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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
04/21/23 2
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
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
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
ilit
y
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
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 1 2 3 4 5 6 7 8
Years from Diagnosis
Pro
bab
ilit
y
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
36
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
37
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
38
Pathology
39
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
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 18
Years from Diagnosis
Pro
bab
ilit
y OS-86 (n=37)
OS-91 (n=47)
P=0.78
Survival of Patients with Metastatic OSBy Protocol
Survival of Patients with Metastatic OSBy Protocol
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
Years from Diagnosis
Pro
babi
lity
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
61
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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