Palliative & Oncological Emergencies

1. Clinical Overview

Summary

Oncological emergencies represent acute, life-threatening or function-threatening complications that can occur at any stage of malignancy, from initial presentation through to end-of-life care. [1] These emergencies require immediate recognition and intervention to prevent catastrophic disability, preserve quality of life, and in select cases, extend survival. [2]

Oncological emergencies can be broadly classified into:

• Structural emergencies: Causing mass effect or obstruction
• Metabolic emergencies: Disrupting normal biochemical homeostasis
• Haematological emergencies: Including neutropenic sepsis and hyperviscosity
• Treatment-related emergencies: Complications of chemotherapy, radiotherapy, or immunotherapy

The "Big Three" classical emergencies that every clinician must recognize are:

1. Metastatic Spinal Cord Compression (MSCC) - affects 5-10% of all cancer patients [3]
2. Superior Vena Cava Obstruction (SVCO) - occurs in 3-4% of patients with intrathoracic malignancy [4]
3. Hypercalcaemia of Malignancy - develops in 20-30% of patients with advanced cancer [5]

Additional critical emergencies include:

• Catastrophic haemorrhage
• Neutropenic sepsis
• Tumour lysis syndrome
• Malignant pericardial effusion with tamponade
• Raised intracranial pressure from brain metastases
• Syndrome of inappropriate antidiuretic hormone (SIADH)

Early recognition and prompt intervention can significantly alter outcomes. For MSCC, ambulatory status at diagnosis is the single most important prognostic factor - 70% of patients ambulatory at presentation remain so after treatment, compared to less than 5% of those who are paraplegic at diagnosis. [6]

Epidemiology

Oncological emergencies are increasingly common as cancer survival improves and populations age. Key epidemiological features include:

MSCC:

• Incidence: 5-10% of all cancer patients develop MSCC [3]
• Most common primaries: Breast (20%), lung (18%), prostate (16%), renal (10%), lymphoma (8%), myeloma (7%) [7]
• Anatomical distribution: Thoracic spine (60%), lumbosacral (30%), cervical (10%)
• Multiple level involvement: 10-38% of cases [8]

SVCO:

• Incidence: 3-4% of patients with intrathoracic malignancy [4]
• Malignant causes (90%): Lung cancer (75% of cases - especially SCLC and right upper lobe tumours), lymphoma (15%), mediastinal tumours
• Benign causes (10%): Thrombosis from central venous catheters, fibrosing mediastinitis, goitre

Hypercalcaemia of Malignancy:

• Incidence: 20-30% of cancer patients at some point in disease course [5]
• Most common malignancies: Multiple myeloma (30% of patients), breast cancer (20-40%), squamous cell lung cancer (12.5%)
• Mechanism: Humoral (80% - PTHrP mediated), osteolytic metastases (20%), combined mechanisms
• Poor prognostic marker: Median survival 1-3 months after diagnosis [9]

Clinical Pearls

MSCC Warning - The 24-Hour Window: The earliest symptom of spinal cord compression is back pain, typically radicular (band-like distribution) and characteristically worse on lying down due to venous engorgement and spinal instability. Do NOT wait for motor weakness or bladder dysfunction to diagnose MSCC - by the time these signs appear, irreversible neurological damage has often occurred. The window for preserving ambulatory status is typically less than 24-48 hours from onset of motor symptoms. [6]

Pemberton's Sign: Classic clinical test for SVCO. Ask the patient to elevate both arms above their head and hold the position. A positive sign develops within 60 seconds and consists of facial plethora, cyanosis, and distension of neck veins as the mass (tumour or thyroid) is pushed into the thoracic inlet, further compromising venous return. Sensitivity approximately 50-60% but highly specific when positive. [10]

Corrected Calcium - The Hidden Danger: Always interpret calcium levels relative to albumin concentration. Palliative care patients are frequently hypoalbuminaemic due to malnutrition, inflammatory states, or hepatic dysfunction. A "normal" total calcium of 2.4 mmol/L in a patient with albumin of 25 g/L translates to a corrected calcium of approximately 2.8 mmol/L - significantly elevated. Use the formula: Corrected Ca²⁺ = measured Ca²⁺ + 0.02 × (40 - albumin g/L). Even better, request ionized calcium measurement when available. [11]

The "Squamous Calcium Connection": Squamous cell carcinomas (lung, head & neck, oesophageal) have particular propensity to cause hypercalcaemia via PTHrP secretion. Always check calcium levels in these patients presenting with confusion, polyuria, or constipation.

Neutropenic Sepsis - Time is Life: Each hour delay in antibiotic administration in neutropenic sepsis increases mortality by 15-20%. [12] Door-to-needle time should be less than 60 minutes, ideally less than 30 minutes. Piperacillin-tazobactam 4.5g IV is standard first-line unless local resistance patterns or patient factors dictate otherwise.

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2. Metastatic Spinal Cord Compression (MSCC)

Definition and Classification

Metastatic Spinal Cord Compression is defined as compression of the thecal sac and its contents (spinal cord and/or cauda equina) by extradural tumour mass or vertebral collapse/instability. [13]

Classification by anatomical level:

• Cervical (10%): C1-C7 - Risk of respiratory compromise, tetraplegia
• Thoracic (60%): T1-T12 - Most common site, paraplegia risk
• Lumbosacral (30%): L1-S5 - Cauda equina syndrome pattern

Classification by extent:

• Single level: One vertebral level involved
• Multi-level: Non-contiguous involvement (10-38% of cases) [8]
• Extensive: Multiple contiguous levels

Frankel Grading Scale (used to assess severity):

• Grade A: Complete motor and sensory loss
• Grade B: Sensory only, no motor function
• Grade C: Motor useless (gravity eliminated)
• Grade D: Motor useful (against gravity)
• Grade E: Normal motor and sensory function

Pathophysiology

MSCC occurs through three principal mechanisms:

1. Posterior Expansion of Vertebral Metastasis (85% of cases) Haematogenous spread deposits tumour in the vertebral body (preferentially posterior body, adjacent to Batson's venous plexus). The tumour expands posteriorly through the pedicles into the epidural space, compressing the thecal sac. The thoracic spine is most vulnerable due to narrow spinal canal diameter. [14]

2. Paravertebral Mass Extension Tumour in paravertebral soft tissues extends through neural foramina into epidural space. More common with lymphoma and neuroblastoma.

3. Vertebral Collapse Pathological fracture causes retropulsion of bone fragments or vertebral body collapse with kyphotic deformity, causing mechanical compression. Associated with spinal instability.

Mechanisms of Neurological Damage:

• Direct mechanical compression: Distortion of neural tissue
• Vascular compromise: Compression of radicular arteries and spinal cord vessels causing ischaemia
• Venous congestion: Impaired drainage leading to oedema
• Cytotoxic oedema: Secondary inflammation and oedema propagating injury

Time course is critical: Rapid onset compression (hours to days) has worse prognosis than slow progressive compression over weeks, as the latter allows some neural adaptation.

