Sirisopa Techawathanawanna, MD.

,
Medical Oncology Division,
Siriraj Hospital

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Outlines
Superior vena cava syndrome
Cardiac tamponade
Spinal cord compression
Hypercalcemia
Syndrome of inappropriate antidiuretic
hormone secretion (SIADH)
Febrile neutropenia
Chemotherapy extravasation

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Superior Vena Cava Syndrome
The clinical expression of obstruction of blood
flow through the SVC.
SVCS usually has an insidious onset and
progresses to typical symptoms and signs.
Malignant disease is the most common cause of
SVCS. The percentage of patients in different
series with a confirmed diagnosis of malignancy
varies from 78% to 86%
The prognosis of patients with SVCS strongly
correlates with the prognosis of the underlying
disease.

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Superior Vena Cava Syndrome
The clinical expression of obstruction of blood
flow through the SVC.
SVCS usually has an insidious onset and
progresses to typical symptoms and signs.
Malignant disease is the most common cause of
SVCS. The percentage of patients in different
series with a confirmed diagnosis of malignancy
varies from 78% to 86%
The prognosis of patients with SVCS strongly
correlates with the prognosis of the underlying
disease.

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Clinical Presentation of SVC Syndrome
Symptoms: dyspnea, facial swelling, cough, arm
swelling, chest pain, dysphagia

Sign: venous distention of neck and chest

wall, facial edema, cyanosis, plethora of
face, edema of arms

Investigation:
CXR: superior mediastinal widening and
pleural effusion
CT chest
Contrast venography
radionuclide venography
tumor marker: AFP, beta-HCG
tissue diagnosis
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Causes of SVC OBSTRUCTION
Lung cancer 65 %
Lymphoma 8%
(diffuse large cell, lymphoblastic lymphoma)
Other malignancies 10 %
(Germ cell tumors, Thymoma, Metastatic breast
cancer)
Non-neoplasms 12%-22%
(catheter-induced thrombosis, retrosternal
goiter, thymoma, fibrosing mediastinitis, aortic
aneurysm)
Undiagnosis 5%

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Lung Cancer Subtypes Associated with
Superior Vena Cava Syndrome

Small call 38 %
Squamous call 26 %
Adenocarcinoma 14 %
Large cell 12 %
Unclassified 9%

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Diagnostic Procedures
Emergency mediastinal irradiation before
biopsy is rarely used because it may
preclude proper interpretation of the
specimen in almost one-half of patients.
The clinical identification of SVCS is simple
because the symptoms and signs are
typical and unmistakable.
An efficient diagnostic effort should be
attempted before any oncologic treatment
is given.

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Positive Yield of Diagnostic Procedures for Patients With
Superior Vena Cava Syndrome

Procedure Percent
Positive
Sputum cytology 49
Thoracocentesis 71
Bone marrow Bx 23
Lymph node Bx 67
Bronchoscopy 52
Mediastinoscopy 90
Thoracotomy 98
Percutaneous transthoracic 75
CT-guided needle biopsy

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Diagnositic Plans
Three deep-cough sputum specimens for cytology
Thoracocentesis if pleural effusion is presented
Biopsy of suspicious palpable supraclavicular
node

Bronchoscopy for brushing, washing and biopsy

Percutaneous transthoracic CT-guided biopsy

Mediastinoscopy or thoracotomy
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Management of SVC syndrome
The goals of treatment of SVCS are to relieve
symptoms and to attempt the cure of the primary
malignant process.
SCLC, NHL, and germ cell tumors constitute
almost one-half of the malignant causes of SVCS
These disorders are potentially curable, even in
the presence of SVCS.
The treatment of SVCS should be selected
according to the histologic disorder and stage of
the primary process.

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Treatment of SVC Syndrome

General measures:

low-salt diet
bed rest with head elevation
oxygen administration
Diuretic: furosemide
corticosteroid: dexamethasone

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Intravenous access via lower extremities

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Treatment of SVC Syndrome

Specific treatment

radiotherapy: 3000-5000 cGy

non-small cell lung cancer
Deterioration of SVC syndrome
Chemotherapy:
small cell lung cancer
Lymphoma
Germ cell tumors (non-seminoma)
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Treatment of SVC Syndrome
Endovascular Stenting and Angioplasty
For non-malignant causes
Recurrence SVC syndrome after radiation therapy
Urgent treatment of SVC obstruction
Direct bypass graft
Should be considered only after other therapeutic
maneuvers with irradiation, chemotherapy, and stenting
have been exhausted.
Thrombolytic therapy
An important component of endovascular therapy
Treatment of catheter-induced SVCS.

