1

Pediatric Cancer Update

Gregory A. Hale, M.D.July 2015

Pediatric Cancer

• Worldwide, every 3 minutes a child is diagnosed with cancer

• 1/285 children in US will be diagnosed with cancer before 20 years of age

• 15,400 new pediatric cancer cases per year• 2nd leading cause of death in childhood after

accidents• 1% of all new cancer diagnoses in the US• Pediatric cancer is much different than adult cancer

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Distribution of Cancer Diagnoses: 0-14 Years

ALL23.5%

AML4.7%

Brain22.1%

Neuroblastoma7.9%

Wilms' tumor6.0%

NHL5.7%

Hodgkin's3.6%

Rhabdomyosarcoma3.6%

Non-RMS3.5%

Germ cell (gonadal)3.5%

Retinoblastoma3.2%

Osteosarcoma2.6%

Other 10.1%

Pediatric vs Adult Cancer

Pediatric Adult

New cases per year 15,780 1,658,370

Age at diagnosis 6 years 67 years

Tumor types Embryonal Carcinoma

Diseases Leukemia/CNS Breast/Lung/Prostate

Somatic mutations Limited Abundant

Survival rate 80% 50%

Deaths per year 1,960 589,430

Research funding (% NCI budget)

4% 96%

Cure Rate is Improving

Hereditary Component of Pediatric Malignancies

Tumor Type Hereditary component (%)

Adrenocortical carcinoma 50-80

Optic glioma 45

Retinoblastoma 40

Pheochromocytoma 25

Wilms tumor 3-5

CNS neoplasm <1-3

Leukemia 2.5-5

Acute Lymphoblastic Leukemia

Genetic Classification of ALL

T-lineage

Hyperdiploidy>50 chromosomes

25% TEL-AML1t(12;21)

22%

Hypodiploidy<45 chromosomes

1%

Others22%

E2A-PBX1t(1;19)

5%

HOX1110q240.7%

TAL1Ip327%

HOX11L25q352.5% LYL1

19p131.5%

MLL rearrangementse.g. t(4;11),t(11;19),

t(9;11)8%

BCR-ABLt(9;22)

3%

B-lineage

MLL-ENL0.3%

Pui CH et al, NEJM, 350:1535-48,2004

MYCt(8;14), t(2;8),t(8;22)2%

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 2 4 6 8 10 12 14 16

91%±3% Hyperdiploidy >50 (n=205)

32%±12% MLL-AF4 (n=15)

37%±12% BCR-ABL (n=22)

73%±5% T-cell (n=135)

82%±3% Other B-lineage (n=261)

86%±7% E2A-PBX1 (n=40)

89%±3% TEL-AML1 (n=163)

Years from Diagnosis

EFS According to Genotype and Phenotype

Pui et al. Lancet 2008;371:1030-43.

Gene Expression Profiling Identifies Markers for Minimal Residual Disease Detection

Gene expression profile of ALL cells and normal CD19+CD10+ cells

Gene filters (~4,000 probes)

GeneChip (~23,000 probes)~300 ALL samples hybridized

4 ALL samples hybridized → CD58

MRD +

MRD –

Use of 9+ color flow cytometry

Increase sensitivity of MRD detection

0.04%

Study biologic features of MRD

Stem cells?

Potential of Pharmacogenomics

1

2Treat with alternative

drug or dose

Treat with conventionaldrug or dose

Genetic profile fornon-response

or toxicity

Genetic profile forfor favorable response

0

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0.8

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0 1 2 3 4 5 6 7 8

Years From Start of Treatment

Pro

bab

ility

Event-free Survival86 ± 3.6%

Isolated CNS Relapse3.1% ± 1.1%

Survival 94% ± 2.3%

N=501

Survival Outcomes for ALL

Treatment Outcome According to MRD at Remission

MRD level No. Patients 5-year EFS (SE)

0.01% to <1% 49 81 (11)

1% to 5%

>5%

9

6

46 (34)

50 (35)

Proteins involved in differentiation

• AML1 Fusion (AML1-ETO) or PM• CBF Fusion (CBF-MYH11)• PML Fusion (PML-RAR)• MLL Fusion (e.g., MLL-AF9)• HOX Fusion or mutation• C/EBP Mutation• PU.1 Mutation• GATA1 Mutation

