1. Paediatric Spinal Cord Tumors Tumors M.ZERAH Université PARIS V. Hopital Necker Enfants Malades

2. Paediatric Spine Tumours 40% Intramedullary 20% intradural / extramedullary 40% extradural

3. 1 : 1 million of children / y 15 / y in France Bicêtre-Necker 1984 - 2004 : 148 children (<16y) Literature 1924 - 2005 : 1923 children New-York (Fred Epstein) : 164 “children” (<21 y) Intramedullary Tumours Personal Series & Literature

5. Spinal Cord Tumors 26 %

6. Pain : 72% Spinal deformity : 68% Motor Signs : 79% Gait : 63% Upper Limbs : 16% Bowel/Bladder dysfunction 18% Hydrocephalus : 8% Miscellaneous : 12% Initial Symptoms

7. Age at first sign

8. Age at surgery Med : 30 m (2-72w)

9. Solid part of the tumor 2 to 20 levels (average : 7)

10. Cystic Part Present in 86% of the cases Rostral and caudal in 62% of the cases Average of 11 levels 20% of brain stem extension

12. Diagnosis One exam : MRI One goal : Cystic / Solid No histological diagnosis on MR...

13. AstrocytomaEpendymoma Neurinoma Mélanoma Germinoma

14. Astrocytome grade IV

15. Pathology French Series (1998) - Pilocytic 55% - Grade II 23% - Grade III 17% - Grade IV 5%

16. Surgery

17. Surgical Procedure Laminotomy Ultrasonography Evoked potential ? Gross total removal of the solid part of the tumor (except in malignant astrocytomas) No cyst removal Laminoplasty Brace (3 to 6months)

18. Laminotomy “open book”Unilateral

19. Laminotomy Monobloc

20. Gross total removal 1984 - 2004 Astrocytoma (90%) I & II (90%)* 87% III & IV (10%) 15% Ependymoma (10%) 100% * 2/3 pilocytic

21. Spinal Deformity Group I : Laminectomy 1984 - 1988 : 20 Children post operative appearence or worsening of a spinal deformity Group II :Laminotomy 1988 -1993 :21 Children post operative appearance or worsening of a spinal deformity 16 4 p < 0,0001 M.ZERAH 1995

22. Consolidation90% 8 to 36 months (Mean :20 months) Reinterventions :11 (9 children) Laminotomy always possible Total consolidations in the 2 nd and 3 rd procedures Spinal Deformity

23. Grade Definition I Neurologically normal; mild focal deficit not significantly affecting function of involved limb; mild spasticity or reflex abnormality; normal gait II Presence of sensitivomotor deficit affecting function of involved limb; mild to moderate gait difficulty; severe pain or dysesthetic syndrome impairing patient quality of life; still functions and ambulates independently Spinal Cord Tumors Clinical / Functionnal classification scheme

24. Clinical / Functionnal classification scheme GradeDefinition III More severe neurological deficit; requires cane/brace for ambulation or significant bilateral upper extremity impairement; may or may not function independantly IV Severe deficit; requires wheelchair or cane/brace with bilateral upper-extremity impairement; usually not dependent from Mc Cormick J NeuroSurg (1990) 72 : 523-532 Spinal Cord Tumors

25. Post-Operative Status Spinal Cord Tumors

26. Late Follow-up Spinal Cord Tumors 92% ambulatory 23% clinically normal 85% normal schooling

27. Surgical removal must be the goal in the pediatric spinal cord tumours In most of the cases the prognosis is good

28. Remaining problems (Astrocytomas) Is there a difference between partial and total removal ? Followup and treatment in case of partial removal Treatment of recurrences ? treatment of “non surgical” tumours (panmedullary, multipolar, metastatic Tumours) Grade IV

29. Problèmatique (Astrocytomes) Place des réinterventions Place de la radiothérapie Place de la chimiothérapie Place de la surveillance “armée”

30. Is there any difference between Total and Subtotal Removal ? Przybylski, CNS 1997 N = 18. 1976 - 1992 “No patients relapse after total resection, whereas more than two-thirds treated with other than complete resection relapsed within 3 years (p = 0.029)… …prolonged relapse-free survival was observed in all patients treated with complete resection, including 3 with anaplastic tumors”

