Oncologic Emergencies Haskell (Gill) Kirkpatrick M.D. 9/22/05.

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Oncologic Emergencies Haskell (Gill) Kirkpatrick M.D. 9/22/05

Transcript of Oncologic Emergencies Haskell (Gill) Kirkpatrick M.D. 9/22/05.

Oncologic Emergencies

Haskell (Gill) Kirkpatrick M.D.

9/22/05

Malignant Spinal Cord Compression (MSCC)

• Affects 5-10% cancer patients – Most commonly: breast, prostate, lung, lymphoma and multiple

myeloma• 20% MSCC cases are initial presentation• Bone (axial skeleton) common site of metastasis

– Vertebral and epidural venous plexus (Batson’s plexus)• Most common mechanisms

– Hematogenous met to vertebral body extending into epidural space

– Pathologic fracture of vertebral body (infiltrated with tumor) resulting in cord injury from bone fragmentation or instability

• 65% cases affect thoracic spine– 20% cases lumbar spine (colon and prostate predilection)– Cervical and sacral involvement rare

Clinical Presentation of MSCC

• Back pain: In certain cancer patients should be considered metastatic origin until proven otherwise

• Periostium richly innervated– Vertebral body tender to palpation/percussion

• Pain worse with recumbancy• Usually precedes neurologic symptoms (1-2 months) • Radicular pain most common with lumbosacral lesions• Thoracic radicular pain usually bilateral, band-like

Clinical Presentation of MSCC

• Progression of motor findings: weakness, loss of gait, paralysis

• Majority of compressions at thoracic level: paraparesis• Upper lumbar spine: conus medullaris syndrome

– Distal lower extremity weakness, saddle paraesthesias and overflow leakage from bowel and bladder

• Loss of bladder and bowel function generally a late finding

• Majority of patients not ambulatory at time of diagnosis

Diagnosis of MSCC

• Average time from onset symptoms to diagnosis: 3 months

• MRI of whole spine is most sensitive test• Decision to use modality based on history of back pain

– Suspicion for pain secondary to Degenerative disease • mostly affects lower cervical and lower lumbar spine

• Waxes and wanes

• Responds to NSAIDs and bed rest

– Suspicion for pain secondary to MSCC• Thoracic spine

• Progresses despite conservative treatments

• Aggravated by supine position

Treatment of MSCC

• Corticosteroids: Optimal dose?– “High dose” studied in only randomized trial (+/- XRT)

• 96 mg IV bolus then 24 mg 4 X /day (tapered over 10 days)• Serious side effects (GI perforations and bleeding)

– Most common regimen: • 10 mg bolus then 16 mg/day (divided over 4 doses)

• Radiation therapy– Relieves pain in most patients– Pre-treatment neurologic fxn strong predictor of response– Underlying tumor type also predictor

• Aggressive surgery– New data shows that all patients should be considered for

decompressive radical resection

Patchell et al, ASCO 2003

Patchell et al, ASCO 2003

Patchell et al, ASCO 2003

Febrile Neutropenia

• Should be considered an emergency– Early studies have shown high mortality when delay

initiation of appropriate antibiotics– Before era of empiric antibiotics infection accounted

for up to 75% of deaths associated w/ chemotherapy

• Definitions:– Fever: single temp > 38.3°C (101.3°F) or 38.0°C

(100.4°F) sustained greater than 1 hour– Neutropenia: usually ANC < 500

• Absolute neutrophil count (ANC)=total WBC X (%neutrophils + %bands)

Infection as Cause of Death in

Cancer PatientsBodey GP et al, Ann Intern Med 1966;64:328

PatientsAcute

Leukemia LymphomaSolid

Tumors

Number studied atautopsy 315 206 816

Number dying ofinfection 234 (74%) 104 (51%) 380 (47%)

Due to bacterialinfections (%) 76 87 93

Due to gram-negativebacilli (%) 78 60 68

Organisms Causing Infection During Chemotherapy of Acute Leukemia

Bodey GP et al, Ann Intern Med 1966;64:328

Type Number %Gram negative bacilli 617 51Gram positive 52 4Anaerobes 19 2Fungal 68 6Multiple 116 9Viral 9 0.7Pneumocystis and toxoplasma 3 0.3Unidentified 325 27

Infections

0

20

40

60

80

100

1 2 3 4 5 6 7

DAYS

PE

RC

EN

T

MO

RT

ALIT

Y

Pseudomonas sp Klebsiella sp E. coli

Febrile Neutropenia

• Seeding of the bloodstream from endogenous flora in the GI tract most common cause