Heterogeneity of AML: Genetics

Other MLL11q23

8%

Translocation not identified

22%RMB15-MKL1

t(1;22)1%

Monosomy 71%

Random25%

PML-RARPLZF-RAR

t(15;17) t(11;17)8%

MLL-AF9t(9;11)

8%

DEK-CANt(6;9)1%

AML-ETOt(8;21)12%CBF-MYH11

inv(16)10%

NPM-MLF1t(3;5)1%

EVl1t(3;v)2%

Population-Based Registry (SEER) 5-Year Survival (%)

Diagnosis 83-85 86-88

89-91 92-97 Now

AML 34.4 31.7 38.5 41.1 50%

ALL 66.7 75.4 77.3 82.8 90%

http://seer.cancer.gov/Publications/CSR1973_1998/child.pdf

AML97 (n=40)

AML87 (n=41)

AML91 (n=63)

AML80 (n=65)

AML83 (n=45)

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

00 5 10 15 20 25

Time (years)

Results of Serial AML Trials

0 2 14

1

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

Pro

bab

ilit

y

4 6 8 10 12

p = 0.004

FLT3-WT (n=83)

FLT3-ITD (n=20)10% ± 7%

43% ± 6%

Years from diagnosis

EFS in AML Patients by FLT3 Status

0

0 2 14

1

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

Pro

bab

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4 6 8 10 12

70% ± 15%

Years from diagnosis

EFS of AML Patients With inv(16)

11% ± 7%

16 180

1988-1996 (n=10)

1980-1987 (n=9)

Epidemiología de Cáncer

LymphomaLymphoma

14%14%

Epidemiology

SEER Program 2006

NS

45%

LP

17%

MC

32%

Other

6%

NS

72%LP

10%

LD

2%

MC

13%Other

3%

Age 10 Age 11-15

PathologyDistribution of Histologic Subtypes

NS=nodular sclerosingMC=mixed cellularity

LP=lyphocyte predominantLD=Lymphocyte depleted

What is favorable risk?

IA IB IIA Extranodal extension

“E”

Peripheralbulk

Mediastinalbulk

Comment

COG + -- + -- -- --

GPHOD + + + + + +

SJ + -- < 3 -- + --

CCG + + < 5 -- < 10 cm -- No hilar

adenopathy

POG + -- + -- + --

Favorable Risk

Event-free survivalAlylator-free regimens

VAMP PatientsEvent Free Survival

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Years from Diagnosis

Pro

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2 - year EFS 94.8% ± 3.1%3 - year EFS 90.6% ± 4.6%

3 year OS 100% ± 4.6%

Epidemiology

SEER Program 2006

Non-Hodgkin Lymphomas

Renal Tumors in Childhood

Tumor Type %

Wilms' Tumor 87%

Clear Cell Sarcoma 6%

Rhabdoid tumor 2%

Mesoblastic Nephroma

2%

Others 3%

Wilms’ Tumor

• AKA nephroblastoma• Most common renal malignancy of childhood• Arises from embryonic nephroblastic cells• May also see nephrogenic rests

– Persistent embryonal nephroblastic tissue– 1% of normal children– 35% of children with unilateral WT– Almost 100% of children with bilateral WT

“Renal Tumors” in Principles and Practice of Pediatric Oncology, pp 865-893

Wilms’ Tumor Epidemiology

• Incidence: 8.1 cases/million <15 years of age– 500 cases/yr in US

• 5-6% of childhood cancers in US

• Blacks > Whites > Asians

• Male:Female is .92:1 with males presenting earlier

• Age: Unilateral Bilateral

Males 41.5 mo 29.5 mo

Females 46.9 mo 32.6 mo

Scott, et al. J Med Genet, 2006, 43:705-715

Patterns of SpreadLocal:• Through renal capsule-into perirenal fat• Blood vessels-tumor thrombi• Regional lymph nodesHematogenous Metastases:• Lung (80% only lung if mets exist)• Liver (15%)• brain/bone for CCSK and RTK

Wilms Tumor Pathology

• Favorable Histology– Blastemal– Epithelial– Stromal

• Unfavorable Histology (5-10%)– Anaplasia

• Multipolar polypoid mitotic figures

• Enlarged, hyperchromatic nucleii

– May be focal or diffuse

Metzger and Dome, The Oncologist (2005) 10:815-26

Neuroblastoma

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Opsoclonus Myoclonus Ataxia “Dancing eyes, dancing feet”

