Acute Oncology Initial Management Guidelines - Version 3.0

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Introduction

These guidelines relate to the initial assessment and immediate management of Acute Oncology patients, i.e. patients presenting with an acute problem, demonstrating symptoms deemed as having been caused by:

• Systemic Anti-Cancer Therapy (SACT),
• Radiotherapy,
• Malignant disease,
• A previously undiagnosed cancer where an urgent oncology/haematology assessment is required.

It is emphasised that these guidelines focus on initial assessment at presentation and management for the first 24 hours. Patients should be referred to, or discussed with the Acute Oncology Team as soon as possible following presentation. The Acute Oncology team will provide further advice and on-going management guidance.

To aid in this urgent initial assessment, each protocol follows a RAG (Red, Amber, Green) format and quick reference assessment, which is in line with the UKONS Oncology/Haematology 24-Hour Triage Tool (V2, 2016):

https://www.ukons.org/site/assets/files/1134/triage_tool_poster.pdf

The Common Terminology Criteria for Adverse Events (CTCAE Version 4.3), an international standard set of criteria for defining adverse events (AE) and their grading within clinical trials and the routine management of Oncology/Haematology patients, has been applied to assist with the recognition and management of AE:

http://www.hrc.govt.nz/sites/default/files/CTCAE%20manual%20-%20DMCC.pdf

Intended Audience

These guidelines are intended for use by all health care professionals who assess and/or manage acute oncology patients at presentation. The guidelines may also be useful as an adjunct to the UKONS Triage tool when providing care advice following telephone triage Appendix Page.

They are mostly single-page "see-and-treat" guides. Whilst drug names may be referenced within each protocol, this is offered as a guide only; it is acknowledged that local variation may apply.

Please be aware of NICE National Guidelines/ Pathways for the management of:

• Neutropenic Sepsis: NICE - Pathways - Neutropenic Sepsis
• Metastatic Spinal Cord Compression: NICE - Pathways - Metastatic Spinal Cord Compression.
• Metastatic malignant disease of unknown primary origin in adults: diagnosis and management: NICE - Metastatic malignant disease of unknown primary origin in adults: diagnosis and management

The development and consultation group worked to provide a set of generic guidelines based on national guidance and clinical expertise. They have now been reviewed and updated to ensure that they remain applicable and cover current best practice in the management of treatment induced toxicity and acute disease related complications.

The authors request that the original source is acknowledged in all copies or adaptations.

Disclaimer

These Guidelines are for the use of medical professionals only. They are not intended for public use, including by oncology patients. UKONS does not permit the creation of derivative works, unless they are authorised.

The information contained in these guidelines is a consensus of the development and consultation groups' views on current treatment. They should be used in conjunction with any local policies/ procedures/ guidelines and should be approved for use according to the trust clinical governance process. Care has been taken in the preparation of the information contained in the guidelines. Nevertheless, any person seeking to consult the guideline, apply its recommendations or use its content is expected to use independent, personal medical and/or clinical judgment in the context of the individual clinical circumstances, or to seek out the supervision of a qualified clinician. The United Kingdom Oncology Nursing Society makes no representation or guarantee of any kind whatsoever regarding the guidelines content or its use or application and disclaim any responsibility for its use or application in any way.

The development of this App has been supported by grants from Bristol Myers Squibb (BMS) and Roche Products Limited. BMS and Roche Products Limited has had no control over the content of this App.

The following professional bodies have reviewed the guidelines and support use in practice:

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General Information and Principles

• Please consider drug toxicity as a possible cause of presenting problem. Systemic Anti - Cancer Therapy (SACT) . Systemic Anti - Cancer Therapy (SACT) includes cytotoxic chemotherapy, monoclonal antibodies, targeted agents, immunotherapy and new and novel therapies.
• SACT toxicities can cause acute deterioration but are often reversible if managed rapidly and appropriately. All patients on SACT may develop toxicities and are at risk; they may also have or develop additional toxicities to the one they are complaining of. Patients may be on new, novel, or trial therapy, and may present with unexpected or unknown side effects.
• Patients should know what treatment they are receiving, and have written information about their SACT and an alert card with their 24-hour advice line telephone number. These advice lines provide telephone triage and assessment for patients receiving treatment and will advise regarding the need for urgent assessment or review and follow up. In most cases, if a patient or carer telephones your department for advice it would be wise to redirect their call to the specialist advice line. However, if you are worried about the patient or their ability to give an accurate history, or you think that this may be a medical emergency then urgent medical review is essential.
• If a patient sounds unwell from SACT toxicities, it is sensible to arrange oncological/haematological review or assessment in hospital. If asking a GP or member of the primary health care team to review, it is essential to speak to them outlining what is required, what to look for and who to contact if further advice is needed.
• All licensed anticancer drugs have specific toxicities and the length of time that side effects can occur following completion of treatment varies. Most cytotoxic chemotherapies can cause side effects for up to 6 to 8 weeks after the last treatment is given. The newer immunotherapies and targeted agents can cause side effects for up to 2 years after the last treatment is administered - please ask for details and/or advice from the acute oncology team, the site specific specialist team, the hospital pharmacy or see the Summary of Product Characteristics: https://www.medicines.org.uk/emc/browse-medicines
• Please see specific toxicity guideline and manage the patient according to their condition, severity, concomitant medications and other medical problems.
• Aggressive management (including HDU/ITU) is appropriate if unstable, sometimes, even in the context of advanced cancer. Escalate care if the patient is becoming haemodynamically compromised/drowsy/shut down, discuss with specialist team if unsure of appropriateness.
• Organisations should consider using a standard triage and assessment format, such as the UKONS Triage Tool, for the assessment of patients with cancer.
• Assessment should include as standard the following questions:
  • Is the patient on active treatment (including radiotherapy) at present or have they received SACT treatment in the previous 2 years?
  • Names of SACT drugs and last date of treatment (NB may be on tablets)?
  • Performance status, general condition, ability to carry out normal function at home? Has this changed recently?
    Eastern Cooperative Oncology Group
    Karnofsky Performance Status
  • It is important to ask about all SACT related toxicities/problems in addition to the initial complaint, as several occurring together elevate risk and need closer management.
• Reversible toxicities and/or problems can be treated even in the presences of any DNACPR orders; decisions should be made on an individual basis. Please discuss with acute oncology/haematology team or on call oncology/haematology consultant.
• Neutropenia can occur:
  • At any time during a course of certain SACT or up to 6 weeks after
  • With certain radiotherapy treatment
  • At any time in a patient with disease-related immunosuppression

