Spinal cord tumor

A concise presentation about spinal cord tumors, including different treatment options

1. SPINAL CORD TUMOR DR DODUL MONDAL MD, DNB All India Institute of Medical Sciences, New Delhi Dodul Mondal

2. INTRODUCTION ANATOMY EPIDEMILOGY NATURAL HISTORY CLASSIFICATION ROUTES OF SPREAD CLINICAL PESENTATION DIAGNOSTIC WORKUP PROGNOSTIC FACTOR DISEASE SPECIFIC MANAGEMENT CONCLUSION Dodul Mondal

3. INTRODUCTION Rare tumor Constitutes 3-4% of all CNS and 6% of pediatric CNS tumors Oversimplified anatomical classification Young children more affected than adults Lack of RCT Mainly retrospective series Surgery and radiation mainstay of treatment Judicious use of radiation important Dodul Mondal

4. ANATOMY CSF DURA INTERVERTEBRAL DISC SPINAL CORD VERTEBRAL BODY EPIDURAL SPACE Dodul Mondal

5. Normal transverse spine Transverse spine with extradural mass Intradural extramedullary mass Intramedullary mass Dodul Mondal

6. EPIDEMIOLOGY Primary Spinal Cord Tumors – Uncommon Primary Brain Tumor : Primary Spinal Cord Tumor = 20:1 (children) ** 5:1 (adult ) Younger individuals affected more than adults Constitutes 3-4 % of all primary CNS tumors & 6% of CNS tumors of children** ** CBTRUS-Statistical Report 2011 Dodul Mondal

7. EPIDEMIOLOGY cont… Primary tumor of SC are more frequent in children & more than half occur below 10 years of age* 36 % intramedullary 27 % extramedullary 24 % extradural 75 % of intramedullary tumor were astrocytomas * * * John K, Howard L. Weiner Pediatric Intramedullary Spinal Cord Tumors: Special Considerations . Journal of Neuro-Oncology Volume 47, Number 3 / May, 2000 Dodul Mondal

8. NATURAL HISTORY Mostly benign IM tumors produce damage by local invasion & cystic compression EM tumors compress, stretch or distort the cord & nerves May involve focally or entire length of spinal cord Dodul Mondal

9. CLASSIFICATION Dodul Mondal

10. ROUTES OF SPREAD Low Grade-Generally localized High Grade-Spread via CSF Occasionally h ematogenous route to Lungs Lymph Node spread is generally not seen as CNS has no lymphatics Dodul Mondal

11. CLINICAL PRESENTATION Depends on the anatomical location & site of the lesion Local Focal Pain(75 %): In EM tumors pain is more in the night due to venous congestion Distal Neurological: Paresis & Numbness Autonomic Dysfunction Sensory Deficits Muscle Wasting Loss of Reflexes Failure to achieve milestones Gait disturbance Dodul Mondal

12. DIAGNOSTIC WORK UP GENERAL History Physical examination Complete neurological evaluation IMAGING Plain radiography MRI whole spine with contrast MRI brain CT myelography Intraoperative ultrasound LABORATORY TESTS CSF chemistry CSF cytology Dodul Mondal

13. Radiography/Myelography Overall 50% lesions of primary spinal tumors detected with plain X-ray Features are due to raised ICP Erosion of pedicles Increased AP diameter Scalloping of posterior vertebral body Scoliosis or kyphosis in children Calcification in meningioma Myelography in patients unsuitable for MRI CT myelography better Dodul Mondal

14. Computed Tomography Better for bony lesions and bony extent detection Extradural pathologic processes Paraspinal soft tissue masses Erosion of bone Calcification of meningioma Dodul Mondal

15. MRI Gd-DTPA enhanced MRI imaging modality of choice CSF, white and gray matter, bone and bone marrow, fat, and flowing blood can be distinguished MRI brain should also be done Maximum impact in the field of spinal tumors amongst all spinal pathologies Preoperative study of choice so as to narrow the differential diagnosis and guide surgical resection . All spinal cord gliomas enhance LP should be done after MRI Dodul Mondal

