Childhood cancer-An Overview

Dr.K.S.Reddy
Director, Regional Cancer Center,
JIPMER, Pondicherry

BURDEN OF CHILDHOOD CANCER

Cancer generally regarded as a disease of
adults
Globally Annually No of New Cancers in
children: >200,000
More than 80% are in developing world
MOST COMMON :
LEUKEMIAS
CNS TUMORS
LYMPHOMAS

 IN UK 0.5% OF ALL CANCERS ARE SEEN IN CHILDREN

(18% POPULATION ARE CHILDREN)
IN INDIA VARIES FROM 1.6 TO 4.8%
(33% POPULATION ARE CHILDREN)

In the United States, the incidence of childhood cancer

overall is approximately 125 per million (0-15yrs) with
slightly increased rates in males and white children.

Leukemias account for approximately 25% of all

childhood cancers, followed by
Tumors of the CNS (17%),
Neuroblastoma (7%), Non-Hodgkin lymphoma (6%),
Wilms tumor (6%), Hodgkin disease (5%),
Rhabdomyosarcoma (3%), retinoblastoma (3%),
Osteosarcoma (3%), and Ewing sarcoma (2%).
Numerous rare tumor types account for the remainder.

MALE TO FEMALE RATIO OF MAJOR CHILDHOOD CANCER TYPES IN EACH POPULATION BASED
CANCER REGISTRY
CANCER TYPE
(ICD 10 CODE)

AHMEDABAD

BANGALOR
E

BARSHI

BHOPAL

CHENNAI

DELHI

MUMBAI

NORTH
EAST

LEUKEMIA

0.95

1.20

1.86

0.69

1.55

2.26

1.21

1.09

LYMPHOID LEUKEMIA (C91)

0.70

1.51

1.32

0.81

1.64

2.60

1.26

1.32

MYELOID LEUKEMIA (C92-94)

0.77

0.29

0.92

1.79

1.54

0.46

LEUKEMIA UNSPECIFIED (C95)

0.32

2.99

0.62

1.82

1.44

0.82

1.41

LYMPHOMA

4.29

1.56

11.26

3.25

4.93

2.19

0.75

HODGKINS DISEASE (C81)

3.84

3.57

3.71

11.85

3.11

0.00

NON HODGKINS LYMPHOMA

(C82-85, C96)

4.81

0.00

7.78

2.81

3.11

1.74

0.98

BRAIN, CNS(C70-72)

1.66

2.09

0.31

1.74

1.37

1.65

0.00

ADRENAL GLAND (C74)

0.27

0.81

1.81

1.23

0.00

EYE (C69)

0.60

0.90

0.92

1.10

1.90

0.95

1.17

KIDNEY (C64)

1.21

0.00

2.05

1.31

1.31

1.38

1.13

LIVER (C22)

0.15

0.00

0.20

3.04

2.02

BONE (C40-41)

1.39

1.50

1.10

1.34

1.52

1.23

0.66

CONNECTIVE & SOFT TISSUE

(C47, C49)

0.83

0.82

0.91

1.53

0.82

1.62

GONADAL (C56, C62)

0.00

0.31

1.16

0.32

0.89

0.88

OTHER SPECIFIED AND

UNSPECIFIED

1.63

0.83

0.55

5.91

1.12

1.42

0.92

0.31

ALL SITES

2.24

1.26

1.29

1.07

1.55

1.92

1.34

0.75

GLOBOCAN-2012- INDIA
CHILDHOOD CANCER BOTH SEXES AGE ADJUSTED

CHILDHOOD CANCERS AT JIPMER - 2012/13

S.NO
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.

DIAGNOSIS
ALL
AML
CML
CNS
GCT
HL
HCC
LCH
NEUROBLASTOMA
NON-HODGKINS LYMPHOMA
NASOPHARYNGEAL
OSTEO SARCOMA
PNET
RETINOBLASTOMA
RMS
SKIN CANCER
STOMACH
SIGMOID COLON
WILMS TUMOR
TOTAL

2012
36
9
3
15
6
14
2
4
5
5
4
5
2
2
3
2
1
1
4
123

2013
40
07
01
11
06
15
02
03
04
07
09
10
02
01
05
03
01
01
06
134

Cancer Predisposition Factors

The increased numbers of adults withcancer have
enabled the ascertainment of causative factors, such
as alcohol and smoking.
Relatively few causative factors have been identified
for childhood cancer.
The small numbers of children with cancer have
made environmental factors difficult to evaluate.
However, analysis for inherited factors is increasingly
fruitful, given the explosion in availability of
molecular biologic technology and
Resources engendered by the Human Genome
Project

At its most basic level, CANCER IS A GENETIC DISEASE.