Patients with a suspected neutropenic sepsis will require IV antibiotics within 1 hour of presentation for assessment; this should be managed as per Guideline 12 - Neutropenic Sepsis

• Review concomitant medications and consider stopping those that may affect renal function/ potentiate hypotension (e.g. ACE-inhibitors, diuretics) if unwell or hypotensive, and benefits outweigh the risks of doing so.
• Establish intravenous access, or utilise indwelling lines if appropriately trained to do so, and hydrate according to clinical condition. Monitor fluid balance closely.
• Patients require daily medical review and daily bloods may also be required (watch for neutropenic sepsis/ dehydration). Be aware that administering paracetamol/antipyretics to neutropenic patients may mask signs of sepsis.
• Rectal examination. Due to the risk of damage to rectal mucosa, it is recommended that in patients receiving SACT rectal examination is not performed. If it is deemed necessary to conduct rectal examination, this should be undertaken with caution.
• The patient's site-specific specialist team providing cancer treatment must be informed of any admission/assessment, as adjustments to the subsequent cycle may be required. If patient is in a clinical trial, the trials team should be contacted about the admission.
• Consider the involvement of the palliative care team for symptom control advice if the problem is disease related.

Signs and symptoms:

• Bronchospasm
• Headache
• Urticaria
• Arthralgia
• Swelling of tongue/throat
• Cough
• Hypertension
• Tachycardia
• Myalgia
• Dizziness
• Hypotension
• Rigors/chills
• Asthenia
• Dyspnoea
• Nausea, vomiting
• Pruritus/itching
• Rash

Assessment: ABCDE approach

Observations: Calculate and monitor NEWS score. ECG cardiac monitoring.

Questions:

• What treatment/ drug is the patient receiving?
• Any known allergies?
• Cancer diagnosis/primary disease?
• Concurrent medications?

Differential diagnosis includes:

• Infusion reaction
• Septic shock
• Asthma
• Cytokine release syndrome
• Transfusion reaction

If this occurs during administration of treatment - STOP infusion/transfusion immediately.

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant, they may be myelosuppressed/ neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis immediate antibiotics if sepsis suspected.

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es and Ca²⁺.

For patients receiving or received immunotherapy consider:

• Endocrine function panel -TSH and Free T4, ACTH, LH, FSH and Cortisol, Prolactin, Blood Glucose, +/- Testosterone/Oestrogen and refer to Guidelines 18 to 27
• CK and ESR as intial assessment for Autoimmune Arthritis/Myositis. CRP measurement may also be useful.
• Consider viral infection as a cause of arthralgia. Discuss investigation and infection prevention with local microbiologist

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so, what treatment and when did it stop?
• Has the patient taking anything for pain?
• Where is the pain? If not widespread then consider other causes of joint pain e.g. localised pain in isolated joint/back/spine may be related to metastatic deposit and need investigation and discussion.
• How long has the patient had the pain? Is the pain affecting what they can do?
• Has/is the patient receiving GCSF, filgrastim/ pegfilgrastim injections? Some patients receiving GCSF may experience severe muscle pain commonly in the pelvic area, lower back and/or shoulders, which will usually improve after stopping GCSF. When was the last injection?
• Are there any comorbidities that may cause arthralgia/ myalgia e.g. Autoimmune Rheumatoid Arthritis or Systemic Lupus Erythaematosis
• Is the patient on any blood thinning drugs or steroids?

Identify: patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant, they may be myelosuppressed / neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis immediate antibiotics if sepsis suspected.

Many haematological disorders (malignant and non-malignant) can cause thrombocytopenia. Some patients, e.g. those with chronic lymphocytic leukaemia (CLL) or lymphoma may develop idiopathic thrombocytopenic purpura (ITP).

Consider viral infection e.g. parvovirus B19 as a cause of thrombocytopenia.

Patients who are receiving certain systemic anti-cancer treatment are at risk of thrombocytopaenia

If present, these conditions should be managed according to approved guidelines.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, LFT. Consider group and cross match, coagulation screen, INR (if on Warfarin), APTT ratio (if on IV Heparin). Anti-Xa level if on low molecular weight (LMW) heparin, as it can accumulate in the presence of renal failure. Fibrinogen if considering DIC.

Examination: Associated symptoms: Light headed, pallor, clammy, thirst, rash (petechial/purpura/punctate)

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so, what treatment and when did it stop?
• Is the patient actively bleeding? Site of active bleeding? Injury related or spontaneous?
• How much blood has the patient lost?
• Onset and duration - when did bleeding and/or bruising start and how long has it persisted?
• Have they had similar bleeding and /or bruising before?
• Allergies/ current medications? - Anticoagulants, aspirin, clopidogrel, NSAIDS, DOACs (new anticoagulants e.g. rivaroxaban /apixaban) - NB Heparin can cause thrombocytopaenia.
• Relieving factors - Is it stopped via direct pressure or other measures?

Identify: Patients within 6/52 of chemotherapy specifically patients currently receiving 5 fluorouracil (5FU) or capecitabine, which can cause coronary artery spasm. Patients may be taking these drugs orally at home or via continuous infusion. Other chemotherapy drugs/monoclonal antibodies can cause reduction in heart function, but this is not usually an acute presentation.

