gt
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How to minimise the risks from neutropenic sepsis

• Appropriate dosage of treatment
• Chemo adjusted for patients size (BSA body
  surface area)
• Chemo usually adjusted for advanced age
• Doses altered in renal or hepatic insufficiency
• Patient and Medical Education
• Educating patients re the risks and need for
  urgent hospital assessment in the event of
  symptoms or raised temperature
• Nadir counts in patients at risk
• Educating other medical teams who patients may
  present to

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Prophylactic treatment for neutropeniaGranulocyte
Colony Stimulating Factors

• G-CSF
• Controls proliferation of committed progenitor
  cells and influences their maturation into mature
  neutrophils.
• Stimulates the release of neutrophils from bone
  marrow storage pools and reduces their maturation
  time.
• Acts to increase the phagocytic activity of
  mature neutrophils.
• In patients receiving cytotoxic chemotherapy,
  G-CSF can accelerate neutrophil recovery, leading
  to a reduction in duration of the neutropenic
  phase .

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Daily G-CSF (Neupogen)

• We have been using daily G-CSF injections for
  many years to minimise the risk of neutropenic
  sepsis. A course is usually 5 days
• More recently a single injection, long acting
  form Neulasta has been available. Is it any
  better?

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Studies submitted for Neulasta Approval

• Two randomized, double-blind, non-inferiority
  studies
• Dosing
• Study 1 used 100 ug/kg dose
• Study 2 used a fixed 6 mg dose
• Population
• High-risk Stage II or Stage III/IV Breast Cancer
  patients
• Age 18 years
• Receiving Docetaxel and Doxorubicin
• Endpoint
• Duration of severe neutropenia comparing
  Neulasta to Neupogen

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STUDY RESULTS
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Study Results
? In both studies the results for the following
were similar for both Neulasta and Neupogen
?DSN in cycles 2 through 4 ?Depth of ANC nadir
in cycles 1 through 4 ?Rates of FN by cycle and
across all cycles ?Time to ANC recovery by cycle
and across all cycles
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Neutropenic sepsis

• Neulasta and daily G-CSF have similar efficacy.
• Daily G-CSF is a hassle to give
• Daily G-CSF is often poorly used
• Conclusion
• In treatment when neutropenia is a high risk
  15
• Use Neulasta if the cycle is 14 days or longer
• Use G-CSF for shorter cycles or stem cell
  mobilisation

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Case 1

• 51 y female presents to AE
• 24 hr history of shivering, fever, unwell
• Diagnosed with breast cancer 2 months previously
• What other elements of history are important?
• What examination would you perform?

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Case 1

• She is 12 days post- chemotherapy
• Temp 37.8 C
• P 120, BP 90/70
• No focal signs of infection
• What tests need to be done?
• Would you initiate any treatment at this stage?

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Investigations

• History (Chemotherapy ? Symptoms?).
• Examination (focus of infection?).
• Blood cultures (also from indwelling
  catheters if present).
• MSU and urine dipstick.
• Chest X ray.
• Throat swab for culture.
• FBC, LFT, UE, CRP.

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Case 1

• Urgent FBC
• Hb 11.4, WC 1.1, Neut 0.5, Plt 75
• Na 135, K3.7, Urea 11.0, Creat 120
• What treatment would you initiate at this stage?

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Case 1

• She is started on first line antibiotics for
  neutropenic sepsis according to hospital protocol
• In cases such as this the antibiotics should have
  been started without waiting for the FBC results!

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Treatment (1)

• Fever may be absent in neutropenic patients.
• Dont delay while waiting for culture results or
  full blood counts if any clinical suspicion! It
  is better to treat even if subsequently the blood
  count is normal.
• Usually bacterial pathogens, but investigations
  are frequently negative.
• Empirical use of broad spectrum antibiotics.
• Local guidelines but typically iv
  aminoglycoside with either a cephalosporin or
  broad-spectrum penicillin.

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Treatment of Neutropenic sepsis

• Admission last for 2-10 days until the neutrophil
  count rises above 1.0 and the patient has been
  apyrexial for 24hrs.
• Antibiotics are given intravenously
• G-CSF (daily G-CSF not Neulasta) support can be
  considered for patients admitted and on IV
  antibiotics
• Death in patients admitted to hospital is rare

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Imperial Antibiotic Guidelines for Neutropenic
Sepsis

• First Line
• Tazocin 4.5g IV tds
• Amikacin kg 15mg/kg IV od (Amikacin is C-I in
  renal impairment or recent exposure to
  nephrotoxic drugs)
• In renal impairment etc use Meropenem
• If still pyrexial after 48hrs
• Second Line
• add teicoplanin
• Or switch to Meropenem (after d/w micro)
• Third Line
• add antifungal
• Continue IVAB 48hrs after becoming afebrile
  completed at least 5 days treatment