Clinical Presentation

Pain (Present in 90% at diagnosis) [15]

• Characteristics: Constant, progressive, severe
• Pattern: Radicular (band-like), worse at night and when lying flat (due to venous engorgement and loss of axial loading)
• Location: Localized back pain at level of compression ± radicular radiation
• Red flag: Pain that wakes patient from sleep or prevents lying flat
• Timeline: Usually precedes neurological deficit by median of 7 weeks (range: days to months)

Motor Weakness (Present in 75% at diagnosis)

• Pattern: Upper motor neurone signs below level of lesion (increased tone, hyperreflexia, upgoing plantars)
• Progression: Typically starts with heavy/weak legs, progressing to complete paralysis if untreated
• Examination: Assess power in all myotomes, particularly hip flexion (L1-L2), knee extension (L3-L4), ankle dorsiflexion (L4-L5)
• Critical point: Presence of motor weakness indicates advanced compression - median time from motor deficit to complete paralysis is 24-48 hours without intervention [6]

Sensory Changes (Present in 50% at diagnosis)

• Pattern: Sensory level on trunk corresponding to compression site
• Modalities: Reduced pinprick, light touch, temperature
• Examination: Carefully map sensory level bilaterally from feet upward
• Sacral sparing: Preservation of perianal sensation suggests incomplete lesion

Autonomic Dysfunction (Present in 40% at diagnosis - Late Sign)

• Bladder: Urinary retention (most common), overflow incontinence
• Bowel: Constipation, faecal incontinence
• Sexual: Erectile dysfunction
• Clinical assessment: Palpable bladder, reduced anal tone, absent bulbocavernosus reflex
• Prognostic significance: Presence of sphincter dysfunction indicates severe compression and poor functional prognosis

Atypical Presentations:

• Cauda equina syndrome: Lower motor neurone pattern (flaccid paralysis, reduced reflexes, saddle anaesthesia)
• Brown-Séquard syndrome: Hemisection pattern (ipsilateral motor and proprioception loss, contralateral pain and temperature loss)
• Anterior spinal artery syndrome: Motor loss with preserved posterior column function

Investigations

Imaging - MRI Whole Spine (Gold Standard) [13]

• Indication: Any cancer patient with new or progressive back pain, or any neurological signs
• Timing: Within 24 hours of suspected diagnosis (NICE guideline) [13]
• Protocol: Whole spine imaging (not just symptomatic region) due to 10-38% multi-level involvement
• Sequences: T1 (anatomy), T2 (cord oedema), STIR (bone metastases), T1 post-gadolinium (enhancing tumour)
• Findings:
  • Epidural mass with thecal sac compression
  • Cord signal change (T2 hyperintensity indicates oedema/ischaemia)
  • Vertebral body replacement/collapse
  • Assessment of spinal stability

Alternative Imaging (if MRI contraindicated/unavailable):

• CT myelography: Second-line if MRI not possible (pacemaker, severe claustrophobia)
• Plain radiographs: Insensitive - 50% of bone destruction needed to visualize lytic lesions. May show pedicle erosion, vertebral collapse
• Bone scintigraphy: Sensitive for bony metastases but poor soft tissue resolution

Laboratory Investigations:

• Baseline bloods: FBC, U&E, LFTs, bone profile (calcium, phosphate, ALP), coagulation
• Inflammatory markers: CRP (sepsis screen)
• Tumour markers: PSA (prostate), Ca-125 (ovarian), Ca 15-3 (breast) if primary unknown

Functional Assessment:

• Ambulatory status: Critical prognostic indicator - document clearly (independently ambulatory / ambulatory with aid / non-ambulatory)
• Neurological examination: Power (MRC scale 0-5), sensation (dermatomes), reflexes, plantar responses, anal tone, bladder palpation

Management Algorithm

1. IMMEDIATE ACTIONS (Within 1 Hour of Suspicion)

High-Dose Corticosteroids [16]

• Drug: Dexamethasone (preferred - minimal mineralocorticoid activity)
• Dose: 16 mg STAT (oral or IV if unable to swallow)
• Mechanism: Reduces vasogenic oedema around compressed cord, temporarily stabilizes neurological function
• Continuation: 16 mg once daily (morning) with proton pump inhibitor cover
• Evidence: Historical RCT showed improved outcomes with steroids, though optimal dose debated. Doses up to 96 mg used historically but higher bleeding/infection risk without proven benefit over 16 mg. [16]
• Precautions: Monitor blood glucose, risk of GI bleeding (co-prescribe PPI), immunosuppression

Immediate Referral

• Contact: Acute oncology team + neurosurgery/spinal orthopaedics (depending on local pathways)
• Information to relay: Cancer history, ambulatory status, neurological deficit, pain severity, imaging availability

Urgent MRI Whole Spine

• Timing: Within 24 hours of presentation (within business hours) or immediately if rapid progression/cauda equina syndrome [13]
• Protocol: T1, T2, STIR sequences; whole spine coverage

Nursing Care

• Bed rest: Flat bed rest with log-rolling until spinal stability confirmed on imaging
• Pressure area care: High risk of pressure sores in paralyzed/immobile patients
• Bladder management: Catheterization if retention (measure residual volume)
• VTE prophylaxis: LMWH unless contraindicated (check platelets, coagulation)

2. DEFINITIVE TREATMENT (Within 24-48 Hours)

Treatment selection based on:

• Number of compression sites (single vs. multiple)
• Spinal stability (vertebral collapse, > 50% body involvement)
• Histology (radiosensitive vs. radioresistant)
• Performance status and fitness for surgery
• Prior radiotherapy to site
• Life expectancy

Surgical Decompression + Stabilization [6]

Indications:

• Single level compression
• Spinal instability or bone compression (rather than soft tissue mass)
• Radioresistant tumour (e.g., renal, melanoma, sarcoma)
• Progression during/after radiotherapy
• Tissue diagnosis required
• Good performance status (expected survival > 3 months)

Procedures:

• Posterolateral decompression: Laminectomy + instrumented fusion
• Anterior corpectomy: For ventral compression from vertebral body tumour
• Vertebroplasty/Kyphoplasty: Cement augmentation for pain relief and stability in vertebral collapse

Evidence - Patchell Trial (Lancet 2005): [6] Landmark RCT comparing surgery + radiotherapy vs. radiotherapy alone. Results:

• Ability to walk: 84% (surgery group) vs. 57% (radiotherapy alone), p=0.001
• Regained ability to walk: 62% vs. 19%
• Maintained continence: 87% vs. 61%
• Survival: 126 days vs. 100 days (p=0.03) Trial stopped early due to clear benefit of surgery in ambulatory or paraplegic patients with single-level compression.

Radiotherapy [17]

Indications:

• Radiosensitive tumours (lymphoma, myeloma, SCLC, prostate, breast)
• Multiple level compression
• Poor surgical candidate
• Post-operative adjuvant treatment

Regimens:

• Single fraction: 8 Gy (convenience, suitable for frail patients)
• Short course: 20 Gy in 5 fractions (most common in UK)
• Longer course: 30 Gy in 10 fractions (if good prognosis, potential for long-term control)

Evidence: Cochrane review found no significant difference in outcomes between single-fraction and multi-fraction radiotherapy for pain relief or neurological function in MSCC. [17]

Oncological Systemic Therapy

• Chemotherapy: For highly chemosensitive tumours (lymphoma, germ cell, SCLC) - may be used alongside or instead of radiotherapy
• Hormonal therapy: Prostate cancer (androgen deprivation), breast cancer (endocrine therapy)
• Targeted therapy: Depends on tumour biology

3. SUPPORTIVE AND REHABILITATIVE CARE

Pain Management:

• Neuropathic pain: Gabapentin (starting 300 mg nocte, titrate to 300-900 mg TDS) or pregabalin
• Nociceptive pain: Regular paracetamol + opioids (morphine, oxycodone) titrated to effect
• Bone pain: NSAIDs if renal function permits
• Incident pain: Breakthrough opioid doses (1/6 of total daily dose)

Rehabilitation:

• Early physiotherapy: Even during acute phase to prevent contractures and pressure sores
• Occupational therapy: Adaptive equipment, home modifications
• Mobility aids: Wheelchairs, walking frames as appropriate
• Bladder/bowel management: Intermittent self-catheterization training, bowel regimen

Psychological Support:

• Adjustment to paralysis and loss of independence
• Involvement of palliative care team, clinical psychology
• Family education and support

Prognosis

Ambulatory Status at Diagnosis (Most Important Prognostic Factor):

• Ambulatory at diagnosis: 70-80% remain ambulatory after treatment [6]
• Non-ambulatory but not paraplegic: 30-40% regain ambulation
• Paraplegic at diagnosis: less than 5% regain ability to walk

Other Prognostic Factors:

• Time to motor deficit: Rapid onset (less than 24 hours) worse than gradual (weeks)
• Primary tumour: Breast, prostate, lymphoma better than lung, melanoma, renal
• Performance status: Better baseline function predicts better outcome
• Number of compression sites: Single level better than multiple
• Prior treatment: Radiotherapy-naïve better than recurrence

Survival: Median survival post-MSCC diagnosis: 3-6 months overall, but highly variable:

• Favourable histology (breast, prostate, myeloma): 12-24 months
• Unfavourable histology (lung, melanoma): 2-4 months

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3. Superior Vena Cava Obstruction (SVCO)

Definition and Pathophysiology

Superior Vena Cava Obstruction is compression or invasion of the SVC leading to impaired venous drainage from the head, neck, and upper extremities. [4]

Anatomy: The SVC is a thin-walled, low-pressure vessel located in the right anterior mediastinum, surrounded by:

• Right lung and pleura (laterally)
• Aorta (posteriorly)
• Sternum (anteriorly)
• Lymph nodes (mediastinal and paratracheal)
• Thymus (anterior)

This confined anatomical space means any mass lesion readily causes external compression.

Pathophysiology:

Malignant Causes (90% of cases):

1. Lung cancer (75-80%): Especially right upper lobe and mediastinal involvement; SCLC and NSCLC
2. Lymphoma (10-15%): Non-Hodgkin lymphoma (especially diffuse large B-cell), Hodgkin lymphoma
3. Metastatic disease (5%): Breast, colon, oesophageal
4. Germ cell tumours: Mediastinal non-seminomatous germ cell tumours
5. Thymoma: Locally invasive thymic tumours

Benign Causes (10% of cases, increasing with device use):

1. Thrombosis: Central venous catheters (Hickman lines, PICC lines, pacemaker wires)
2. Fibrosing mediastinitis: Histoplasmosis, tuberculosis, sarcoidosis
3. Goitre: Retrosternal thyroid extension
4. Aortic aneurysm: Rare

Mechanism of Obstruction:

• External compression: Tumour mass (most common)
• Invasion: Direct tumour infiltration of vessel wall
• Thrombosis: Tumour-related or catheter-related thrombus

Haemodynamic Consequences: Obstruction increases venous pressure proximal to blockage (head, neck, upper limbs) leading to:

• Venous engorgement and distension
• Facial and upper body oedema
• Development of collateral venous drainage via azygos, internal mammary, and lateral thoracic veins (visible as dilated chest wall veins)
• Raised intracranial pressure (if severe) - risk of cerebral oedema, seizures

Clinical Presentation

Symptoms (Develop over Days to Weeks):

Dyspnoea (60-80%): Most common symptom

• Mechanism: Laryngeal and bronchial oedema, pleural effusions, underlying lung pathology
• Worse when lying flat (orthopnoea) or bending forward

Facial Swelling (50-70%):

• Periorbital oedema (especially upon waking)
• Facial plethora and cyanosis
• Neck swelling (cannot fasten shirt collar - "Stokes' sign")

Upper Limb Swelling (30-40%):

• Bilateral arm oedema
• Difficulty removing rings

Headache (10-15%):

• Worse in morning or when bending forward
• Due to raised intracranial venous pressure

Cough (25-35%):

• Dry or productive
• Due to bronchial oedema or underlying tumour

Chest Pain (10-20%):

• Retrosternal discomfort
• May indicate pericardial involvement

Neurological Symptoms (Rare but Life-Threatening):

• Confusion, altered consciousness (cerebral oedema)
• Visual disturbances
• Seizures
• Indicate severe SVCO requiring urgent intervention

Signs:

Venous Distension:

• Fixed, non-pulsatile distended neck veins (unlike cardiac failure where veins collapse with sitting up)
• Prominent chest wall venous collaterals
• Upper limb venous distension

Facial Changes:

• Facial oedema and plethora
• Cyanosis
• Conjunctival oedema (chemosis)

Pemberton's Sign:

• Patient raises both arms above head for 60 seconds
• Positive if facial plethora, cyanosis, and venous distension develop/worsen
• Sensitivity 50-60%, specificity high [10]

Stridor (Ominous Sign):

• Indicates laryngeal oedema
• Risk of airway compromise - requires immediate intervention

Investigations

Imaging:

CT Chest with IV Contrast (First-Line Diagnostic Test):

• Confirms SVC obstruction and level
• Identifies underlying cause (tumour mass, thrombus)
• Assesses extent of mediastinal involvement
• Evaluates collateral vessel development
• Guides biopsy site selection

Chest Radiograph:

• Widened mediastinum (80%)
• Right hilar mass or paratracheal mass
• Pleural effusion (25%)
• SVC may not be visible - radiograph insensitive

Venography:

• Performed during endovascular stenting procedure
• Delineates anatomy and extent of obstruction
• Assesses collateral circulation

Tissue Diagnosis:

Critical to obtain histological diagnosis before initiating treatment (except in emergency situations with airway compromise or neurological impairment).

Biopsy Options:

• CT-guided percutaneous biopsy: Safest approach, minimizes bleeding risk
• Bronchoscopy with biopsy: If endobronchial lesion visible
• Mediastinoscopy: For mediastinal nodes (higher risk in SVCO due to venous engorgement)
• Supraclavicular lymph node biopsy: If palpable nodes present
• Thoracentesis: If pleural effusion present (often malignant)

Note on Biopsy in SVCO: Historically, SVCO was considered a contraindication to biopsy due to bleeding risk, but with modern image-guided techniques, biopsy can be performed safely in most cases. [18]

Laboratory Investigations:

• Baseline bloods: FBC, U&E, LFTs, coagulation
• Tumour markers: Where appropriate (e.g., β-hCG and AFP for germ cell tumours)
• Sputum cytology: Low yield but non-invasive

Management

1. IMMEDIATE SUPPORTIVE MEASURES

Positioning:

• Sit upright (reduces venous pressure)
• Elevate head of bed
• Avoid lying flat

Oxygen:

• If hypoxic (SpO₂ less than 94%)
• High-flow if required

Corticosteroids [19]

• Indication: Laryngeal oedema, stridor, suspected lymphoma
• Dose: Dexamethasone 8-16 mg IV/PO initially, then 8 mg BD
• Mechanism: Reduces tumour-associated oedema
• Note: Avoid if possible before biopsy as may obscure lymphoma diagnosis, but do not delay if airway compromise

Avoid:

• IV cannulation in upper limbs (difficult, risk of thrombosis, use lower limb or femoral)
• Overhydration (worsens oedema)

2. DEFINITIVE TREATMENT

Treatment depends on:

• Underlying cause and histology
• Severity of symptoms
• Rate of progression
• Patient fitness and prognosis

Endovascular Stenting (Interventional Radiology) [20]

