CNS tumors_MG
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CNS tumors_MG Presentation Transcript

  • 1. CNS Malignancies Michael Guiou, M.D.
  • 2. Outline
    • I. Benign primary brain tumors (5/4/2011)
    • II. Malignant primary brain tumors (5/6/2011)
    • III. Metastatic brain tumors (5/6/2011)
  • 3. Annual Incidence of Brain Tumors (USA)
    • Adults
    • Primary: 17,000
    • Metastatic: 180,000
    • Children
    • Primary: 2,500
  • 4. Primary Brain Tumors
    • Glioma
    • Astrocytoma, oligo, mixed glioma, ependymoma
    • Meningioma
    • Benign
    • Atypical
    • Malignant
    • Pituitary adenoma
    • Acoustic schwannoma
    • Craniopharyngioma
    • Pediatric tumors
    40 - 50% 15 - 20% 10% 6 - 10% 5% 5% Brain Tumors: Prevelance
  • 5. Benign tumors
    • Menigniomas
    • Pituitary tumors
    • Vestibular schwannoma
    • Craniopharyngioma
  • 6. Meningioma
    • Incidence 6/100,000 persons
    • Peak occurrence 60-70yrs
    • Women > men
    • Multiple in patients with NF2
    • Vascular, non-glial tumors that arise from arachnoidal cells of leptomeninges; attached to dura
    • WHO classification based on grade, histology, proliferative index, brain invasion
    • Incidental meningiomas at autopsy 1.4%
  • 7. Histopathology
    • WHO I
    • Low proliferative index
    • Limited invasion
    • WHO II (a typical, choroidal, clear cell)
      • Increased mitotic activity ( > 4 or more mitoses per 10 hpf)
      • 3 or more of following (inc cellularity, hi N/C ratio, prominent nucleoli, sheet-like growth, foci of spontaneous or geographic necrosis)
    • WHO III (anaplastic, papillary, rhabdoid)
    • Histologic features of frank malignancy
    • Hi mitotic index (20 or more mitoses/10 hpf)
    • Usually fatal (<2yrs)
  • 8. Meningioma
    • Neuroimaging
    • Isodense dural masses
    • Intense contrast enhancement
    • Characteristic feature is ‘dural tail’
  • 9. Treatment
    • Incidental
    • Can observe with periodic imaging
    • Anything else
    • Gross total resection (GTR) is desirable.
    • Extent of resection associated with risk of recurrence
    • Radiotherapy
    • Adjuvant after STR
    • Salvage therapy
    • Primary therapy in elderly
    • Improves progression free survival (PFS)
    • No impact on overall survival (OS)
  • 10. Meningioma: RT
    • Dose
    • Benign (54 Gy)
    • Atypical or Malignant (59.4 - 63 Gy)
    • Volumes (fractionated tx)
    • GTV: residual tumor volume or gross tumor
    • CTV: GTV + 1 cm
    • PTV: 3-5 mm
    • SRS
    • Limited to lesions < 3 cm with acceptable separation from critical structures. Ctrl rate ~ 90%
  • 11. Meningioma
    • Local Recurrence
    • S S+RT
      • GTR 12%
      • STR 40% 18%
      • STR at recurrence 76% 43%
      • Overall Survival
      • 5yr 10yr
      • 85% 77%
      • Goldsmith et al, J Neurosurg 1993
  • 12. Vestibular schwannoma
    • Epidemiology
    • WHO grade I (a.k.a. acoustic neuroma )
    • Association with NF2
    • Bilateral lesions
    • Incidence 1/100,000 persons per year
    • Peak in 4 th and 6 th decades
    • Presentation
    • Tinnitus, hearing difficulties, facial paresthesia
  • 13. Vestibular schwannoma: Imaging
    • MR-well-circumscribed, cystic, enhancing mass in the CP angle extending into IAC
  • 14. Treatment
