State of the Art Radiotherapy for Pediatric...
Transcript of State of the Art Radiotherapy for Pediatric...
State of the Art Radiotherapy for Pediatric Tumors
Suzanne L. Wolden, MDSuzanne L. Wolden, MDMemorial SloanMemorial Sloan--Kettering Cancer CenterKettering Cancer Center
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
Distribution of pediatric malignancies
Pediatric cancer cure rates
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)
7 year old boy with Hodgkin lymphomafrom Reed’s 1902 paper
1970 1995 2009
Total Lymphoid Irradiation (TLI)
44 Gy
Involved-Field Radiation(IFRT)21 Gy
Involved Node Radiation (INRT)21 Gy
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
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
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
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
Neuroblastoma: primary site 21 Gy
Neuroblastoma bone metastases: Brain sparing whole skull RT
4 months
Pretreatment right adrenal primary tumor
Local recurrence after chemotherapy, surgery
and 21 Gy external beam
Intraoperative radiation therapy
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)
Survival by treatment era
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
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
RT for PM RMS at age 4 in 1978
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
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
• 2 year old with alveolar rhabdomyosarcoma of the left thigh.
• PET scan shows pelvic node involvement
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”
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
Local control with IMRT
0102030405060708090
100
0 1 2 3 4 5 6Years
% L
ocal
Con
trol
p = 0.60
parameningeal
orbit/head &neck
Fusion of CT, MRI, and PET Scans
Infratemporal fossa with PM extension
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
Bone sparing for soft tissue sarcoma
Ewing sarcoma: Askin tumor + whole lung
IMRT for Osteosarcoma of C2
100%90%70%50%
PTVCord
Whole Abdomen / Pelvis IMRTfor DSRCT
Whole Abdomen / Pelvis IMRTfor DSRCT
Lower Eyelid RMS
Custom Eye Shield
Electron set-up
Extremity brachytherapy
Interstitial Tongue Brachytherapy
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
Medulloblastoma
• MRI w/ contrast of entire neural axis• Lumbar puncture
Medulloblastoma boost
2D 3D IMRT
Medulloblastoma: cochlea dose
IMRT2D3D
Craniospinal RT with protons
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
Image-guided radiotherapy (IGRT)
• Respiratory Gating
• Diagnostic level X-rays– KV plain films– Fluoroscopy
• Cone-beam CT
Radiosurgery: Cyberknife
Synchrony™
camera
Treatment couch
Synchrony™
camera
Treatment couch
Linearaccelerator
Manipulator
Imagedetectors
X-ray sources
Robotic Delivery System
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.
Suzanne L. Wolden, MDDept of Radiation OncologyMemorial Sloan-Kettering 1275 York AvenueNew York, NY 10021
Phone: 212-639-5148E-mail: [email protected]