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Causative Organisms in neutropenic sepsis

• Majority from host bowel/skin
• 80 not identified
• Gram negatives -E Coli -Klebsiella -Pseu
  domonas
• Gram Positives -Staph Aureus
• -Staph
  Epidermidis -Strep Faecalis
• Rarely pneumocystis, CMV, fungal

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Potential Sources
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GCSF

• prolonged neutropenia
• haemo-dynamically compromised
• clinical deterioration (hypoxia, multi-organ
  dysfunction)
• fungal infection
• Continue GCSF until neutrophils gt1.0

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Thrombocytopenia

• Low platelet counts are common after chemotherapy
• Blood risks only rise significantly when the
  count is less than 10-20
• What is the treatment
• Platelet transfusion
• As yet there are no growth factor treatments of
  platelets

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Hypercalcaemia

• Serum Ca gt 3.0 mM.
• Most common life-threatening metabolic
  abnormality in cancer patients.
• Often under-diagnosed.
• Significant impact on quality of life if treated
  sub-optimally.

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Symptoms of hypercalcaemia

• Fatigue
• Nausea and vomiting
• Constipation
• Polyuria polydypsia
• Psychological disturbance
• Related to degree of hypercalcaemia and rate of
  increase in Ca

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Hypercalcaemia of malignancy

• Incidence varies with cancer type highest for
  breast and myeloma (40). Lung 12-35, SCC 5-25,
  renal cancer 5-20, lymphoma 5.
• Results from aberrant Ca homeostasis in bone,
  gut and kidney.
• Hypercalcaemia is not a result of bone
  metastases and can happen in their absence
• Presenting symptoms often vague and easily
  missed.
• Check the Ca in every cancer patient you see
  in A and E

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What is the mechanism of hypercalcaemia?

• Direct bony destruction is not the mechanism
• Metastatic Breast Cancer 85 get bone mets but
  only 15 gets hypercalcaemia
• Small cell lung cancer patients frequently get
  bone mets but hypercalcaemia is rare
• Squamous cell lung cancer rarely get bone mets
  but 25 get hypercalcaemia

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Factors contributing to hypercalcaemia

• Ectopic PTHrP (most common)
• 1, 25 (OH)2 vitamin D3 (B lymphomas)
• TNF
• Interleukin 6
• TGF alpha and beta

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Bisphosphonates

• Analogues of pyrophosphate.
• Inhibit bone resorption by osteoclasts.
• No effect on renal tubular absorption of Ca.
• Zometa is the most potent and simplest to give
  (4mg iv over 15 minutes in the day treatment
  unit) and is most commonly used.

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Case 3

• A 63 yr old man with NSCLC is brought to hospital
  by, having been found by his wife at home
  confused.
• She gives a history of the patient not being
  himself for several days. There are no other
  symptoms of note.
• What are your differential diagnoses?
• What investigations do you perform?

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Case 3

• Bloods (Do not just do U and Es in cancer
  patients. Always do full biochem in A and E)
• FBC Hb 10.4, WBC 5.7 Neuts 4.0 Plts 157
• UE Na 134 K 3.7 Ur 11.5 Creat 168
• LFTs NAD
• Bone profile Corr Ca 3.4, ALP 130
• Would you like any further investigations?
• What is your management?

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Management

• Best treatment treat underlying malignancy.
• Stop drugs which inhibit Ca excretion
  (thiazides, NSAIDs).
• Careful intravenous fluid replacement.
• Bisphosphonate
• Corticosteroids useful in appropriate
  malignancies (myeloma, lymphoma).
• Loop diuretic may be helpful if in positive fluid
  balance and when fully hydrated.

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Spinal cord compression

• Caused by metastatic disease.
• Affects up to 5 of patients.
• An important source of morbidity despite
  treatment being effective in gt 90 of (DIAGNOSED)
  cases.
• Symptoms are frequently vague and often become
  worse before the diagnosis is made.

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Tumours producing cord compression

• Breast 29
• Lung 17
• Prostate 14
• Lymphoma 5
• Myeloma 4
• Renal 4
• Sarcoma 2
• Others 23

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First symptoms

• 1st symptom Present at diagnosis
• Back pain 94 97
• Weakness 3 74
• Autonomic 0 52
• Sensory loss 0.5 53

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Signs to look for

• Symmetrical weakness (marked).
• Reflexes can be absent or increased at ankle and
  knee.
• Upgoing plantar.
• Symmetrical sensory deficit with a level.
• Sphinters Loss occurs late.