16. Cord expansion-Essential imaging criterion for intramedullary spinal neoplasm* MR sensitive to hemorrhage- can identify intratumoral bleeding Cysts are common associated finding Majority of intramedullary neoplasms show at least some enhancement Contrast study essential: Enhancement useful in focal masses, especially hemangioblastoma and mets Contrast helpful in differentiating suspected neoplasms from other etiologies. e.g. infection , syrinx. Actual lesion smaller than area of cord enlargement-Useful to pinpoint sites for biopsy . *Epstein et al: IM tumors of spinal cord , Journal of Neurosurgery1993;79:204-209. Dodul Mondal

17. PROGNOSTIC FACTORS Major factors: Tumor type and grade Tumor extent and location Patient age, presenting neurologic function Treatment-related factors: Tumor resectability U se of radiation therapy for certain tumor types L ower grade, younger age, and surgical resection were associated with significantly better overall survival and cause-specific survival for both astrocytomas and ependymomas* Milano MT, et al. Primary spinal cord glioma : a Surveillance, Epidemiology, and end results database study .  J Neurooncol 2010;98(1):83–92 Dodul Mondal

18. PROGNOSTIC FACTORS…cont Patients with ependymoma survive longer without recurrence than patients with astrocytoma Rostral tumors have a worse survival and neurologic outcome Cervical lesions had a higher surgical risk and complication rate Tumors affecting the rostral or cervical spinal cord were more likely to be astrocytoma Tumors in the caudal spinal cord, filum terminale , or cauda equina were more likely to be ependymomas High histopathologic tumor grade is associated with a high rate of disability and death Extensive involvement of the spinal cord with an ependymoma is associated with a worse outcome Younger age is associated with a better than 5-year recurrence-free survival rate Dodul Mondal

19. MANAGEMENT OF INTRAMEDULLARY TUMORS Most common: Astrocytoma, Ependymoma (95%) Complete surgical excision without compromising neurologic function Introduction of bipolar forceps Microsurgical techniques, use of CUSA ( Cavitron Ultrasonic Surgical Aspirator ) CUSA allows aspiration of tissue fragments from within 1 mm of the vibrating tip Intraoperative ultrasonography: Localize the lesion D efine its extent C haracterize the tumor as cystic or solid Facilitates placement of a myelotomy incision and initiation of tumor resection Assess the progress of tumor resection and adjacent cyst drainage with internal spinal cord decompression Risk of paralysis after surgery less Dodul Mondal

20. MANAGEMENT OF INTRAMEDULLARY TUMORS .. cont Resection of astrocytic tumors begins from within the tumor at the initial midline myelotomy Removal until interface between tumor and normal spinal cord evident Complete excision achieved no postoperative therapy Delaying adjuvant radiation important in children C omplete resection not achieved PORT PORT can be delayed even after STE till time of recurrence Recurrence assess for reresection and judicious use of PORT Dodul Mondal

21. ASTROCYTOMA Low backache Painful scoliosis Thoracic cord (67 %)* C ervical cord (49%) Entire spinal cord ( holocord presentation) common in children (up to 60%) quite rare in adults Isolated conus medullaris ( 3%)& rare in filum terminale Less than 10% of pediatric and 25% of spinal cord astrocytomas are malignant .** *Epstein et al Adult IM Astrocytoma of SC, J of Neurosurgery 77:355-359;2002 ** Stein et al.IM tumors in adults .Neurosurgery Clin of N America 1998:1:609-630 Dodul Mondal

22. ASTROCYTOMA Arise from the cord parenchyma not from the central canal, are usually eccentric within the cord Usually have poorly defined margins Multisegment involvement of the cord is rule Associated polar and intratumoral cysts. Usually low grade fibrillary Astro is MC type followed by anaplastic Astro GBM is rare. Dodul Mondal

23. ASTROCYTOMA cont.. Iso- to hypo intense relative to the cord on T1W Hyper intense on T2W images Enhancement is seen in all cord astrocytomas, Inhomogenous enhancement Tumor , syrinx and cysts can be delineated on MR Rare SC GBM has propensity of leptomeningeal spread in 60% of patients* Completely resected tumor do not require PORT Incompletely removed tumor PORT should be considered Ciappetta et al, Spinal GBM: Report of 7 patients with spinal GBM and Review of literature.Neurosurgery 28:302-306,1991. Dodul Mondal

