Acute Oncology Initial Management Guidelines - Version 4.0

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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 5.0), 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:

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, P.56/57). They are mostly single-page “see-and-treat” guides. Whilst drug names may be referenced within a guideline, this is offered as a guide only, it is acknowledged that local variation may apply.

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 Guideline
• Metastatic Spinal Cord Compression: NICE Guideline.
• Metastatic malignant disease of unknown primary origin in adults: diagnosis and management: NICE Guideline

• Scottish Palliative Care Guidelines
• United Kingdom Acute Oncology Society:UKAOS
• Directory of Ambulatory Care for Adults:AEC Directory
• UK Oral Management in Cancer Care Group:UKOMiC Guidelines
• Royal Society of Radiographers:sor.org

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 consider same day emergency care (SDEC) 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. Life threatening emergencies to be seen in the emergency department (ED).
• 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.
• Consider early involvement from the cancer site specific clinical nurse specialist (CNS) where appropriate
• 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
• Cough
• Dyspnoea
• Dizziness
• Headache
• Hypertension
• Hypotension
• Rash
• Urticaria
• Tachycardia
• Rigors/chills
• Arthralgia
• Nausea, vomiting
• Pruritus/itching
• Myalgia
• Asthenia
• Swelling of tongue/throat

Examinations: ABCDE approach, Clinical evaluation, history, physical examination, and review of observations.

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:

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

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

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 taken 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 – think SPINE
• 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?
• Other medications such as fluroquinolones or antibiotics.

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es and Ca²⁺. TSH and Free T4, Cortisol, Blood Glucose, CK and ESR as initial assessment for Autoimmune Arthritis/Myositis. CRP measurement may also be useful

Differential diagnosis:

• Treatment related
• Viral infection
• Autoimmune Arthritis/Myositis

Discuss investigation and infection prevention with local microbiologist.

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 on P.19, immediate antibiotics if sepsis suspected.

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?
• Any history of trauma.

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

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

Signs and symptoms:

• Lightheaded
• Clammy
• Pallor
• Thirst
• Rash (petechial/purpura/punctuate)

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.

Consider:

• 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).
• Viral infection- e.g. parvovirus B19 as a cause of thrombocytopenia.
• Systemic anti-cancer treatment patients who are receiving certain drugs are at risk of thrombocytopaenia.

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?
• Are there exacerbating/relieving factors, and characteristics of pain?
• Are there associated symptoms, e.g. SOB, syncope, oedema, palpitations?
• Consider - is this pain cardiac? - ESC Guidelines Chapter 6. Diagnosis and management of acute and subacute cardiovascular toxicity in patients receiving anticancer treatment

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, Coagulation screen, Cardiac markers/Troponin. Urgent ECG. Chest X-Ray. Consider ABG’s, Wells score, D-Dimers.

Differential diagnosis:

• Cardiac cause
• Pulmonary embolism (PE)
• Effusions
• Chest infections
• Disease progression
• Indigestion/reflux

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.

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: Clinical evaluation, history, physical examination, and review of observations - PR Examination (caution in pancytopaenic 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.

Observations: Calculate and monitor NEWS score. Presence of bowel sounds.

Investigations: Urgent FBC, U&Es, CRP, Ca²⁺, and LFT. Coagulation screen. Consider abdominal X-ray +- Erect Chest X-ray.

Differential diagnosis:

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

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. If present, this should be managed as per Guideline 12 - Neutropenic Sepsis, immediate antibiotics if sepsis suspected.

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?

Examination: Clinical evaluation, history, physical examination, and review of observations.

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, for viral causes. Consider Abdominal X-ray. Do NOT assume this is infective it is most likely to be drug induced in this group of patients.

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.

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.

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

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 new neck or arm swelling /distended veins - assess for signs of Superior vena cava obstruction (SVCO)
• Is there any pain or swelling in legs? – Assess for signs of DVT

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, Sputum and viral throat swab for C&S, blood cultures and CRP if pyrexial. ECG and CXR. Coagulation screen. Consider haematinics, ABGs and troponin. 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.

