State of the Art Radiotherapy for Pediatric...
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State of the Art Radiotherapy for Pediatric Tumors
Suzanne L. Wolden, MDSuzanne L. Wolden, MDMemorial SloanMemorial Sloan--Kettering Cancer CenterKettering Cancer Center
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Introduction
• Progress and success in pediatric oncology• Examples of low-tech and high-tech radiation
solutions in common pediatric cancers– Hodgkin lymphoma– Neuroblastoma– Rhabdomyosarcoma– Medulloblastoma
• Global perspective
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Distribution of pediatric malignancies
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Pediatric cancer cure rates
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Evolution of radiation techniques• External beam radiation therapy
– Co-60 2D linac 3D treatment– Stereotactic radiosurgery– Intensity modulated radiation therapy (IMRT)– Protons, electrons, other particles– Image guided radiation therapy (IGRT)
• Brachytherapy– Permanent seeds– Remote afterloading: LDR -> HDR– Intraoperative radiation therapy (IORT)
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7 year old boy with Hodgkin lymphomafrom Reed’s 1902 paper
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1970 1995 2009
Total Lymphoid Irradiation (TLI)
44 Gy
Involved-Field Radiation(IFRT)21 Gy
Involved Node Radiation (INRT)21 Gy
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CCG 5942 Hodgkin lymphoma trial
• Chemotherapy by stage of disease• Randomization +/- 21 Gy IFRT• Study closed at 1st interim analysis
– 3 year EFS 93% vs 85% favoring RT (p<.01)– all subgroups benefitted from radiation
Nachman et al. JCO 20:3765, 2002
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Hodgkin lymphoma techniques
• Advances in imaging (PET) have significantly impacted RT field design
• IMRT and protons have no obvious benefit over AP/PA fields for most cases
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Neuroblastoma
• 650 cases per year in U.S.• Majority of patients are < 5 years of age• Radiation is used for primary site, lymph nodes,
and bone metastases in high risk patients• Local control 90% at primary site with RT• Most effective palliative therapy for metastases
Kushner et al., JCO (2001) 19:2821-28
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Stage 4 neuroblastoma (>1 year age): treatment outcome
Months from diagnosis
250200150100500
Pro
porti
on a
live
prog
ress
ion-
free
1.2
1.0
.8
.6
.4
.2
0.0
N7=CAV/PV + 131I-3F8 + 3F8N6=CAV/PV + 3F8
N5=CAV/PV + ABMTN4=CAV + ABMT
N4 (80’s)
N6 (89-94)
N5 (87-89)
N7 (94-99)
Cheung et al, Med Ped Onc 36:227, 2001
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Neuroblastoma: primary site 21 Gy
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Neuroblastoma bone metastases: Brain sparing whole skull RT
4 months
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Pretreatment right adrenal primary tumor
Local recurrence after chemotherapy, surgery
and 21 Gy external beam
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Intraoperative radiation therapy
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Rhabdomyosarcoma
• The most radiosensitive sarcoma• Majority of patients (in the U.S.) receive RT
– Definitive local control for Group III– Post-operatively
• Group I (alveolar or undifferentiated histology)• Group II (positive margins)• Group III (after second look surgery)
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Survival by treatment era
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Log Rank Test: p<0.001
Extremity
GU B/P
GU non-B/P H & N
Orbit
Other PM
Failure-free survival for local/regional tumors by primary site
0.00.10.20.30.40.50.60.70.80.91.0
Years0 1 2 3 4 5 6
Failu
re-fr
ee S
urvi
val
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IRS IV (1991-1997)
• 5-yr local control for Group III RMS– Extremity 96% – Orbit 95%– Bladder/prostate 90%– Head and neck 88%– Parameningeal 84%– Other 90%.
Crist et al. JCO 19:3091, 2001Donaldson et al. IJROBP 51:718, 2001
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RT for PM RMS at age 4 in 1978
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Failure-free survival for patients with Group III tumors by radiation schedule
Years
Log Rank Test: p=0.76
Hyperfractionated
0.00.10.20.30.40.50.60.70.80.91.0
0 1 2 3 4 5
Conventional
Failu
re-fr
ee S
urvi
val
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FDG-PET scan for staging MSKCC experience
• 21 patients, 84 sites evaluated pre-treatment– correlated with standard imaging and pathology– all primary tumors PET positive– sensitivity 81%
• some missed nodal and bone metastases– specificity 97%– Therapy altered in 3 of 21 (14%) cases
• due to LN involvement detected only on PET
Klem et al. J Pediatr Hematol Oncol 29:9, 2007
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• 2 year old with alveolar rhabdomyosarcoma of the left thigh.