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What does this mean ?

• Any cancer patient with back pain requires urgent
  investigation.
• Upper motor neurone signs cord compression
  until proven otherwise.
• Look carefully for a sensory level and ask about
  sphincter symptoms.
• You can save your patient from incontinence and
  spastic paraparesis!

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What should you do?

• High dose iv corticosteroids (eg dexamethasone
  8mg TDS) should be given on clinical suspicion
  alone. Dont wait for imaging!
• Call the Imperial/NWLCN Spinal cord Compression
  Coordinator. This is the Clinical Oncology SpR
  and they can be reached 24/7 on
• 020-3311-7866 (ex 17866 if call internally)
• Follow the Imperial/NWLCN spinal cord compression
  guidelines and arrange Urgent MRI spine

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• Pretreatment ambulatory function is the main
  determinant of post-treatment gait function.
• Tumour type influences time to presentation with
  cord compression, ambulatory function at
  presentation and response to therapy.
• Thus, the key to gait and continence preservation
  is prompt diagnosis and treatment. Ambulatory
  function can be preserved in gt 80 of patients
  who are ambulatory at presentation.

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Case 4

• 75 year old man treated with goserelin for his
  known prostate cancer, presents to AE with 2 day
  history of bilateral leg weakness, and recent
  onset urinary retention
• What would you be concerned about?
• How would you proceed?

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Case 4

• On further questioning, the patient admits he has
  had thoraco-lumbar back pain for several days,
  and also noticed numbness of his feet legs
• Neuro examination of lower limbs
• Power 3 bilat, reflexes , increased tone,
  decreased sensation up to level of umbilicus

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Case 4

• What is the level of the lesion?
• What investigations do you request?
• What is your immediate management?

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MRI showing SCC
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Spinal Cord CompressionManagement

• Dexamethasone 8mg TDS
• PPI cover
• Neurosurgery followed by RT
• If no histological diagnosis
• Fit with a long life expectancy
• Radiotherapy
• Chemotherapy
• Chemoresponsive tumours e.g. NHL, HD, Germ cell,
  neuroblastoma

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Neurosurgery
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Neurosurgical Referral

• Spinal stability
• Diagnosis
• Bony fragments causing cord compression
• Neurological deterioration despite RT
• 1-2 vertebral bodies involved
• Good Performance Status
• Stable disease/long disease free interval
• Life expectancy gt3months

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Radiotherapy
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Radiotherapy

• Treated with high energy X-rays using single
  posterior field
• Treatment field includes one vertebra and above
  below involved vertebra/e
• Prescribed to the depth of the cord (as measured
  on MRI)
• Dose 20 Gray (Gy) in 5 daily fractions

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Cauda Equina Lesions

• Cord ends at L1/2, so lesions below this cause
  cauda equina syndrome.
• What signs would you expect to find if there is a
  lesion at this level?
• Flaccid paralysis
• Reduced reflexes
• Sensory loss (saddle parasthesia)
• Urinary retention
• Decreased anal tone

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Key Points

• Back pain Malignancy Spinal Cord Compression
• Image the whole spine
• 30 will live for a year so important for quality
  of life

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Tumour lysis syndrome (TLS)

• Hyperuricaemia
• Hyperkalaemia
• Hyperphosphataemia
• Secondary hypocalcaemia

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What causes TLS?

• Rapid destruction of malignant cells by
  treatment.
• Usually associated with high tumour burden and
  rapid response to treatment.
• Most commonly seen with high grade lymphomas,
  acute leukaemias and small cell lung cancer. But
  can complicate other cancers during chemotherapy.

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Tumour Lysis Syndrome

• Chemotherapy induced cell lysis
• Can be spontaneous e.g. Burkitts lymphoma
• Large tumour bulk, rapid doubling time and
  sensitivity to chemo
• Metabolic triad

Hyperurecaemia
Hyperkalaemia
Hyperphosphataemia
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TLS Clinical Findings

• Lethargy, nausea, vomiting, renal colic,
  haematuria
• Renal failure, mental status changes
• Cardiac arrhythmias
• Seizures/sudden death

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Management

• Treat specific metabolic disorder
• Decrease production ? allopurinal,
  rasburicase
• Reduce concentration ? volume expansion
• Promote solubility ? alkalinization
• Controversial rarely used in practice
• Remove from circulation ? haemodialysis

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Hyperphosphotaemia/Hypocalcaemia

• Lymphoblasts 4x more P04
• Sole elimination via glomerulus
• Management
• IV fluids
• Diuretics
• Calcium gluconate

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Management

• Frequent checks on electrolytes
• Every 2 hours
• Dialysis
• K gt7
• Uric acid gt10
• P04 gt10
• Volume overload

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Risk factors for TLS

• Bulky chemosensitive disease, especially
  high-grade lymphomas.
• High blast count in leukaemia.
• Elevated pre-chemotherapy serum urate.
• Elevated serum LDH.
• Poor renal function.