Differential diagnosis includes:

• Pulmonary embolism (PE)
• Cancer progression
• New cancer diagnosis
• Pleural effusion
• Chest infection
• Consolidation
• SVCO
• Cardiac ischaemia
• Anaemia
• Pneumonitis
• Lymphangitis
• Viral Infection such as Covid or Influenza

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.

Questions:

• Is there a cancer diagnosis/primary disease?
• Is the patient taking anticancer treatment now 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?

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, group and save, Ca²⁺, CRP, blood glucose, consider blood cultures.

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/phychological problems

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.

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.

• Examination: Clinical evaluation, history, physical examination, and review of observations Full neurological assessment and on-going review
• Observations: Calculate and monitor NEWS score.
• Investigations: Urgent MRI whole spine within 24 hours of clinical suspicion. Urgent FBC, U&Es, LFT, bone profile Consider Group & Save and /or clotting screen.
• If new diagnosis of suspected cancer arrange CTCAP and appropriate tumour markers to aid diagnosis
• If considering myeloma/plasmacytoma then Immunoglobulins/electrophoresis, serum light chains
• If considering lymphoma, then LDH.

Key signs/symptoms:

• The patient may or may not have a cancer diagnosis/primary disease.
• Back pain that is multi segmental or band like and or local spinal tenderness.
• 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 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.

• 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?

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, LFT, 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)

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) or receiving radiotherapy head and neck/upper GI tract. 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.

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?

Examination: Clinical evaluation, history, physical examination, and review of observations

Observations: Calculate and monitor 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.

Differential diagnosis includes:

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

Identify: Patients who have received/receiving systemic anti-cancer treatment or are at risk of disease related immunosuppression or radiotherapy (especially to brain, abdomen, GI Tract) 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.

Questions: THINK SEPSIS SIX TRIGGER QUESTIONS – Does the patient look sick or has NEWS or similar triggered? Do they have any sepsis six red flag?

• When was the last SACT given?
• Is there a history of transplant?
• Is there a history of myelosuppression or known bone marrow failure? This can be due to a haematological malignancy, bone marrow transplant or high dose radiotherapy to pelvis or sternum
• Is there a history of previous neutropenic episodes?
• Focus infection screening questions to identify potential source
• Patients may appear well initially but if untreated can rapidly progress to septic shock + death. Early diagnosis will normally prevent death
• Neutrophil count below 0.5 x 10⁹ /L OR neutrophil count awaited and SACT within the past six weeks, OR neutrophil count below 1.0 x 10⁹ /L and expected to fall, OR bone marrow transplant patient.

Investigations: FBC, U&Es, LFTs include albumin, Coagulation screen, G+S, Ca²⁺, PO^4-, Mg²⁺, Urate, CRP, and Lactate, peripheral and central line blood cultures. Consider ABG and blood or plasma glucose.

• Calculate and monitor NEWS score.
• Calculate MASCC score - if no evidence of sepsis and low risk score consider Low Risk Febrile Neutropenic pathway Urinalysis and monitor urine output. FULL SEPTIC SCREEN – consider sputum and stool samples Consider: throat swab, central line swab, wound swab CXR and consider ECG if clinically indicated.

Examination: Clinical evaluation, history, physical examination, and review of observations Full history (consider current or recent SACT) + examination If SACT infuser connected – stop it.

Symptoms: The progression of infection in neutropenic patients can be rapid, and neutropenic patients with early bacterial infections cannot be reliably distinguished from non-infected patients at presentation.

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.

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

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

Differential diagnosis includes:

• Side effect of medication
• Allergic reaction
• Infection e.g. shingles/ impetigo
• Thrombocytopenia

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.

Initial Assessment: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor 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.

Questions:

• What SACT regimen is the patient on? When was the last dose?
• Is this a continuous intravenous administration via pump? Does this need to be discontinued?
• Is the patient still taking oral SACT? Does this need to be discontinued?
• 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.

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

Investigations: If indicated bloods.

Identify: Patients who have received/receiving systemic anti-cancer treatment or receiving radiotherapy 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.

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?

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor NEWS score.

Investigations: Urgent FBC, U&Es, CRP, LFT, Mg²⁺, Ca²⁺, Glucose, CRP, Cortisol, Check CO2 in serum, or blood gases (arterial or venous) for pH / bicarbonate if metabolic alkalosis suspected. Consider Blood cultures if infection suspected. 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.