• PET scan shows pelvic node involvement
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IRS V (1999-2004)
• Experimental dose reductions for selected patients:– Group I alveolar/undifferentiated: 41.1 -> 36 Gy– Group II N0: 41.4 -> 36 Gy– Group III orbit/eyelid: 50.4 -> 45 Gy– Group III “second look surgery”– negative margins: 50.5 -> 36 Gy– microscopically + margins: 50.4 -> 41.4 Gy– Group III requiring 50.4: eligible for “conedown”
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IMRT for H&N rhabdomyosarcoma
• 28 patients, median age 8 (1-29) years• Primary sites
– 21 parameningeal• 71% with intracranial extension (ICE)
– 4 other head and neck and 3 orbit• Tumor greater than 5 cm: 57%• Involved regional lymph nodes: 25%
Wolden et al. IJROBP 61: 1432, 2005
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Local control with IMRT
0102030405060708090
100
0 1 2 3 4 5 6Years
% L
ocal
Con
trol
p = 0.60
parameningeal
orbit/head &neck
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Fusion of CT, MRI, and PET Scans
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Infratemporal fossa with PM extension
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Results:• Improved dose conformality of protons spared most normal
tissues examined except for a few ipsilateral structures such as the parotid and cochlea.
Parameningeal RMS: Dose Comparison (IMRT v Protons)
(Kozak, Yock, in press IJROBP)
% Dose10510080604020
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Bone sparing for soft tissue sarcoma
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Ewing sarcoma: Askin tumor + whole lung
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IMRT for Osteosarcoma of C2
100%90%70%50%
PTVCord
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Whole Abdomen / Pelvis IMRTfor DSRCT
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Whole Abdomen / Pelvis IMRTfor DSRCT
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Lower Eyelid RMS
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Custom Eye Shield
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Electron set-up
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Extremity brachytherapy
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Interstitial Tongue Brachytherapy
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Medulloblastoma
• Common brain tumor in the posterior fossa• Requires craniospinal radiation & chemotherapy• Survival is 60-85% depending upon stage• IMRT or protons can be used for the “boost” to
spare inner ears and other normal tissues
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Medulloblastoma
• MRI w/ contrast of entire neural axis• Lumbar puncture
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Medulloblastoma boost
2D 3D IMRT
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Medulloblastoma: cochlea dose
IMRT2D3D
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Craniospinal RT with protons
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Intrathecal radioimmunotherapy
• Anti-GD2 IgG2 Ab (3F8)conjugated to 131I
• IT by Ommaya reservoir• 2 mCi test dose, followed
by 10 mCi 7 days later• CSF dosimetry: 15-80 cGy/mCi• 18 Gy CSI w/ IMRT tumor-bed
boost to 5400• Concurrent vincristine, then
vincristine, cisplatin, CCNU x 8
131I
Kramer K, et al. JCO, 2007
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Image-guided radiotherapy (IGRT)
• Respiratory Gating
• Diagnostic level X-rays– KV plain films– Fluoroscopy
• Cone-beam CT
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Radiosurgery: Cyberknife
Synchrony™
camera
Treatment couch
Synchrony™
camera
Treatment couch
Linearaccelerator
Manipulator
Imagedetectors
X-ray sources
Robotic Delivery System
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Conclusions• Radiation therapy plays a vital role in treating
childhood cancer.• New radiation technologies promise improve
tumor control with fewer late effects.• Older techniques remain useful in many cases.• Access to treatment is limited for the majority
of the world’s children.• Cost-effectiveness of new therapies and global
resource allocation is a critical issue.
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Suzanne L. Wolden, MDDept of Radiation OncologyMemorial Sloan-Kettering 1275 York AvenueNew York, NY 10021
Phone: 212-639-5148E-mail: [email protected]