Production of genetic instability that confers some kind of

mutator phenotype is most likely the chief characteristic of
any inherited predisposition for cancer.
These instabilities take one of several forms:
(1) mutations in key genes that are directly involved in tumoral
development(eg, WT1, WT2),
(2) mutations in genes that generate mutations and gross
chromosomal deletions at key loc(eg, in Fanconi anemia and
mismatch repair),
(3) mutations in genes directly involved in DNA repair of
specific lesions (eg, xeroderma pigmentosum), and
(4) complex chromosomal syndromes that increase the
person's susceptibility to develop cancer

Down syndrome
Children with Down syndrome have a 1% risk of
developing leukemia before age 10.
The ratio of types is different in these children than in
children overall in that 60% of children with Down
syndrome develop acute lymphoblastic leukemia
(ALL), and 40% develop acute myelogenous leukemia
(AML). In general, the prognosis in some reported
series is no better or worse in children with Down
syndrome and ALL than in children without Down
syndrome and ALL.
In contrast, outcomes tend to be better in children with
Down syndrome and AML than in children without
Down syndrome and AML.
Interestingly, AML in Down syndrome is skewed
toward the megakaryoblastic form.

 Turner syndrome
Retention of the Y chromosome in female individuals with
Turner syndrome mosaicism or androgen insensitivity
syndrome increases their lifetime risk of gonadoblastoma.
This risk is as high as 25% by adulthood.[67]
Wilms tumor
Association of gross deletions at the 11p13 locus with Wilms
tumor led to isolation of the WT1 gene. Clinical
abnormalities associated with WT1 mutations include aniridia,
genital abnormalities, and mental retardation. As
many as 40% of individuals with Wilms tumor have some
familial component

Autosomal recessive disorders

Xeroderma pigmentosum results from
several genetic complementation groups
that are part of the nucleotide excision
repair system and transcriptional
apparatus.
Patients with xeroderma pigmentosum are
at increased risk for basal cell carcinoma,
squamous cell carcinoma, and melanoma.

Severe combined immunodeficiency

Patients with severe combined immunodeficiency are
difficult to examine because of the severity of their
underlying defect.
However, their inherent propensity toward lymphoid
malignancy is clear.
Patients with prolonged survival may have some
residual immune function, and, thus, a prolonged
period before cancer develops.
Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome is an immunodeficiency
disorder characterized by thrombocytopenia, eczema,
and T-cell dysfunction.
It increases the risk of non-Hodgkin lymphoma (NHL)

Lymphoproliferative syndromes
Lymphoproliferative syndromes, which may be both genetic
and therapeutic, increase the risk of lymphoid proliferation
triggered by Epstein-Barr virus (EBV) infection.
In the X-linked form of the disease, EBV infection accounts
for 70% of deaths.
After prolonged immunosuppression (eg, chronic graft versus
host disease after bone marrow transplantation), the patient's
susceptibility to lymphoproliferative disease increases
HIV infection
HIV has not left the paediatric population unaffected, despite
promising regimens for preventing vertical transmission and
promotion of safe sex practices.
The progression to AIDS is generally more rapid in children
than in adults.
The spectrum of cancers associated with HIV includes
Kaposi sarcoma, NHL (especially in the CNS), and
leiomyosarcoma.

 Environmental Factors
Ionizing radiation

Although increased cancer rates in children have been associated with

radiation exposure, no threshold effect has been noted.
Data derived from the atomic bomb exposures at Hiroshima and Nagasaki
represent the most convincing body of evidence.
A link also has been established between third-trimester radiologic
examinations and leukemia.
Exposure to ionizing radiation in Japan resulted in increased AML risks.
Data from Japan link atomic bomb exposures, exposures to nuclear fallout
from testing, and therapeutic radiation for tonsillitis and tinea have all been
associated with increased risks of leukemia and thyroid cancer.
Preconception radiation exposure remains a source of controversy.