All cancer patients have an increased risk of pulmonary embolism.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, Cardiac markers/Troponin. Urgent ECG. Consider ABGs, CTPA.

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient currently receiving 5FU/capecitabine?
• Does the patient have a history of angina, or other heart disease?
• Exacerbating/relieving factors, and characteristics of pain?
• Associated symptoms, e.g. SOB, syncope, oedema, palpitations
• Consider - is this pain cardiac?
• Differential diagnosis includes:
  • Cardiac cause
  • Pulmonary embolism (PE)
  • Indigestion
  • Disease progression
  • Metastases

Identify: Patients who have received/receiving SACT or are at risk of disease related immunosuppression or a history of stem cell transplant. These patients may be myelosuppressed / neutropenic and at risk of sepsis. Immediate antibiotics if sepsis suspected. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis

Observations: Calculate NEWS score. Presence of bowel sounds.

Investigations: Urgent FBC, U&E, CRP, Ca²⁺, and LFTs. Consider abdominal X-ray.

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• When did the patient's bowels/stoma move last? Are they passing wind?
• What is normal bowel habit? Any recent changes? N.B. loose runny stools could be overflow.
• What medication are they taking and has there been any recent changes? Certain medication can cause constipation e.g. anti-emetics (5HT3 Antagonists), opioids, SACT including vinca-alkaloids
• What food and fluids have they been taking over last few days? Decreased fluid and/or food intake can be significant factors in constipation
• Is there any nausea or vomiting?
• Is there any abdominal pain? Is it getting worse?
• Are they passing water/urine normally?

Examination: PR Examination (with caution in haematology patients). Presence and nature of bowel sounds. Rule out signs and symptoms of bowel obstruction.

N.B. constipation may be a presenting symptom of MSCC or hypercalcaemia. Ascites can often aggravate constipation - if present consider drainage.

Differential diagnosis includes:

• Drug related e.g. SACT, opiates, anti-emetics.
• Bowel obstruction/ileus secondary to disease or ascites.
• Hypercalcaemia.

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant. These patients may be myelosuppressed / neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis immediate antibiotics if sepsis suspected.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, Mg²⁺, LFT, CRP, phosphate. CDT screen. Consider checking total CO₂ in serum or blood gases (arterial or venous) for pH/ bicarbonate with severe diarrhoea and potential bicarbonate loss. Stool sample for C&S/ova/cysts/parasites to rule out infective causes of diarrhoea-e.g. Campylobacter/salmonella, and CDT screen. Abdominal X-ray.

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• Is the patient receiving radiotherapy to the abdomen or pelvis and when was their last treatment?
• How many stools a day above normal amount? Or how much stoma output is there above normal amount? Have they had any nocturnal movements? For how many days have they had diarrhoea? Is it interfering with activities of daily living?
• Are stools/stoma outputs formed, loose or watery? Any faecal incontinence or urgency? Any blood or mucous in the stool?
• Is there any abdominal pain e.g., cramping pains coming in waves?
• Is the patient able to eat and drink normally? Are they passing plenty of clear urine?
• Does the patient have any other SACT related toxicities, e.g. mouth ulcers, mucositis, nausea/vomiting, red hands/feet?
• Has the patient taken any antibiotics recently or been in hospital recently?
• What medication have they taken? Have they taken any laxatives or anti-sickness medication or any anti-diarrhoeal medication in the last 24 hours? If so what?

Differential diagnosis includes:

• Graft versus host disease in stem transplant patients - contact transplant haematologist urgently.
• > Secondary to SACT e.g. 5FU or CAPECITABINE, IRINOTECAN, any TKI, please see next page and specific DRUG INFORMATION SHEET for further management guidance. Consider DPD deficiency.
• Gastrointestinal symptoms due to IMMUNOTHERAPY- proceed to Guideline 21 - Gastro Intestinal Immune-Related Adverse Event (irAE) for further guidance.
• Infection.
• Constipation with overflow.
• Radiotherapy - secondary to treatment.

Follow hospital infection control/prevention guidelines but -
Do NOT assume this is infective it is most likely to be drug induced in this group of patients.

Initial Management

1. Consider infective diarrhoea:
   • Isolate until infection excluded.
   • Send stool sample urgently - Inform microbiology and discuss management with microbiologist.
   • If haematology patient or strong suspicion of infective diarrhoea, withhold anti-diarrhoeal medication until stool result available.
   • Give antibiotics according to local policy (e.g. for C.Difficile or neutropenic sepsis).
2. Consider graft versus host disease in stem transplant patients - contact transplant haematologist urgently.
3. Secondary to SACT e.g. 5FU or CAPECITABINE, IRINOTECAN, ERLOTINIB any TKI or Targeted Therapy please see specific DRUG INFORMATION SHEET for specific management guidance.
4. Gastrointestinal symptoms due to IMMUNOTHERAPY - proceed to Guideline 21 - Gastro Intestinal Immune-Related Adverse Event (irAE) for further guidance
5. Neutropenic Sepsis - if there is suspicion of, or potential for neutropenic sepsis start antibiotic management immediately as per policy (Guideline 12 - Neutropenic Sepsis) - do not wait for FBC.
6. IV fluid resuscitation. Replace fluid and electrolyte losses. Adjust on-going fluids according to fluid balance status and renal function.
7. Full medication review - Stop ACE-inhibitors/ diuretics/ NSAIDs. NB Folic Acid can potentiate and increase side effects of some SACT drugs.
8. Nil by mouth(except sips) if abdominal pain or distension or abnormal abdominal X-ray.
9. Antidiarrhoeal - Anti-motility agents should be used with caution - only use if diarrhoea not due to infection.
   • Haematology - Discuss with haematology team on call before commencing antidiarrhoeal.
   • Oncology:
     • Consider loperamide 4mg initially then 2mg after each loose stool (maximum 16mg per 24 hours)N.B. Caution with high doses or prolonged use of loperamide as it can cause paralytic ileus.
     • If loperamide ineffective, then consider codeine phosphate instead of or in addition.
     • Reduce/stop antidiarrhoeal after 12-24 hours free of diarrhoea.
     • If Grade 4 - consider the use of octreotide by sc injection and immediate IV broad-spectrum antibiotic (even if afebrile). Withhold if not on maximal antidiarrhoeal prior to admission but review every 24 hours.
     • Do not withhold antidiarrhoeal for more than 12-24 hours without thorough senior medical review.
10. Consider hyoscine butylbromide if abdominal spasms

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant. These patients may be myelosuppressed/neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis suspected.