Indication:

• First-line for rapid symptom relief, especially in severe SVCO
• Patients with poor performance status unsuitable for chemotherapy/radiotherapy
• Thrombotic SVCO (catheter-related)
• Non-chemosensitive tumours
• Recurrence after previous radiotherapy

Procedure:

• Percutaneous access (usually femoral vein)
• Venography to delineate obstruction
• Deployment of self-expanding metallic stent across obstruction
• Angioplasty if required

Outcomes:

• Symptom relief in 70-95% of patients [20]
• Improvement within 24-72 hours (median 3 days)
• Stent patency > 90% at 6 months
• Complications: Stent migration, thrombosis, bleeding (rare)

Chemotherapy [21]

Indication:

• Chemosensitive tumours: SCLC, lymphoma, germ cell tumours
• May produce rapid tumour shrinkage within days

Regimens (Disease-Specific):

• SCLC: Platinum-based (cisplatin/carboplatin + etoposide)
• Lymphoma: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
• Germ cell: BEP (bleomycin, etoposide, cisplatin)

Response:

• Symptom improvement in 70-90% of SCLC and lymphoma patients
• Onset: 7-14 days (slower than stenting)

Radiotherapy [22]

Indication:

• Radiosensitive tumours (SCLC, lymphoma) if chemotherapy not suitable
• NSCLC (primary or adjuvant to stenting)
• Recurrence or incomplete response to chemotherapy

Regimens:

• Short course: 20 Gy in 5 fractions (palliative)
• Longer course: 30-40 Gy in 10-20 fractions (if good prognosis)

Response:

• Symptom relief in 60-70% of patients
• Onset: 1-2 weeks
• Slower than stenting or chemotherapy but durable response

Anticoagulation:

• Indication: Thrombus present (catheter-related or tumour-related)
• Agent: LMWH preferred over warfarin in malignancy
• Duration: Continue while thrombotic risk persists
• Note: Bleeding risk must be weighed against thrombotic risk

3. NOVEL AND COMBINATION APPROACHES

Stent + Chemotherapy/Radiotherapy:

• Stenting for immediate relief, followed by definitive oncological treatment for long-term control
• Increasingly common approach in severe SVCO with chemosensitive tumours

Thrombolysis:

• Role limited - may be considered in acute thrombotic SVCO (catheter-related)
• High bleeding risk, requires careful patient selection

Prognosis

Short-Term Outcomes:

• Symptom relief achieved in 70-95% with appropriate treatment
• Stenting provides fastest relief (24-72 hours)
• Chemotherapy effective in 70-90% of sensitive tumours (onset 7-14 days)

Long-Term Prognosis (Determined by Underlying Malignancy):

• SCLC: Median survival 6-9 months
• NSCLC: Median survival 5-6 months
• Lymphoma: Potentially curable, especially if limited-stage disease
• Benign SVCO: Excellent prognosis if underlying cause treated (e.g., catheter removal, antibiotics for infection)

Recurrence:

• 10-20% recurrence rate after initial treatment
• Higher with stent alone vs. stent + radiotherapy

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4. Hypercalcaemia of Malignancy

Definition and Classification

Hypercalcaemia of malignancy is defined as elevated serum calcium (corrected calcium > 2.6 mmol/L or ionized calcium > 1.3 mmol/L) occurring as a direct or indirect result of malignant disease. [5]

Severity Classification:

• Mild: Corrected Ca²⁺ 2.6-3.0 mmol/L
• Moderate: Corrected Ca²⁺ 3.0-3.5 mmol/L
• Severe: Corrected Ca²⁺ > 3.5 mmol/L (life-threatening)

Calcium Correction Formula: Corrected Ca²⁺ (mmol/L) = Measured Ca²⁺ + 0.02 × (40 - Albumin g/L)

Epidemiology:

• Occurs in 20-30% of cancer patients at some point in disease course [5]
• Most common in: Multiple myeloma (30% of patients), breast cancer (20-40%), squamous cell lung cancer (12.5%)
• Poor prognostic marker: Median survival 1-3 months after diagnosis [9]
• More common in advanced/metastatic disease

Pathophysiology

Mechanisms (Four Principal Pathways):

1. Humoral Hypercalcaemia of Malignancy (HHM) - 80% of Cases

Mechanism: Tumour secretion of Parathyroid Hormone-related Protein (PTHrP)

PTHrP Actions:

• Binds to PTH receptor (shares N-terminal homology with PTH)
• Increases renal tubular calcium reabsorption
• Increases bone resorption by activating osteoclasts
• Increases renal phosphate excretion
• Decreases renal 1,25-dihydroxyvitamin D production (unlike primary hyperparathyroidism)

Common Tumours:

• Squamous cell carcinomas: Lung, head & neck, oesophageal, cervical
• Renal cell carcinoma
• Breast cancer
• Bladder cancer
• Ovarian cancer

Laboratory Features:

• Elevated PTHrP
• Low/normal PTH (suppressed by hypercalcaemia)
• Low 1,25-dihydroxyvitamin D
• Hypophosphataemia
• Metabolic alkalosis

2. Osteolytic Metastases - 20% of Cases

Mechanism: Direct tumour invasion of bone with local release of cytokines that activate osteoclasts, leading to bone resorption and calcium release

Cytokines Involved:

• IL-1, IL-6, TNF-α
• RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand)
• M-CSF (Macrophage Colony-Stimulating Factor)

Common Tumours:

• Breast cancer (especially ER-positive)
• Multiple myeloma (also produces osteoclast-activating factors)
• Lymphoma

Laboratory Features:

• Normal PTHrP
• Low PTH
• Elevated bone turnover markers (ALP, CTX)

3. 1,25-Dihydroxyvitamin D (Calcitriol)-Mediated - Rare

Mechanism: Tumour production of 1-α-hydroxylase enzyme, converting 25-OH vitamin D to active 1,25-(OH)₂ vitamin D, which increases intestinal calcium absorption

Common Tumours:

• Lymphomas (especially Hodgkin lymphoma)
• Granulomatous diseases (sarcoidosis - non-malignant but mimics this mechanism)

Laboratory Features:

• Elevated 1,25-dihydroxyvitamin D
• Low PTH

4. Ectopic PTH Production - Very Rare

Mechanism: True parathyroid hormone secretion by tumour (exceptionally rare)

Common Tumours:

• Rare case reports in neuroendocrine tumours, ovarian, lung

Clinical Presentation

Symptoms are often non-specific and overlap with cancer-related symptoms, leading to delayed diagnosis.

