Estratégias Terapêuticas no Manejo dos Gliomas do Tronco Cerebral

Dr. Luis SouhamiMcGill University

Montreal - Canada

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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

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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

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

Dellaretti M et al. Neurooncol 2012

MR vs. Histopathology

Dellaretti M et al. Neurooncol 2012

MR vs. Histopathology

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

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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

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Brainstem Gliomas - Adults

Kesari et al. J Neurooncol 2008 Guillamo et al. Brain 2001

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Brainstem Gliomas - Adults Prognostic Factors

Kesari et al. J Neurooncol 2008

Guillamo et al. Brain 2001

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2012

2008

2005

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2011

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2012

2003 2005 2012

Strategies used to improve outcome

RadiotherapyCan altered fractionation/higher doses improve outcome?

Chemotherapy Temozolomide

Other agents?

Target therapy Can target therapy change outcome?

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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

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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

POG 9239: Survival

Mandell et al. Int J Radiat Oncol Biol Phys 1999

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

Accelerated Radiotherapy

SurvivalMedian 8.6 months1 year 32%2 year 11%

Lewis et al. Int J Radiat Oncol Biol Phys 1997McGill

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

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IMRT PlanningIsodoses Gy

6054

53.25030

Brainstem

Chiasm

Pituitary

Cochlea

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Chemotherapy/Target Therapy

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