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es, Sputum and viral throat swab for C&S, blood cultures and CRP if pyrexial. ECG and CXR. Risk assess for VTE. Consider ABGs and troponin. Consider CTPA/VQ investigations to rule out pulmonary embolism, pneumonitis. Consider D-dimer. Serum β-D-glucan/galactomannan for fungal/Pneumocystis investigation in neutropenic/lymphopenic patients. If TB possible then test respiratory specimens for Mycobacterium tuberculosis. Consider GeneXpert PCR for TB in selected patients.

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• Cardinal questions related to breathlessness including history of underlying chest complaint, asthma, COPD, ischaemic heart disease.
• Is there any chest pain?
• What is the patient's current medication?
• Is there a history of dyspnoea? What is their normal level? Is this a new symptom?
• Are there any exacerbating/relieving factors?
• Is there any pain or swelling in legs? - Assess for signs of DVT.

Differential diagnosis includes:

• Chest Infection
• Disease progression
• New cancer diagnosis or metastases
• Pleural effusion
• Pulmonary embolism (PE)
• Consolidation
• Superior vena cava obstruction (SVCO)
• Cardiac ischaemia
• Anaemia
• Pneumonitis
• Exacerbation of respiratory condition e.g. Asthma
• Lymphangitis

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant. These patients may be myelosuppressed / neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis suspected.

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es, group and save, Ca²⁺, CRP, blood glucose, consider blood cultures. If the patient is receiving or has received immunotherapy in the past 12 months, check random cortisol, TSH and free T4.

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• How many days have they been feeling like this?
• Do they have any pain? Have they taken any painkillers? If so, what?
• Are they able to eat and/or drink?
• Are they short of breath?
• Are they able to mobilise - ambulant - performance status? http://ecog-acrin.org/resources/ecog-performance-status
• Are they passing usual amounts of urine and are bowels functioning normally?
• Patient mood? Has their mood changed recently? Are they receiving any psychological support?

Differential diagnosis includes:

• Anaemia
• Side effect of treatment
• Immunotherapy induced endocrinopathy
• Hormone disturbance e.g. thyroid dysfunction
• Disease progression
• Patient entering the dying phase
• Depression/psychological problems

Identify:

• Patients with known diagnosis/history of, or suspected cancer. Please note to rule out spinal cord compression, whole spine MRI scan must be performed within 24 hours of clinical suspicion.

Patients who have received/receiving systemic anti-cancer treatment or have a history of stem cell transplant are at risk of disease related immunosuppression. These patients may be myelosuppressed / neutropenic and are at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis suspected.

• Observations: Calculate and monitor NEWS score.
• Examination: Full neurological assessment and on-going review
• Investigations: Urgent MRI whole spine within 24 hours of clinical suspicion.Urgent FBC, U&Es, LFT, Group & Save, bone profile. If considering myeloma/plasmacytoma then Immunoglobulins/electrophoresis, serum light chains and urine bence jones protein. If considering lymphoma then LDH. If new diagnosis of cancer consider appropriate tumour markers to aid diagnosis.

Key signs/symptoms:

• The patient may or may not have a cancer diagnosis/primary disease.
• Referred back pain that is multi segmental or band like.
• Escalating pain, which is poorly responsive to treatment, including medication.
• Different character or site to previous symptoms.
• Funny feeling, odd sensations or heavy legs (multi segmental), pins and needles.
• Lying flat increases back pain.
• Pain, worsening on coughing or sneezing.
• Agonising pain causing anguish and despair.
• Gait disturbance, unsteadiness, especially on stairs (not just limp).
• Sleep grossly disturbed due to pain being worse at night.
• Established motor/sensory/bladder / bowel disturbances incontinence are late signs.

If you have suspicion of MSCC then contact the Acute Oncology team and/or MSCC coordinator for advice regarding management.

Identify: Patients who have received/receiving SACT or are at risk of disease related immunosuppression or a history of stem cell transplant (PBSCT). These patients may be myelosuppressed /neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis suspected.

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es, LFTs, CRP, Lactate and Blood Cultures (Oncology patients - consider the need for pathology investigations in grade 1 and 2 presentations on an individual basis and in light of any other presenting symptoms or risk factors)

• Is there a cancer diagnosis/primary disease?
• Is this a haematology patient? If so please contact haematology team as soon as possible.
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• Is there evidence of super added infection? Does the patient have any blisters, ulcers or white patches on tongue/ lips mouth?
• Is there any pain or bleeding from the mouth?
• Are they able to eat and/or drink?
• Does eating or swallowing make the pain worse?
• Are they using any mouthwashes, painkillers or other treatments within the mouth?
• Do they also have diarrhoea?
• Is there any dryness, pain, inflammation of genitals and/or rectum - consider rectal mucositis.
• Are they passing usual amounts of urine?
• Have they had any recent radiotherapy treatment to the head and/or neck?

Differential diagnosis includes:

• Radiotherapy reaction
• SACT related
• Viral/bacterial infection
• Candidiasis

Identify: Patients who have received/receiving SACT or are at risk of disease related immunosuppression or a history of stem cell transplant (PBSCT). These patients may be myelosuppressed /neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis suspected.