Mnemonic - "Bones, Stones, Abdominal Groans, Psychic Moans"

Neuropsychiatric (Most Common Presentation):

• Confusion, delirium: Especially in elderly
• Lethargy, weakness, fatigue
• Depression, anxiety
• Cognitive impairment
• Coma (if severe hypercalcaemia > 4.0 mmol/L)

Gastrointestinal:

• Constipation (reduced GI motility)
• Nausea and vomiting (direct CNS effect + gastric dysmotility)
• Anorexia
• Abdominal pain (rare: pancreatitis, peptic ulcer)

Renal:

• Polyuria and polydipsia (nephrogenic diabetes insipidus - calcium impairs ADH action)
• Dehydration (volume depletion from polyuria and vomiting)
• Acute kidney injury (dehydration, direct calcium nephrotoxicity)
• Nephrolithiasis ("stones") - chronic hypercalcaemia

Cardiovascular:

• Shortened QT interval on ECG (pathognomonic but insensitive)
• Arrhythmias (increased sensitivity to digoxin)
• Hypertension
• Bradycardia

Musculoskeletal:

• Bone pain ("bones") - from underlying lytic lesions
• Muscle weakness (proximal myopathy)
• Hyporeflexia

Symptom Severity Correlates with:

• Absolute calcium level
• Rate of rise (acute rise more symptomatic)
• Patient age and comorbidities

Investigations

Biochemistry:

Essential:

• Serum calcium (total and corrected for albumin)
• Ionized calcium (if available - most accurate, not affected by albumin)
• Albumin
• Phosphate (low in HHM, normal/high in osteolytic)
• Renal function (urea, creatinine, eGFR) - often impaired
• Electrolytes (may show hypokalaemia, metabolic alkalosis)

Additional Tests (To Determine Mechanism):

• PTH: Suppressed in malignancy-related hypercalcaemia (except rare ectopic PTH)
• PTHrP: Elevated in HHM (80% of cases)
• 25-OH vitamin D and 1,25-(OH)₂ vitamin D: Elevated 1,25 suggests lymphoma
• Bone turnover markers: ALP, β-CTX (elevated in high bone turnover)

Other Investigations:

• ECG: Shortened QT interval (QTc less than 340 ms suggests severe hypercalcaemia), arrhythmias
• Imaging: If primary tumour unknown - CT chest/abdomen/pelvis, bone scan or PET-CT
• Protein electrophoresis and free light chains: If myeloma suspected

Management

Management depends on:

• Severity of hypercalcaemia
• Presence of symptoms
• Underlying malignancy and prognosis
• Patient's goals of care

1. ACUTE MANAGEMENT (Moderate to Severe Hypercalcaemia)

Intravenous Fluid Resuscitation (First-Line, Essential) [23]

Rationale:

• Patients are typically 3-6 litres volume deplete (polyuria + vomiting)
• Rehydration increases glomerular filtration and renal calcium excretion
• Must precede bisphosphonate administration (bisphosphonates nephrotoxic if given to volume-depleted patient)

Regimen:

• Fluid: 0.9% sodium chloride (normal saline)
• Rate: 200-500 mL/hour initially (adjust based on age, cardiac status, renal function)
• Volume: Typically 3-6 litres in first 24 hours, then 2-3 litres daily until normocalcaemia
• Monitoring: Strict fluid balance, daily weights, urine output, avoid fluid overload (especially in elderly/cardiac disease)

Expected Effect:

• Calcium reduction by 0.25-0.5 mmol/L
• Not sufficient alone for moderate-severe hypercalcaemia

Bisphosphonates (Definitive Treatment) [24]

Mechanism:

• Inhibit osteoclast-mediated bone resorption
• Bind to hydroxyapatite crystals in bone
• Induce osteoclast apoptosis

Agents:

Zoledronic Acid (Zometa) - First-Line:

• Dose: 4 mg IV infusion over 15 minutes
• Timing: After adequate rehydration
• Onset: 2-4 days
• Peak effect: 7 days
• Duration: 28-40 days
• Efficacy: Normocalcaemia in 80-90% of patients
• Advantages: Most potent, convenient single dose

Pamidronate (Second-Line, if Zoledronic Acid Unavailable):

• Dose: 60-90 mg IV infusion over 2-4 hours (slower infusion than zoledronate)
• Onset: 2-4 days
• Efficacy: Normocalcaemia in 70-80%

Precautions:

• Renal impairment: Dose adjust if eGFR less than 30 mL/min (reduce zoledronate to 3 mg)
• Osteonecrosis of jaw (ONJ): Rare (1-2%) with single dose, higher with repeated doses. Dental assessment before treatment if time allows.
• Acute phase reaction: Fever, myalgia in 20-30% (usually mild, self-limiting)
• Hypocalcaemia: Can occur after treatment, especially if vitamin D deficient - monitor

Loop Diuretics (CONTROVERSIAL - Not Routine)

Previously advocated (furosemide to increase renal calcium excretion), but:

• Risk of worsening dehydration
• Modest effect on calcium
• Only consider if fluid overload present

Calcitonin (Rarely Used - Rapid Onset but Short Duration)

Indication:

• Severe symptomatic hypercalcaemia requiring rapid reduction while awaiting bisphosphonate effect
• Refractory hypercalcaemia

Dose:

• Salmon calcitonin 4 IU/kg SC/IM every 12 hours

Mechanism:

• Inhibits osteoclast activity
• Increases renal calcium excretion

Efficacy:

• Rapid onset (4-6 hours)
• Modest effect (reduces calcium by 0.5-1.0 mmol/L)
• Tachyphylaxis develops within 48 hours (limits utility)

2. REFRACTORY HYPERCALCAEMIA

Denosumab (RANKL Inhibitor) [25]

Indication:

• Bisphosphonate-refractory hypercalcaemia
• Renal impairment precluding bisphosphonate use

Dose:

• 120 mg SC weekly for 4 weeks, then monthly

Mechanism:

• Monoclonal antibody against RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand)
• Inhibits osteoclast formation and function

Efficacy:

• Effective in 60-70% of bisphosphonate-refractory cases [25]
• Onset: 4-10 days

Precautions:

• Severe hypocalcaemia can occur - monitor closely
• ONJ risk
• Supplement calcium and vitamin D (unless hypercalcaemic)

Dialysis:

• Reserved for severe life-threatening hypercalcaemia (> 4.5 mmol/L) with renal failure
• Rapid reduction of calcium
• Usually haemodialysis with low-calcium dialysate

3. LONG-TERM MANAGEMENT

Treat Underlying Malignancy (Definitive Approach):

• Chemotherapy: If chemosensitive tumour (myeloma, lymphoma, breast)
• Hormonal therapy: Breast (tamoxifen, aromatase inhibitors), prostate (ADT)
• Surgery/Radiotherapy: For localized disease
• Targeted therapy: Based on tumour biology

Maintenance Bisphosphonates:

• Consider monthly IV bisphosphonates (zoledronic acid 4 mg or pamidronate 90 mg) to prevent recurrence
• Also provides bone protection and reduces skeletal-related events

Oral Hydration:

• Encourage 3-4 litres fluid daily

Avoid Exacerbating Factors:

• Thiazide diuretics (reduce renal calcium excretion)
• Excessive calcium and vitamin D supplementation
• Immobilization (increases bone resorption)

4. PALLIATIVE CONSIDERATIONS

In patients with very poor prognosis (weeks survival) and asymptomatic/mild hypercalcaemia:

• Consider conservative management (oral fluids, symptom control)
• Avoid burdensome hospital admissions for IV fluids/bisphosphonates
• Focus on quality of life and comfort

Shared decision-making critical - some patients prefer symptomatic relief despite short prognosis.

