State of the Art Radiotherapy for Pediatric Tumors. Suzanne L. Wolden, MD Memorial Sloan-Kettering Cancer Center

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1 State of the Art Radiotherapy for Pediatric Tumors Suzanne L. Wolden, MD Memorial Sloan-Kettering Cancer Center

2 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

3 Distribution of pediatric malignancies

4 Pediatric cancer cure rates

5 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)

6 7 year old boy with Hodgkin lymphoma from Reed s 1902 paper

7 Total Lymphoid Irradiation (TLI) 44 Gy Involved-Field Radiation (IFRT) 21 Gy Involved Node Radiation (INRT) 21 Gy

8 CCG 5942 Hodgkin lymphoma trial Chemotherapy by stage of disease Randomization +/- 21 Gy IFRT Study closed at 1 st interim analysis 3 year EFS 93% vs 85% favoring RT (p<.01) all subgroups benefitted from radiation Nachman et al. JCO 20:3765, 2002

9 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

10 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:

11 Stage 4 neuroblastoma (>1 year age): 1.2 treatment outcome Proportion alive progression-free N7 (94-99) N7=CAV/PV I-3F8 + 3F8 N6=CAV/PV + 3F8 N5=CAV/PV + ABMT N4=CAV + ABMT N6 (89-94) N5 (87-89) N4 (80 s) Months from diagnosis Cheung et al, Med Ped Onc 36:227, 2001

12 Neuroblastoma: primary site 21 Gy

13 Neuroblastoma bone metastases: Brain sparing whole skull RT 4 months

14 Pretreatment right adrenal primary tumor Local recurrence after chemotherapy, surgery and 21 Gy external beam

15 Intraoperative radiation therapy

16 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)

17 Survival by treatment era

18 Failure-free survival for local/regional tumors by primary site Failure-free Survival Log Rank Test: p<0.001 Extremity Orbit GU non-b/p Other Years H & N GU B/P PM

19 IRS IV ( ) 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

20 RT for PM RMS at age 4 in 1978

21 Failure-free Survival Failure-free survival for patients with Group III tumors by radiation schedule Conventional 0.6 Hyperfractionated Log Rank Test: p= Years

22 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

23 2 year old with alveolar rhabdomyosarcoma of the left thigh. PET scan shows pelvic node involvement

24 IRS V ( ) Experimental dose reductions for selected patients: Group I alveolar/undifferentiated: > 36 Gy Group II N0: > 36 Gy Group III orbit/eyelid: > 45 Gy Group III second look surgery negative margins: > 36 Gy microscopically + margins: > 41.4 Gy Group III requiring 50.4: eligible for conedown

25 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

26 Local control with IMRT % Local Control orbit/head &neck parameningeal p = Years

27 Fusion of CT, MRI, and PET Scans

28 Infratemporal fossa with PM extension

29 Results: Parameningeal RMS: Dose Comparison (IMRT v Protons) (Kozak, Yock, in press IJROBP) Improved dose conformality of protons spared most normal tissues examined except for a few ipsilateral structures such as the parotid and cochlea. % Dose

30 Bone sparing for soft tissue sarcoma

31 Ewing sarcoma: Askin tumor + whole lung

32 IMRT for Osteosarcoma of C2 100% 90% 70% 50% PTV Cord

33 Whole Abdomen / Pelvis IMRT for DSRCT

34 Whole Abdomen / Pelvis IMRT for DSRCT

35 Lower Eyelid RMS

36 Custom Eye Shield

37 Electron set-up

38 Extremity brachytherapy

39 Interstitial Tongue Brachytherapy

40 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

41 Medulloblastoma MRI w/ contrast of entire neural axis Lumbar puncture

42 Medulloblastoma boost 2D 3D IMRT

43 Medulloblastoma: cochlea dose IMRT 2D 3D

44 Craniospinal RT with protons

45 Intrathecal radioimmunotherapy Anti-GD2 IgG2 Ab (3F8) conjugated to 131 I IT by Ommaya reservoir 2 mci test dose, followed by 10 mci 7 days later CSF dosimetry: cgy/mci 18 Gy CSI w/ IMRT tumor-bed boost to 5400 Concurrent vincristine, then vincristine, cisplatin, CCNU x I Kramer K, et al. JCO, 2007

46 Image-guided radiotherapy (IGRT) Respiratory Gating Diagnostic level X-rays KV plain films Fluoroscopy Cone-beam CT

47 Radiosurgery: Cyberknife X-ray sources Synchrony camera Synchrony Manipulator camera Linear accelerator Robotic Delivery System Treatment Treatment couch couch Image detectors

48 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.

49 Suzanne L. Wolden, MD Dept of Radiation Oncology Memorial Sloan-Kettering 1275 York Avenue New York, NY Phone:

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