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Cardiac Tamponade
Life-threatening, but treatable condition
Recognition and treatment may prolong survival and
improve the quality of life
Caused by:
Accumulation of fluid containing malignant cells in the
pericardial sac
Encasement of the heart by tumor
Postirradiation pericarditis with fibrosis
Common cancers:
Metastatic tumor to pericardium: lung, breast cancer,
melanoma, GI malignancy, leukemia, lymphoma
Primary tumors of pericardium: malignant teratoma,
sarcoma, mesothelioma
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Clinical Presentation of Cardiac Tamponade

Symptoms: dyspnea, cough, chest pain, orthopnea,

edema
Signs: low output (peripheral vasoconstriction;
cold, clammy extremities; poor capillary
refill; and diaphoresis), jugular venous
distention, distant heart sounds, pulsus
paradoxus, and narrowed pulse pressure.
Investigation:
CXR: a large globular heart
EKG: sinus tachycardia,low voltage QRS
complex,electrical alternans
2-D ECHO: diastolic right atrial and right
Ventricular collapse
Pericardiocentesis
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EKG

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Treatment of Cardiac Tamponade
Catheter drainage
Prevention of the reaccumulation of
effusion
intrapericardial sclerosis with doxycycline
surgical intervention: pleuropericardial
window,pericardiectomy
Radiotherapy: for lymphoma and breast
cancer
Systemic chemotherapy for responsive
tumor

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Pericardiocentesis

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Spinal cord compression

Tumor metastasis to vertebral body or pedicle and

compress the dura (epidural metastasis)
Paraspinal tumor extending through intervertebral
foramen into spinal canal (10%)
eg.lymphoma,neuroblastoma
Common cancers: lung, breast, prostate, kidney
cancer, lymphoma, multiple myeloma
Site of involvement:
70% thoracic spine
20% lumbrosacral spine
10% cervical spine

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Spinal cord compression
Clinical Presentation

Localized back pain with tenderness to

percussion over the involved spine
Radicular pain
Motor weakness, sensory loss, and bladder
and bowel dysfunction

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Spinal Cord Compression

80% of patients who are ambulatory remain so

30% - 40% of patients who are nonambulatory
begin walk again
5% of patients who are paraplegia recover to
ambulate again

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Spinal Cord Compression

Investigation

MRI spine: procedure of choice

Plain films of spine
CT and/or Myelography
Bone scan

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Spinal Cord Compression
Goals of therapy:

- recover or preservation of normal

neural function
- local tumor control
- spinal stability
- pain relief

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Treatment of spinal cord compression

o Dexamethasone
o Rediation therapy: 3000-4000 cGy
o Surgery: laminectomy
o Chemotherapy

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Indication for Surgical Treatment of
Epidural Metastasis

Histopathology is unknown
Previous radiation to cord tolerance or
known radioresistant tumor
Progressive deterioration in spite of steroids
and radiation
Compression by bone from a pathologic
fracture or instability of the spine
To rule out epidural abscess or hematoma

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Spinal Cord Compression
Chemotherapy-responsive Tumors

Germ cell tumor

Small call lung cancer
Breast cancer
Neuroblastoma
Ewings sarcoma
Lymphoma
Multiple myeloma

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Hypercalcemia

The most common life-threatening metabolic

disorder with cancer
85% caused by bone metastasis
15% caused by paraneoplastic syndrome
Common cancers: breast cancer, lung cancer
(squamous cell,large cell type), head and
neck cancer, hypernephroma, small cell ovarian
cancer, hepatocellular carcinoma, multiple
myeloma,lymphoma

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Clinical Manifestations of
Cancer-related Hypercalcemis

General: dehydration, weight loss, anorexia

polydipsia, fatigue
Neuromuscular: fatigue, lethargy, proximal muscle
weakness, hyporeflexia,
confusion, psychosis
Seizure, obtundation, coma
Gastrointestinal: nausea, vomiting, constipation
Genitorenal: polyuria, renal insufficiency
Cardiac: bradycardia, prolonged P-R interval,
shortened Q-T interval, arrhythmias
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Corrected calcium (mg/dl) =
measured calcium + [4.0-albumin (g/dl) x 0.8