Differential diagnosis includes:

• Medication related e.g. SACT
• Gastrointestinal infection
• Gastric stasis/ outlet obstruction
• Disease related
• Hypercalcaemia
• CNS disease
• Sub-acute or acute bowel obstruction
• Endocrinopathy/ Hyper-or-hypoglycaemia

Identify: Patients who have received/receiving systemic anti-cancer treatment or receiving radiotherapy 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.

Supportive Measures

Hyperglycaemia
A baseline HbA1c should be requested at steroid initiation and random blood sugar monitoring (BM) alongside biochemical monitoring should be undertaken whilst on treatment. If new hyperglycemia is detected, then the UK Chemotherapy Board and The Joint British Societies for Inpatient care joint guideline on the management of glycaemic control in patients with cancer should be followed including advice from local endocrinology teams. Patients may require oral anti-diabetic medication or insulin in the short term.

Insomnia
This is the most common steroid-related side effect. Sleep hygiene counselling is important. Patients may require short-term use of zopiclone (benzodiazepines should only be considered in rare circumstances for a max 3-5 days). Patients should be counseled about the importance of early morning steroid administration.

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 bone density scan and AdcalD3 and alendronate (or another bisphosphonate should be considered).

Infection
In patients receiving the equivalent of prednisolone 25mg for > 6 weeks or 2 or more immunosuppressant’s, PCP prophylaxis with co-trimoxazole (800/160mg Mon/Wed/Fri) should be considered (incidence of PCP in this patient group is very low).

The oropharynx should be monitored for candidiasis and may require topical therapy such as Nystatin or oral antifungals. Azole antifungals commonly cause hepatitis and so should be used with caution in prophylactic setting.

If patients are on other immuno-modulatory agents e.g. Mycophenylate mofetil (MMF), consideration may be given to CMV prophylaxis with gancyclovir, especially if CMV IgG negative and lymphopenic. Acyclovir prophylaxis should be considered in patients who are immune-suppressed and have required treatment for oral viral infection.

General
Ensure all patients are given a national Steroid Alert Card when commencing on corticosteroids.

Ensure steroid sick day rules are implemented as required.

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor 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
• Decreasing appetite
• Dyspnoea
• Nausea
• Vomiting
• Increased fatigue
• Bulging flanks with dullness to percussion

Investigations:

• Previous cancer diagnosis or malignancy of unknown origin (MUO)
• Differential diagnosis would include liver disease.

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 guidelines.

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 pulmonary carcinomatous lymphangitis is poor as it is associated with last stage malignancy.

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?

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: Calculate and monitor 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 (MRI with contrast maybe required to rule out meningeal disease).

Full Clinical / neurological assessment:
Signs and symptoms may include:

• New onset of seizures
• Headache
• Visual disturbance
• Motor dysfunction, symptoms of stroke
• Cognitive dysfunction, confusion, disorientation and/or memory loss

NOTE: If there is no history of previous malignancy, please see MUO/CUP guideline 40 on P48.
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. f present, this should be managed as per guideline 12 on P.19, immediate antibiotics if sepsis suspected.

Suspect Peripheral Extravasation If

1. Patient complains site pain, burning, aching/discomfort, around the cannula.
2. There is evidence of swelling, induration, and leakage at site
3. There is resistance on plunger of syringe or absence of of flow at infusion
4. Action: If extravasation occurs during peripheral administration of SACT; Act immediately according to your local guidelines

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

Suspect CVAD extravasation if Signs and symptoms include:

• Patient complains of pain around the insertion site, along the skin tunnel or over the port area.
• There is evidence of redness and swelling around the insertion site, along the skin tunnel or over the port area.
• There is visible leaking of the drug fromhe skin tunnel, round the catheter exit site or around the Huber needle insertion site.

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

If it is discovered the local Acute Oncology or Plastics Team (according to policy) should be contacted immediately. The local extravasation policy should be followed

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.

Examination: Clinical evaluation, history, physical examination, and review and monitoring of NEWS score.

• Assess for symptoms of hypercalcemia and duration.
• Fluid balance status.