Electromagnetic fields

Research has produced great controversy but little solid evidence of a

relationship between cancer and electromagnetic fields.
Published reports have suggested that electromagnetic fields have some
potential effect on the promotion of leukemia.
However, when the available data are combined, the relative risk is probably
no morethan 1.5, and in many cases no correlation has been seen

Chemicals
Most data about chemical exposure and its relationship to adult
cancers imply that a lifetime of exposure is required to cause
cancer. This supposition is exemplified by tobacco exposure.
However, exceptions have been reported.
Dioxin has been associated with thyroid cancer, acute
myelogenous leukemia (AML), and Hodgkindisease.
Trichloroethane has been implicated in a case in Woburn,
Massachusetts, that suggested a link between exposure and
leukemia.
A strong relationship has been suggested between parental
exposure and subsequent childhood cancer.
Agents and their associated cancers include pesticides (CNS
tumors), solvents (eg, CNS tumors, leukemia, neuroblastoma,
hepatoblastoma), metals (hepatoblastoma), petroleum products
(eg, Wilms tumor, leukemia, hepatoblastoma), lead (Wilms
tumor), boron (Wilms tumor), furnaces (lymphoma), and
chemotherapy (leukemia).
Exposure to chemotherapeutic agents such as Topo II drugs
and alkylators also predispose to secondary AML.

Viral
Associations with viruses have been difficult to
ascertain in childhood cancer.
Perhaps the strongest link has been to Epstein-Barr
virus (EBV), with a clear connection in African Burkitt
lymphoma.
On the other hand, a causal link remains more
obscure in Hodgkin lymphoma and nasopharyngeal
carcinoma, in which the EBV genome is found,but
the question of etiology is less established.
In the case of HIV, malignancies such as CNS
lymphoma and leiomyosarcoma are correlated but
are probably the result of HIV-induced
immunosuppression.

 Leukemias are the most common type of childhood

cancer, accounting for 25% of new diagnoses
Nearly 80% of childhood leukemias are acute
lymphoblastic leukemia (ALL). The advent of
modern molecular techniques has resulted in the
further dissection of ALL into several subtypes with
therapeutic implications.
For example, the recently described TEL-AML1
translocation is present in approximately 20% of
pediatric cases ofALL.
The TEL-AML1 translocation is now considered to
be a favorable prognostic indicator for the outcome
of ALL,
Whereas the presence of Philadelphia
chromosome, a 9;22 translocation involving the bcr
and abl oncogenes, is a poor prognostic indicator

Acute myelogenous leukaemia

Approximately 18% of childhood leukaemia cases
involve AML. This ratio of ALL-to-AML remains
constant throughout childhood, except for a
predilection for AML in the neonatal period.
AML comprises a heterogeneous array of
subtypes. Molecular diagnostic methods have
advanced the ability to subtype myeloid leukemias
The analysis of translocations is helping to define
and confirm the histologic designations.
For example, the t(8;21) translocation is found in
15% of patients with AML. Of interest, this
translocation is a favorable predictor of long-term
survival.

 For instance, the risk of acute

myelogenous leukemia (AML) with the
9;11 translocation is approximately 3-6%
within 5 years of therapy that includes
high-dose etoposide or alkylating agent
therapy, depending on dosage and tumor
type.
Additionally, in utero exposure to
diagnostic radiation has been associated
with an increased risk of childhood cancer

Tumors of the CNS

Roughly 20% of childhood cancers are brain tumors.
Patients with CNS tumors remain an underreported
segment of the pediatric population with cancer
because only one half are referred to specialty
centers.
Morbidity is clearly the greatest problem in patients
with brain tumors because many of these tumors are
in locations that are difficult to treat.
Most pediatric brain tumors occur in the first decade
of life.
Unlike adult brain tumors, most true childhood brain
tumors occur in the posterior fossa

 The most common brain tumor in children is

medulloblastoma, which accounts for 10-20% of
childhood brain tumors and 40% of tumors in the
posterior fossa.
Most brain tumors, chiefly medulloblastomas and glial
tumors, involve the posterior fossa after the first 2 years
of life.
Most CNS tumors are glial tumors, which are classified
by their location as supratentorial,cerebellar, or
brainstem.
Supratentorial astrocytomas comprise 30-40% of cases,
with cerebellar astrocytomas and brainstem gliomas
(15% each) comprising the remainder of the glial tumors.
Unique variants in each of these groups have strong
prognostic significance.
For example, patients with exophytic gliomas do
extremely well, whereas individuals with diffuse
infiltrative tumors do poorly.