31. Is there any difference between Total and Subtotal Removal ? … Sandler Neurosurg. 1992 (n = 21) Lunardi Acta Neurochir 1993 (n = 25) Hulshof Radioth & Oncology 1993 (n = 50) Huddart J Neurosurg 1993 (n = 27) Cristante Neurosurg. 1994 (n = 69) O’Sullivan J. Neurosurg 1994 (n = 31) Minehan J. Neurosurg 1995 (n = 79) Innocenzi CNS 1996 (n = 45) Jyothirmayi J Neuro Oncology 1997 (n = 23) Goh Pediatr Neurosurg 1997 (n = 44)... No difference

32. N = 73. 13 Departments. 1971-1994

34. Is there a difference between Total removal and Subtotal removal + Radiotherapy ? “ we would recommend postoperative radiation therapy in all the intraspinal gliomas where total resection was not possible” Hulshof, 1996 “ Conservative surgery followed by radiotherapy appears to have a role in achieving tumor control and neurologic recovery in patients with low grade astrocytomaa of the spinal cord” Jyothirmayi, 1997

35. Is there a difference between Total removal and Subtotal removal + Radiotherapy ? Yes No Lunardi, 1993 Cristante, 1994 Innocenzi,1996 Zileli, 1996 Przybylski, 1997 Goh, 1997 Jallo, 2001 Huddart, 1993 O’Sullivan, 1994 Minehan, 1995 Shirato, 1995 Sandler, 1992

36. What is the real efficacy of Radiotherapy ? O’Sullivan, 19941959 - 1990n = 31 (Toronto) “These statistic suggest that irradiation treatment without resection may achieve long-term control in children with astrocytoma or ependymoma of the spinal cord” 10-year survival rate = 80% 20-year survival rate = 53% Biopsy + RxTherapy

37. Is there any advantage of adjuvant radiotherapy in case of total removal ? Yes No Rossitch, 1990 Sandler, 1992 Lunardi, 1993 Huddart, 1993 Cristante, 1994 Epstein, 1994 O’Sullivan, 1994 Minehan, 1995 Shirato, 1995 Innocenzi,1996 Zileli, 1996 Przybylski, 1997 Goh, 1997 Jallo, 2001

41. What are the true complications of Surgery, Radiotherapy and Chemotherapy ? Radical Surgery : Clinical deterioration10 - 40% Radiotherapy : Second cancer 10% (O’Sullivan) Malignant recurrence ChemotherapySecond Cancer? Toxicity

42. Chemotherapy and Glial tumors in children Allen, JNS : 1998(CCG) 13 children High-grade astrocytomas 8-in-1 5-year survival : 54% (median : 76 Mo) But Surgery + RxTherapy - Bouffet, Med & Ped Oncol : 1997 - Biopsy - Vincristine + Carboplatin - FU : 14 Mo - Full neurologic recovery - Complete radiologically remission

43. Chemotherapy and Glial tumors in children ä Doireau, Grill, Zerah (IGR, Necker) : 1998 ä 8 children ä Astrocytomas ä 5 progressive diseases, 3 relapses ä 3 metastases ä BB SFOP (CPVCEC) ä No Radiotherapy  Median FU : 3 years  7 alive  5 progression free  4 radiologically complete remission

45. To conclude

46. PSCT. Removable. McC ≤ III. Gr < IVTotal Removal (Frozen section ?) Clinical Surveillance whatever the quality of the surgery Gr I or II AstroMR at 3 months

47. Nl 70% Nl 100% Remaining Tumor 30% “Stable” 50% Progression 50% Astro I, II

48. T ProgressionSecond SurgeryChemotherapy ? ? Surveillance Failure Radiotherapy Astro I, II CR, PR, Stab.

49. Holocord Tumor. McC = 4. Gr III or IVBiopsy. Debulking Gr I, II, III Chemotherapy Gr IV RxT ± ChT Second look Surgery ?

50. Mik. 2000. 6m-o untreatable Pain. Complete Paralysis of the left superior limb Astro Gr II “70% removal”(US)

51. Mik. 2000. 3 m post-op No more Pain. Persistance of the paralysis Chemotherapy (BBSFOP)

52. 2008 Mik. 2008. 8 y F-U Total Recovery Stabilisation of the MR

53. El. 2 year-old girl - Neck Pain -Torticollis - “Mild Traction” -Tetraplegia

54. El. Apr 1998

55. El. Oct 98 (3months) “< 90%” Removal. Mild tetraparesis Astro Gr I Wait and See

56. El. Apr 1999 (1y F-U) No Clinical Signs

57. El. Apr 2000 (2 y F-U)

58. El. April 2002 (4 y F-U)

59. El. Apr 2008 (10 y F-U)