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Pediatric Solid Tumors

Bambang Sudarmanto
Hematology-oncology working group
Kariadi Hospital Semarang
Indonesia

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Pediatric Tumors
Kariadi

Hospital is referall hospital Central


Java and part of Borneo
Class of patients: Jamkesmas (poor
people), Askes (health insurance), private
Many are treated in Private Hospitals
many

hospitals do not treat children with


cancer

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Pediatric Solid Tumors (<14)


9,000

new cases, 1500 deaths of pediatric


cancers annually in the U.S.
Cancer- 2nd leading cause of death in
children (1st infections)
1/3 deaths from leukemia
CNS tumors most frequent SOLID tumors
in pediatric population
Indonesia data not viable (Semarang?)
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Pediatric solid tumors


Childhood
requires

cancer

multidisciplinary treatment groups

emotional

needs of patient/family
nutritional needs
coordinated care- medical, surgical, oncology,
nursing, social services, therapists, educators

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Distribution of Childhood Cancer


NBL
8%
Soft Tissue
Sarcoma
7%
Wilm's
Tumor
6%
Bone
5%
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Hodgkin's
NHL
5%
3%

Germ Cell
Other
3%
8%
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CNS
18%
Liver
1%
Leukemia
33%
Retina
3%
5

Pediatric Neck Mass

Congenital
Thyroglossal
Duct Cyst

Acquired
Branchial
cleft cyst

Neoplasms

Infectious/
Inflammatory

Cystic
hygroma
Dermoid
cyst
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Congenital Masses
Thyroglossal

duct

cysts
Branchial cleft cysts
Lymphatic
malformations
Hemangiomas
Teratomas
Dermoid cysts
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Laryngoceles
Thymic

cysts
Vascular
malformations
SCM tumors of
infancy
Plunging ranulas

Acquired Masses
Infectious

Inflammatory

Bacterial

Kawasaki

Viral

Sinus

Histiocytosis
Drug-induced
lymphadenopathy
Sarcoidosis

Fungal
Sialadenitis

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Abdominal masses

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Abdominal masses
History
Symptoms
abdominal

discomfort, increased abdominal


size or assymptomatic
Presence of systemic symptoms
bone

Other

pain, limping, malaise, fever

symptoms

hematuria

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Abdominal masses
Physical findings
Presence of abdominal mass
upper

Other

abdomen or lower abdomen

associated physical findings

other

masses: orbital
bruises
hypertension
pain
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Abdominal Mass
Differential diagnosis
depends on location
Upper abdominal
mass
Neuroblastoma
Wilms

tumor
Hepatoblastoma
Rhabdomyosarcoma
Germ cell tumor
Lymphoma
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Abdominal Mass
Differential diagnosis (cont)
Lower abdominal/pelvic
mass
Neuroblastoma
Rhabdomyosarcoma
Germ

cell tumor
Lymphoma
Ewings sarcoma

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Abdominal Masses
Laboratory evaluation
Bone marrow aspirate
neuroblastoma,

lymphoma,
rhabdomyosarcoma or
Ewings sarcoma

CSF

tap

if

lymphoma is a
consideration

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Abdominal masses
Radiologic work-up
Abdominal/pelvic ultrasound
useful

screening test: helps define location and


quality (solid or cystic)
not useful to assess for retroperitoneal adenopathy
Computed

tomography

location

of mass
presence of calcification
obstructive signs
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Wilms Tumor
Accounts

for 6% childhood malignancies


Median age at diagnosis 3 years
Metastasizes to lung and lymph nodes
70%

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patients present with localized disease

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Wilms Tumor: Signs & Symptoms


Most

commonly
presents as painless
abdominal mass
Hypertension (2030%)
Pain (20-30%)
Hematuria (25%)

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Wilms Tumor
Diagnosis:
Ultrasound
CT
Lymph

node and lung mets


Right sided tumors- liver mets
Mets to bone and brain possible with some
histologies

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Wilms Tumor: Staging System


Stage

Definition

Tumor limited to kidney, completely excised

II

Tumor extends beyond the kidney, completely


resected; no residual tumor beyond resection margins

III

Residual non-hematogenous tumor confined to


abdomen

IV

Hematogenous metastases

Bilateral renal involvement

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Bilateral Wilms

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Survival by Stage and Histology

