Clinical Oncology Flashcards
Superior vena cava obstruction
Aetiology
• Malignancy (80%): NSCLC (50%), SCLC (25%), NHL (10%), others e.g. germ cell tumors, CA breast, thymoma
• Non-malignant causes: thrombosis 2o to central venous catheters, infection (e.g. TB, syphilitic aortitis), indwelling cardiac device / pacemaker wire, aortic aneurysm, post-RT
Clinical features
• Symptoms: SOB (MC, >50%), cough (50%), hoarseness of voice
• Signs
o Dilated superficial veins over anterior chest wall
o Distended neck veins (60%) +/- facial and arm veins
o Facial edema (MC, >80%), neck and upper extremities with cyanosis
o Pemberton’s sign (fig.)
• Complications
o Laryngeal edema (lethal) - stridor
o Cerebral edema (lethal) - headache / lightheadedness / confusion
Investigations
• CXR: increased width of paratracheal soft tissue density (bilateral mediastinal LN)
• Duplex USG (‘B’ USG + Doppler) +/- digital subtraction venography
• CT thorax with contrast
• Investigations for underlying malignancy: o CBC D/C, clotting, LRFT, blood film, CaPO4, TFT
o Tumour markers: epithelial markers (CEA), germ cell markers (AFP, HCG, LDH)
o Obtain tissue diagnosis before empirical treatment (do not withhold if life-saving)
- Solid cancer: FNAC, lymph node biopsy, biopsy (EBUS/ EUS/ CT-guided/ open),
pleural tap, …
- Lymphoma: excisional biopsy of LN +/- BM biopsy
• Rule out co-existing pericardial effusion / cardiac tamponade / secondary pulmonary embolism
Management (SAQ!!)
• Resuscitation (ABC): prop up head elevation + protect airway + O2
• Urgent consult oncology
• IV dexamethasone 4mg Q6h (do NOT withhold to wait for the biopsy)
o Immediate RT (first-line): response rate ≥ 80%
o Chemotherapy: if RT not possible (e.g. very large tumour) / chemosensitive tumour (e.g. SCLC, teratoma, lymphoma) + haemodynamically stable
- Concern: fluid load might exacerbate symptoms
o SVC stenting (if other options exhausted): post-op DAPT for 3months
- Total SVC occlusion and SVC thrombus are not absolute C/I
• CVC thrombosis: anticoagulation + remove offending catheters
• SVC thrombus: consider thrombolysis (mechanical/pharmacological) + anticoagulation for 3-6mo or longer (LMWH and apixaban/rivaroxaban preferred over warfarin)
Complications of RT to thorax
• Pulmonary fibrosis
• RT-induced vasculitis (pulmonary vessels)
• Secondary malignancies: CA thyroid, secondary leukaemia
Differential diagnosis of SOB in oncology
• Pericardial effusion ± cardiac tamponade (decreased BP)
• Pulmonary embolism
• Atelectasis
Anterior mediastinal mass
• Thyroid, thymus, teratoma, terrible lymphoma
Malignant pericardial effusion & cardiac tamponade
Clinical features
• Most common symptom: SOB
o Clinical symptoms depend on rate of fluid accumulation
• Signs:
o Beck’s triad: hypotension, elevated JVP, muffled heart sounds
o Others: pulsus paradoxus > 10mmHg, Kussmaul sign (rare), LL edema
Investigations
• ECG: small voltage, electrical alternans
• CXR: globular heart, but clear lung fields
• Echocardiogram (gold standard): systolic RA collapse à diastolic RV collapse à left chambers collapse;
distended IVC
Management
• Immediate resuscitation: O2, gentle IV fluids (pre-load), avoid diuretics / vasodilators (do NOT treat as CHF)
• Echo-guided pericardiocentesis and pigtail
o Send fluid for biochemistry, C/ST, cytology
• Treat underlying malignancy (usually CA lung / breast)
• Pericardial window if recurrent
Malignant hypercalcaemia
Aetiology (in order of frequency)
• PTHrP (humoral hypercalcaemia of malignancy): SQCC, RCC, TCC
• Bony metastasis (osteolytic): breast, MM, lymphoma, RCC
• Calcitriol secretion: Hodgkin’s lymphoma
• Ectopic PTH secretion: lung, ovary, HCC
Clinical features
Dehydration due to
• n/v
• Delirium
• Hypercalcaemia-induced nephrogenic DI
Investigations
• Corrected calcium – severity:
o Mild: ≥ 2.6
o Moderate ≥ 3
o Severe ≥ 3.5 or presence of renal (AKI), neurological (confusion), cardiac arrhythmias
• RFT
• ECG: shortened QT interval, prolonged PR interval, bradyarrhythmia
Management [MED-REN] (SAQ!!)
