Youmans Neurological Surgery

1. 250 Fractionated Radiation Therapy for
Malignant Brain Tumors
Youmans Neurological surgery
13/09/2559
George M. Cannon
Minesh P. Mehta

2. Outline
• Brain metastasis
• Malignant glioma
• Anaplastic Astrocytoma
• Anaplastic Oligodendroglioma
• Primary CNS lymphoma
• Malignant meningeal tumor
• Primitive Neuroectodermal Tumors
• Germ Cell Neoplasms

3. Brain metastasis
• Most common : lung, breast, melanoma
• Less common : primary tumors of the gastrointestinal tract and
genitourinary system, lymphomas, sarcomas, and prostate cancer
• Median survival time of untreated patients with brain metastases is
approximately 1 month

4. Fractionation Trials

5. Prognostic Factor analysis
Class I : KPS ≥ 70, Age ≤ 60, control primary and absence of extracranial metastasis
Class III : KPS < 70

6. Prognostic Factor analysis
• 0-1 median survival time 2.6 months
• 1.5-2.5 median survival time 3.8 months
• 3 median survival time 6.9 months
• 3.5-4.0 median survival time 11 months

7. Role of Adjuvant Whole-Brain Radiotherapy
no significant difference in overall survival between the two groups,
even though the study was not powered to detect a survival difference

8. Side Effects of Whole-Brain Radiotherapy
• Acute side effect
• fatigue, hair loss, particularly along the midline and vertex, erythema, and
otitis
• Months to years side effect
• Impairment of neurocognitive function
• Survived longer than 1 yrs
• Neurotoxicity with progressive dementia, ataxia and urinary incontinence
• Neurocognitive function factor
• presence of brain metastases, neurosurgical interventions, chemotherapy,
and other neurotoxic therapies such as steroids and anticonvulsants

9. Reirradiation of Brain metastasis
• Aggressive, primary treatment interventions to provide durable local
control is obviously preferable to being backed into this unfortunate
situation of recurrent intracranial disease with limited treatment
options.

10. Summary
• 30 Gy in 10 fractions given over 2 wks

12. Glioblastoma multiforme
• Diffusely infiltrative the brain parenchyma
• Can’t complete microscopic surgical excision
• Grade IV

13. Utility of radiation therapy
Compare mithramycin vs surgical alone
; no differ in mithramycin use
Post-operative carmustine(BCNU)
; WBRT improve survival
Post-operative semustine(MeCCNU)
; MeCCNU infeior
GBM surgical resection with or without RT
; improve in WBRT

14. Radiation Target Volume
• Planned target volume 1 (PTV1)
• the contrast-enhancing lesion,
• resection cavity
• surrounding edema if present (best
seen on T2-weighted images)
• followed by a 2.0-cm expansion
• Planned target volume 2 (PTV2)
• After 46 Gy of radiation
• the contrast-enhancing lesion with a
2.5-cm expansion

15. Recurrence Patterns
• The recurrent tumor that surpassed the outside surface of the PTV
was still predominantly centered within the tumor bed
• Central or in-field

16. Dose Escalation

17. Prognostic Factor Analysis

18. Prognostic Factor Analysis
Methylguanine-deoxyribonucleic acid methyltransferase (MGMT) methylation has
also proved to be a powerful predictor of survival in patients receiving RT and TMZ

19. Anaplastic Astrocytoma
• Grade III astrocytoma
• Median survival in the 2- to 3-year range
• Partial brain fields
• GTV(Gross total volume) : hypodense edema or T2 abnormality,
contrast-enhancing volume
• CTV(Clinical target volume): 2- to 3-cm margin of tissue surrounding
the GTV.
• The initial volume is typically treated to 46 Gy and the boost volume
to 60 Gy
• Median survival decreased with more aggressive therapy
• RT + CMT did not achieve better compare with RT alone

20. Anaplastic Oligodendroglioma
• Chemotherapy potentially improves PFS, but the effect on survival is
not statistically obvious
• Patients with 1p and 19q deletions had significantly better outcomes
• MGMT promoter methylation : TMZ

21. Primary central nervous system lymphoma
• lymphoma confined to the CNS
• Dissemination through the craniospinal axis
• Radiosensitive tumor
• 40-50 Gy total
• Chemotherapy
• Younger than 60 yrs,better prognois

22. Malignant Meningeal Tumors
• Hemangiopericytoma
• Slow but progressive radiographic response to ionizing radiation
• Significant metastasis : liver, lung, bone and soft tissue
• Effetiveness is dubious [Greenberg]
• Malignant meningioma
• Aggressive surgical resection followed by postoperative high-dose RT
• 5 Yr survival less thans 20%
• GTV : expan 1.5-2 cm.
• 55-60 Gy [Greenberg]

23. Primitive Neuroectodermal Tumors
• sheets of small round blue cells with scant cytoplasm
• supratentorial PNET, pineoblastoma, medulloblastoma, and
ependymoblastoma
• “standard risk” or “high risk”
• age, Chang M stage, location, and extent of resection
• Standard-risk patients :
• Chang M0 stage disease (no evidence of microscopic or macroscopic
dissemination along the craniospinal axis)
• posterior fossa origin
• age older than 3 years
• less than 1.5-cm2 tumor residual after surgery

24. Primitive Neuroectodermal Tumors
• Craniospinal RT at recommended doses of 36 Gy to the craniospinal
axis and a posterior fossa boost to 54 Gy
• 35-40 Gy to whole craniospinal axis + 10-15 Gy boost to tumor
bed(usually posterior fossa) [Greenberg]
• Combination chemotherapy given with craniospinal RT continues to
be pursued

25. Germ Cell Neoplasms
• CNS germinomas have been managed with craniospinal RT
• Nongerminomatous germ cell tumors of the CNS, survival is
significantly poorer, and both surgical resection and chemotherapy
are the primary modalities of treatment

26. Complication
• Acute : occur during and immediately after completion of a course of
external beam
• Acute skin reaction : dry desquamation, erythema
• Temporary alopecia
• Fatigue
• Flash of light
• Serous otitis media
• Uncommon : Nausea, increase intracranial hypertension

27. Complication
• Subacute : several week of month after complete RT
• Lethargy and somnolence
• Children : acute somnolence syndrome
• N/V, ataxia, dysphagia, cerebellar ataxia
• Keratoconjunctivitis
• Radiation necrosis : PET or MRS

28. Complication
• Late complication : several month to years
• Unclear because short-term survivor
• Impairment of intellectual function : memory and mathmetical ability
• Dementia, ataxia, confusion