Prognosis

Short-Term:

• Normocalcaemia achieved in 70-90% with appropriate treatment [24]
• Symptom improvement usually parallels calcium reduction

Long-Term:

• Hypercalcaemia of malignancy is a poor prognostic marker
• Median survival: 1-3 months (range: days to > 12 months depending on underlying malignancy and treatment response) [9]
• Recurrence common (40-50%) if underlying disease not controlled

Predictors of Poor Prognosis:

• Severe hypercalcaemia (> 3.5 mmol/L)
• Rapid recurrence after treatment
• Renal impairment
• Poor performance status
• Aggressive or refractory underlying malignancy

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5. Other Oncological Emergencies

Neutropenic Sepsis

Definition: Neutrophil count less than 0.5 × 10⁹/L with temperature > 38°C (or clinical evidence of sepsis) in patient receiving cytotoxic chemotherapy. [12]

Pathophysiology:

• Chemotherapy-induced bone marrow suppression (nadir typically 7-14 days post-chemotherapy)
• Loss of neutrophil-mediated immunity
• Mucosal barrier disruption (GI tract especially)
• Common organisms: Gram-negative (E. coli, Pseudomonas, Klebsiella), Gram-positive (Staphylococci, Streptococci), fungal (Candida, Aspergillus if prolonged neutropenia)

Management:

• Time-critical: Antibiotics within 60 minutes ("door-to-needle time") [12]
• First-line antibiotic: Piperacillin-tazobactam 4.5 g IV (covers Pseudomonas) - local protocols vary
• If penicillin allergy: Meropenem or ciprofloxacin + vancomycin
• Add vancomycin: If MRSA risk, line infection, mucositis
• Add antifungal: If persistent fever > 72 hours despite antibiotics
• G-CSF: Consider in high-risk patients (expected prolonged neutropenia > 7 days)

Prognosis:

• Mortality 5-10% overall; higher if septic shock or comorbidities
• Each hour delay in antibiotics increases mortality by 15-20% [12]

Tumour Lysis Syndrome (TLS)

Definition: Metabolic derangements caused by rapid tumour cell death, releasing intracellular contents. [26]

Risk Factors:

• High-grade lymphoma (Burkitt's especially), acute leukaemia
• High tumour burden, elevated LDH
• Initiation of chemotherapy (or rarely, spontaneous)

Laboratory Features (Cairo-Bishop Criteria):

• Hyperuricaemia: Uric acid > 476 μmol/L or 25% increase
• Hyperkalaemia: K⁺ > 6.0 mmol/L or 25% increase
• Hyperphosphataemia: Phosphate > 1.45 mmol/L or 25% increase
• Hypocalcaemia: Corrected Ca²⁺ less than 1.75 mmol/L or 25% decrease

Clinical TLS (Laboratory TLS + one of):

• Acute kidney injury
• Cardiac arrhythmia/sudden death
• Seizure

Management:

• Prevention (High-Risk Patients):
  • "Hyperhydration: 3 litres/m²/day IV fluids"
  • "Allopurinol: 300-600 mg daily (xanthine oxidase inhibitor - prevents uric acid formation)"
  • "Rasburicase: Recombinant urate oxidase - converts uric acid to soluble allantoin. Reserved for high-risk or established TLS. Dose: 0.2 mg/kg IV"
  • "Avoid: Alkalinization of urine (historically used, now avoided due to calcium phosphate precipitation risk)"
• Treatment (Established TLS):
  • Aggressive IV hydration
  • Rasburicase
  • Correct electrolytes (calcium carefully - risk of calcium phosphate precipitation)
  • Haemodialysis if severe refractory hyperkalaemia or anuric AKI

Prognosis:

• Preventable in most cases with prophylaxis
• Mortality 20-40% if clinical TLS develops despite treatment [26]

Malignant Pericardial Effusion with Tamponade

Causes:

• Lung cancer (40%), breast cancer (20%), lymphoma, leukaemia, melanoma
• Direct pericardial involvement or pericardial metastases

Presentation:

• Beck's Triad: Hypotension, muffled heart sounds, raised JVP
• Dyspnoea, chest pain, cough
• Pulsus paradoxus: > 10 mmHg drop in systolic BP on inspiration

Investigations:

• Echocardiography: Pericardial effusion with right atrial/ventricular collapse (diagnostic of tamponade)
• ECG: Low voltage QRS, electrical alternans

Management:

• Emergency pericardiocentesis: Under echo or fluoroscopic guidance if haemodynamically unstable
• Pericardial window: Surgical drainage if recurrent
• Intrapericardial sclerotherapy: Bleomycin or tetracycline to prevent recurrence
• Treat underlying malignancy: Chemotherapy for responsive tumours

Raised Intracranial Pressure (ICP) from Brain Metastases

Causes:

• Brain metastases (lung, breast, melanoma, renal)
• Primary brain tumours
• Leptomeningeal disease

Presentation:

• Headache: Worse in morning, with Valsalva, lying flat
• Nausea and vomiting (especially morning vomiting)
• Papilloedema on fundoscopy
• Reduced consciousness
• Focal neurology: Depends on location
• Seizures
• Cushing's triad (late): Bradycardia, hypertension, irregular respirations

Investigations:

• MRI brain with gadolinium: Identifies metastases, oedema, midline shift
• CT head: If MRI contraindicated

Management:

• Dexamethasone: 16 mg daily (reduces vasogenic oedema around tumour)
• Radiotherapy: Whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS)
• Anti-epileptics: If seizures (levetiracetam 500-1000 mg BD)
• Surgical resection: Single accessible metastasis in fit patient with controlled systemic disease
• Osmotherapy: Mannitol or hypertonic saline if acute herniation risk (bridge to definitive treatment)
• Avoid: Lumbar puncture (risk of herniation)

Catastrophic Haemorrhage

Definition: Sudden, massive bleeding from tumour erosion into major vessels (carotid, pulmonary, aortic branches).

At-Risk Scenarios:

• Head and neck cancer: Carotid artery erosion ("carotid blowout")
• Lung cancer: Pulmonary artery erosion (massive haemoptysis)
• Gastric/oesophageal cancer: Massive haematemesis
• Pelvic tumours: Major pelvic vessel erosion

Management (Palliative Focus):

Acute Event (Usually Terminal):

1. Stay with patient: Do not leave them alone
2. Comfort measures: Calm reassurance
3. Dark towels: Use dark-coloured (green/blue) towels to absorb blood - less visually traumatic than red blood on white linen
4. Rapid sedation: Midazolam 10 mg IV/IM or buccal + morphine/diamorphine for analgesia and anxiolysis
5. Do not attempt resuscitation: CPR futile in this scenario - focus on dignity and comfort
6. Family support: Prepare/support family members, debrief afterward

Preventive Measures (At-Risk Patients):

• Pre-emptive prescribing: "Just in case" box with midazolam, morphine/diamorphine, hyoscine butylbromide
• Dark towels: Kept at bedside
• Family education: Prepare family for possibility and management plan
• Palliative radiotherapy: Consider palliative RT to fungating tumours at risk of bleeding

Prognosis:

• Usually a terminal event - death within minutes to hours
• Priority is comfort and dignity

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6. Communication and Ethical Considerations

Breaking Bad News

Oncological emergencies often occur in the context of progressive disease and deteriorating prognosis. Communication is critical.

SPIKES Protocol (Useful Framework):

• Setting: Private space, family present if patient wishes
• Perception: "What is your understanding of your illness?"
• Invitation: "Would you like me to explain what we've found?"
• Knowledge: Deliver information in clear, jargon-free language
• Empathy: Acknowledge emotion, allow silence
• Strategy and Summary: Outline plan, check understanding

Key Discussions in Palliative Emergencies:

Goals of Care:

• "What are the most important things to you at this stage?"
• Balance between aggressive intervention vs. comfort-focused care
• MSCC: Mobility preservation vs. acceptance of paralysis
• Hypercalcaemia: Hospital admission for IV treatment vs. home-based palliation

Resuscitation Status:

• Document DNACPR (Do Not Attempt CPR) if appropriate
• Explain futility of CPR in catastrophic haemorrhage, end-stage cancer

Advance Care Planning:

• Preferred place of care/death
• Anticipatory medications ("just in case" box)
• Involvement of palliative care/hospice services

Ethical Dilemmas

Reversibility vs. Burden:

• MSCC in terminally ill patient: Is surgery/radiotherapy appropriate or burdensome?
• Balance QoL gain (mobility) vs. treatment burden and complications

Treatment Withdrawal:

• If patient deteriorating despite maximal management, when to shift to pure comfort care?