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es, LFTs, Ca²⁺, blood cultures and CRP. N.B. consider the need for pathology investigations in grade 1 and 2 presentations on an individual basis and in light of any other presenting symptoms or risk factors.

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• How often are they feeling sick/nauseous?
• Have they been sick/vomited?
• Assess bowel movements, any symptoms that suggest constipation? Any diarrhoea? Bowel obstruction?
• What food and fluids have they been taking over last few days?
• Any evidence of reflux/gastritis?
• Any signs of dehydration e.g. decreased urine output, fever, thirst, dry mucous membranes etc.
• What is the extent of the disease? - e.g. known metastases to brain, bone, liver etc.
• Are they taking any medication and has there been any recent change?
• Are they currently receiving radiotherapy? (Especially to brain, liver, GI Tract).
• Do they have any abdominal pain? Is this a new symptom?

Differential diagnosis includes:

• Medication related e.g. SACT
• Gastric stasis
• Hypercalcaemia
• CNS disease
• Gastro intestinal infection
• Disease related

Initial assessment:

• Identify patients with clinical suspicion of infection and potential for neutrophils < 0.5 x10⁹/L (received or receiving SACT or history of myelosuppression or known bone marrow failure)
• Patients may appear well initially but if untreated can rapidly progress to septic shock + death. Early diagnosis will normally prevent death.

START TREATMENT AT POINT OF SUSPICION

Immediately:Take bloods and administer 1^st IV antibiotics (DON'T wait for FBC result)

• Urgent: FBC, U&Es, LFTs include albumin, Coagulation screen, G+S, Ca²⁺, PO^4-, Mg²⁺, Urate, CRP, and Lactate. Peripheral and central line blood cultures, prior to antibiotic administration. Consider ABG and blood or plasma glucose.
• Observations: Calculate NEWS score. Assess urine output
• Commence: NEWS chart - patients can deteriorate rapidly and should be monitored closely. Monitor urine output.

Clinical assessment:

• Full history (consider current or recent SACT) + examination
• Assess urine output
• Urine, sputum + stool cultures
• Consider: throat swab, central line swab, wound swab and CXR

Helpful link ED/AMU Sepsis Screening & Action Tool;
Sepsis Trust - ED/ AMU Sepsis Screening & Action Tool

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of allogeneic stem cell transplant. These patients may be myelosuppressed / neutropenic and are at risk of neutropenic sepsis and/or thrombocytopenia due to reduced marrow production or marrow infiltration and/or graft versus host disease: If present, this should be managed as per Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis suspected.

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es, LFTs, CRP, blood cultures if signs of systemic sepsis.

Questions:

• Is there a cancer diagnosis/ primary disease?
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop? Is skin rash a commonly associated and sometimes serious toxicity of their treatment, please see specific DRUG INFORMATION SHEET.
• Have they received immunotherapy proceed to Guideline 26 - Skin toxicities - Immune Related Adverse Event
• Have they received oral targeted agents: EGFR antagonists, BRAF and MEK inhibitors; see Guideline 14 - Skin Toxicities - Targeted Therapy Related
• Have they received radiotherapy recently: see Guideline 15 - Skin Rash - Radiotherapy Reactions
• Have they had a stem cell/ bone marrow transplant? If yes contact the haematology team.
• If the patient has received 5FU, Capcitabine: see Guideline 16 - Palmar Plantar Erythrodysesthesia (Hand Foot)
• Are they otherwise well? Does the patient have any signs of infection e.g. pain, swelling, pustules, fever, discharge?
• Has the patient recently started any other medication including antibiotics?
• Does the patient have a history of skin complaints?
• Where is the skin rash, what % BSA does it cover and what does it look like
• Does the rash itch? Itch only, consider liver/ kidney problems/ dry skin/ allergy.
• Has the patient been in recent contact with infectious disease e.g. shingles/chicken pox?
• Does the patient have any other SACT toxicity related symptoms; if so please see symptom specific guideline

Differential diagnosis includes:

• Side effect of medication
• Allergic reaction
• Infection
• Thrombocytopenia

Initial management:

• Assessment of fluid balance status, establish IV access if any signs of dehydration or sepsis.
• Intravenous fluids according to fluid balance status and renal function.
• Treat any infected lesions as appropriate and adjust antibiotics according to clinical condition, myelosuppression, swab results and local antibiotic guidelines.
• Delineate and record area affected area - photograph.
• Check platelet count - rash may be secondary to thrombocytopenia.
• If ulcers: Topical acyclovir for lips/oral acyclovir for herpes infection in mouth.
• Consider that the rash may be infectious and consider infection prevention precautions.

On-going management:

• Reassess daily and continue close monitoring of routine observations as at risk of infection.
• Observe for development of sepsis, neutropenia, or other chemotherapy toxicities.
• Fluid balance or daily weights.
• Daily full blood count.
• Dermatology review if concerns/uncertainty of diagnosis.

Ensure general care measures:

• Good fluid intake
• Keep area clean and dry
• Avoid hot baths/ tight clothes
• Mild soaps/ cleansers/ detergents.
• Consider Prescribing:
  • Topical creams/lotions (alcohol free, hypoallergenic e.g. E45) - apply regularly to all affected areas
  • Anti-histamines if rash causes itchiness
  • Analgesia if painful (caution with paracetamol/aspirin if risk of neutropenic sepsis)
  • Oral or topical steroids may be required.

Initial Assessment

Observations: Calculate NEWS score.

Investigations: FBC, U&Es.