Histology/stage

# pts

2 yr-s*

4 yr-s*

FH/I

546

98

97

II

281

96

94

III

290

91

88

IV

126

88

82

UH/I

20

89

89

UH/II-IV

40

56

54

survival

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Wilms tumor
Treatment:
Remove

kidney- nephrectomy

Lymph

nodes biopsied
Can spread also through blood
Tumor spill is possible- abdominal cavity is at risk
Chemo

and RT- sometimes preop to reduce


tumor spill

RT

late stages, residual dx, LN mets,


bilateral dx, lung mets

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Wilms Tumor
Chemo
Actinomycin-D
Added

vincristine, Adriamycin- 80-100% cure rates


Mets = 70% cure rate

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Wilms Tumor: Prognosis & Future Directions


Prognostic

Future

factors: stage and histology

directions

Minimize

therapy for favorable histology

patients
Identify biologic factors predictive of outcome
Intensify therapy for patients with unfavorable
histology

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Pediatric Brain Tumors


(CNS Tumor)

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Brain tumors: pediatric vs. adult


Adults:

70% of tumors are supratentorial

meningioma
pituitary

adenoma
High grade astrocytoma
Anaplastic

astrocytoma (grade III)


Glioblastoma multiforme (grade IV astrocytoma)

Pediatric:

70% in posterior fossa

pilocytic

astrocytoma (cerebellar astrocytoma)


medulloblastoma

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CNS TUMORS
Most

common solid tumors in children


2nd most frequent (16.6% of all childhood
malignancies)
Incidence has increased over the past 2
decades
Leading cause of cancer death in children
Result in more morbidity than any other
malignancy in childhood
Metastatic brain cases are rare
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CNS TUMORS
Signs

& Symptoms
(related to the location, histologic grade
of tumor & age of child)
General
-Headache
-Seizures
-Mental status changes
-Increased intracranial Pressure (ICP)

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Astrocytoma

- high grade
- low grade
Medulloblastoma
Benign tumor : adenoma

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Medulloblastomas

25% of all childhood brain tumors


Occurs in the posterior fossa

2-12 yr old

Arises in the midline of the cerebellum and spreads to the in the


4th ventricle and brain stem
High propensity to spread through CSF
peaks at 5 yr old

Rare in adults
arises from primitive neuroepithelial cells
histologically cells appear as small, round, blue cells
forming pseudorosettes. Purple friable tumor

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medulloblastomas
invasion

of the fourth ventricle causes sx

CSF

does not flow causing hydrocephalus


headaches early- morning vomit get progressively
worse
Ataxia
cranial nerve abnormalities from invasion of the
brain stem
Staging correlates with survival
CT/MRI, myelography of entire CNS necessary
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Medulloblastomas
Can

develop mets in bone


Neurosurgery is first treatment
remove

gross disease
ventricular shunts are discouraged because of possible
seeding into peritoneal cavity

CSI-

Craniospinal Irradiation

postop-

RT
lateral- opposed brain fields
cover

retroorbitally through mid-cervical cord


The divergence of the spinal field determines the collimator
twist

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CSI-

Craniospinal Irradiation

Depending

on the length of the spine, two spinal fields


may be necessary
Whole spine is treated- down to S2 or S3
Electrons are used many times to avoid treating
anterior structures
Gaps (photons) between fields are feathered
Some institutions are encouraging a small gap
between lateral brain fields and the upper spinal field
See page 326 Red

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CSI -Craniospinal Irradiation


Immobilization

important

What

position?
Anesthesia may be necessary
RT

Doses:

1.5

Gy day to 36 Gy
Boost to posterior fossa area- 54 Gy @ 1.8
day
Chemo

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investigation
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34

Retinoblastomas
Most

common intraocular tumor in


children
200 U.S. annually (Indonesia: no data)
Most occur 6 mos-4yrs old
Hereditary risk factors- 10% of cases
Can

be bilateral- 35% cases

Rarely

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curative

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Retinoblastomas
Discovered
White

by light reflex

vs. red

Ophthalmologist
No

exam

biopsy

Avoid

possibility of vitreous seeding

CT: detect

1/14/17 08:57:25 AM

extraocular extension

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Retinoblastomas
CSF

disease

Assessed

by lumbar puncture

Bone

marrow may be biopsed


Staging systems developed
Preferred

treatments outlined
Predict success rates
Most common
Reese-Ellsworth

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Retinoblastomas
Treatment

Techniques

Photocoagulation
Cryosurgery
Small

tumors not near optic disc and macula

Enucleation
Unilateral

disease
Sacrifices globe

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Retinoblastomas
Treatment

Techniques:

Surgery
Radiation

Implants

RT
Inoperable

or bilateral dx
Spare lens and cornea
Treat retina

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Retinoblastomas
Treatment

Method: if disseminated dx

Chemo
Good

response expected
VAC- Vincristine, Adriamycin, cyclophosphamide
OPEC- vincristine, cisplatin, etoposide,
cyclophosphamide

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Retinoblastomas
Late

Effects of Treatment

Enucleation
Several

prosthetics will be needed as child grows

RT
Facial

growth affected
Small orbits
Blind spots
Radiation retinitis, and dry eyes
2nd malignancy
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41

Neuroblastomas
500

cases annually U.S.