Observations: Calculate and monitor NEWS score.

Investigations:

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

• 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

Questions:

• Are they on any contributory medications? E.g. PPI's
• Do any medications need caution? E.g. antiemetics.
• Are they on any anti-cancer treatment? If so, what?
• Do they have any nausea, vomiting or diarrhoea?

Examination: Clinical evaluation, history, physical examination, and review observations.

• 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 Hypersensitivity: Irritability and combativeness; disorientation; psychosis; ataxia, vertigo, nystagmus & seizures.

Observations:Calculate and monitor NEWS score.

Investigations:

• Check bloods including potassium levels and Ca²⁺
• ECG - Findings could include Prolonged QT interval, Paroxysmal atrial and ventricular dysrhythmias; repolarisation alternans. Consider continuous cardiac monitoring.

Symptoms:

• > 0.50mmol/L - most patients may be asymptomatic.
• < 0.50mmol/L - patients may have non-specific symptoms but 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.

Questions - The clinical signifiance of hyponatraemia depends on:

• Severity/grade?
• Speed of onset? - Acute < 48 hours. Chronic> 48 hours or more
• Underlying cause? - range and degree of disease and co-morbidities. Could this be caused by the anti-cancer treatment.

Examination: Clinical evaluation, history, physical examination, and review of observations.

Observations: : Calculate and monitor NEWS score. Fluid balance.

Investigations:

• FBC, U&Es.
• Cortisol, Thyroid Function, LFT, Paired Serum and Urine Osmolalities, to confirm true hypo-osmolar hypoNa, Urinary Sodium Concentration, Plasma Glucose to exclude hyperglycaemia as a cause.

Symptoms:

• Mild or Absent
• Lethargy.
• Moderately Severe:
• Vomiting.
• Nausea without vomiting.
• Confusion.
• Headache.
• Severe:
• Cardiorespiratory arrest.
• Reduced level of consciousness.
• GCS less than 8 Seizures.

Questions

• Cancer diagnosis/primary disease.
• Cardinal questions related to breathlessness.
• What anti-cancer therapy has the patient had? E.g. Radiation-induced pericarditis or SACT-induced pericarditis.

Examination:

• Elevated JVP.
• NEWS - Tachycardia, Hypotension, Hypoxia.
• 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).

Obeservations: Calculate and monitor NEWS score.

Investigations:

• FBC, U&E, CRP, Clotting, consider blood gases.
• Chest X-ray may show a widened cardiac shadow.
• Echocardiography to evaluate the size of the effusion and degree of haemodynamic compromise.
• ECG may show small complexes.

Symptoms:

• Dyspnoea (majority).
• Fatigue, or asthenia may be the initial symptoms.
• Chest pain (worse on lying flat).
• Cough.
• Orthopnoea.

Most malignant pericardial effusions result from direct malignant involvement with the pericardium - Disease progression.Other causes include:

• Chest infection.
• Myocarditis.
• Acute Coronary Syndrome.
• Pulmonary embolism (PE).
• Ascending aortic aneurysm - Due to indwelling intravascular catheter.

Questions:

• Does the patient have a Cancer diagnosis?
• Where is the primary disease?
• Have they had recent radiology?
• Cardinal questions related to breathlessness.

Examination:

• Clinical evaluation.
• History.
• Physical Examination.
• Review of Observations.

Observations:

• Calculate and monitor NEWS score.

Investigations:

Signs and Symptoms:

Differential Diagnosis:

Seek advice from the Acute Oncology and/or the Respiratory team as soon as possible to guide investigations and management.

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

Project Development and Review Leads

Consultation Group and Specialist Advisors

Consultation Group and Specialist Advisors

Aknowledgements

The UKONS Board and the Project Development and Review Leads wish to thank:

• The development group of the original set of guidelines V.1 and all who have contributed to the review and development of V.2 and V3
• The Clatterbridge Cancer Centre NHS Foundation Trust for sharing their updated 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
• Media1 for their support with coordination and design
• British Oncology Pharmacy Association (BOPA) committee
• Society of Radiographers (SoR) Radiation Induced Skin Reactions Special Interest Group (RISR SIG).

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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