24. Treatment Recommendations for Pediatric Spinal Cord Astrocytoma Nadkarni TD, Childs Nerv Syst 1999;15:17-28 Dodul Mondal

25. EPENDYMOMA Most common intramedullary spinal neoplasm in adults* Common in young adults Common in male patients Location: 2/3 rd arise in lumbosacral region 40% arise from filum terminale * Torres et al: Intramedullary ependymoma of spinal cord , J Neurosurgery 62;523-532;1992 Dodul Mondal

26. Arise from ependymal cells of the central canal, and symmetric cord expansion is the rule. Slow growth and tends to compress adjacent spinal cord tissue rather than infiltrate it. Usually histologically benign and have long and indolent course. EPENDYMOMA Dodul Mondal

27. HISTOLOGICAL TYPES Cellular Ependymoma - mostly in cervical cord Myxopapillary Ependymoma - exclusively in conus medullaris and cauda equina Primary Anaplastic Ependymoma of spinal cord are rare Other histological types: Subependymal Epithelial Mixed Dodul Mondal

28. MR Imaging characteristics: Iso or hypointense relative to spinal cord on T1. Occasional hyperintense mass secondary to hemorrhage . Hyperintense relative to spinal cord on T2. Cap sign , a rim of extreme hypointensity (hemosiderin) seen at the poles of the tumor on T2W (20%—30%) …. thought to be secondary to hemorrhage. Cord edema around the masses (60%). Dodul Mondal

29. Cysts In Ependymoma Cysts are a common feature Mostly non tumoral (polar) (70-80%) NON TUMORAL CYSTS Located at the poles of the solid portion of the tumor . Reactive dilatation of the central canal ( syringomyelia ). Not part of the tumor itself . No enhancement. TUMORAL CYSTS Contained within the tumor itself. Peripheral enhancement More in astrocytomas than ependymomas . Dodul Mondal

30. Filum Terminale Ependymoma (Myxopapillary ) Dodul Mondal

31. EPENDYMOMA T 1W-HYPO to ISO T 2W-HYPERINTENSE T 1W- CONTRAST Dodul Mondal

32. EPENDYMOMA WITH BLEED Plain T1W sagittal Iso to Hypo on T1 Hyper on T2 Bleeding-Hyper on T1 Enhancement Homogeneous Cap sign seen BLEED Dodul Mondal

33. Nadkarni TD. Childs Nerv Syst 1999;15:17-28 Treatment Recommendations for Pediatric Spinal Cord Ependymoma Dodul Mondal

34. Difference Between Astrocytoma and Ependymoma ASTROCYTOMA EPENDYMOMA Cervical & Thoracic cord LS spine, Cauda equina & conus medullaris Centrally located in cord Eccentric Hemorrhage uncommon Hemorrhage common Infiltrative with poorly defined margins(multiple segment inv.) Well defined due to pseudocapsule Heterogenous enhancement Homogenous enhancement Dodul Mondal

35. RADIOTHERAPY FOR INTRAMEDULLARY TUMORS Dose: 50.4 Gy. 1.8 Gy per fraction for low grade tumor 5 fractions per week Dose for high grade tumor is 54Gy in 1.8Gy/ fx Limited data for dose response Dose below 50Gy is associated with high failure rate Where CSI is indicated, entire Craniospinal axis receives 36Gy to 45 Gy followed by boost to gross tumor to a dose of 50.4-54 Gy Dodul Mondal

36. RADIOTHERAPY TECHNIQUE CONVENTINOAL TECHNIQUE Position: Supine/Prone Usually direct posterior field Superior and inferior border: Myelography defined gross tumor plus 2 vertebrae above and below L ateral border: To include tip of the lateral process of vertebral body Field placement should be judicious to avoid exit dose to vital OAR s Cervical vertebra can be treated with bilateral parallel opposed fields Lumbar region tumors can be treated with antero posterior field arrangement Oblique wedge pairs can also be used for thoracolumbar region For female patients lateral fields may be better for lumbosacral spine Dose distribution should be homogenous and toxicity minimal Combination of low and high energy depending on site Image courtesy: Unknown contributor Dodul Mondal