NB: Isotretinoin is not indicated for the treatment of papulopustular rash

General management and advice (and management of other skin toxicity patterns)

• For hand-foot skin reaction, see Guideline 16 - Palmar­-Plantar Erythrodysaesthesia
• Patients should be advised on general skin care at the commencement of treatment
• The use of soap substitutes, light emollients, sun cream and alcohol-free lotions should be advised
• Emollient creams are preferred over ointments as they can increase acneiform eruptions, g. aveeno, epaderm, hydromol.
• Topical or oral steroids may be required
• Avoid tight footwear and damage to the nail and surrounding skin if nail changes are observed
• Trichomegaly of the eyelashes can cause discomfort and trichiasis, which should prompt referral to an Ophthalmologist

Xerosis

• Eczema
  • Face & Neck: 1% hydrocortisone cream
  • Body: 0.05% clobetasone butyrate cream
  • Treat secondary bacterial superinfection as guided by microbiology swabs.
• Fissures
  • Greasy emollients e.g. Hydromol ointment, 50% propylene glycol under clingfilm or plastic glove occlusion
  • Fludroxycortide impregnated tape or Zinc oxide paste with salicylic acid.

Nail changes

• Inflammation of nail folds
  • Milton sterilising solution for 20 minutes daily
  • Topical steroid/antifungal
    e.g. 1% hydrocortisone/miconazole cream.
• Purulent paronychia
  • Oral antibiotics.
• Nail fold pyogenic granuloma
  • Curettage and cautery.

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant. These patients may be myelosuppressed/neutropenic and at risk of sepsis. If present, this should be managed according to Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis.

Observations: Calculate NEWS score.

Investigations: FBC, U&Es.

Questions:

• What SACT regimen is the patient on? When was the last dose?
• Is this a continuous intravenous administration? E.g. 5-fluorouracil (5FU)
• Is the patient still taking oral SACT? E.g. capecitabine, sunitinib.
• Is the patient otherwise well? Any other symptoms e.g. diarrhoea/stomatitis? if yes refer to specific management guidelines:
  • Guideline 6 - Diarrhoea
  • Guideline 10 - Mucositis/ Stomatitis/ Oesophagitis
• Have they experienced this side effect before on previous treatment cycles?
• Any signs of infection in the affected areas? - Discuss treatment options with the acute oncology team.

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant. These patients may be myelosuppressed/neutropenic and at risk of sepsis. If present, this should be managed according to Guideline 12 - Neutropenic Sepsis. - immediate antibiotics if sepsis suspected

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es, CRP, LFT, Mg²⁺, Ca²⁺, Glucose, Blood cultures and CRP, Cortisol, consider check CO₂ in serum, or blood gases (arterial or venous) for pH/bicarbonate due to H+ potentially causing metabolic alkalosis.

N.B. consider the need for pathology investigations in grade 1 presentations on an individual basis and in light of other presenting symptoms or risk factors.

Questions:

• Is there a cancer diagnosis/primary disease?
• What is the extent of the disease? - E.g. known metastases to brain, bone, liver etc.
• Is the patient taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• How often are they being sick? And are they also feeling nauseous?
• Assess bowel movements, any symptoms that suggest constipation? Any diarrhoea? Bowel obstruction?
• What food and fluids have been taken over last few days?
• Is there any evidence of reflux/gastritis?
• Are there any signs of dehydration e.g. decreased urine output, fever, thirst, dry mucous membranes etc.
• Are there any signs of infection?
• Are they taking any medication e.g. steroids, and has there been any recent change?
• Are they currently receiving radiotherapy? (Especially to brain, liver, GI Tract)
• Does the patient have any abdominal pain? Is this a new symptom?
• How is the patient fed? Do they have a feeding tube? Is this in the correct position?

Differential diagnosis includes:

• Medication related e.g. SACT
• Gastric stasis/ outlet obstruction
• Bowel obstruction
• Hypercalcaemia
• CNS disease
• Endocrinopathy
• Gastro intestinal infection
• Disease related
• Hyper-or-hypoglycaemia

MASSC guidelines here (User Details Required) - http://www.mascc.org/antiemetic-guidelines

Endocrine function panel:

TSH, Free T4, ACTH, cortisol prolactin, blood glucose, LH, FSH +/- testosterone/oestrogen

(9am cortisol is preferable but random cortisol measurement should be performed if the patient is unwell)

NB Values will be lab assay specific.

Clinical presentation

Typically, hypophysitis presents with headache, fatigue and visual loss. There are a range of non-specific symptoms including nausea, diarrhoea, malaise and anorexia, which may represent pituitary dysfunction and a low threshold for clinical suspicion is required. However, these typical symptoms are common in patients with complications of cancer undergoing SACT and other differentials, such as CNS metastases need to be considered.

Endocrine function panel:

TSH, Free T4, ACTH, cortisol prolactin, blood glucose, LH, FSH +/- testosterone/oestrogen.

(9am cortisol is preferable but random cortisol measurement should be performed if the patient is unwell)

NB Values will be lab assay specific.

Mandatory investigations and actions at initial assessment:

• AST/ALT
• gGT
• CK
• Amylase
• Clotting (INR)
• Hepatitis PCR screen
• Ferritin
• EBV/CMV
• HSV & parvovirus
• Lactate and venous/arterial blood gases for assessment of acidosis
• Auto immune screen
• Hepatitis ABCE screen
• Direct bilirubin if bilirubin is markedly elevated
• FBC - document cytopenia especially lymphopenia and monoctyopenia

Ultra Sound Scan in the first 12- 24 hours to assess spleen size and include doppler to assess flow in hepatic veins and arteries

Observations: Monitor and document Glasgow Coma Scale and NEWS

Insomnia

This is the most common steroid-related side effect. Sleep hygiene counseling is important. Patients may require short-term use of 1st line treatment for insomnia e.g. zopiclone.

Hyperglycaemia

A baseline HbA1c should be requested at steroid initiation and random afternoon blood sugar monitoring (BM) should be undertaken whilst on treatment. If new hyperglycemia is detected, Endocrinology advice should be sought (many patients will require short term insulin in this setting). Pre-existing diabetes may require escalation in oral hypoglycaemic agents or insulin.