2nd most common pediatric solid tumorafter brain tumors
Age range- newborns-several yrs old
Median age 2 yrs old

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Neuroblastomas
Occur

mainly in the abdomen

Originate

in adrenal gland or paraspinal ganglia

Lethargic,

ill appearing child under 2 with


abdominal mass is common
Spinal cord invasion will promote neurological sx
Horners syndrome present with upper
sympathetic ganglia involvement
Flushing, diarrhea

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Neuroblastomas
Many

children present with mets


Children older than 18 months have 70%
chance of developing mets
CT- chest, abd (US)
Lungs

and liver assessed

MRI

spine
Bone marrow biopsy
Bone scan
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Neuroblastomas
Prognosis
Dependent

on age at presentation
< 1 yr old disease may regress if acute sx are
managed
Treatment

Techniques

RT

and chemo- low cure


Surgery if no mets- high cure rate
Chemo and BMT
RT- palliation
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Lymphoma

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Lymphomas
3rd

most common cancer in children. 60% are


NHL; 40% Hodgkins disease
Extranodal disease is common in children with
1/3 rd involving the mediastinum, abdomen or
head and neck
Multi agent chemotherapy is the mainstay of
treatment, surgery and radiotherapy
Anticipation and treatment of complications is
extremely important (lysis tumor syndrome, SVC
syndrome)
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Non Hodgkins lymphoma


NHL

result from malignant proliferation of


cells of lymphocytic ar histiocytic linage.
Generally restricted to lymphoid tissue
such as lymphnodes and spleen
NHL categorized as low, intermediate and
high grade on the base of their clinical
aggressiveness.

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Non Hodgkins lymphoma


Epidemiology

peak is between 5-15 years median age 9


years; male preponderance , 3:1
Increase risk include patient with immunologic
defect (AIDS, etc), immunosuppresive therapy
(post transplant)
EBV is almost invariably associated with the
African Burkitts lymphoma

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Non Hodgkins lymphoma


Clinical

feature:

are

varied depend on the location of the tumor, the


extent of the disease (stage) and histologic subtype
Extranodal involvement :
Mediastinum: may produce SVC syndrome
Abdomen: ileocaecal region, appendix, colon and
retroperitoneal area. Cayse pain, vomiting,
intussuception, ascites, obstructive
Head and neck: enlargement of cervical node, paritis,
tonsilar hyperthropy; jaw swelling
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Non Hodgkins lymphoma


Diagnosis

and staging:

History

and physical exam


Blood count, BMA and Biopsy
LDH level
Evaluation of liver test (bil, SGOT/SGPT;
alkphospatase)
Chest radiography; USG; CT Scan abdomen
Adequate surgical biopsy
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Non Hodgkins lymphoma


Staging:
Stage

I: a single tumor (extranodal) or single


anatomic areawith exclusion of mediastinum
and abdomen
Stage II: stage I + two or more nodal area on
the same side of diaphragna
Satege III: stage II + all extensive node
enlargement
Stage IV: stage III + with initial involvement of
CNS or bone marrow or both
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Non Hodgkins lymphoma


Principal
Multi

therapy :

agent chemotherapy : CHOP

Anticipation

and treatment of complication:

Two

complication :
- Arising Space occupying tumor:
intrathoracic complication

pericardial effusion
Metabolic complication of chemotherapy:
tumor lysis syndrome

Management of relaps
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Bone tumors
Benign

and malignant tumor


Fracture pathologic
Plain radiography is lytic bone lesion;
cortical destructions soft tissue extension.
Two most common cancers of bone :
osteosarcoma and Ewing sarcoma and
the fascinating group of disorders known
as histiocytosis
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Osteosarcoma
Epidemioloy

and etiology:

Most

frequent adolescent and young adults


Annual 600 new cases in USA
Correlated with radiation exposure
Incidence increase among survival
retinoblastoma (Rb) and p53 tumor supressor
gen.

