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SPINAL CORD TUMOR
DR DODUL MONDALMD, DNBAll India Institute of Medical Sciences, New Delhi Dodul Mondal
• INTRODUCTION• ANATOMY• EPIDEMILOGY• NATURAL HISTORY• CLASSIFICATION• ROUTES OF SPREAD• CLINICAL PESENTATION• DIAGNOSTIC WORKUP• PROGNOSTIC FACTOR• DISEASE SPECIFIC MANAGEMENT• CONCLUSION
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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
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ANATOMY
CSF
DURAINTERVERTEBRAL DISC
SPINAL CORD
VERTEBRAL BODY
EPIDURAL SPACE
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Normal transverse spine Transverse spine with extradural mass
Intradural extramedullary mass Intramedullary massDodul Mondal
EPIDEMIOLOGYPrimary Spinal Cord Tumors – UncommonPrimary Brain Tumor : Primary Spinal Cord Tumor = 20:1 (children) ** 5:1 (adult)Younger individuals affected more than adultsConstitutes 3-4 % of all primary CNS tumors & 6% of CNS tumors of children**
**CBTRUS-Statistical Report 2011 Dodul Mondal
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
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NATURAL HISTORY
Mostly benignIM tumors produce damage by local invasion & cystic compressionEM tumors compress, stretch or distort the cord & nervesMay involve focally or entire length of spinal cord
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CLASSIFICATION
SPINAL CORD TUMOR
Intra Dural
EXTRAMEDULLARYMeningiomaNerve sheath tumorVascular tumorEpendymoma
INTRAMEDULLARYEpendymomaAstrocytomaOligodendroglioma
Extra DuralMetastatic Osteoid osteoma Osteoblastoma ABC Plasmacytoma / Myeloma Chordoma Chondrosarcoma Osteosarcoma Ewing’s sarcoma Epidural hemangioma Lipoma Extradural meningioma Nerve sheath tumor LymphomaDodul Mondal
ROUTES OF SPREAD
Low Grade-Generally localizedHigh Grade-Spread via CSFOccasionally hematogenous route to LungsLymph Node spread is generally not seen as CNS has no lymphatics
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CLINICAL PRESENTATIONDepends on the anatomical location & site of the lesion LocalFocal Pain(75%):• In EM tumors pain is more in the night due to venous congestionDistal Neurological:
Paresis & NumbnessAutonomic DysfunctionSensory DeficitsMuscle WastingLoss of ReflexesFailure to achieve milestonesGait disturbance
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DIAGNOSTIC WORK UPGENERALHistoryPhysical examinationComplete neurological evaluationIMAGINGPlain radiographyMRI whole spine with contrastMRI brainCT myelographyIntraoperative ultrasoundLABORATORY TESTSCSF chemistryCSF cytology
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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
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COMPUTED TOMOGRAPHY
• Better for bony lesions and bony extent detection• Extradural pathologic processes• Paraspinal soft tissue masses• Erosion of bone• Calcification of meningioma
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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
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• 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 metsContrast 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.
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PROGNOSTIC FACTORSMajor factors:
Tumor type and gradeTumor extent and locationPatient age, presenting neurologic function
Treatment-related factors:Tumor resectabilityUse of radiation therapy for certain tumor types
Lower 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 Neurooncol2010;98(1):83–92
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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 deathExtensive involvement of the spinal cord with an ependymoma is associated with a worse outcomeYounger age is associated with a better than 5-year recurrence-free survival rate
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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 Define its extent Characterize 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
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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• Complete resection not achieved PORT• PORT can be delayed even after STE till time of recurrence• Recurrence assess for reresection and judicious use of PORT
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ASTROCYTOMA
Low backache Painful scoliosis Thoracic cord (67%)* Cervical 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
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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 AstroGBM is rare. Dodul Mondal
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.
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Treatment Recommendations for Pediatric Spinal Cord Astrocytoma
Nadkarni TD,Childs Nerv Syst 1999;15:17-28
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EPENDYMOMA
Most common intramedullary spinal neoplasm in adults*
Common in young adults
Common in male patients
Location:2/3rd arise in lumbosacral region40% arise from filum terminale
*Torres et al: Intramedullary ependymoma of spinal cord , J Neurosurgery 62;523-532;1992Dodul Mondal
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
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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
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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%).
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Cysts In EpendymomaCysts are a common feature
Mostly non tumoral (polar) (70-80%)
NON TUMORAL CYSTSLocated 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 CYSTSContained within the tumor
itself.Peripheral enhancementMore in astrocytomas than
ependymomas.