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 HYPERCALCEMIA

Anorexia, nausea Renal salt and

vomiting water loss

Ca excretion

ECF Volume Contraction

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Treatment of Hypercalcemia

Symptomatic patients
Serum calcium > 12 mg/dl

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Treatment of Hypercalcemia of Malignancy
General measures:
Intravenous hydration: isotonic saline 2-3 L/d
Diuretics: furosemide 20-40 mg IV
Mobilization
Remove thiazide diuretic and vitamin A and D
Agents to decrease bone resorption
Bisphosphonates - drug of choice:
pamidronate, zoledronic acid
Corticosteroid for lymphoma, myeloma
Calcitonin - for severe and symptomatic cases
Renal dialysis
Specific antitumor therapy
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Treatment of Hypercalcemia

Drug Administration Interval

Pamidronate 60-90 mg diluted in 0.9% NSS 250- q 3-4 wks
500 ml IV infusion over 2-4 hours

Zoledronic acid 4 mg diluted in 0.9% NSS100 ml IV q 3-4 wks

infusion over 15 min

Calcitonin 4 units/kg SC or IM q 12 hrs

Prednisolone 40-100 mg PO daily

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Syndrome of Inappropriate Antidiuretic Hormone
Secretion (SIADH)

Hyponatremia with inappropriately concentrated

urine
Tumor secretes arginine vasopressin, the
antidiuretic hormone
The most common cancer is small call lung cancer
10% of patients with small call lung cancer develop
clinically evident SIADH

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Syndrome of Inappropriate Antidiuretic Hormone
Secretion (SIADH)

Clinical Presentation

fatigue, anorexia, nausea, myalgia, headaches

Confusion, lethargy, psychosis, seizures, coma

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Diagnosis of SIADH

1. Serum sodium level < 135 mEq/L

2. Plasma osmolarity 280 mOsm/kg
2. Urinary osmolarity 500 mosm/Kg
3. Urinary sodium 20 mEq/L without diuretics
4. Absence of signs of volume depletion
5. Normal renal function
6. Normal adrenal and thyroid function

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Differential Diagnosis for the SIADH

Tumors: Small cell lung cancer/Other types

Pulmonary:
Infection: tuberculosis, abscess, pneumonia
Central nervous system:
Trauma: subdural, subarachnoid hemorrhage,
thrombosis
Intracranial space-occupying lesions
(primary or metastatic tumor)
Infection: meningitis, encephalitis
Drugs: diuretic, chlorpropamide, morphine, ethanol,
cyclophosphamide,vincristine, vinblastine,
cisplatin

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Treatment of SIADH

1. Fluid restriction: 500-1000 ml/24 hr

2. 3% hypertonic saline or
normal saline with furosemide diuretics
( when Na < 110 mEq/L or with symptoms)

3. demeclocycline

4. Treatment of the underlying cancer

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Febrile neutropenia
criteria for neutropenic fever:
(1) a single oral temperature measurement of higher
than 38.3C (101F) or a temperature of 38C
(100.4F) or higher for longer than 1 hour
and (2) neutropenia with an absolute neutrophil
count of fewer than 500/ L or fewer than 1000/ L with
predicted rapid decline to fewer than 500/ L.

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Febrile Neutropenia

55%-70% caused by infection, especially in

granulocytopenic patients
sign and symptoms of infection often missing
in the granulocytopenic cancer patients
pyuria 11%,purulent sputum 8%
undetected and untreated infection can be
rapidly fatal in the granulocytopenic patients
70% mortality rate within 48 hours for
neutropenic patients not receving antibiotics
at the onset of fever

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Febrile Neutropenia

Sites of infection

Skin: ecthyma gangrenosum

Mouth,sinuses,teeth

Perianal area

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 Percentage of cancer patients who develop serious infections with
granulocytopenia and the cumulative risk of infection with
prolonged granulocytopenia

Granulocyte level Percentage of serious infection

(per mm3) (duration of granulocytopenia in wks)
Initial Change 1 2 3 4 6 10 12

any level any fall 12

any level to 2000 2
any level to 1500 5
any level to 1000 10 30 45 50 65 70 85
any level to 500 19
any level to 100 28 50 72 85 100