    • Surgery for lesions >3cm
    • Radiotherapy for lesions <3cm
    • SRS (12 Gy x 1)
    • Hypofractionated FSRT (5Gy x 5)
    • Conventional FSRT (45 -50 Gy)
      • ** Hearing preservation ~50-65% if serviceable hearing at baseline
  • 15. Craniopharyngioma
    • Epidemiology
    • 1-5% of all intracranial tumors
    • 0.5-3/million/yr
    • Histology
    • WHO grade I; b enign
    • Partly cystic, partly solid epithelial tumor of sellar region
    • Derived from Rathke pouch epithelium
    • Bimodal incidence; peaks 5-14 yrs and >50 yrs
  • 16. Craniopharyngioma
    • Presentation
    • Visual disturbances
    • Endocrine deficiencies
    • GH, LH/FSH, ACTH, TSH, DI
    • Cognitive impairment & personality changes in 50%
    • Freq signs elevated ICP from compression of 3 rd vent
  • 17. Craniopharyngioma
    • Imaging
    • CT : contrast enhancement of solid portions and cyst capsule, calcifications
    • MR : cystic portion isointense, and solids parts hyperintense
    • Treatment
    • Surgery
    • GTR
    • diff due to location; 10 yr PFS 30-40% w/ surg alone)
    • STR
    • observe
    • postop RT (EBRT 50-54Gy or SRS); 10 yr PFS 55-90%
    CT MRI
  • 18. Glioma
    • WHO grade
    • I pilocytic astrocytoma
    • II astrocytoma, oligodendroglioma, mixed
    • III anaplastic astrocytoma
    • IV glioblastoma multiforme
  • 19. Low Grade Glioma (LGG)
    • Epidemiology
    • 1/100,000 adults
    • Assoc w/ NF1, tuberous sclerosis
    • Presentation
    • Sz, HA, focal neurological deficit
    • Imaging
    • CT: hypodensity
    • MRI: T1 (hypodense), T2/FLAIR (hyperintense)
    • Don't often contrast enhance
  • 20. LGG: Treatment
    • Early management unclear
    • Surgery
    • No class I data to support improved survival with maximal safe resection
    • Class II data suggests improved survival & lower recurrence
    • Chemotherapy
    • Not all respond though role in some tumors
    • Oligo > astro
    • LOH 1p, 19q: predicts response to chemo as well as OS
    • Current clinical trials investigating RT + TMZ
  • 21. LGG: Radiotherapy
    • Is early RT better?
    • RTOG 98-02 had observation only arm (pts < 40 yrs, completely resected with PFS-3 & OS-3 of 97%, 73%
    • Factors predicting recurrence
    • Age > 40, astrocytoma histo, max tumor dimension > 6 cm, tumor crossing midline, presence of neurological deficit prior to surgery
    • 0-2 = low risk (survival 7.8 yrs)
    • > 2 = high risk (survival 3.7 yrs)
    • Dose / Target volumes
    • GTV = T2 enhancement; CTV = GTV + 2 cm
    • Dose = 45 - 50.4 Gy (no benefit to dose escalation; higher toxicity)
  • 22. Glioblastoma
    • 50-60% of all astrocytic neoplasms
    • 2-3 new cases per 100,000 population
    • Peak 45-70 years
  • 23. Role of RT in GBM
    • Address residual infiltrating disease
    • Improve progression-free survival
    • Improve overall survival
  • 24. RTOG Target Delineation
  • 25.
    • T1 post contrast
  • 26. RTOG Boost Volume Delineation
  • 27.
    • T1 post contrast delineation
  • 28.  
  • 29. Anaplastic astrocytoma
    • RT guidelines are identical 60Gy/30 Fx
  • 30. Poor KPS, Elderly GBM
    • Short course RT
    • 50 Gy/ 20 fx/4 weeks
    • 30 Gy/10 fx ->2 wk break-> 21 Gy/7
    • 40 Gy/15 fx/3 weeks
    • 30 Gy/10 fx
  • 31.  