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Osteosarcoma
Pathology:
Clinical

history and radiographic appereance


of bone lesion
Correct diagnosis requires of bone biopsy
Biology

Genetic

alteration occur in the tumor


suppresor genes p53 and Rb to play
important role in tumorogenesis

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Osteosarcoma
Pathology:
Clinical

history and radiographic appereance


of bone lesion
Correct diagnosis requires of bone biopsy
Biology

Genetic

alteration occur in the tumor


suppresor genes p53 and Rb to play
important role in tumorogenesis

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Osteosarcoma
Clinical

presentation:

Painful

hard of the bone


History of trauma
Osteosarcoma can occur in any body but usually
develop in metaphysis of long bone, common site is
distal femur; proximal humerus,
Systemic symptom are fever, night sweats, weight
loss.
Metastatic disease: other bone; pulmonary; soft tissue

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Osteosarcoma
Diagnosis

and staging:

Plain

radiography lytic and/or sclerotic bone


abnormality
A sunburst appearance
Cortical distruction and periosteal reaction
MRI and biopsy

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Osteosarcoma
Treatment

: local control of tumor and systemic


therapy to eradicated microscopic metastasis
disease at distant sites
Preoperative

chemotherapy : reduced tumor bulk;


prognostic implication; making surgical resection
easier
HDX MTX; doxorubicin and cisplatin
Post operative chemotherapy 12 month
Non metastatic disease : 60 -65% to be cured
Metastatic
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diseases indicated poor prognosis


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Ewing sarcoma
Ewing

sarcoma is one of a group of


tumors referred to as the Ewing sarcoma
family tumors (ESFT): Ewing sarcoma of
bone; soft tissue Ewing sarcoma and
peripheral primitive neuro ectodermal
tumor (PNET)
Arise from share the same chromossomal
abnormality
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Ewing sarcoma
Epidemiology

and etiology

Less

than 20 years at diagnosis


Annual incidence 2.7 case permillion
The cause of ESFT is unknown, unrelated
with radiation
Pathology

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and biology:

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Soft Tissue Sarcomas


Arise

from mesenchymal tissue


Can arise anywhere in body
Wide variety of histologies
Most

common 60 %

Rhabdomyosarcomas
Undifferentiated

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Soft Tissue Sarcomas


Diagnosis

and Staging

Depends

on area involved
H&N, genitourinary, extremities and trunk
A large

painless mass- extremity


Painful orbit
In

genitourinary areas- urinary problems


(male)
Exophytic mass vagina
Mets to lung and bone marrow most common
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Soft Tissue Sarcomas


Staging
Physical

exam

US
CT

or MRI
BM biopsy/Chest CT (mets)
Stage and histology dictate tx

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Staging
Treatment
Surgery
First

choice is removal

RT
Improves

local control, spare organs


Field covers entire muscular compartment
50.4 Gy 1.8 Gy fx
Shield growth plates
Spare BM in pelvis if possible
Brachy
Chemo-

resected/nonresected tumors

Vincristine

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and actinomycin-D

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Unusual Childhood Tumors


Germ

Cell Tumors

Can

occur anywhere in the midline from CNS to


ovaries and testes
Sacrococcygeal teratomas often seen in newborns
Nonseminomas
Embryonal

carcinoma
Choriocarcinoma
Yolk-sac tumors
These often produce AFP, HCG chemical markers
Seminoma-

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dysgerminoma
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Unusual Childhood Tumors


Liver

tumors
Appear much like Wilms tumor or
neuroblastoma
CT or US will differentiate
Hepatoblastoma-

under 2 yrs old


Hepatocellular carcinoma- after 10 yrs old, multifocal
Surgery- primary tx
Chemo-

often used
RT- rarely used
Poor survival rates

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Unusual Childhood Tumors


Histiocytosis

X syndromes

Spectrum

of disease
Involves Langerhans cells
Miscellaneous

Tumors

Nasopharyngeal

angiofibromas
Undifferentiated nasopharyngeal
Thyroid tumors- benign and malignant, Iodine 131ablation
Keloids or fibromas
Kaposis sarcoma
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Pediatric Patients- Special


Considerations
Extra

Time Needed

Anesthesia
Psychosocial

needs of family- jobs/home

Understanding/compassionate

therapist

Use

of rewards- stickers/toys
Protocols
Info

sent for immediate review


Careful adherence to guidelines important

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