 Various genetic syndromes predispose to

brain tumors, including neurofibromatosis,
Li-Fraumeni syndrome, and tuberous
sclerosis.
Environmental exposure and
immunosuppression are also associated
with increased risk, including radiation
(gliomas) and HIV (lymphoma)

Hodgkin Disease
Hodgkin disease, which accounts for 5% of
childhood cancers, peak in children younger
than 14 years, in young adults, and in adults
older than 55 years. Most statistical reports
comment on childhood cancers in individuals
aged 14 years or younger.
Like non-Hodgkin lymphoma (NHL), Hodgkin
disease is reported to be associated with
immunodeficiency and infection with the
Epstein-Barr virus (EBV), as well as
cytomegalovirus.[

 Patients who survive Hodgkin disease

remain at high risk for secondary tumors, a
phenomenon that may indicate an
underlying immunodeficient state.
Breast cancer in young patients with a
history of Hodgkin disease is mostly
associated with irradiation as a treatment
modality.

Non-Hodgkin lymphoma
Lymphomas make up a large, if heterogeneous, category of
childhood cancers. Chief among these cancers are the NHLs,
which are responsible for 6% of all pediatric cancers.
NHL is a disease of young children and is more prevalent than
Hodgkin lymphoma in the first decade of life; it has an overall
predilection for boys, probably because of a subset of T-cell
lymphoma. A major factor in NHL is its association with
immunodeficiency secondary to underlying genetic diseases,
viral infection, or drugs]
Burkitt lymphoma, roughly 40% of all NHL, is associated with
EBV infection and endemic on the African continent.
Burkitt lymphoma accounts for roughly one half of all incidents
of NHL, a number which translates to an incidence of
approximately 2-3% among childhood cancers.
In its endemic form, the incidence of Burkitt lymphoma can
increase as much as 50-fold. Endemic Burkitt lymphoma is
associated with EBV and appears to occur in equatorial Africa.
Additional environmental factors appear to be at work in the
pathogenesis of Burkitt lymphoma

Neuroblastoma
Neuroblastoma is the most common non-CNS solid tumor. Both
long-term survival and short-term treatment remain challenges
in the care of patients with neuroblastoma.
Of interest, the patient's age at presentation has prognostic
implications.
The type that emerges in infancy greatly improves the likelihood
of long-term survival and is marked by a lack of N-myc
amplification; by hyperdiploidy; by low-stage, limited distant sites
in stage I or II disease (marrow, liver, or skin involvement in <
10% of patients); by the absence of 1p chromosomal
abnormalities; by a lack of changes on chromosome 17; and by
evidence of neuronal differentiation.
However, the form that emerges in children aged 1-10 years
has a much worse prognosis. Association with genetic
alterations have been characterized, including germline
mutations in the ALK gene and chromosome 1p deletions

Renal Tumors
Wilms tumor is the most common renal tumor overall,
comprising approximately 5-6% of childhood cancers;
However, in infancy, related tumors such as mesonephric
nephroma are more common.
As in neuroblastoma, the patient's age affects the prognosis, in
that patients who present in infancy have the best outcomes.
Wilms tumor is strongly associated with a host of genetic
syndromes, including Beckwith-Wiedemann syndrome; DenysDrash syndrome; and Wilms tumor, aniridia, genitourinary
abnormalities, and mental retardation (WAGR) syndrome.
Studies of chromosome 11 have led to the description of the
products of the WT1 and WT2 genes, which are associated with
WAGR syndrome and Beckwith-Wiedemann syndrome,
respectively.
Prognostic factors associated with long-term survival include
low-stage disease, favorable histology, and young age.[

Retinoblastoma
With an overall incidence of around 2%,
retinoblastoma is a relatively rare but classic solid
tumor.
Its study led tothe development of the 2-hit
hypothesis of carcinogenesis.
Studies of family trees and analysis of known
mutations have demonstrated an incidence of
unilateral plus sporadic (60%), unilateral plus
inherited (15%), and bilateral plus inherited (25%).
Hereditary retinoblastoma occurs early, often at
birth and 80% before age 2 years and is most
likely to be bilateral, implying that a second
mutation in the RB gene with the first hit having
been inherited in the germline.

