1. PEDITRIC ONCOLOGY AN INTRODUCTION
DR. K. S. REDDY
PROFESSOR OF RADIATION ONCOLOGY, MGMC & RI, PONDICHERRY

3. 13% DEATHS WORLD WIDE ARE CANCER RELATED
70% OF THESE OCCUR IN LOW/MIDDLE INCOME COUNTRIES
FOCUS IN OUR COUNTRY IS ON
CERVICAL CANCER, BREAST CANCER,
ORAL CAVITY/OROPHARYNGEAL CANCER
PALLIATIVE CARE

4. CHILD HEALTH CANCER IS NOT YET A MAJOR FOCUS AREA
PRIORITY HEALTH ISSUE
REDUCTION OF MORTALITY IN INFANTS/UNDER FIVES
PROMOTION OF BREAST FEEDING
RATIONAL ANTIBIOTIC THERAPY
ORAL REHYDRATION THERAPY
IMMUNIZATION PROGRAM ETC.
CANCER IS NOT YET A MAJOR FOCUS AREA

5. 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

6. In UK 0.5% of all cancers are seen in children
(18% Population ARE CHILDREN)
IN US 1% OF ALL CANCERS ARE SEEN IN CHILDREN
( 24% POPULATION ARE CHILDREN)
IN INDIA IT VARIES FROM 1.6 TO 4.8%
(33% POPULATION ARE CHILDREN)

7. 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.

8. INCIDENCE AROUND THE WORLD VARIES FROM 75-150 PER MILLION CHILDREN
IN INDIA PER MILLION CHILDREN
Highest reported from Chennai
Lowest from rural Ahmedabad
Other NCRs (Mumbai, Bangalore, Delhi, Bhopal) is generally higher than in rural areas

10. VARIATION BY SEX MORE COMMON AMONG MALES
Incidence in males :39-150/ million children
Incidence in females: 23-97/million children
Male:Female = 1.2:1.0
It is highest in Delhi
Some cancers like Retinoblastoma, Wilms’ tumor,
Osteosarcoma, Germ cell tumor more in females
This ratio is much higher than in the developed world – Gender bias in seeking health care
In North East it is higher in females

11. Male to female ratio of major childhood cancer types in each population based cancer registry
(ICD 10 Code)
Ahmed-abad
Bangalore
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
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
Hodgkin’s disease (C81)
3.84
3.57
3.71
11.85
3.11
0.00
Non Hodgkin’s lymphoma
(C82-85, C96)
4.81
7.78
2.81
1.74
0.98
Brain, CNS(C70-72)
1.66
2.09
0.31
1.37
1.65
Adrenal gland (C74)
0.27
1.81
1.23
Eye (C69)
0.60
0.90
1.10
1.90
1.17
Kidney (C64)
2.05
1.31
1.38
1.13
Liver (C22)
0.15
0.20
3.04
2.02
Bone (C40-41)
1.39
1.50
1.34
1.52
0.66
Connective & soft tissue (C47, C49)
0.83
0.91
1.53
1.62
Gonadal (C56, C62)
1.16
0.89
0.88
Other specified and unspecified
1.63
0.55
5.91
1.12
1.42
All Sites
2.24
1.29
1.07
1.92

12. GLOBOCAN-2012- INDIA CHILDHOOD CANCER BOTH SEXES AGE ADJUSTED

13. Variation by Cancer Type
25-40% are Leukaemias
85% of these are ALL
T-cell ALL predominates- Related to Lower socio economic status
Lymphomas are more common
Hodgkin’s L exceeds NHL particularly in Males
NHL is more commonly T-Cell
In developed world 25% are CNS tumors
It is around 10% in India

14. CHILDHOOD CANCERS AT JIPMER - 2012/13
S.NO
DIAGNOSIS
2012
2013 1.
ALL 36 40 2.
AML 9 07 3.
CML 3 01 4.
CNS 15 11 5.
GCT 6 06 6. HL 14 7.
HCC 2 02 8.
LCH 4 03 9.
NEUROBLASTOMA 5 04
10.
NON-HODGKIN’S LYMPHOMA
11.
NASOPHARYNGEAL 09
12.
OSTEO SARCOMA 10
13.
PNET
14.
RETINOBLASTOMA
15.
RMS 05
16.
SKIN CANCER
17.
STOMACH 1
18.
SIGMOID COLON
19.
WILM’S TUMOR
TOTAL
123
134

15. Cancer Predisposition Factors
The increased numbers of adults with cancer 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

16. At its most basic level, cancer is a genetic disease
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

17. 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.

18. 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

19. 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.

20. 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

21. 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
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.
Asmany as 40% of individuals with Wilms tumor have some familial component

22. 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.

23. 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)

24. 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.

25. 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

26. 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.

27. 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.

28. 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

29. 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.

30. 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)

31. 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.[

32. 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.

33. 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

34. 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

35. Renal Tumors
Wilm’s 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; Denys-Drash 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.[

36. 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.

37. 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, Beckwith-Wiedemann, and neurofibromatosis have all been reported

38. 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

39. 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%)

40. Population registry data
Five-year overall survival (expressed in percentage) of common childhood cancers in India, Europe and USA
Cancer type
(Categorized by the International Childhood Cancer Classification)
Population registry data
Single Hospital
Bangalore
Chennai
Mumbai
Europe
USA
1982 to 1987
1990 to 2001
Various periods
1993 to 1997
1996 to 2004
Leukemia 36 77 81
Lymphoid leukemia 35 39 60 82 86
Acute myeloid leukemia 10 30 58 52 57
Lymphomas 55 85 87
Hodgkin’s disease 72 65 94 93 95
Non-Hodgkin’s lymphomas 33 47 79 84
CNS tumors 27 67 71
Astrocytoma 40
Medulloblastoma 43
Neuroblastomas and other PNS tumors 26 70
Neuroblastomas 28 37
Retinoblastomas 48 97
Renal tumors 88
Nephroblastoma 64 89
Hepatic tumors 11
Malignant bone tumors 31 63
Osteosarcoma 44 69 61 68
Ewing’s and related sarcomas of the bone 23 66
Soft tissue sarcomas
Rhabdomyosarcomas 13
Germ cell tumors 38
Other malignant epithelial and melanomas 90
All Cancers 75

41. 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.

42. 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.

43. Thank You