• Monitor I/O, RFT, CaPO4, cardiac monitoring
• Withhold Ca & vit D supplement, thiazide diuretics
• Rehydration: IV NS 2-3L/day, adjust against urine output > 2L/day
o No role for Lasix in acute Mx of severe malignant hyperCa
• Bisphosphonates (after correcting dehydration: ensure CrCl > 30)
o Example: pamidronate IV 60-90mg in 500ml NS over 2-4h / zoledronic acid IV 4mg over 15min
o Onset 24-72h (do NOT repeat dose until Day 7)
o MOA: inhibit bone resorption by osteoclasts
o Renal adjustment:
§ Lower dose, slower infusion rate
§ Switch to calcitonin if CrCl < 30
• Salmon calcitonin IM/SC: if need acute ¯Ca
o Onset: 2-3h
Clinical oncology 45
o Risk of tachyphylaxis after 2-3 days – ICU monitoring
• Hydrocortisone: only for steroid-sensitive cancers e.g. lymphoma, myeloma
o MOA: inhibit vit D conversion to calcitriol
• Denosumab SC: if refractory / cannot use bisphosphonates due to CKD
• ?Haemodialysis with low Ca dialysate
• Consult oncology: treatment of underlying cancer
Cord compression in oncology
Aetiology
• Extradural: vertebral body metastasis (90%) - CA prostate, breast, lung > MM, NHL, RCC
• Intradural: meningioma, schwannoma
• Intramedullary: astrocytoma, ependymoma
Sites of compression
Thoracic (70%), lumbosacral (20%), cervical (10%)
Clinical features
• Back pain (70-95%): exacerbated by cough/ lying down /
straining, followed by
• Neurological signs – appear in the order of:
o Motor weakness: 70% could walk at first
o Sensory level: unreliable – the sensory level
corresponds with nerve roots within 2 levels above or 4 levels below the compressed cord
o Sphincter dysfunction (“neurogenic bladder”): AROU
- Spinal cord: detrusor-sphincter dyssynergia
- Sacral nerve (e.g. conus): detrusor areflexia
- Peripheral nerve (e.g. cauda): hypo/areflexic bladder
• Autonomic dysreflexia if lesion above T6 (fig.): vasodilation above lesion & vasoconstriction below lesion, bradycardia, hypertension, spastic bladder
Cord compression
Site: above L1
Onset: acute
Pain: LBP + radicular pain
Pattern: LMN at affected level; UMN below affected level
Motor: Spinal shock, then spastic paralysis (pyramidal pattern), hyperreflexia
Sensory: sensory level, symmetrical
Automatic: spastic sphincters (AROU, constipation)
Investigations
• Initial: Plain XR spine, bloods (CBC, LRFT, CaPO4), tumor markers (e.g. PSA, CEA)
• Diagnostic:
o Anatomical: MRI whole spine with contrast (1/3 has >1 level of compression) —> CT myelography (if MRI contraindicated)
o Cancer: staging workup (PET-CT, bone scan), tissue diagnosis if N/A
Management
• Diagnose & treat ASAP: functional status at the time of treatment is the most important prognostic factor
• IV dexamethasone 4mg Q6h: reduce oedema around the lesion
• Supportive care: pain control, bowel care, Foley catheterisation, compression stockings, ± prophylactic LMWH
• Definitive treatment: surgery (consult ortho) or RT (consult oncology), considering
o Disease factor:
- Radiosensitivity of tumor
—> Sensitive e.g. prostate, breast, SCLC, MM, NHL
—> Resistant e.g. melanoma, sarcoma, RCC
- Need for definitive tissue diagnosis