Rhabdomyosarcoma
Comprises roughly 3% of childhood cancers, is another solid
tumor with an incidence that peaks in children younger than 6
years and again in early adolescence

This incidence is roughly correlated with the type of tumor.

Head and neck tumors are generally diagnosed in young
patients (two thirds of cases), and the histology is usually
embryonal.
Older patients (one third of cases) are most likely to have
tumors in the extremities with alveolar histology.
In general, patients with embryonal tumors and individuals
with hyperdiploidy have improved outcomes
However, these data remain somewhat controversial.
Associations with Li-Fraumeni syndrome, BeckwithWiedemann, and neurofibromatosis have all been reported

Osteosarcoma
Although more common overall, it is less common
than Ewing sarcoma in the first decade of life.
Osteosarcoma is most common in patients who
are taller than their peers and is diagnosed at an
early age in more girls than boys.
Tumors are localized to the metaphyseal part of
long bones, with most common sites including
distal femur (30%), proximal tibia (15%), and
proximal humerus (10%).
Radiation and alkylating agents have been
implicated in the etiology of osteosarcoma, along
with retinoblastoma and Li-Fraumeni syndrome

Ewing sarcoma
Ewing sarcoma represents a group of tumors that includes
peripheral primitive neuroectodermal tumors and primary
bony tumors.
The diagnostic standard involves detection of either the
chromosome 11;22 or the 21;22 translocation, at least one of
which is found in as many as 95% of individuals with Ewing
sarcoma.
An interesting feature of Ewing sarcoma is its extreme rarity
among blacks and significant occurrence in whites.
Although the greatest incidence is observed in the second
decade of life, Ewing sarcoma occurs more throughout the
age spectrum than does osteosarcoma.
Ewing sarcoma is not associated with rapid bone growth and
may be found anywhere along the bone or adjacent soft
tissue or may even occur as an isolated soft-tissue mass.
The most common sites of Ewing sarcomas are the pelvis
(26%), femur (20%), tibia (10%), and chest wall (16%)

FIVE-YEAR OVERALL SURVIVAL (EXPRESSED IN PERCENTAGE) OF COMMON CHILDHOOD CANCERS IN INDIA, EUROPE AND USA
Population registry data
CANCER TYPE
(CATEGORIZED BY THE INTERNATIONAL
CHILDHOOD CANCER CLASSIFICATION)

Single Hospital

Population registry data

Bangalore

Chennai

Mumbai

Europe

USA

1982 to 1987

1990 to 2001

Various periods

1993 to 1997

1996 to 2004

77

81

LEUKEMIA

36

LYMPHOID LEUKEMIA

35

39

60

82

86

ACUTE MYELOID LEUKEMIA

10

30

58

52

57

85

87

LYMPHOMAS

55

HODGKINS DISEASE

72

65

94

93

95

NON-HODGKINS LYMPHOMAS

33

47

58

79

84

67

71

CNS TUMORS

27

ASTROCYTOMA

40

MEDULLOBLASTOMA

43

NEUROBLASTOMAS AND OTHER PNS TUMORS

39

85
52

26

67

70

NEUROBLASTOMAS

28

37

RETINOBLASTOMAS

71

48

95

97

58

86

88

86

89

RENAL TUMORS
NEPHROBLASTOMA

27

64

70

85

HEPATIC TUMORS

11

64

58

MALIGNANT BONE TUMORS

31

63

67

OSTEOSARCOMA

44

44

69

61

68

EWINGS AND RELATED SARCOMAS OF THE BONE

23

58

66

64

SOFT TISSUE SARCOMAS

36

66

71

RHABDOMYOSARCOMAS

13

36

68

65

64

GERM CELL TUMORS

36

38

87

89

89

OTHER MALIGNANT EPITHELIAL AND MELANOMAS

61

35

86

90

ALL CANCERS

 The decreased mortality rate of pediatric

cancers has been one of the major success
stories of medicine in the last 30 years.
Improvements in the survival rates of
leukemias, Hodgkin disease, and sarcomas
have been notable successes.
Most of these improvements can be traced to
the use of aggressive multimodal therapy and
The judicious use of blood products, use of
cytokines, and improved supportive care to
prevent and treat infections.

 The success of the treatment of pediatric cancer engenders

the new challenge of caring for the growing number of
cancer survivors.
The risk of a second cancer appearing within 20 years after
an initial diagnosis of cancer is approximately 8%.
The existence of this group also suggests that risk factors (eg,
treatment, heredity, other environmental factors) might be
identifiable.