• 2-3% of children with neuroblastoma• 50% of children with this triad have neuroblastoma• Majority between 1-3 years old• Mainly favorable biology and localized tumors• Immunologically mediated, anti-Hu antibody• Treatment with immunosuppressive therapy

– Rituximab, IVIG, steroids

• 1/3 had normal intelligence and asymptomatic– Worse prognosis with more severe presentation, younger age

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Diagnostic criteria

• One of 2 criteria must be met: – Diagnostic histopathology of primary tumor or metastasis OR– Bone marrow metastases AND elevated urine HVA and/or VMA

• For patients with metastatic disease: – < 18 months: Biopsy is necessary for prognostic tests (MYCN,

pathology, ploidy) – > 18 months: Biopsy IS NOT necessary if the second criterion is

met

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Pathology

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Epidemiology

• A “common” pediatric solid tumor– Most common solid tumor before age 1– Most common extracranial solid tumor – 1/10,000 births– 11/1,000,000 children/year– Accounts for 15% of pediatric cancer deaths

• Diagnosed prenatally in some cases– median age at diagnosis is 2 years– 36% < age 1, 88% < age 5, 97% < age 10– 1/200 children <1 year have ‘neuroblastoma in situ’ in the

adrenal gland

Heme/Onc Annals 1(3):189-201, 1993 Pediatric Onc Text p. 762

Staging (INSS)

• 1: localized tumor, GTR• 2A: localized tumor, gross residual dz• 2B: localized tumor + ipsilateral nodes

(resectable or not)• 3: Tumor crosses midline and unresectable or

localized + contralateral nodes• 4: Distant dissemination• 4S: <1 yr w/ localized primary + dissemination

limited to skin, liver, or marrow (<10% nucleated cells)

Determinants of Prognosis

• Age of patient (<1 better)• Stage of disease (lower better)• Histopathology• MYCN gene copy number (not amp)• DNA index (hyperdiploid better)• Other: LOH of 1p or 11q, TRK family

expression, ferritin, LDH, NSE, location of tumor (?thoracic better), sites of metastases (bone worst)

Brodeur and Maris in Principles and Practice of Pediatric Oncology, pp895-937

Park et al. Pediatr Clin N Amer (2008) 55:97-120

High-Risk Neuroblastoma Treatment

Phase Objective Treatment

Induction Reduction amount of cancer cells

Chemotherapy (CDDP,ETO,DOX,CYC)

Hematopoietic stem cell harvest, (purging) and cryopreservation

Surgery +/- RT Consolidation Erradication of cancer

cells Myeloablative therapy +

Auto-HSCT

Post-Consolidation

Erradication of minimal residual disease

Biological therapy (13-cis-retinoic acid, antibodies, vaccines)

3891: Survival According to First and Second Randomization

0

0.25

0.5

0.75

1

0 2 4 6 8 10 12

YEARS

ABMT + Cis-RA

ABMT + No Cis-RA

CC + Cis-RA

CC + No Cis-RA

Matthay et al, NEJM 1999 341:1165-73

OtherMFHChondrosarcoma

Ewing's sarcoma

Osteosarcoma

Other 13 (2.0%)

MFH 10 (1.5%)

Chondrosarcoma 11 (1.7%)

Ewing’s sarcomafamily of tumors

253 (38%)

Osteosarcoma377 (57%)

Pediatric Malignant Bone Tumors by Histology(n=664)

Sixth most common malignant neoplasm in children; third most common in adolescents

~400 patients <20 yr diagnosed each yr in US

Peak incidence in second decade of life

More common in males

EpidemiologyEpidemiology

TreatmentTreatment

Surgery is the primary treatment Limb salvage Amputation

Chemotherapy Preoperative Adjuvant Active agents include doxorubicin, cisplatin,

HDMTX, ifosfamide, and carboplatin in combination with ifosfamide

Radiation has a limited role

Limb SalvageLimb Salvage

Limb SalvageLimb Salvage

Limb SalvageLimb Salvage

Presurgical Chemotherapy

Facilitates limb salvage

Time to fabrication of customized prosthesis

Histologic evaluation of tumor response

Early treatment of micrometastasis

Custom-tailoring of postoperative chemotherapy

Rosen GradingRosen Grading

Grade I < 50% tumor necrosis Grade II 50 % and < 90% tumor

necrosis Grade III 90 % tumor necrosis with

some foci of viable tumor Grade IV 100% necrosis - no viable tumor

Survival of Patients with Localized OS by Protocol

Survival of Patients with Localized OS by Protocol

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Years from Diagnosis

Pro

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OS-91 (n=47)