Osteoporosis

Vitamin D and calcium levels should be taken at baseline and if low, replaced as appropriate. In patients on steroids for >3 months, or with pre-existing osteoporosis, a bisphosphonate should be considered e.g. weekly alendronic acid.

Infection

In patients receiving the equivalent of prednisolone 25mg for > 6 weeks we suggest PJC prophylaxis with co-trimoxazole (80/400mg Mon/Wed/Fri).

Prophylactic antifungals i.e. Fluconazole and monitoring of patient's oropharynx.

If patients are on other immuno-modulatory agents e.g. Mycophenylate mofetil, consideration may be given to CMV prophylaxis with valgancyclovir, especially if CMV IgG negative and lymphopenic.

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of stem cell transplant. These patients may be myelosuppressed /neutropenic and at risk of sepsis. If present, this should be managed according to Guideline 12 - Neutropenic Sepsis.

Observations: Calculate NEWS score.

Investigations:

• FBC
• U&Es
• LFT
• Clotting screen
• Albumin
• Consider CRP in spontaneous bacterial infection
• CXR
• AXR
• Abdominal USS

Signs and symptoms:

• Abdominal pain and distension
• Dyspnoea
• Bulging flanks with dullness to percussion
• Nausea
• Vomiting
• Increased fatigue
• Dyspnoea
• Decreasing appetite

Clinical presentation

Clinically patients present with:

• Increasing breathlessness
• May also have a progressive dry cough or haemoptysis.

Radiation pneumonitis/treatment related pulmonary fibrosis should be considered as can cause similar symptoms. Diagnosis is based on clinical suspicion in a patient with metastatic cancer and appropriate symptoms. Chest X-rays can appear normal in 30-50% of cases, but characteristic changes include:

• Bronchovascular markings with irregular outlines
• Reticular-nodular shadowing
• Bilateral lower lobe changes

Investigations: consider checking ABGs.

Other more general changes include:

• Hilar and mediastinal lymphadenopathy
• Pleural effusions.

High resolution CT Scanning is the investigation of choice if CXRs are equivocal or the clinical picture is not obvious.

Treatment:

• Corticosteroids (such as dexamethasone 4mg bd, with appropriate PPI cover and not be taken later than 2pm to avoid insomnia) may be beneficial to aid in the management of the associated dyspnoea.
• Discussion with the patient’s oncology team is warranted as to whether there are any systemic oncological treatments available, as treating the malignancy itself is the only long-term option.
• Unfortunately, the prognosis of patients who develop carcinomatous lymphangitis is poor, with less than 50% surviving 3 months.

Consider urgent referral to the palliative care team for symptom management and advice.

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or a history of bone marrow transplant. These patients may be myelosuppressed/ neutropenic and at risk of sepsis. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis - immediate antibiotics if sepsis suspected.

Observations: Calculate NEWS score.

Investigations: Urgent FBC, U&Es, CT scan of head (If CT negative and strong suspicion of brain lesion, due to clinical presentation, consider MRI brain).

Full Clinical / neurological assessment: Signs and symptoms may include new onset of seizures, headache, visual disturbance, nausea and/or vomiting, cognitive dysfunction, confusion, disorientation and/or memory loss, motor dysfunction, symptoms of stroke.

Questions:

• Cancer diagnosis/ primary disease/ known metastatic disease
• Currently receiving or have recently completed SACT treatment
• Currently receiving or have recently completed radiotherapy treatment
• Are the presenting symptoms new?
• Are there any co-existing conditions such as epilepsy, hypertension or medication that may account for the patients' symptoms?

NOTE: If there is no history of previous malignancy please see Guideline 38 - Malignancy of Unknown Origin (MUO) Cancer of Unknown Primary (CUP)

Suspect Peripheral Extravasation If

1. Patient complains of burning or stinging pain at or around cannula site
2. There is evidence of swelling, induration, and leakage at site
3. There is resistance on plunger of syringe or absence of free flow of infusion
4. There is no blood return There is no blood return (if found in isolation via a peripheral cannula this should not be regarded as an indication of a non-patent vein).

Action:

• If extravasation occurs during peripheral administration of SACT; Act immediately according to your local extravasation guidelines.
• If a patient presents as an emergency following previous peripheral administration of SACT;

Act immediately - Extravasation of a vesicant drug should be treated as an emergency. If it is discovered the local Acute Oncology Team should be contacted, if out of hours use the Acute Oncology on call rota contact. The local extravasation policy should be followed, and recommended antidotes should be administered appropriately.

Although administration of drugs via CVADs carry less risk of extravasation than peripheral administration, if it does occur the damage is likely to be larger and more severe than with peripheral administration. This is because the event is not likely to be noticed immediately and delays to the treatment of extravasation result in damage limitation rather than cure.

Suspect CVAD Extravasation If

Signs and symptoms include:

• The patient complains of pain around the insertion, along the tunnel or over the port area
• There is evidence of redness and swelling around the insertion, along the tunnel or over the port area
• There is visible leaking of the drug via the skin tunnel or around the exit site.

Extravasation of a vesicant drug should be treated as a medical emergency.

If it is discovered the local Acute Oncology Team should be contacted, if out of hours use the 24 hour telephone on call contact. The local extravasation policy should be followed, and recommended antidotes should be administered appropriately.

Questions:

• Is there a cancer diagnosis/primary disease?
• Are they taking anticancer treatment at the moment or recently? If so what treatment and when did it stop?
• Have they previously suffered from hypercalcaemia?
• Are they taking any other medication? (Stop any calcium supplements).

Investigations:

• ECG - look for shortened QT interval or other conduction abnormalities
• Bloods - Ca²⁺ adjusted for albumin, Phosphate, PTH, Vitamin D, U&Es.