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 RECOVERY FROM NEUTROPENIA REDUCES
MORTALITY DUE TO INFECTION

27%
1.0
Rise to
>1.0
Neutrophil count (109/I)

40%
Rise but
still<1.0

none or
59%
fall
0.1

none 80%

(Bodey et at.,
Initial Change Infection mortality 1966)

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Management of febrile neutropenia

Initial antibiotic regimens are divided into

three categories:
(1) monotherapy
(2) duotherapy without vancomycin
(3) vancomycin plus one or two drugs

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Management of febrile neutropenia
Addition of vancomycin should be reserved for
specific settings, which include:
(1) clinically apparent, catheter-related infection
(2) positive blood culture for a gram-positive
bacterium before identification and susceptibility
testing
(3) known colonization with MRSA or penicillin- and
cephalosporin-resistant pneumococci
(4) hypotension or septic shock without an identified
pathogen

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Management of febrile neutropenia

Combination therapy: Aminoglycosides plus

Beta-lactam antipseudomonas penicillin or plus
third-generation cephalosporin
Monotherapy: ceftazidime, cefepime, imipenem,
and meropenem
Oral Antibiotics: ciprofloxacin plus amoxicillin-
clavulanate

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Management of febrile neutropenia
Monotherapy
for uncomplicated febrile neutropenia
Combination therapy
for severe sepsis or septic shock
high prevalence of multi-drug resistant gram-
negative bacilli
Oral antibiotics
low risk for complications of neutropenia
no identifiable focus of infection and lack clinical
finding of systemic infection other than fever

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Antibiotics for febrile neutropenia

Ceftazidime 2 gm. IV q 8 hr.

Cefepime 2 gm. IV q 8 hr.
Imipenem 500 mg. IV q 6 hr.
Meropenem 1 gm. IV q 8 hr.
Oral therapy:
ciprofloxacin 500-750 mg po q 12 hr. +
amoxicillin/ clavulanate (1 gm) po q 12 hr.

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Multinational Association for Supportive Care in
Cancer (MASCC) index
Characteristic Score

Burden of illness:
no or mild symptoms +5
moderate symptoms +3
no hypotension +5
no chronic obstructive pulmonary disease +4
solid tumor or no previous fungal infection in patients
with hematologic malignancies +4
no dehydration +3
outpatient status +3
and age younger than 60 years +2

A MASCC index of 21 or more has been associated with

a relatively low frequency of severe complications.

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 Management of febrile neutropenia
Empiric antibiotics

evaluable after 3-5 days

Afebrile Febrile

FUO Documented infection

If PMN 500 continue combination Add ampho-B

Stop after 7 d until PMN 500 after day 7
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Role of G-CSF in febrile neutropenia

- Accelerated neutrophil recovery

- Shortened the duration of febrile neutropenia

- Shortened the duration of hospitalization

- does not afford the benefit of reducing the incidence

of hospitalization due to FN

- No reduction of febrile mortality

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Certain conditions to use G-CSF in
febrile neutropenia

A long delay in marrow recovery is anticipated

and who have been diagnosed with
pneumonia, hypotension, severe cellulitis,
severe sinusitis, systemic fungal infections, or
sepsis with multi-organ dysfunction
Severe neutropenic patients (ANC < 100) who
have a documented but refractory infection
that is not responding to antimicrobial therapy

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VESICANT AGENTS

Subcutaneous infiltration of these agents

usually causes immediate and intense pain
Edema and painful erythema - within a few
hours
Marked induration within a few days
Necrosis with ulceration within 1-4 weeks

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 VESICANT AGENTS

Dactinomycin
Nitrogen mustard
Doxorubicin, epirubicin, idarubicin
Mitomycin-C
Vincristine, vinblastine, vinorelbine

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EXTRAVASATION

VESICANT AGENTS
0.1 6%
SITE
SCALP VEIN SET
TWO SYRINGE TECHNIQUE
ANY DOUBT STOP

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Management of vesicant drug extravasation

Stop the drug administration with any

questionable pain or swelling at the IV site
Using the original indwelling needle or catheter,
try to aspirate drug from the infiltrated site
Apply cold compress for all drugs except vinca
alkaloids for 30 to 60 minutes and then 15
minutes off and on for 1 day.
Vinca alkaloid extravasations require dry warm
compresses.
Elevated the affected extremity for 24 to 48 hours
Administer an antidote ?
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