  • 32. Ependymomas
  • 33. Ependymoma Kun, Tarbell ASTRO 2003 Refresher Course
  • 34. RT for ependymoma
    • Grade 2 (Low grade)- 50-54 Gy
    • Grade 3 (High grade)- 60 Gy
    • Volume:
    • Involved field RT if no disease in CSF
    • Craniospinal RT to 36 Gy followed by boost to involved field to 50-54 Gy (low grade) and 60 Gy (high grade)
  • 35. Posterior Fossa Delineation
  • 36. Adult medulloblastoma
    • CSI alone
    • chemo reserved for relapse
    • 54Gy PF, 36Gy CSI, 1.5Gy/day
  • 37. Technical pitfalls- Cribiform plate recurrences
    • Important to clearly define cribiform plate on simulation film or on sagittal DRR
  • 38. Technical pitfalls- Cribiform plate recurrences
    • site of increased recurrences related to inadvertent shielding of the cribiform plate in attempt to shield the orbits
  • 39. Cranial field design
    • Blocks are drawn to include the entire cribiform plate which extends below the frontal lobes and the superior orbit
    • block is drawn just anterior to vertebral bodies of cervical spine
    • inferior border defined so that exit dose from spine field is below oropharnyx but above shoulders
  • 40. Spinal field design
    • Width typically 5-8cm
    • target volume is spinal canal
    • Spade design or flaring out at sacrum is not necessary
  • 41. Conventional PF field design
    • Approximated by drawing a line from foramen magnum to vertex
    • draw perpendicular bisector of this line and divide into thirds
    • PF is defined by connecting inion to posterior 1/3 and connecting to posterior clinoid
  • 42. Junctioning fields
    • junction is shifted 0.5cm every 5 fractions (usually 3 times)
    • to match between upper and lower spine field if two spine fields --use standard gap calculation or computerized treatment planning
    • match occurs at center of the spinal cord
  • 43. Exact match
    • Inferior border of cranial fields and upper border of spine fields form an exact match on skin by rotating the couch towards the gantry
  • 44. Divergent match
    • Alternatively, the couch can remain stationary
    • this results in directly opposed cranial fields that diverge slightly into spine field
  • 45. Divergence into lens
    • Gantry rotated to avoid divergence into contralateral lens
    • bony canthi are wired out for conventional simulation
  • 46. Geometric match
    • Collimator of cranial field is rotated to match divergence of spinal field
    • This completes the geometric match
  • 47. Various junction techniques
    • Figure A demonstrate MDACC technique
    • Figure B shows exact match created by kicking couch
    • Figure C shows a gap introduced as an extra margin of safety
    • Illustration taken from Leibel et al Textbook of Radiation Oncology p946
  • 48. Brain Metastases -Epidemiology -WBRT + SRS
  • 49. Histology and Frequency
    • Lung accounts for 30-60% of all brain mets
      • Ranks 2 nd among tendency to metasize to brain
      • 18-65% of lung ca pts develop brain mets
      • >40% SCLC pts and adenoca have brain mets,2x that of other types such as squamous
  • 50. Histology & Frequency
    • Ranks 2 nd to lung as most frequenly occurring primary tumor in brain mets pts
    • Among women, breast cancer is the most common cause of brain metastasis (5-30% of all brain mets)
    • Ranks 3 rd in tendency to metastasize to brain
  • 51. Histology and Frequency
    • Melanoma ranks 3 rd among giving rise to brain mets
    • Of patients with brain mets, 5-21% will have melanoma as primary
    • Melanoma (4% of all cancers) has highest propensity of all malginant tumors to metastasize to brain (6-43% clinical,12-90% autopsy series)
  • 52. Other histologies
    • Renal cell frequency of brain metastases 11%
    • Colorectal cancers metastasize to brain 0.74-10%, representing 1.8-4.8% of all metastatic brain tumors
    • Prostate cancer metastasizes 0.6-4.4%, most detected at autopsy. Small cell+TCC much more likely than adenocarcinomas
  • 53. Role of RT
    • Plays major role in brain metastases