Examination:

• Assess for symptoms of hypercalcaemia and duration
• Fluid balance status

Signs/ symptoms

• Polyuria and thirst
• Anorexia
• Nausea/Vomiting
• Constipation
• Abdominal pain
• Fatigue / Lethargy
• Mood disturbance
• Cognitive dysfunction
• Confusion
• Seizures
• Renal impairment
• Pancreatitis
• Peptic ulceration
• Muscle weakness
• Band keratopathy
• Hypertension
• Cardiomyopathy
• Shortened QT interval
• Dysrhythmias
• Coma

Hypomagnesaemia is often detected on blood tests when the patient is being assessed for other reasons therefore most patients are asymptomatic as the levels are only mildly depressed ( > 0.50mmol/L).

When serum magnesium levels drop more significantly ( < 0.50mmol/L) most patients have non-specific symptoms but they may then go on to develop:

• Cardiac or muscle related symptoms such as weakness, cramping, tachycardia / palpitations.
• Neurological complaints can be that of vertigo, ataxia, depression, and in severe cases seizures or altered mental state.

Investigation:  ECG and consider continuous cardiac monitoring. Check potassium levels and Ca²⁺.

Note: review antiemetics there may be contraindications in patients with low magnesium. Review PPIs and stop if possible as these are frequent causes of hypomagaesaemia.

Examination Findings

Neuromuscular Irritability: Hyperactive deep tendon reflexes, muscular fibrillation, +ve Trousseau (facial nerve hypersensitivity) & Chvostek (metacarpal hyper flexion) signs, dysarthria or dysphagia secondary to oesophageal dysmotility.

CNS Hyper sensitivity: Irritability and combativeness, disorientation, psychosis, ataxia, vertigo, nystagmus & seizures

Cardiac findings (ECG): Paroxysmal atrial and ventricular dysrhythmias, repolarisation alternans

Initial Assessment

Observations: Calculate NEWS score. Fluid balance.

Investigations: FBC, U&Es. Cortisol, Thyroid Function, LFT, Serum Osmality, to confirm true hypo-osmolar hypoNa, Plasma Glucose to exclude hyperglycaemia as a cause, Urine osmolality and Na+

Symptoms:

Severe

• Vomiting
• Cardiorespiratory arrest
• Seizures
• Reduced consciousness
• Coma - GCS < 8

Moderately severe

• Nausea without vomiting
• Confusion
• Headache

The clinical significance of hyponatraemia depends on its:

• Severity
• Speed of onset
• Underlying cause
• Range and degree disease and of co-morbidities.

Management decisions should be based on presenting clinical symptoms rather than the degree of hyponatraemia. 

N.B. Severe symptoms are unlikely with serum sodium >130 mmol/L and alternative causes of neurological dysfunction should be considered in this context.

Causes

Most malignant pericardial effusions result from direct malignant involvement with the pericardium. Other, rarer causes of effusions in cancer patients include radiation-induced pericarditis or chemotherapy-induced pericarditis associated with agents such as doxorubicin or cyclophosphamide.

Clinical Findings

• Dyspnoea (majority), fatigue, or asthenia may be the initial symptoms. Monitor oxygen saturation and consider ABGs

Other common symptoms include:

• Cough
• Chest pain
• Orthopnoea

On examination, findings include:

• Elevated JVP
• Tachycardia
• Hypotension
• Pulsus paradoxus (an abnormally large decrease in pulse and systolic blood pressure (> 20mmHg) with inspiration)
• Kussmauls's sign (increased distension of jugular veins with inspiration)

Diagnosis:

• Chest X-ray may show a widened cardiac shadow
• Echocardiography shows the size of the effusion and haemodynamic consequence
• ECG to investigate small ECG complexes

Questions:

• Cancer diagnosis/primary disease
• Cardinal questions related to breathlessness

Differential diagnosis would include

• Chest infection
• Pulmonary embolism (PE)
• Disease progression (i.e. consolidation / pleural effusion)
• Ascending aortic aneurysm due to indwelling intravascular catheter

Questions:

• Cancer diagnosis/primary disease
• Cardinal questions related to breathlessness

Differential diagnosis would include:

• Chest infection
• Pulmonary embolism (PE)
• Disease progression i.e. consolidation / pleural effusion
• Ascending aortic aneurysm (due to indwelling intravascular catheter)

Signs and symptoms:

• Dyspnoea
• Stridor - due to laryngeal oedema
• Non-pulsatile JVP
• Headaches
• Dilated anterior chest wall veins
• Confusion
• Chest pain
• Swelling of face and neck
• Coma

Investigations: CTPA to define tumour extent, site of occlusion or stenosis and extent of any thrombus. SVCO can be an incidental finding on CT.

Manage in accordance with trust local guidelines depending upon differential diagnosis and clinical status.

Further management may include:

• Stent insertion - performance status
• Chemotherapy - performance status
• Radiotherapy - any contraindications e.g. previous radiotherapy to chest. Inability to lie flat.
• If thrombus is present consider anticoagulation if no contraindications.

Glossary

Consultation and development group

Development Group

Development group (alphabetical order)

Consultation and specialist opinion group (alphabetical order)

Organisations

Aknowledgements

The UKONS Board and project leads wish to thank:

• The development group of the original set of guidelines V.1
• The Clatterbridge Cancer Centre NHS Foundation Trust and The Royal Marsden NHS Foundation Trust for sharing their original Immune-Related Adverse Event (irAE) management guidelines which have been used to develop guidelines within this document
• The development group, specialist advisors and consultation group members for helping throughout the project.

Appendix

ONCOLOGY/HAEMATOLOGY ADVICE LINE

TRIAGE TOOL, VERSION 2

Patients may present with problems other than those listed below, these would be captured as “other” on the log sheet checklist. Practitioners are advised to refer to the NCI-CTCAE common toxicity criteria V4.03 to assess the severity of the problem and/or seek further clinical advice regarding management.

CAUTION! Please note patients who are receiving or have received IMMUNOTHERAPY may present with treatment related problems at anytime during treatment or up to 12 months afterwards. If you are unsure about the patient's regimen, be cautious and follow triage symptom assessment.

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