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What happens if untreated?

• Acute renal failure.
• Acidosis.
• Hyperkalaemia.
• Arrythmias.
• Death.

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Management

• Identify at risk patients. Prevention is better
  than cure.
• Allopurinol.
• Intravenous fluids .
• Alkalinise the urine ( pH 7.0 - 7.5) with
  bicarbonate which increases solubility of uric
  acid and reduces precipitation in the renal
  tubule.
• Rasburicase (Fasturtec) recombinant urate
  oxidase now licensed for treatment and
  prophylaxis of hyperuricaemia.
• Dialysis.

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TLS prevention

• Rasburicase
• Most patients with a high risk of TLS now get
  prophylaxis with rasburicase which safely
  minimises the risk of the tumour lysis syndrome
• It is given IV prior and during chemotherapy

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Superior vena cava obstruction

• Essentially a clinical diagnosis.
• Obstruction of venous drainage of upper body.
• Clinical picture
• Oedema of the arms and face.
• Distended neck and arm veins, with loss of
  pulsation.
• Headaches.
• Dusky red skin colouration over chest, arms and
  face.
• Collaterals may develop (takes several weeks).

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Superior vena cava obstruction

• Severity of symptoms relates to the rate of
  degree of obstruction and development of
  compensatory collateral venous drainage.
• Symptoms often made worse by lying flat or
  bending over.

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Symptoms of SVCO syndrome

• Dyspnoea 63
• Facial swelling/ exploding head 50
• Cough 24
• Arm swelling 18
• Chest pain 15
• Dysphagia 9

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SVCO physical findings

• Venous distension of neck 66
• Venous distension of chest wall 54
• Facial oedema 46
• Cyanosis 20
• Plethora of face 19
• Oedema of arms 14

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Common causes of SVCO syndrome

• Small cell lung cancer
• Non-small cell lung cancer
• Lymphoma
• Mediastinal germ cell tumours
• Breast cancer

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Management of SVCO syndrome

• Treat underlying cause.
• Treatment aimed at symptom control as well as
  underlying cause.
• Whenever possible obtain a tissue diagnosis
  (urgently) as some tumours are better treated
  with chemotherapy than radiotherapy (eg SCLC).
• Mediastinal radiotherapy is optimal treatment for
  most tumours and is effective in up to 90 of
  cases within two weeks.
• With lymphoma, germ cell tumours and SCLC urgent
  chemotherapy.

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Management of SVCO syndrome

• In the acute situation, it is vital to exclude
  airway compromise.
• Patients nearly always feel better if you sit
  them up and give them oxygen.
• Many clinicians routinely use corticosteroids in
  SVCO syndromes (sometimes diuretics help).
• Patients with lymphoma, SCLC and germ cell
  tumours can have an excellent response to
  treatment and in some cases prognosis, even in
  the presence of SVCO.

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Case 5

• A 62 year lady presents with a swollen right arm
  and shortness of breath when lying flat
• On examination she has a facial and neck oedema
  and a raised JVP
• What would you be concerned about?
• How would you proceed?

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SVCO
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Investigations

• CXR
• Widened mediastinum
• Contrast CT
• Assess extent and level of obstruction
• MRI
• Arm venogram

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Investigations
Outline of SVC stent
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Management

• No longer considered an oncological emergency
  unless STRIDOR
• Steroids/Sit up
• HISTOLOGY
• Via minimally invasive technique
• Increased risk of bleeding
• Treat tumour ? RT or Chemo
• RT?symptom relief in 63 NSCLCa
• 77 SCLCa
• Stent
• Rapid relief of symptoms 24-48 hours
• Or in refractory disease

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And finally

• Perhaps the most important take home message is
  that prompt diagnosis and institution of
  appropriate management can save cancer patients
  from premature mortality and morbidity.
• A significant number of such patients may do well
  and live for a long time even with advanced
  malignancies.

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Further information

• There are clinical guidelines for all the common
  emergency cancer presentations available on the
  Acute Oncology pages of the Trust Intranet.
• There is a full on call SpR and Consultant
  Oncologist service available 24/7 for advice and
  clinical review.

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Background

• November 2008 Chemotherapy Services in England
  Ensuring quality Safety
• 60 increase in chemotherapy
• National Confidentiality Enquiry into Patient
  Outcome Death
• 35 care judged as good
• 49 room for improvement
• 8 less than good