37. RAD I O T HE RA P Y T ECHN I QU E Image taken from Principles and Practice of Radiation Oncology, 6 th Ed, Perez and Brady Dodul Mondal

38. RADIOTHERAPY TECHNIQUES cont .. For Low grade: CTV = GTV+ 0.5 to 1 cm margin CTV includes pre op tumor seen on MRI with intratumoral cysts Not necessary to include syrinx, unless radiographically or Sx evidence of tumor For High grade: CTV = GTV +1.5 to 2 cm margin craniocaudally Should encompass inter vertebral foramina (IVF) if involved If cauda equina involved - CTV should include entire thecal sac to cover meningeal sleeves in the IVF Myxopapillary ependymomas involving the conus, a 1.5-cm CTV margin cephalad and caudal to the GTV is used N ot beyond the thecal sac, which is typically at the level of S2-3 Dodul Mondal

39. Pioneering work by Merchant and Thompson et al from St.Judes on EBRT in pediatrics Spinal cord tumors. In a retrospective study of High grade tumors with a post op margin to GTV less than 1.5 cm yielded increase local failure rate.(13% vs. 39%) P-signicant .* * Merchant TE,Thompson SJ et al.High grade pediatrics spinal cord tumors . Pediatrics Neurosurgery 1999;39:1-5. Dodul Mondal

40. STEREOTACTIC RADIOSURGERY Single fraction high dose radiation to the target and reduced dose to normal tissue to reduce toxicity Most experiences in metastatic disease Intradural benign tumors 16-18 Gy in single fraction to 24-30Gy in 4-5 fractions Spinal Cord tolerance 13Gy/1fx, V10<10%(2-3mm above and below the target) Dodul Mondal

41. Dodul Mondal

42. CRANIOSPINAL IRRADIATION IN SPINAL TUMOR Multifocal dissemination Leptomeningeal spread CSF positive for malignant cells Dose: 36-45 Gy to whole spine followed by boost Radiation dose de-escalation not discussed Dodul Mondal

43. Craniospinal Irradiation cont.. one of the most complex radiotherapy techniques The CTV for CSI has an irregular shape that consists of the whole of the brain and spinal cord and overlying meningeal coverings Dodul Mondal

44. Patient Positioning and Immobilization Traditionally prone position Supine position also safe M ore comfortable I f anesthesia is required, allows better control of the airway Immobilization is essential and involves the use of a head shell or full-body immobilization Dodul Mondal

45. Target Volume Definition C overage of the entire target volume is critical CT simulation is invaluable for target volume definition - adequate coverage of the CTV in the subfrontal region, cribriform plate, anterior and temporal lobes are more easily ensured CT is also helpful in identifying the lateral aspect of CTV for the spine field that includes the extensions of the meninges along the spinal nerve roots MRI is better to determine the lower limit of CTV for the spine field. Traditionally the lower border of the spine field was placed at the lower border of the S2 (it is below S2 in 7% of children) Dodul Mondal

46. Treatment Planning and Delivery Photons ( 6 to 10 MV range) - provide satisfactory PTV coverage Blocks are used in the lateral fields to shield facial structures and teeth The field must be wide enough to encompass the intervertebral foramina Block heart , lung, kidney, gonad Compensators may be needed to achieve dose homogeneity throughout the target volume. Dodul Mondal

47. The use of CT simulation with contouring of the cord and overlying meninges that extend laterally to the lateral aspect of the spinal ganglia results in a field width that is narrower than one based on bony anatomy. The addition of shielding reduces even further the volume of normal tissues included in the treated volume Treatment planning by Dobbs Dodul Mondal

48. Field matching To cover the clinical target volume for CSI, lateral opposed fields upto the lower border of C3-4, are used to treat the brain and a direct posterior field is used to cover the spinal axis Precise matching of beam divergence is required – cranial fields with a collimator rotation of 7–10° are used to match the divergence of the posterior spinal beam The field junction may be shifted or feathered by 1 to 2 cm once or twice to avoid any excessive overlap of dose over the cervical spine – moving junction/ feathering technique Dodul Mondal