P=0.78

Survival of Patients with Metastatic OSBy Protocol

Survival of Patients with Metastatic OSBy Protocol

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Years from Diagnosis

Pro

babi

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P=0.046

OS-86 (n=12)

OS-91 (n=17)

5-year estimates

OS-86: 41.7% ± 13.0%

OS-91: 11.8% ± 6.4%

Daw et al, Cancer 2006

Study (yr) N Chemotherapy EFS Survival

St. Jude OS99 7272 Carbo/Ifos/Doxo 2 yr 75%±5% 2-yr 87%±4%

P97542004

111111

5454

5656

CDDP/Doxo 600 mg/m2/HDMTX

CDDP/Doxo 600 mg/m2/HDMTX+Ifos

CDDP/Doxo/HDMTX+Ifos/VP-16

2-yr EFS 69%

INT 0133POG-9351CCG-7921(2005)

677 CDDP/Doxo/HDMTXCDDP/Doxo/HDMTX+MTPCDDP/Doxo/HDMTX+IfosCDDP/Doxo/HDMTX+Ifos+MTP

3-yr EFS 71%3-yr EFS 68%3-yr EFS 61%3-yr EFS 78%

POG-8651(2003) 55

45

CDDP/Doxo/HDMTX Surgery week 0 vs.Surgery week 10

5-yr EFS 69%5-yr EFS 61%

5-yr S 79%5-yr S 76%

St. Jude OS-91(2001)

47 Carbo/Ifos/Doxo/HDMTX 5-yr EFS 66% 5-yr S 75%

T12(1998)

3130

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HDMTX/BCD/CDDP/DoxoHDMTX/BCD/CDDP/Doxo (more intensive preop chemo)Both regimens

5-yr EFS 73%

5-yr EFS 78%5-yr EFS 76%

IOR/OS-4(2001)

133 HDMTX/CDDP/Doxo/Ifos 5-yr EFS 56% 5-yr S 71%

SSG VIII(2003)

113 HDMTX/Doxo/CDDP 5-yr EFS 61% 5-yr S 74%

EOI(2003)

250254

CDDP/doxo q 3 weeks vs. CDDP/doxo+G-CSF q 2 weeks

3-yr PFS 41%3-yr PFS 46%

3-yr S 64%3-yr S 67%

A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on

Histological Response to Pre-operative Chemotherapy

A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on

Histological Response to Pre-operative Chemotherapy

RE

GIS

TE

R

MAP

SU

RG

ER

Y

MAPIfn

MAP

GR

RANDOM I ZE

MAP

MAPIE

RANDOMI

ZE

POOR

Authors N EFS OS

Marina 1992

St. Jude18

50%

(3 years)

Meyers 1992

N.Y.62

11%

(5 years)

Pacquement 1996

France73 15%

Harris 1998

POG30

46.7%

(5 years)

53.3%

(5 years)

Ferguson 2001

COG36

24%

(3 years)

32%

(3 years)

Goorin 2002

POG41

43%

(2 years)

55%

(2 years)

Kager 2003

COSS202

31%

(5 years)

Petrilli 2006

Brazil41

12.2%

(5 years)

12.2%

(5 years)

Daw 2006

St. Jude29

6.9%

(5 years)

24.1%

(5 years)