    • treatment with WBRT 20-40Gy/1-4wks results in survival of 4-6 months (RTOG)
    • improved symptoms: H/A, seizures, symptoms increased intra-cranial pressure, cranial nerve deficits
    • CR to WBRT 50% cases, durability 65% 1y
  • 54. Prognostic factors -RPA Class
    • Gaspar et al defined RPA Class from database of 3 RTOG trials
    • Class I -KPS > 70, controlled primary, brain sole site of metastasis, <65 years
    • Class II-KPS > 70 not in class I
    • Class III KPS <70
    • Survival 7.1, 4.2 ,2.3 mos respectively
  • 55. RTOG Dose-fractionation schemes
    • 30Gy/10fx vs 30Gy/15fx vs 40Gy/2.67Gy/ 15 vs 40Gy/20fx
    • 20Gy/5fx vs 30Gy/10fx vs 40Gy/2.67/15fx
    • 10Gy/1fx
    • 50Gy/20 fx vs 30Gy/10fx favorable pts
    • 48Gy-70.4Gy/1.6bid
    • 30Gy/10 vs 54.4Gy/1.6bid
  • 56. RTOG dose fractionation schemes
    • All treatment schedules comparable: frequency, duration improvement TTP, survival , palliation
    • WBRT improved neuro function 50%
    • Neurologic response in “ultra-rapid” treatment comparable to more protracted but duration of improvement less
  • 57. RTOG altered fractionation
    • Accelerated fractionation tested in RTOG Phase III study in 445 pts KPS > 60 to 54.4Gy/1.6bid or 30Gy/30fx
    • study failed to demonstrate any improvement in survival in group receiving 54.4Gy
  • 58. Postoperative WBRT
    • Majority (4/6) retrospective studies do not show a survival benefit but are conflicting
    • Patchell study is only randomized trial
      • 95 patients with resected single brain met
      • Surgery +/- WBRT 50.4Gy/1.8Gy fx
      • recurrences 18% vs 70% p<0.001 original site 10% vs 46% p<0.01 other sites in brain 14% vs 37% p<0.01 neurologic deaths 14% vs 44% p=0.003
      • overall survival 10-11mos p=NS
  • 59. Stereotactic Radiosurgery
    • Growing body of experience from different institutions supports use and effectiveness of SRS which must be compared to surgery
    • Surgical gold standard Patchell study 1990 S+RT(n=25) v. RT(n=23) single brainmet local recurrence 20% vs 52% p<0.02 overall survival 40wks vs 15wk p<0.01 function indep 38wks vs 8wk p<0.005
  • 60. Radiosurgery data
    • Multi-institutional outcome and prognostic factor analysis of RS for resectable brain met using same criteria as Patchell
    • RS + WBRT for single brain met can produce substantial functional survival of 56 weeks [Auchter IJROBP 1996]
  • 61. Patient selection for surgery verus radiosurgery
    • Surgery allows complete resolution of mass effect, tissue diagnosis, no risk of radiation necrosis
    • Radiosurgery advantages are decreased risk of hemorrhage and infection, no risk of tumor seeding, reduced costs
    • cost-utility analysis [Mehta]
      • $31,454 vs $15,502/QALY, where QALY defined as functional indep living
  • 62. Complications of WBRT
    • Acute effects-mild fatigue, hair loss, scalp erythema, hyperpigmentation
    • Subacute-(3-10wks)somnolence syndrome or persistance fatigue especially in children
    • Long term-DeAngelis reported 12 pts developed dementia, ataxia, urinary incontinence leading to severe disability
    • total dose ranged from 25-39Gy/3-6Gy
  • 63. WBRT +/-SRS for KPS > 70 and controlled primary or Surgery (if highly symptomatic, or mass effect) + WBRT or WBRT for KPS <70 or uncontrolled primary Primary Therapy for Metastatic Brain Disease Lesion number Diagnostic uncertainty and asymptomatic Observation If grows, surgery or SRS+/-WBRT Surgery 1 <1cm >1cm Convincing Metastasis Single Solitary 2-3 >3 KPS > 70 and controlled primary KPS < 70 or uncontrolled primary Surgery +/- WBRT or SRS (<3cm) +/- WBRT for non-surgical candidate (if >3cm, WBRT only) WBRT (surgery to lesions causing mass effect) WBRT (Surgery if tumor causes mass effect) *Surgery or SRS (<3cm) +/- WBRT or
  • 64. RTOG 90-05
    • Maximum tolerated dose for radiosurgery
      • 24 Gy < 2cm
      • 18 Gy 2-3 cm
      • 15 Gy 3-4 cm
    Shaw E, et al Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):291-8.