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Estratégias Terapêuticas no Manejo dos Gliomas do Tronco Cerebral
Dr. Luis SouhamiMcGill University
Montreal - Canada
McGill
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Brainstem Gliomas
15-20% of all pediatric brain tumorsRare in adults
Heterogeneous, varying radiology findingsVariable prognosis
Focal extension: <50% of organ diameterDiffuse extension: >50% of organ diameterDiffuse intrinsic pontine glioma
Poorly demarcatedMost common
McGill
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Brainstem Gliomas in Adults
Less common (1% of adult brain tumors)DIPG typically low-grade in adults Better outcome than children (DPIG)Overall survival: 45-65% (at 2 to 5 years)Median survival: 4.5 – 7 years
Data available hard to interpretMixed population (children and adults)Mixed histopathology
Molecular biological patterns poorly studiedMcGill
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ClassificationChoux M et al. 2000
Based on CT and MR imagesType I DiffuseType II Intrinsic, focalType III Exophytic, focalType IV Cervicomedullary
I II III IV
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Dellaretti M et al. Neurooncol 2012
MR vs. Histopathology
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Dellaretti M et al. Neurooncol 2012
MR vs. Histopathology
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Brainstem Gliomas Adults
Author # Pts Median Age (yrs)
Therapy Clinical Response
Radiological Response
Median Survival
Kesari1
(USA)101 36 RT
(54 Gy)88% 85 mos
Guillamo2
(France)48 29 RT
(52 Gy)40% PR 18%
Stable 64%Prog 18%
65 mos
Salmaggi3
(Italy)32 31 RT
(54 Gy)48% Minor 19%
Stable 32%59 mos
1- Kesari et al. J Neurooncol 2008; 2- Guillamo et al. Brain 2001; Salmaggi et al. J Neurol 2008
McGill
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Brainstem Gliomas (INCA)
Ueoka D.I. et al. J Neurol Sci 2009
86 Pts: 24 adults (28%)
Median survival = 9 mos
McGill
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Brainstem Gliomas - Adults
Kesari et al. J Neurooncol 2008 Guillamo et al. Brain 2001
McGill
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Brainstem Gliomas - Adults Prognostic Factors
Kesari et al. J Neurooncol 2008
Guillamo et al. Brain 2001
McGill
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2012
2008
2005
McGill
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McGill
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McGill
2011
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McGill
2012
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2003 2005 2012
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Strategies used to improve outcome
RadiotherapyCan altered fractionation/higher doses improve outcome?
Chemotherapy Temozolomide
Other agents?
Target therapy Can target therapy change outcome?
McGill
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Radiotherapy for DIPGAltered Fractionation
Hyperfractionated radiotherapySmaller dose/fx, >1 fx/day, higher total dose
Accelerated radiotherapySame dose/fx, >1 fx/day, shorter overall
treatment time
Hypofractionated radiotherapyLarger dose/fx, shorter overall treatment time
McGill
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Hyperfractionated RTPOG 9239
• Phase III; Children
RANDOMIZE
Conv. RT – 54 Gy/30 fxs + cisplatin
HFRT – 70.2 Gy/60 fxs BID
Cisplatin: 100 mg/m2, continuous infusion weeks1, 3 and 5
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POG 9239: Survival
Mandell et al. Int J Radiat Oncol Biol Phys 1999
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Hypofractionated Radiotherapy
Janseens GO et al. Int J Radiat Oncol Biol Phys 2012
27 children39 Gy/ 3 Gy fx44.8 Gy/ 2.8 Gy fx
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Accelerated Radiotherapy
SurvivalMedian 8.6 months1 year 32%2 year 11%
Lewis et al. Int J Radiat Oncol Biol Phys 1997McGill
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Altered FractionationSummary
No benefit for hyperfractionated radiotherapy with doses up to 78GyStandard dose is 54 Gy
No benefit for accelerated radiotherapyHypofractionated radiotherapy probably safeNo survival advantage
New techniques: IMRT, FSRT, SRS
McGill
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IMRT PlanningIsodoses Gy
6054
53.25030
Brainstem
Chiasm
Pituitary
Cochlea
McGill
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Chemotherapy/Target Therapy
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Concluding Remarks
Major differences between children and adultsRT remains the mainstay of therapyNumerous chemotherapy regimens have not
changed outcome in DIPGEmerging molecular data may aid therapy
optimizationFurther translational studies are urgently
needed McGill