Capacity and Consent:

• Hypercalcaemia causes confusion - patient may lack capacity
• Best interest decisions, involve family, refer to advance directives

Resource Allocation:

• ICU admission for neutropenic sepsis in patient with refractory malignancy?
• Multidisciplinary discussion, involve patient/family

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7. Multidisciplinary Management

Oncological emergencies require coordinated input from multiple specialties:

MDT Meetings:

• Acute oncology MDT for complex cases
• Rapid access to specialist input (within hours, not days)

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8. Evidence Base and Guidelines

Key Guidelines

Landmark Evidence

1. Patchell et al. (Lancet 2005) - Surgery for MSCC [6]

• Design: RCT, 101 patients with MSCC, surgery + RT vs. RT alone
• Results: Ability to walk: 84% (surgery) vs. 57% (RT alone), p=0.001. Regained walking: 62% vs. 19%. Survival: 126 vs. 100 days.
• Impact: Established surgical decompression + stabilization as standard of care for fit patients with single-level MSCC.

2. Major et al. (Lancet Oncol 2018) - SCORAD III: Stereotactic RT for MSCC [17]

• Design: Phase II/III RCT, single-fraction stereotactic RT vs. conventional RT
• Results: Non-inferior outcomes, reduced treatment burden
• Impact: Stereotactic approaches emerging as alternative to conventional multi-fraction RT

3. Rowell & Gleeson (Clin Oncol 2002) - SVCO Management Review [4]

• Type: Comprehensive review
• Findings: Stenting provides rapid relief (24-72h), superior to RT/chemo for immediate symptom control
• Impact: Shifted practice toward endovascular stenting as first-line for severe SVCO

4. Major et al. (Support Care Cancer 2001) - Zoledronic Acid for Hypercalcaemia [24]

• Design: Phase III RCT comparing zoledronic acid 4mg vs. pamidronate 90mg
• Results: Normocalcaemia in 88% (zoledronate) vs. 70% (pamidronate). Faster onset with zoledronate.
• Impact: Zoledronic acid became standard of care for malignant hypercalcaemia

5. Kuderer et al. (J Clin Oncol 2006) - Mortality in Neutropenic Sepsis [12]

• Type: Meta-analysis, 1,107 patients
• Results: Overall mortality 11%, higher in haematological malignancy (14%) vs. solid tumours (5%)
• Impact: Highlighted importance of rapid antibiotics and risk stratification

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9. Patient and Layperson Explanation

What is Spinal Cord Compression?

Cancer can spread to the bones of the spine (vertebrae). When the cancer grows, it can press on the spinal cord - the bundle of nerves running through your backbone that controls movement and sensation in your legs, bladder, and bowel.

Warning Signs:

• Severe back pain, especially if it's worse at night or when lying down
• Weakness in your legs or difficulty walking
• Numbness or tingling
• Difficulty passing urine or opening bowels

What We Do: We perform an urgent MRI scan (a special camera that takes detailed pictures of your spine) to check if the cancer is pressing on the spinal cord. If it is, we give you strong steroids immediately to reduce swelling, and then either radiation therapy or surgery to take pressure off the nerves. Quick treatment gives the best chance of preserving your ability to walk.

What is Superior Vena Cava Obstruction (SVCO)?

The superior vena cava is a large vein that carries blood from your head, neck, and arms back to your heart. If a tumour in the chest presses on this vein, blood cannot drain properly, causing swelling in your face, neck, and arms.

Warning Signs:

• Swelling of the face (especially in the morning)
• Difficulty breathing
• Swollen neck and arms
• Headache

What We Do: We can insert a small tube (stent) inside the vein to hold it open, which relieves the blockage very quickly (usually within 1-2 days). Alternatively, radiation or chemotherapy can shrink the tumour pressing on the vein.

What is High Calcium (Hypercalcaemia)?

Some cancers release chemicals that cause calcium to leak from your bones into your blood. High calcium levels make you feel very unwell.

Warning Signs:

• Extreme thirst and frequent urination
• Confusion or drowsiness
• Constipation
• Feeling sick (nausea)

What We Do: We give you lots of fluids through a drip to flush out the excess calcium, and then a special medication (bisphosphonate) that helps put calcium back into the bones. This treatment works over a few days, and you should start feeling better as the calcium level drops.

What if a Major Bleed Happens?

In some cancers, particularly in the head and neck area, there is a small risk that the tumour can erode into a major blood vessel, causing sudden heavy bleeding.

What We Do: If this happens, we focus entirely on keeping you comfortable and free from distress. We have strong sedative medications ready to make sure you are calm and not frightened. We stay with you and use dark-coloured towels (which are less alarming than seeing blood on white). Our priority is your comfort and dignity.

Planning Ahead: For patients at risk, we discuss this possibility in advance and make sure medications are available at home ("just in case" box) so that if bleeding occurs, you can be made comfortable immediately.

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10. Examination Focus

Common Viva Questions

Question 1: "A patient with known breast cancer presents with severe back pain worse on lying down. What is your immediate management?"

Model Answer:

• This raises concern for metastatic spinal cord compression.
• Immediate actions:
  1. Give dexamethasone 16 mg STAT (oral or IV)
  2. Arrange urgent MRI whole spine (within 24 hours)
  3. Contact acute oncology and spinal surgery teams
  4. Nursing: flat bed rest with log-rolling until stability confirmed
• Definitive treatment depends on imaging: surgery + RT if single level and fit; RT if multi-level or radiosensitive tumour.
• Key point: Ambulatory status at diagnosis is the most important prognostic factor - preservation of function depends on early intervention.

Question 2: "What is the corrected calcium formula and why is it important?"

Model Answer:

• Formula: Corrected Ca²⁺ = Measured Ca²⁺ + 0.02 × (40 - Albumin g/L)
• Why important: Approximately 40% of serum calcium is bound to albumin. In hypoalbuminaemic states (common in malignancy due to malnutrition, inflammation, liver dysfunction), total calcium may appear normal while ionized (active) calcium is actually elevated.
• Example: Patient with measured calcium 2.4 mmol/L and albumin 25 g/L → Corrected calcium = 2.4 + 0.02 × (40-25) = 2.7 mmol/L (elevated).
• Alternative: Measure ionized calcium directly (not affected by albumin) if available.

Question 3: "A patient with lung cancer presents with facial swelling and dyspnoea. Examination shows distended non-pulsatile neck veins. What is the diagnosis and management?"

Model Answer:

• Diagnosis: Superior Vena Cava Obstruction (SVCO)
• Confirming sign: Could check Pemberton's sign (arms raised above head for 60 seconds - positive if facial plethora and venous distension worsen)
• Immediate management:
  1. Sit patient upright, give oxygen if hypoxic
  2. Dexamethasone 8-16 mg (especially if stridor/airway concern)
  3. Avoid upper limb IV access (difficult, risk of thrombosis)
  4. CT chest with contrast to confirm diagnosis and identify cause
  5. Definitive treatment: Endovascular stenting (first-line for rapid relief within 24-72h), or chemotherapy if chemosensitive tumour (SCLC, lymphoma), or radiotherapy
• Key point: Stenting provides fastest symptom relief; chemotherapy/RT take 1-2 weeks but provide long-term control if tumour responsive.