- Patient fitness of surgery
o Mechanical factor:
- No. of compression
- Spinal column stabilit
Neutropenic fever
Definition
• Fever: oral temperature ≥ 38.3°C or ≥38°C for ≥1h
• Neutropenia: ANC < 0.5 or ANC < 1 with projected decrease to 0.5 within 48h
• Mortality 11% (50% if septic shock)
Risk factors
• Obstructions (lymphatics, GI tract, urinary tract, biliary tract)
• Presence of FB (stents, catheters)
• Rate of fall, absolute level (<0.5) and duration (≥7 days) of neutropenia
o Note: Neutrophil count usually nadir ~D14 after chemo, except Taxane (D4-5) or post-BM transplant (D21)
• Number and dose of chemotherapy used
• Types of cancer: haematological cancer, BM transplant, advanced stage
• Patient factors: advanced age, poor performance status, organ dysfunction
Pathogens
Culture positive only in 30%
• GN > GP, polymicrobial
• Fungal: PCP, candidiasis, aspergillosis
• TB: extra-pulmonary
Investigations
• Bloods: CBC d/c, LRFT, CaPO4 lactate
• Septic work-up: blood (peripheral site, each central line), urine, sputum, others if localising S/S (e.g. stool, CSF)
• Imaging: CXR (consolidation may be absent due to inability to mount inflammatory response)
Management
• Admit all patients
• Risk stratification: Is the patient in septic shock?
o High risk (inpatient): any of
- Anticipated prolonged (≥ 7 days) / profound (ANC < 0.1) neutropenia
- Medical co-morbidities e.g. haemodynamically unstable, deranged LRFT, altered mental state
- MASCC score < 21
o Low risk (outpatient – seldom in HK)
• Immediate blood culture x 1 set, then
• Empirical IV broad-spectrum anti-pseudomonal antibiotics for a course of at least 7 days
o IV Tazocin 4.5g Q8h ± gentamicin (if haemodynamically unstable)
o Other options: ceftazidime (Fortum), cefepime 2g Q12h, meropenem 1g Q8h, imipenem 500mg Q6h
• Adjust antimicrobials:
o Persistent fever > 2-3 days: antifungals, antivirals, TB, rarer organisms (e.g. mould)
o Suspected catheter-related infections, skin & soft tissue infections, known MRSA carriers: MRSA coverage (vancomycin / linezolid)
o ILI during flu season: empirical Tamiflu
o Thrush/ dysphagia: candida
o Abdominal pain/ diarrhoea (neutropenic enterocolitis/ typhilitis): CT abdomen, bowel rest, antibiotics with C. diff coverage (metronidazole)
Prevention of recurrent neutropenic fever
• Chemotherapy dose reduction: preferred if
other toxicities present
• Prophylactic antibiotics: oral Augmentin /
fluoroquinolones
• G-CSF (Filgrastim): decrease duration of
neutropenia, but not improve survival —> daily injection, 72 hrs after chemotherapy —> cannot exclude neutropenia but reduce the period of time
If breast cancer adjuvant chemotherapy —> GCSF given and not reduce dose of cytotoxic chemotherapy
Tumour lysis syndrome
Pathophysiology
• Massive breakdown of tumour cells triggered spontaneously or by
chemotherapy
• High risk malignancies: Burkitt’s lymphoma, acute leukaemia
(ALL, AML, CML in blast crisis), SCLC
Risk factors
• Tumor factor: high tumor burden (LDH), high proliferating index,
high sensitivity to chemotherapy
• Patient factor: old age, impaired RFT