Ewing Sarcoma Family of TumorsEwing Sarcoma Family of Tumors

Ewing SarcomaExtraosseous Ewing Sarcoma

Peripheral NeuroepitheliomaPrimitive Neuroectodermal Tumor

Askin Tumor

EWS-FLI1EWS-ERG

Exact cell of origin unknown

Translocation Gene Fusion Incidence (%)

t(11;22)(q24;q12) EWS-FLI1 80-95%

t(21;22)(q22;q12) EWS-ERG 5-10%

t(7:22)(p22;q12) EWS-ETV1 rare

t(17;22)(q12;q12) EWS-EIAF rare

t(2;22)(q33;q12) EWS-FEV rare

Chromosomal Translocations in ESFTEWS-ETS

Ewing SarcomaEwing Sarcoma

Age 5–25 years Peculiar predilection to white persons Diaphysis of bone, soft tissue 25% of patients have metastatic disease

at diagnosis Metastatic sites: lung, bone, bone

marrow

Clinical PresentationClinical Presentation

Pain Mass Pathologic fracture–tumors of long bones Fever and weight loss often indicate

metastatic disease Petechiae or purpura–bbone marrow

metastasis Neurologic symptoms/signs Respiratory symptoms/signs–chest wall

tumors

Ewing Sarcoma Family of Tumors

H&E Stain CD99

Small round-cell tumor ~90% express MIC2 gene product

Treatment and OutcomeTreatment and Outcome Chemotherapy: alternating cycles of

vincristine/doxorubicin/cyclophosphamide with ifosfamide/etoposide

Local control Surgery Radiotherapy in absence of minimally morbid

surgery DFS for patients with localized disease ~70% 20%–25% of patients with metastatic disease

survive 5 years

Local ControlLocal Control

Surgery Wide local excision has superior outcome Selection bias: small, peripheral tumors Local failure rates < 10%

Surgery + XRT Positive margins Local failure rates 10-15% Dose: 40-45 Gy

Definitive XRT Higher local failure rates: 10-30% Direct correlation with tumor size Dose: 55-60 Gy

Treatment of Newly-diagnosed Ewing Sarcoma orPrimitive Neuroectodermal Tumor of Bone or Soft

TissuePOG 9354/CCG 7942 Intergroup StudyRegimen A (weeks)

0VDC

3IE

6VDC

9IE

12VDC

15IE

18IE

21VDC

24IE

27VDC

30IE

33V C

36IE

39V C

42IE

45V C

48V C

Local Control

Regimen B (weeks)

0VD

C*

1V

2V

3IE

6VD

C*

7V

8V

9IE

12VDC

15IE

18IE

21VDC

24IE

27VDC

30IE

Local Control

Regimen A:V = Vincristine 1.5 mg/m2

D = Doxorubicin 75 mg/m2 over 48 hrsC = Cyclophosphamide 1.2 gm/m2

E = Etoposide 100 mg/m2/day X 5 I = Ifosfamide 1.8 gm/m2/day X 5G-CSF 5 g/kg/day

Regimen B:C* = Cyclophosphamide 2.1 gm/m2/day X 2 I = Ifosfamide 2.4 gm/m2/day X 5

VariableVariable Overall SurvivalOverall Survival Event-free SurvivalEvent-free Survival

RR (95% CI)RR (95% CI) p-valuep-value RR (95% CI)RR (95% CI) p-valuep-value

Age< 13.7† (Median)≥ 13.7

1.59 (1.08 – 2.33) 0.018 1.45 (1.02 – 2.06) 0.041

Tumor mass size< 8 cm†

> 8 cm1.53 (1.01 – 2.30) 0.044 1.61 (1.10 – 2.36) 0.015

StageLocal diseaseMetastatic disease

2.88 (1.96 – 4.22) <0.001 2.66 (1.85 – 3.82) <0.001

Prognostic FactorsMultiple Cox Regression

Metastatic Ewing SarcomaPulmonary vs Extrapulmonary

CESS81, CESS86, EICESS92Paulussen et al, JCO 1998

Pediatric Soft Tissue Sarcomas

Nomenclature

Skeletal muscle rhabdomyosarcoma

Fat liposarcoma

Smooth muscle leiomyosarcoma

Blood/lymphatic vessels angiosarcoma/hemangiopericytoma

Bone extraosseous osteosarcoma

Peripheral nerves malignant peripheral nerve sheath tumor

Cartilage extraskeletal chondrosarcoma

Fibrous tissue fibrosarcoma

Synovium synovial sarcoma

Melanocytes clear cell sarcoma

sarc = flesh oma = tumor

Distribution of Childhood Cancers

25%

17%

16%7%

7%

6%

5%

4%

13%Leukemia

CNS Tumor

Lymphoma

Soft Tissue Sarcoma

Germ Cell Tumor

Bone Tumor

Neuroblastoma

Wilms' Tumor

Other

SEER Program 1975-1995, NCI

NRSTS Are More Common than RMS

39%

61%

RMSNRSTS

SEER Program 1975-1995, NCI

All types Ionizing radiation Li-Fraumeni syndrome (constitutional p53 mutation) Hereditary retinoblastoma Werner syndrome

RMS Neurofibromatosis, type I Beckwith-Wiedemann syndrome Costello syndrome Cardio-facio-cutaneous syndrome

NRSTS Neurofibromatosis, type I (MPNST) HIV (leiomyosarcoma) Gorlin syndrome (fibrosarcoma, leiomyosarcoma) Chronic lymphedema (lymphangiosarcoma)

Risk Factors

IRSG Clinical Trials Have Improved Outcome

01020304050607080

Overall Survival

Prior to IR

S-I

IRS-I (1972-1978)

IRS-II (1978-1984)

IRS-III (1984-1991)

IRS-IV (1991-1997)

RMS Risk Groups Low risk (survival ~ 90%)

All embryonal tumors except those in unfavorable primary sites that have been incompletely resected

Intermediate risk (survival ~ 70%) All non-metastatic alveolar tumors All embryonal tumors not classified as low or high

risk

High risk (survival ~ 10-20%) Metastatic alveolar tumors

Pediatric Brain Tumors

• Second most common malignancy in pediatrics• Most common solid tumor in pediatrics• ~3000+ new cases annually• Males > Females

Brain Cells…..Brain Tumors

1. Neurons………………….. Ganglioma2. Glia………………………...Glioma

– Astrocytes…………...Astrocytoma– Oligodendrocytes…..Oligodendroglioma– Ependyma…………... Ependymoma

3. Pituitary gland………….Pituitary adenoma/carcinoma4. Choroid plexus………... Choroid plexus adenoma/ca.5. Meninges……………….. Meningioma6. Blood vessels…………..Hemangioma7. Other…………………….. Medulloblastoma/PNET Germ cell tumors Craniopharyngioma

Types of Brain Tumors Astrocytoma47%

Germ cell8%

Ependymoma9%

Other Glioma10%

MB/PNET22%

Craniopharyng4%

Other26%

Meningioma26%

Astrocytoma21%

GBM23%

Ependymoma2%

PNET2%

ADULT

Relative Survival Rates (Age 0-19 Yr)

Chang Staging System: Medulloblastoma

Adolescent Young Adult Cancer (AYA)

• Higher incidence of cancer than in younger ages• Sarcoma, Testicular cancer, Hodgkin disease,

Melanoma, Thyroid cancer• Has lagged behind other age groups in

improvements in survival in the last 3 decades• Tumor biology, compliance, denial, health

insurance may play roles

The Gap in AYA care

Albritton, Eur J Cancer 2003

Cancer Survivorship

• Nearly 80% of children diagnosed with cancer become long-term survivors (> 5 years from diagnosis)

• In 2000, 1 in 900 adults was a survivor of pediatric cancer

• The number of survivors is growing by about 15,000 children per year

Childhood Cancer Survivor Study (CCSS)

• Multi-institutional epidemiologic follow-up study• 5+ year survivors of childhood cancer• Diagnosed at age < 21 years between 1970-1986

• Advantage: thousands of patients• Disadvantage: therapies have evolved

(i.e. less use of radiation)

Late Effects

• Only 1/3 of survivors were free of long term problems

• 62% had chronic health condition• Survivors were 3.3 x more likely to have a

chronic condition and 8.2 x more likely to have a severe or life-threatening condition than their siblings.

Oeffinger, et al. NEJM 2006

Cumulative Incidence of Chronic Health Conditions

With an increasing population of childhood cancer survivors, there is a great need for long term follow-up care

5-Year Survival of Patients with Cancer by Era, SEER, 1975-1998

Age at Diagnosis (Years)

40

50

60

70

80

0 10 20 30 40 50 60 70

Year of Diagnosis

1993-98

1987-92

1981-86

1975-80

Survival (%)

20042004ProjecteProjectedd

Peak to Valley Transformation

Conclusions

• Pediatric is an uncommon disease but accounts for significant loss of life

• Clinical research has been and is a HUGE part of pediatric cancer, being responsible for the marked increase in survival

• Adolescents and young adult cancer patients have not benefited as much from clinical research

• Majority of children will become survivors but monitoring for late effects is needed

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