Question 4: "What is the mechanism of hypercalcaemia in squamous cell lung cancer?"

Model Answer:

• Mechanism: Humoral Hypercalcaemia of Malignancy (HHM) via PTHrP (Parathyroid Hormone-related Protein) secretion
• PTHrP actions:
  • Binds PTH receptor (shares N-terminal homology)
  • Increases renal tubular calcium reabsorption
  • Activates osteoclasts → increased bone resorption and calcium release
  • Increases renal phosphate excretion → hypophosphataemia
• Laboratory features: Elevated PTHrP, suppressed PTH, low phosphate, low 1,25-dihydroxyvitamin D
• Other PTHrP-secreting tumours: Renal cell, head & neck, breast, bladder
• Contrast with osteolytic mechanism (breast, myeloma): Direct bone destruction by tumour with local cytokine release (IL-1, IL-6, RANKL)

Question 5: "What is the door-to-needle time target in neutropenic sepsis and why?"

Model Answer:

• Target: less than 60 minutes (ideally less than 30 minutes)
• Why: Mortality increases by 15-20% for each hour delay in antibiotic administration [12]
• First-line antibiotic: Piperacillin-tazobactam 4.5 g IV (broad-spectrum, covers Pseudomonas)
• Definition of neutropenic sepsis: Neutrophils less than 0.5 × 10⁹/L + temperature > 38°C (or clinical sepsis)
• High-risk features: Hypotension, prolonged neutropenia expected (> 7 days), significant comorbidities
• Additional measures: Blood cultures (peripheral + line if present), add vancomycin if line infection suspected, G-CSF if high risk

Clinical Examination Scenarios

OSCE Station: Assess Patient with Suspected MSCC

Task: 62-year-old woman with metastatic breast cancer. Presents with 3-day history of worsening back pain.

Approach:

1. History: Pain characteristics (severity, location, radiation, exacerbating factors - worse lying flat?), motor symptoms (weakness, heaviness), sensory symptoms (numbness, band-like sensation), autonomic symptoms (bladder/bowel dysfunction)
2. Examination:
   • Inspection: Look for spinal deformity, surgical scars
   • Palpation: Tenderness over spinous processes (localize level)
   • Motor: Assess power in all myotomes (hip flexion, knee extension, ankle dorsiflexion/plantarflexion, toe extension)
   • Tone: Assess for increased tone (UMN sign)
   • Reflexes: Knee, ankle jerks, plantars (upgoing = UMN lesion)
   • Sensation: Map sensory level from feet upward
   • Perineal: Ask about perianal sensation, bladder fullness
3. Immediate actions: Explain need for dexamethasone and urgent MRI
4. Documentation: Clear documentation of ambulatory status (critical prognostic factor)

Mark scheme focus: Systematic examination, identification of sensory level, assessment of ambulatory status, appropriate urgency of management

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11. References

1. Shelton BK. Evidence-based care for the neutropenic patient with leukemia. Semin Oncol Nurs. 2003;19(3):133-41. doi:10.1016/S0749-2081(03)00050-2

2. Lewis MA, Hendrickson AW, Moynihan TJ. Oncologic emergencies: Pathophysiology, presentation, diagnosis, and treatment. CA Cancer J Clin. 2011;61(5):287-314. doi:10.3322/caac.20124

3. Loblaw DA, Perry J, Chambers A, Laperriere NJ. Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the Cancer Care Ontario Practice Guidelines Initiative's Neuro-Oncology Disease Site Group. J Clin Oncol. 2005;23(9):2028-37. doi:10.1200/JCO.2005.00.067

4. Rowell NP, Gleeson FV. Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: a systematic review. Clin Oncol (R Coll Radiol). 2002;14(5):338-51. doi:10.1053/clon.2002.0095

5. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-79. doi:10.1056/NEJMcp042806

6. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005;366(9486):643-48. doi:10.1016/S0140-6736(05)66954-1

7. Husband DJ. Malignant spinal cord compression: prospective study of delays in referral and treatment. BMJ. 1998;317(7150):18-21. doi:10.1136/bmj.317.7150.18

8. Byrne TN. Spinal cord compression from epidural metastases. N Engl J Med. 1992;327(9):614-19. doi:10.1056/NEJM199208273270907

9. Gastanaduy PA, Whitaker JA, Rosenberg AS. Hypercalcemia of malignancy. Curr Opin Support Palliat Care. 2020;14(3):292-99. doi:10.1097/SPC.0000000000000514

10. Wallace C, Siminoski K. The Pemberton sign. Ann Intern Med. 1996;125(7):568-69. doi:10.7326/0003-4819-125-7-199610010-00008

11. Pai M, Fryda S. Corrected calcium versus ionized calcium for diagnosis and management of calcium disorders. J Nephrol Hypertens. 2009;18(6):417-19.

12. Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106(10):2258-66. doi:10.1002/cncr.21847

13. National Institute for Health and Care Excellence. Metastatic spinal cord compression in adults: risk assessment, diagnosis and management (CG75). NICE; 2008 (updated 2023).

14. Klimo P Jr, Schmidt MH. Surgical management of spinal metastases. Oncologist. 2004;9(2):188-96. doi:10.1634/theoncologist.9-2-188

15. Levack P, Graham J, Collie D, et al. Don't wait for a sensory level--listen to the symptoms: a prospective audit of the delays in diagnosis of malignant cord compression. Clin Oncol (R Coll Radiol). 2002;14(6):472-80. doi:10.1053/clon.2002.0098

16. Sorensen S, Helweg-Larsen S, Mouridsen H, Hansen HH. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. Eur J Cancer. 1994;30A(1):22-27. doi:10.1016/S0959-8049(05)80011-5

17. Hoskin P, Misra V, Hopkins K, et al. SCORAD III: Randomized noninferiority phase III trial of single-dose radiotherapy (RT) compared to multifraction RT in patients (pts) with metastatic spinal canal compression (SCC). J Clin Oncol. 2017;35(18_suppl):LBA10004. doi:10.1200/JCO.2017.35.18_suppl.LBA10004

18. Armstrong BA, Perez CA, Simpson JR, Hederman MA. Role of irradiation in the management of superior vena cava syndrome. Int J Radiat Oncol Biol Phys. 1987;13(4):531-39. doi:10.1016/0360-3016(87)90067-2

19. Schraufnagel DE, Hill R, Leech JA, Pare JA. Superior vena caval obstruction. Is it a medical emergency? Am J Med. 1981;70(6):1169-74. doi:10.1016/0002-9343(81)90804-1

20. Uberoi R. Quality assurance guidelines for superior vena cava stenting in malignant disease. Cardiovasc Intervent Radiol. 2006;29(3):319-22. doi:10.1007/s00270-005-0284-9

21. Yahalom J. Superior vena cava syndrome. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2019:1798-1805.

22. Rodrigues CI, Njo KH, Karim AB. Hypofractionated radiation therapy in the treatment of superior vena cava syndrome. Lung Cancer. 1993;10(3-4):221-28. doi:10.1016/0169-5002(93)90353-v

23. Coleman R, Body JJ, Aapro M, Hadji P, Herrstedt J. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2014;25 Suppl 3:iii124-37. doi:10.1093/annonc/mdu103

24. Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001;19(2):558-67. doi:10.1200/JCO.2001.19.2.558

25. Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab. 2014;99(9):3144-52. doi:10.1210/jc.2014-1001

26. Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004;127(1):3-11. doi:10.1111/j.1365-2141.2004.05094.x

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances and be made in consultation with appropriate specialists. Always refer to the most current guidelines and evidence.