CNS tumors_MG

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CNS tumors_MG

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

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