1 Oncological EmergenciesDr Lauren Bradbury Medical Oncologist 21st December 2016

2 Mr RB 74 year old man 2014 found to have PSA 14, declined further investigation/management Sept 2016 presents to Forbes ED on a Sunday with falls, acute urinary retention & new faecal incontinence PSA done 2 days later 9800

3 Spinal Cord Compression

4 Symptoms Pain – often the first symptom & present in up to 95% of patients Muscle weakness present in 60-85% Sensory disturbance – less common than motor symptoms, ascending pattern Look for a sensory level, typically 1 to 5 levels below the actual cord compression Bowel & bladder dysfunction Ataxic gait

5 Investigation & ManagementStart DEX!!! Analgesia Imaging options Radiotherapy vs. surgery Systemic cancer treatment

6 Hypercalcaemia of Malignancy

7 Hypercalcaemia Common problem – occurs in 20-30% of patientsBreast, lung (SCC) & haematological malignancies most common cancers associated Associated with poor prognosis

8 Mechanisms Tumour secretion of parathyroid hormone related protein (PTHrP) – most common accounting for up to 80% - PTHrP causes increased bone resorption & distal renal tubular calcium reabsorption Osteolytic metastases with local release of cytokines (approx 20% of cases) - Increased bone resorption & release of calcium from the bones Tumour production 1,25- dihydroxyvitamin D - Combination increased intestinal calcium absorption & bone resorption

9 Lab Findings Elevated serum PTHrp – levels may predict response to treatment Low/suprssed serum intact PTH Normal to low serum 1,25 dihydroxyvitamin D

10 Symptoms Neurological Gastrointestinal Renal CardiovascularLethargy, confusion, coma, muscle weakness Gastrointestinal Constipation, anorexia, nausea Renal Acute kidney injury Cardiovascular Shortened QT interval, arrhythmias

11 Treatment Depends on severity of hypercalcaemiaCorrected Ca <3.0 can often be managed conservatively Anything over 3.5 needs treatment Levels in between depend on symptom burden Options: IVF +/- loop diuretics Bisphosphonates Denosumab if refractory to bisphosphonates

12 Case – Mr AB 70 year old man Newly diagnosed cancer, presented to chemotherapy unit with rapid onset SOB Feeling pre syncopal Noted to have distension neck veins & facial swelling

13 Superior Vena Cava Obstruction

14 26/07/2016

15 Malignant SVCO Intra thoracic malignancy is responsible for 60-85% of SVCO cases It is the presenting symptom of a previously undiagnosed tumour in up to 60% Lung & NHL account for over 95%

16 Management Depends on the underlying malignancy Supportive managementHead raised to decrease hydrostatic pressure Consider anticoagulation Steroids in haematological causes Radiotherapy Chemotherapy

17 15/08/2016

18 Fluoropyrimidine-Associated Cardiac Toxicity

19 Infusional 5-FU or oral Capecitabine (Xeloda) Lower & upper GI, breast plus head & neck cancer Uncommon but potentially lethal Incidence less than 10% Method of administration Underlying CAD Concurrent RTx Anthracyclines DPD deficiency

20 Mechanism – coronary vasospasmChest pain most common symptom +/- Trop/CK rise Other symptoms – palpitations, SOB, arrhythmias, hypotension & cardiac arrest Stop drug & investigate for native CAD

21 What Next? Rechallenge? Alternative treatments ControversialTreat underlying CAD Prophylaxis (Aspirin, calcium channel blocker etc) Dose reduction Change treatment schedules Alternative treatments Raltitrexed, UFT (FU prodrug) Less effective

22 DPD Deficiency

23 Dihydropyrimidine dehydrogenase (DPD), the first of three enzymes in the fluoropyrimidine metabolic pathway, is the rate limiting enzyme in FU catabolism Patients who are partially or totally deficient in DPD activity cannot adequately degrade fluoropyrimidines, leading to an increased risk of severe, sometimes fatal toxicity

24 Presentation In patients with even partial DPD deficiency, administration of a fluoropyrimidine can lead to life-threatening complications: Severe diarrhoea Mucositis Pancytopenia Nausea & vomiting Rectal bleeding Volume depletion Skin changes Neurologic abnormalities cerebellar ataxia, cognitive dysfunction altered level of consciousness

25 Management Most cases of DPD deficiency are diagnosed only after a severe reaction to FU. Management of these patients should include: aggressive hemodynamic support parenteral nutrition antibiotics hematopoietic colony stimulating factors

26 Immunotherapy Side Effects

27 Immunotherapy Ipilimumab, Nivolumab & Pembrolizumab (plus others!)Similar side effect profiles Only on PBS for melanoma BUT multiple clinical trials running in lung, breast, bladder, renal, haematology

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30 Management Call your friendly medical oncologist  Depends on gradeEarly involvement of other medical specialities Steroids Oral Prednisone 1-2mg/kg daily IV Methylprednisone 2mg/kg/day Targeted monoclonal Ab

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