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Filum Terminale Ependymoma(Myxopapillary)
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EPENDYMOMA T 1W-HYPO to ISO T 2W-HYPERINTENSE T 1W- CONTRAST
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EPENDYMOMA WITH BLEED Plain T1W sagittal
Iso to Hypo on T1 Hyper on T2 Bleeding-Hyper on T1 Enhancement Homogeneous Cap sign seen
BLEED
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Nadkarni TD. Childs Nerv Syst 1999;15:17-28
Treatment Recommendations for Pediatric Spinal Cord Ependymoma
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Difference Between Astrocytoma and Ependymoma
ASTROCYTOMA EPENDYMOMACervical & Thoracic cord LS spine, Cauda equina & conus medullaris Centrally located in cord EccentricHemorrhage uncommon Hemorrhage common
Infiltrative with poorly defined margins(multiple segment inv.) Well defined due to pseudocapsuleHeterogenous enhancement Homogenous enhancement
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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
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RADIOTHERAPY TECHNIQUECONVENTINOAL TECHNIQUE Position: Supine/Prone Usually direct posterior field Superior and inferior border: Myelography defined gross tumor plus 2 vertebrae above and below Lateral 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 regionFor female patients lateral fields may be better for lumbosacral spine Dose distribution should be homogenous and toxicity minimalCombination of low and high energy depending on site
Image courtesy: Unknown contributor Dodul Mondal
RADIOTHERAPY TECHNIQUE
Image taken from Principles and Practice of Radiation Oncology, 6th Ed, Perez and BradyDodul Mondal
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
Not beyond the thecal sac, which is typically at the level of S2-3Dodul Mondal
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.
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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)
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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
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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
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Patient Positioning and Immobilization
• Traditionally prone position• Supine position also safe• More comfortable• If anesthesia is required, allows better control of the airway• Immobilization is essential and involves the use of a head shell or full-body immobilization
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Target Volume Definition• Coverage 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)
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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.
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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 DobbsDodul Mondal
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
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• The field junction, which is over the cervical cord (C3), usually is moved weekly to avoid over- or under dosageTreatment planning by DobbsDodul Mondal
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
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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 MondalImage from Principles and Practice of Radiation Oncology, 6th Ed, Perez and Brady
MENINGIOMA• Usually benign• Well-encapsulated• Easily separated from the spinal cord• Most can be completely excised• Rare• May arise anywhere within the intradural space• Found in the thoracic region in approximately 80% of patients• Uncommon in the lumbar region• Rare in the sacrum• At least 80% of meningiomas occur in women 40 years of age or older
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• Maximal 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• Rarely recur after total excision• Subtotally resected meningiomas may recur late after surgery• Some advocated postoperative radiation using either conventional fractionated
external-beam radiotherapy or stereotactic radiosurgery
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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
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TreatmentCorticosteroidsIn 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:22-7100 mg loading dose followed by 96mg/d
10 mg loading followed by 16mg/d
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Surgical decompressionLife expectancy important determinantLaminectomyReserved for posterior lesionAnterior approach with immediate stabilization for anterior lesionCombination of anterior and posterolateral approachSurgery followed by RT provides higher overall ambulatory rate (85% vs 64%, P<0.001)**Klimo et al. Neuro Oncol 2005:7:64-76
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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
OPTIMUM RT DOSE SCHEDULE??
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NEWER TECHNIQUES
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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
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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
SRS (STEREOTACTIC RADIO SURGERY)• Accurate delivery of high dose of radiation to the target• Use of multiple highly targeted radiation • Reduced dose to surrounding normal tissue• Most spine SRS used in metastatic disease• Limited data in intradural tumorMETASTATIC DISEASE:
1-2 Session8-18 GyImproved pain controlBetter quality of life due to reduced toxicityLess side effects
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SRS IN INTRADURAL TUMOR• Only few reports on intradural tumor• Largest series treated 73 benign tumor• Used CyberknifeTM
• Dose 16-30 Gy• 1-5 fx• Median FU of 37 • Local control rate 98% • Pain improved in:
• 70% of meningiomas• 50% of schwannomas• 0% of neurofibromas.
• Three patients developed radiotherapy-related spinal cord toxicity 5 to 13 months after treatment
• Overall radiographic response rates for benign intradural tumors in the series reported to date range from 28% to 39 Neurosurgery. 2008 Apr;62(4):887-95Dodul Mondal
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
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Stereotactic radiosurgery for an L1 hemangioblastoma. A single dose of 20 Gy was delivered with CyberKnife using 87 noncoplanar beams
Perez, Sixth EdDodul Mondal
CHEMOTHERAPY IN INTRAMEDULLARY LOW GRADE ASTROCYTOMA AND EPENDYMOMA
To delay radiation in young childrenOf no proven value till now Lack of large RCT Mostly extrapolated from intracranial tumor Platinum and Etoposide mostly consideredTemozolomide showed response in a retrospective series of 22 patients with recurrent GrII gliomas*
*Chamberlain MC. Cancer 2008;113(5):1019–1024
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• 16-month polychemotherapy regimen • Seven cycles of carboplatin 15 mg/kg or 450 mg m2 on day D1• Procarbazine 4 mg/kg or 200 mg m2 on D 1–7• Etoposide 5 mg/kg or 150 mg m2 on D2 and 23• Cisplatin 1 mg/kg or 30 mg m2 on D22 and 23 • Vincristine 0.05 mg/kg or 1.5 mg m2 on D 43C• Cyclophosphamide 50 mg/kg or 1500 mg m2 on D 43• For children over 3, doses were calculated in mg/m2 / day
• Doireau V. Br J Cancer 1999;81(5):835–840Dodul Mondal
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
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Children’s Cancer Group 945• N=13• High-grade astrocytic spinal cord neoplasms• Two cycles of “8-drugs-in-1-day” chemotherapy before radiation therapy• Eight additional cycles thereafter• 5 years PFS=46% • 5 year OS=54%
• Conclusion: More intensive therapy necessary
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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
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THANK YOU
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