Average Annual Number (AAN) of cases of cancer and cancer incidence rates standardized for world population
(ASR) in children 0 to 14 years of age
Population based cancer
registry

Male

Female

Total

AAN

% of all
cancer

ASR

AAN

% of all
cancer

ASR

AAN

% of all
cancer

ASR

Ahmedabad (Rural

15

3.8

51

1.9

23

20

3.1

38

Bangalore (Urban)
Barshi (Rural)

69
6

3.5
5.6

87
69

50
4

2.1
3.7

69
53

119
10

2.8
4.6

78
62

Bhopal (Urban)
Chennai (Urban)
Delhi (Urban)

16
78
335

3.1
3.9
6.5

58
150
146

13
47
152

2.8
2.2
3.1

55
97
76

29
125
487

2.9
3.0
4.8

57
124
113

Mumbai (Urban)

173

3.9

105

117

2.6

79

290

3.2

93

North East

25

1.2

39

34

2.1

51

59

1.6

45

Male to female ratio of major childhood cancer types in each population based cancer registry
Cancer type
(ICD 10 Code)

Ahmedabad

Bangalore

Barshi

Bhopal

Leukemia

0.95

1.20

1.86

0.69

Lymphoid leukemia (c91)

0.70

1.51

1.32

Myeloid leukemia (C92-94)

0.77

Leukemia unspecified (C95)

Lymphoma

Chennai

Delhi

Mumbai

North
East

1.55

2.26

1.21

1.09

0.81

1.64

2.60

1.26

1.32

0.29

0.92

1.79

1.54

0.46

0.32

2.99

0.62

1.82

1.44

0.82

1.41

4.29

1.56

11.26

3.25

4.93

2.19

0.75

Hodgkins disease (C81)

3.84

3.57

3.71

11.85

3.11

0.00

Non Hodgkins lymphoma

(C82-85, C96)

4.81

0.00

7.78

2.81

3.11

1.74

0.98

Brain, nervous system (C70-72)

1.66

2.09

0.31

1.74

1.37

1.65

0.00

Adrenal gland (C74)

0.27

0.81

1.81

1.23

0.00

Eye (C69)

0.60

0.90

0.92

1.10

1.90

0.95

1.17

Kidney (C64)

1.21

0.00

2.05

1.31

1.31

1.38

1.13

Liver (C22)

0.15

0.00

0.20

3.04

2.02

Bone (C40-41)

1.39

1.50

1.10

1.34

1.52

1.23

0.66

Connective and soft tissue (C47, C49)

0.83

0.82

0.91

1.53

0.82

1.62

Gonadal (C56, C62)

0.00

0.31

1.16

0.32

0.89

0.88

Other specified and unspecififed

1.63

0.83

0.55

5.91

1.12

4.42

0.92

0.31

All Sites

2.24

1.26

1.29

1.07

1.55

1.92

1.34

0.75

Five-year overall survival (expressed in percentage) of common childhood cancers in India, Europe and USA
Population registry data
Cancer type
(Categorized by the International Childhood
Cancer Classification)

Single Hospital

Population registry data

Bangalore

Chennai

Mumbai

Europe

USA

1982 to 1987

1990 to 2001

Various periods

1993 to 1997

1996 to 2004

77

81

Leukemia

36

Lymphoid leukemia

35

39

60

82

86

Acute myeloid leukemia

10

30

58

52

57

85

87

Lymphomas

55

Hodgkins disease

72

65

94

93

95

Non-Hodgkins lymphomas

33

47

58

79

84

67

71

CNS tumors

27

Astrocytoma

40

Medulloblastoma

43

Neuroblastomas and other PNS tumors

39

85
52

26

67

70

Neuroblastomas

28

37

Retinoblastomas

71

48

95

97

58

86

88

86

89

Renal tumors
Nephroblastoma

27

64

70

85

Hepatic tumors

11

64

58

Malignant bone tumors

31

63

67

Osteosarcoma

44

44

69

61

68

Ewing tumor and related sarcomas of the bone

23

58

66

64

Soft tissue sarcomas

36

66

71

Rhabdomyosarcomas

13

36

68

65

64

Germ cell tumors

36

38

87

89

89

Other malignant epithelial and melanomas

61

35

86

90