State of the Art Radiotherapy for Pediatric Tumors Suzanne L. - - PowerPoint PPT Presentation

State of the Art Radiotherapy for Pediatric Tumors

Suzanne L. Wolden, MD Suzanne L. Wolden, MD Memorial Sloan Memorial Sloan-

• Kettering Cancer Center

Kettering 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 lymphoma from 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
• ver 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

250 200 150 100 50

Proportion alive progression-free

1.2 1.0 .8 .6 .4 .2 0.0

N7=CAV/PV + 131I-3F8 + 3F8 N6=CAV/PV + 3F8 N5=CAV/PV + ABMT N4=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

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Years 1 2 3 4 5 6 Failure-free Survival

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, 2001 Donaldson 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 0.0 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 Conventional Failure-free Survival

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

10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 Years % Local Control p = 0.60

parameningeal

• rbit/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)

% Dose 105 100 80 60 40 20

Bone sparing for soft tissue sarcoma

Ewing sarcoma: Askin tumor + whole lung

IMRT for Osteosarcoma of C2

100% 90% 70% 50% PTV Cord

Whole Abdomen / Pelvis IMRT for DSRCT

Whole Abdomen / Pelvis IMRT for 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

IMRT 2D 3D

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 Linear accelerator Manipulator Image detectors 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
• f the world’s children.
• Cost-effectiveness of new therapies and global

resource allocation is a critical issue.

Suzanne L. Wolden, MD Dept of Radiation Oncology Memorial Sloan-Kettering 1275 York Avenue New York, NY 10021 Phone: 212-639-5148 E-mail: woldens@mskcc.org