• Commonly cultured bacterial pathogens– Gram neg (Pseudomonas, E Coli, Klebsiella etc..)– Gram pos (Coag-neg staph, staph aureus, streptococcus etc…)

• Commonly cultured fungal pathogens– Candida species, Aspergillus

– usually arise later as a secondary infection in patients with prolonged neutropenia and antibiotic use

• Viral pathogens– HSV, VZV

Treatment of Febrile Neutropenia

• Empiric Antibiotics– Appropriate coverage of known or suspected infection based on

history/exam findings/radiographic studies

• Monotherapy:– ceftazidime, imipenem, meropenem, or cefepime

• Double coverage:– beta-lactam and an aminoglycoside

• Awareness of institutional resistance patterns• Addition of empiric Vancomycin

– Skin or catheter site infection, hypotensive, hx of MRSA colonization, mucositis, quinolone prophylaxis

Corey, L. et al. N Engl J Med 2002;346:222-224

Causes of Fever in Patients with Prolonged Neutropenia Who Are Receiving Broad-Spectrum Antibiotics

Treatment of Febrile Neutropenia

• Empiric anti-fungal coverage with persistent fever on broad-spectrum antibiotics and prolonged neutropenia– Amphotericin B (liposomal), caspofungin,

voriconazole

• Colony stimulating factors– Should not be used routinely– Appropriate for critically ill patients

Pizzo, P. A. N Engl J Med 1993;328:1323-1332

General Principles for the Management of Fever in Patients with Neutropenia

Hyperleukocytosis

• Neutrophil count (CML) > 250,000 may cause vasoocclusive complications

• Leukemic blasts (AML) are nondeformable – Cause hyperviscosity at lower counts ( 70,000 +)

• Leukostasis in microvasculature leads to clinical symptoms– Pulmonary: hypoxemia– CNS: headaches, vision changes/loss, focal deficits

• Symptomatic hyperleukocytosis and AML associated with initial high mortality

Treatment of Hyperleukocytosis

• Emergent leukophoresis can be used– Should be used as adjunct to chemotherapy– Temporizing measure

• Initiate cytoreductive therapy ASAP– Blasts are rapidly accumulating– Can result in another oncologic emergency…

Tumor Lysis Syndrome

• Rapid cell death in face of high tumor burden– Large amounts of intracellular metabolites released

• Uric acid, potassium, phosphate..

• Most commonly associated with poorly differentiated lymphomas and leukemias– Burkitt’s– ALL (more commonly than AML)

• Uric acid can deposit in kidney leading to ARF• Dialysis can support patient • Rasburicase or Elitek (urate oxidase): oxidizes uric acid

to allantoin which is water soluble

Prevention of tumor lysis syndrome

• Vigorous hydration• Allopurinol 300-900 mg/day

– Ideally 2 days before cytotoxic therapy

• Role of alkalinizing urine debatable– Increases the solubility of uric acid and decreases

tendency for precipitation but…– Alkalinizing could promote calcium-phosphate

deposition– Animal studies have shown that increased tubular

flow rate is most important protective measure– Vigorous hydration with saline is likely as effective

SVCS: Primary Pathologic Diagnoses

HistologicDiagnosis

Bell159 Cases

(%)

Schraufnagel107 Cases

(%)

Parish86 Cases

(%)

Total352 Cases

(%)

Lung CancerLymphomaOther malignancies

129 (81)3 (2)

67 (63)10 (9)

45 (52)8 (9)

241 (68) 21 (6)

(primary ormetastatic)Non-neoplasticUndiagnosed

4 (3)2 (1)

21 (13)

14 (13)16 (15)

14 (16)19 (22)

32 (9)39 (11)21 (6)

Superior Vena Cava Syndrome

• Invasion or external compression of SVC • Malignant tumors responsible for 80% cases

– Infection and thrombosis account for most of the rest

• Symptoms– Dyspnea– Facial swelling, arm edema, cyanosis

• Signs– Venous distension on neck and chest wall– Facial edema

Superior Vena Cava Syndrome

• 60% cases due to malignancy present without known diagnosis

• CT preferred diagnostic tool• Importance of biospy

– Short delay not compromise outcome most cases– Histology helps determine treatment and prognosis

• Treatment responsive tumors: SCLC, germ cell tumors, NHL

• Role for intraluminal stents?