49. The field junction, which is over the cervical cord (C3), usually is moved weekly to avoid over- or under dosage Treatment planning by Dobbs Dodul Mondal

50. Dose solutions in conventional planning Whole brain - Treatment is given isocentrically using a linear accelerator and opposing lateral beams as defined in the simulator. The position of the lower cranial border is shifted by 1cm every wk to change the level of the junction with the spinal field. Spinal field - Despite the use of an FSD extended up to 140 cm, two adjacent fields are commonly required to cover the spinal cord in adults and older children. Both this and the craniospinal beam junction are moved caudally every wk Dodul Mondal

51. Technique for calculating the gap at spinal beam junctions Half beam blocking using shielding or independent collimator jaws can be used to eliminate divergence up to the match line, but accuracy is then dependent on precise immobilisation and reliability of skin marks It can also be done by using a gap between beams so that the beam edges converge at a planned depth Dodul Mondal Image from Principles and Practice of Radiation Oncology, 6 th Ed, Perez and Brady

52. MENINGIOMA U sually benign Well-encapsulated E asily separated from the spinal cord M ost can be completely excised Rare M ay arise anywhere within the intradural space F ound in the thoracic region in approximately 80% of patients U ncommon in the lumbar region R are in the sacrum At least 80% of meningiomas occur in women 40 years of age or older Dodul Mondal

53. M aximal surgical excision with preservation of neurologic function Posterior approach with a standard posterior laminectomy As much as 15% of spinal meningiomas Prognosis is excellent for most patients R arely recur after total excision S ubtotally resected meningiomas may recur late after surgery Some advocated postoperative radiation using either conventional fractionated external-beam radiotherapy or stereotactic radiosurgery Dodul Mondal

54. METASTASIS Common complication in advanced malignancy Not every metastasis is emergency Malignant epidural spinal cord compression (MESCC) is emergency Acute neurologic deterioration Prompt decision making necessary Pretreatment neurologic function most important determinant Pain is most common presentation (85-95%) Motor deficit 60-80% Sensory deficit 40-60% MRI gold standard investigation modality Dodul Mondal

55. Treatment Corticosteroids In a randomized trial 96mg loading dexamethasone followed by 96mg/d x3d followed by taper before RT vs. no steroid showed increased ambulatory rates at 3m , 6m* Dose: Two different dose schedules *Sorensen S et al. Eur J Cancer 1994:30A:22-7 100 mg loading dose followed by 96mg/d 10 mg loading followed by 16mg/d Dodul Mondal

56. Surgical decompression Life expectancy important determinant Laminectomy Reserved for posterior lesion Anterior approach with immediate stabilization for anterior lesion Combination of anterior and posterolateral approach Surgery followed by RT provides higher overall ambulatory rate (85% vs 64%, P<0.001)* * Klimo et al. Neuro Oncol 2005:7:64-76 Dodul Mondal

57. RADIOTHERAPY Standard of care since 1950 Preservation or improvement of neurologic function Palliation of pain Predictors of outcome: Extent of functional limitation at the beginning Tumor type Rapidity of neurologic deterioration Dose/fractionation: Different dose schedules used 30Gy/10fx/2wk 16Gy/2fx/2d 8Gy/1fx/1d PROTRACTED SCHEDULE REDUCES RISK OF NECESSITY OF REPEAT RADIATION SINGLE FRACTION MORE SUITABLE FOR PATIENTS WITH LIMITED LIFE EXPECTANCY Dodul Mondal

58. OPTIMUM RT DOSE SCHEDULE?? Dodul Mondal

59. NEWER TECHNIQUES Dodul Mondal

60. PROTON THERAPY Conventional photon/X-ray therapy produces tissue damage in the entry and exit path More dose deposited in the entry track Radiation induced normal tissue damage Proton therapy gives high dose to the tumor tissue with reduced dose to entry and exit path Positively charged hydrogen atoms High energy produced by acceleration in cyclotron/synchrotron Bragg peak effect Dodul Mondal

