“Pediatric radiation oncology” R. Miralbell Hôpitaux Universitaires, Genève

1. “Pediatric radiation oncology”R. MiralbellHôpitaux Universitaires, Genève

4. Clinical features favorably influencing survival in pediatric medulloblastoma: univariate analysis Author Period #ptsGender Age T-stageM-stage Hershatter et al 1940-83 127 - - >T2 NE Tait et al 1975-79 286 female - <T3 NE Evans et al 1975-81 233 - >4 years - M0 Jenkin et al 1977-87 72 female - <T3 M0-1 Wara et al 1970-95 109 female >3 years - M0 Miralbell et al 1972-91 86 female - - M0

5. Clinical features favorably influencing survival in pediatric medulloblastoma: multivariate analysis Author Period #ptsGender Age T-stageM-stage Hershatter et al 1940-83 127 - - >T2 NE Evans et al 1975-81 233 - >4 years - M0 Jenkin et al 1977-87 72 - - - - Wara et al 1970-95 109 female - - M0 Miralbell et al 1972-91 86 female - - M0

6. Virtual simulation for cranio-spinal irradiation of medulloblastoma.Clara Jargy, Philippe Nouet, Raymond Miralbell.Radiation Oncology, Geneva University Hospital

7. Mark on the skin for the spine field Lateral mark Patient set-up

8. Set-up of the left lateral brain field with the different structures.

9. Mark on the skin shifts Set-up of the spinal field

10. Junction (brain-spine) in a sagittal slice

11. without with Effect of the table rotation on the field ’s matching

12. Moving junctions between the brain fields and the spinal field. We use asymetric fields (one isocenter for the same region).

13. Moving junction between the two spinal fields. Fields match on the anterior edge of the spinal cord

14. Boost on the posterior fossa

15. Final dosimetry in a sagittal slice passing through the spinal cord. -Dose at the junction. -Dose at the spinal cord (depth and SSD vary).

16. Radiotherapy in pediatric medulloblastoma: quality assessment of POG Trial 9031 R.Miralbell QARC & Swiss POG Geneva, CH

17. Purpose To evaluate the potential influence of the quality of RT on event-free (EFS) & overall survival (OS) in a group of high-riskpediatric medulloblastoma patients treatedin POG Trial 9031

18. POG Trial 9031 • Randomize between: -Arm 1:CDDP+VP16- CSI- vcr+cycloph. - Arm 2:CSI- CDDP+VP16- vcr+cycloph. • 224high-risk stagepatients randomized : - Post-op residual tumor: >1.5 cm3 - T3b, T4 - M+ (1-3)

19. Patient material & RT guidelines • Patients: 197 evaluable • CSI (dose): M0-1 M2-3 dose/fx WBI & spine35.2 Gy 40.0 Gy 1.6 Gy PF (boost)18.0 Gy 14.4 Gy 1.8 Gy Metastases0.0 Gy 4.8 Gy 1.6 Gy

20. CSI treatment volume boundaries • WBI:inf border 0.5 cm below base of skull • Spine: inf border 2 cm below the subdural space • PF: tentorium+1 cm; C1-C2 interspace; post clinoids; post convexity • Tumor: 2 cm around the primary tumor

21. Method of RT quality assessment • WBI: distance between the inf field limit & both the cribiform plate & floor of the middle cranial fossa • Spine: distance between the end of the inf field limit & the end of the dural sac (MRI). • PF: distance between the boost field limits & the tentorium, C1-C2, post clinoids, post convexity • Tumor: distance between the boost field limits & the tumor borders as seen in the pre-op brain MRI/CT

22. Treatment deviation guidelines • WBI: 0-4 mm, minor; <0 mm, major • Spine: Inf field abutting the sac, minor Inf field transsecting the sac, major • PF: < field boundaries, major • Tumor: 10-18 mm, minor; <10 mm, major

23. RT deviations: total dose • Maximum accepted variation: +/- 5% • Major deviation: 10% or more below dose prescription • Delays >51 & >58 days were conpensated with 1 or 2 additional fractions to the PF

24. Endpoints & statistics • Assessment of 1st site of failure • 5-year EFS & OS according to treatment correctness • Kaplan-Meier & log-rank tests

25. Results: overall outcome • EFS (5-y): 69.1% (4.1 SE) • OS (5-y): 74.4% (3.8 SE) • Relapsed: 35 patients • Progressed: 14 patients • Dead: 57 patients

26. Results: treatment deviations • Fully evaluable: 160 patients # deviations # patients 0 69 1 50 2 31 3 09 4 01

27. Results: major deviations by site Site #deviat/total patients WBI: 54/208 (26%) Spine: 12/174 (7%) PF: 82/210 (39%) Tumor: 33/189 (17%)

28. Results: EFS & OS by site and deviation status

29. Results: outcome & cumulative effect of treatment deviations 5-year Deviations EFS OS 0-1 72.1% 76.3% 2-4 59.2% (p=0.06) 70.6% (p=0.04)

30. Summary • Major treatment deviations were observed in 57% of fully evaluable patients. • Underdosage or treatment volume misses did not correlate with a worse EFS or OS. • A «trend» for a better EFS and OS was observed among patients with lesser number of major deviations (i.e., 0-1). • An involved field to boost the tumor bed may be as effective as, and less toxic than, boosting the whole PF.

31. RT in children: a unique treatment paradigm

32. Why? Significant increase in survival in pediatric oncology in the last 25 years Conventional RT frequently associated with severe side effects: Growth & musculoskeletal Endocrine & fertility Neuropsychologic Secondary cancers

34. Bone growth and radiation damage Radiation kills dividing chondroblasts Arrested chondrogenesis in the epiphysis Stop endochondral bone formation: >20 Gy

35. Changes in skeletal growth: the height A consequence of treating the spinal axis: reduced sitting heights Age dependant: <12 years Dose dependent: >20 Gy

38. Craniospinal RT for medulloblatoma/PNET

39. Pituitary gland: 36 Gy

40. Thyroid: 25-30 Gy Ovaries: 2-12 Gy

43. Hodgkin’s Lymphoma in 1950’s-1980’s: «mantle» field irradiation 44 Gy

44. Hodgkin’s Lymphoma in the 1990’s-2000’s: involved field irradiation 20 Gy