Clinical features & investigations:
Cairo-Bishop criteria for TLS:
Laboratory TLS – at least 2 of following
occurring from Day -3 to Day +7 of
chemotherapy despite prophylaxis:
• K ≥ 6 (or ↑25% baseline)
• urate ≥ 0.5 (or ↑25% baseline)
• PO4 ≥ 1.45 (or ↑25% baseline)
• Ca ≤ 1.75 (or ↓25% baseline)
Clinical TLS = Lab TLS + any of:
• Renal impairment: Cr ≥ 1.5 x ULN
• Cardiac arrhythmia
• Seizure
• Sudden death
Prophylaxis
• Avoid nephrotoxic drugs (NSAID, IV contrast)
• Adequate hydration (3-4L/day) ± diuretics to maintain high urine output (150ml/h)
• Urate lowering drugs prior to chemotherapy:
o Allopurinol: check HLAB-5801, need renal adjustment
o Febuxostat: expensive, for HLAB-5801 or poor RFT (not require renal adjustment unless severe), C/I: IHD
o ± Rasburicase: if high risk
• Urine alkalinization: NaHCO3 to keep urine pH ≥7 – not used now (lecture)
Management
• IV hydration to maintain renal perfusion (BP > 95) & high urine output (>70mL/h)
• Rasburicase 0.2g/kg/day if urate/ Cr not improving after 48h
o Check G6PD level
o allopurinol / febuxostat NOT for treatment
• Correct electrolyte disturbances (hyperK, hyperPO4, hyperuricemia, hypoglycemia) and treat arrhythmia:
o Do not replace Ca unless symptomatic (risk of nephrocalcinosis)
o Haemodialysis / Haemofiltration if necessary
- monitor I/O
Hyperviscosity syndrome
Aetiology
• Polycythaemia vera (MC)
• Myeloma: Waldenstrom’s macroglobulinaemia (WM), MM
• Leukaemia: AML, CML
o Hyperleukocytosis: WBC > 100
o Leukostasis: symptomatic hyperleukocytosis —> organ damage, tissue hypoxia and early death
Clinical features
• Neurological: headache, altered mental state, blurred vision (retinal haemorrhage), ICH
• Haematological: DIC, TLS
• Cardiorespiratory: SOB
Management
• TLS prophylaxis: IV hydration + allopurinol
• Reduce hyperviscosity by
o PV: venesection
o Myeloma: plasmapheresis
o Leukaemia: cytoreduction therapy (e.g. hydroxyurea, cytarabine, dexamethasone)
- ± leukapheresis (prophylactic leukapheresis offers no advantage over intensive induction chemo)
• Transfusion:
o Red cells: avoid if WBC > 50 (to prevent hyperviscosity), slow transfusion if absolutely required (e.g. Hb < 5)
o Platelet: transfuse if < 20 to prevent major bleeding or ICH
Renal cel carcinoma
- 70% clear cell carcinoma
Risk factor:
- < 1 year from diagnosis to treatment
- Karnofsky PS < 80%
- low hemoglobulin
- high calcium
- high platelet
- high neutrophil
Ix:
- CT-guided biopsy
- molecular diagnosis —>
1. PDL1 score
2. VHL positive
3. PIK3CAm positive
Mx:
- pembrolizumab (immunotherapy) + sunitinib (anti-VEGF)
- nephrectomy only if minimal extrarenal disease
Chemotherapy-induced toxicity
- Malignancy-induced nausea and vomiting (CINV)
- Alopecia
- Mucositis
- Bone marrow suppression
- Infertility
- Secondary malignancy
Anti-emetic prophylaxis
- HEC (cause CINV >90% patient ): 5HT3-RA, NK1-RA, corticosteroids +/- Do-RA
- MEC (cause CINV >30-90% patient ) : 5HT3-RA + corticosteroids +/- NK1-RA
- LEC (cause CINV >10-30% patient ): 5HT3-RA or corticosteroids or Do-RA
Prophylaxis for alopecia:
- Scalp cooling cap
BM suppression:
