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Transcript of 1 Pediatric Cancer Update Gregory A. Hale, M.D. July 2015.
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1
Pediatric Cancer Update
Gregory A. Hale, M.D.July 2015
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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
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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%
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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%
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Cure Rate is Improving
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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
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Acute Lymphoblastic Leukemia
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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%
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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.
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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?
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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
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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
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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)
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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
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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%
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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
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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
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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
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0 2 14
1
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0.8
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0.2
0.1
Pro
bab
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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)
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Epidemiología de Cáncer
LymphomaLymphoma
14%14%
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Epidemiology
SEER Program 2006
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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
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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 + -- + -- + --
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Favorable Risk
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Event-free survivalAlylator-free regimens
VAMP PatientsEvent Free Survival
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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%
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Epidemiology
SEER Program 2006
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Non-Hodgkin Lymphomas
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Renal Tumors in Childhood
Tumor Type %
Wilms' Tumor 87%
Clear Cell Sarcoma 6%
Rhabdoid tumor 2%
Mesoblastic Nephroma
2%
Others 3%
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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
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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
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Scott, et al. J Med Genet, 2006, 43:705-715
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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
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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
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Metzger and Dome, The Oncologist (2005) 10:815-26
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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
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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)
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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)
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Brodeur and Maris in Principles and Practice of Pediatric Oncology, pp895-937
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Park et al. Pediatr Clin N Amer (2008) 55:97-120
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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)
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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
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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)
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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
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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
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Limb SalvageLimb Salvage
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Limb SalvageLimb Salvage
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Limb SalvageLimb Salvage
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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
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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
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Survival of Patients with Localized OS by Protocol
Survival of Patients with Localized OS by Protocol
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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
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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
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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%
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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
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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)
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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
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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
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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
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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
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Ewing Sarcoma Family of Tumors
H&E Stain CD99
Small round-cell tumor ~90% express MIC2 gene product
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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
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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
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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
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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
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Metastatic Ewing SarcomaPulmonary vs Extrapulmonary
CESS81, CESS86, EICESS92Paulussen et al, JCO 1998
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Pediatric Soft Tissue Sarcomas
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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
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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
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NRSTS Are More Common than RMS
39%
61%
RMSNRSTS
SEER Program 1975-1995, NCI
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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
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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)
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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
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Pediatric Brain Tumors
• Second most common malignancy in pediatrics• Most common solid tumor in pediatrics• ~3000+ new cases annually• Males > Females
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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
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Types of Brain Tumors Astrocytoma47%
Germ cell8%
Ependymoma9%
Other Glioma10%
MB/PNET22%
Craniopharyng4%
Other26%
Meningioma26%
Astrocytoma21%
GBM23%
Ependymoma2%
PNET2%
ADULT
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Relative Survival Rates (Age 0-19 Yr)
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Chang Staging System: Medulloblastoma
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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
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The Gap in AYA care
Albritton, Eur J Cancer 2003
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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
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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)
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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
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Cumulative Incidence of Chronic Health Conditions
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With an increasing population of childhood cancer survivors, there is a great need for long term follow-up care
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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
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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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