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62. PROTON THERAPY cont.. Lack of RCT of proton vs. photon in spinal cord tumor Dosimetric advantage in reducing exit dose to vital anterior structures Particularly promising in radiation of entire craniospinal axis Exit dose to the thyroid, heart, lung, gut, and gonads can be reduced with proton therapy Dodul Mondal Treatment planning by Dobbs

63. SRS (STEREOTACTIC RADIO SURGERY) Accurate delivery of high dose of radiation to the target Use of multiple highly targeted radiation R educed dose to surrounding normal tissue Most spine SRS used in metastatic disease Limited data in intradural tumor METASTATIC DISEASE: 1-2 Session 8-18 Gy Improved pain control Better quality of life due to reduced toxicity Less side effects Dodul Mondal

64. SRS IN INTRADURAL TUMOR Only few reports on intradural tumor Largest series treated 73 benign tumor Used Cyberknife TM Dose 16-30 Gy 1-5 fx M edian FU of 37 Local control rate 98 % Pain improved in: 70 % of meningiomas 50 % of schwannomas % of neurofibromas . Three patients developed radiotherapy-related spinal cord toxicity 5 to 13 months after treatment O verall radiographic response rates for benign intradural tumors in the series reported to date range from 28% to 39 Neurosurgery.  2008 Apr;62(4):887-95 Dodul Mondal

65. SRS IN INTRADURAL TUMOR cont… 7 patients with intramedullary hemangioblastoma and ependymoma treated at Stanford University showed good result* Dose used 16-30Gy in 1-5 fx or 18-25 Gy in 1-3 fx Early results promising * Ryu SI, Kim DH, Chang SD. Stereotactic radiosurgery for hemangiomas and ependymomas of the spinal cord.  Neurosurg Focus  2003;15(5): E10 Dodul Mondal

66. Stereotactic radiosurgery for an L1 hemangioblastoma . A single dose of 20 Gy was delivered with CyberKnife using 87 noncoplanar beams Perez, Sixth Ed Dodul Mondal

67. CHEMOTHERAPY IN INTRAMEDULLARY LOW GRADE ASTROCYTOMA AND EPENDYMOMA To delay radiation in young children Of no proven value till now Lack of large RCT Mostly extrapolated from intracranial tumor Platinum and Etoposide mostly considered Temozolomide showed response in a retrospective series of 22 patients with recurrent GrII gliomas * * Chamberlain MC. Cancer  2008;113(5):1019–1024 Dodul Mondal

68. 16-month polychemotherapy regimen Seven cycles of carboplatin 15 mg/kg or 450 mg m 2 on day D1 Procarbazine 4 mg/kg or 200 mg m 2 on D 1–7 E toposide 5 mg/kg or 150 mg m 2 on D2 and 23 Cisplatin 1 mg/kg or 30 mg m 2 on D 22 and 23 Vincristine 0.05 mg/kg or 1.5 mg m 2 on D 43C Cyclophosphamide 50 mg/kg or 1500 mg m 2 on D 43 For children over 3, doses were calculated in mg/m 2 / day Doireau V.   Br J Cancer  1999;81(5): 835–840 Dodul Mondal

69. Chemotherapy should be considered for children with a poor prognosis due to relapse or metastasis of an intramedullary tumour Chemotherapy could even be the first line of treatment for metastatic and unresectable tumours (e.g. holocord tumours ) and replace extensive irradiation Dodul Mondal

70. Children’s Cancer Group 945 N=13 High-grade astrocytic spinal cord neoplasms T wo cycles of “8-drugs-in-1-day” chemotherapy before radiation therapy E ight additional cycles thereafter 5 years PFS=46 % 5 year OS=54% Conclusion: More intensive therapy necessary Dodul Mondal

71. SUMMARY Rare tumors Children are more affected Intramedullary tumor mainly astrocytoma and ependymoma Contrast enhanced MRI investigation of choice Biopsy for histopathology confirmation Surgery mainstay of treatment Completely resected low grade intramedullary astrocytoma/ependymoma do not require adjuvant treatment High grade tumors require adjuvant radiation Radiation to be delayed if possible Chemotherapy role still not defined Judicious treatment policy and technique of paramount importance Dodul Mondal

72. THANK YOU Dodul Mondal