id2423187 pdfMachine by Broadgun Software - a great PDF writer! - a great PDF creator! - http://www.pdfmachine.com http://www.broadgun.com

Brain stem gliomaBrain stem glioma

�� 20% of childhood and 5% of adult CNS tumours.20% of childhood and 5% of adult CNS tumours.

�� Most frequently in children between 3 and 10 yearsMost frequently in children between 3 and 10 years

�� Tissue confirmation is frequently not feasible with Tissue confirmation is frequently not feasible with

infiltrating, except in expansile tumorsinfiltrating, except in expansile tumors

�� 6060--80%of patients do not have a histological diagnosis80%of patients do not have a histological diagnosis

�� Universally associated with dismal prognosisUniversally associated with dismal prognosis

�� Historically, regarded as a single entityHistorically, regarded as a single entity

Clinical presentationClinical presentation

�� Insidious/sudden onsetInsidious/sudden onset

�� Cranial nerve palsiesCranial nerve palsies

�� Long tract signs Long tract signs

((hemiparesishemiparesis))

�� Cerebellar signs (ataxia)Cerebellar signs (ataxia)

�� Long history Long history �� better better

prognosisprognosis

TypesTypes

FocalFocal 55--10%10%

Dorsal Dorsal exophyticexophytic 1010--20%20%

CervicomedullaryCervicomedullary 55--10%10%

Diffuse intrinsic Diffuse intrinsic 7575--85%85%

Focal tumorsFocal tumors

�� Surgery should be Surgery should be

attemptedattempted

�� Most are JPAMost are JPA

�� If fear of morbidity, RT If fear of morbidity, RT

�� Favourable prognosisFavourable prognosis

Abbott Ped Neurosurg 1991

Dorsal Dorsal exophyticexophytic tumorstumors

�� Insidious onsetInsidious onset

�� Surgery should be attemptedSurgery should be attempted

�� Most are JPA, lowMost are JPA, low--gradegrade

�� Favourable prognosisFavourable prognosis

�� RT for residual/progressive RT for residual/progressive

diseasedisease

Pierre-Kahn J Neurosurg 1993;79:845-52

CervicoCervico--medullarymedullary tumourstumours

�� Typically present with Cr N Typically present with Cr N

palsies, long tract signspalsies, long tract signs

�� Surgery treatment of choice Surgery treatment of choice

(GTR achieved in 75% of (GTR achieved in 75% of

cases)cases)

�� Most are JPA/lowMost are JPA/low--gradegrade

�� RT not given routinely except RT not given routinely except

for residual/progressive for residual/progressive

diseasedisease

Epstein J Neurosurg 1986

Diffuse Diffuse pontinepontine tumourstumours

�� Typically present with short Typically present with short

historyhistory

�� Surgery (including biopsy) Surgery (including biopsy)

not feasiblenot feasible

�� Most are fibrillary, but on Most are fibrillary, but on

autopsy highautopsy high--gradegrade

�� Direct RT in view of typical Direct RT in view of typical

clinicoclinico--radiological pictureradiological picture

�� MRS/perfusion/PET could be MRS/perfusion/PET could be

complementarycomplementary

Major therapeutic challengeMajor therapeutic challenge

Diffuse Diffuse pontinepontine gliomasgliomas

Literally everything tried, but nothing has really Literally everything tried, but nothing has really

changed the outcome of these tumourschanged the outcome of these tumours

FrustratingFrustrating

7%7%39.9%39.9%10107775.6Gy/1.26BID75.6Gy/1.26BID3939IIIIII

23%23%39.6%39.6%10106670.2Gy/1.17BID70.2Gy/1.17BID5757IIII

6.3%6.3%47%47%11116.56.566Gy/1.1BID66Gy/1.1BID3434II

2 YS2 YS1 YS1 YSMedianMedian

OSOS

(mths)(mths)

MedianMedian

PFSPFS

(mths)(mths)

DoseDoseNNGroupGroup

Increased Increased

toxicities toxicities

with 75.6 Gywith 75.6 Gy

2121Skin reactionSkin reaction

2626Otitis media/externaOtitis media/externa

4545Intralesional necrosisIntralesional necrosis

6262Steroid use > 3 mthsSteroid use > 3 mths

%%ToxicitiesToxicities

Freeman et al., IJROBP, 1993: 27(2)

RT Dose Escalation/HyperfractionationRT Dose Escalation/HyperfractionationPOG# 8495

Randomised trialRandomised trialPOG #9239:POG #9239:

132 pts between

6/92 and 3/96

Arm 1: 66 ptsArm 1: 66 pts

54Gy/1.854Gy/1.8

++

Cisplatin 100mg/m2 (120hr Cisplatin 100mg/m2 (120hr

cont. infusion)cont. infusion)

Arm 2: 64 ptsArm 2: 64 pts

HFT: 70.2Gy/1.17Gy BIDHFT: 70.2Gy/1.17Gy BID

++

Cisplatin 100mg/m2 (120hr Cisplatin 100mg/m2 (120hr

cont. infusion)cont. infusion)

randomizedrandomized

Mandell IJORBP; 1999: 43(5)

SurvivalSurvival

Median 8.5 months Median 8.5 months

for 54 Gyfor 54 Gy

8 months for 70.2 Gy 8 months for 70.2 Gy

MandellMandell IJROBP 1999IJROBP 1999

ChemotherapyChemotherapy

Randomised trial (n=74)Randomised trial (n=74)

�� RT alone (50RT alone (50--60Gy)60Gy)

�� RT + chemo (CCNU, vincristine, prednisone)RT + chemo (CCNU, vincristine, prednisone)

�� RT alone RT alone 5 yr survival was 17%; median time to 5 yr survival was 17%; median time to

relapse relapse -- 8 ms8 ms

�� RT + chemo RT + chemo 5 yr survival was 23% (p=0.56); 5 yr survival was 23% (p=0.56);

median time to relapse 7 mths.median time to relapse 7 mths.

J. Neurosurgery 66:1987J. Neurosurgery 66:1987

ChemotherapyChemotherapy

cipslatincipslatin basedbased

Compared 57 patients treated with 70.2Gy (POG #8495)Compared 57 patients treated with 70.2Gy (POG #8495)

toto

64 pts treated with identical RT + 64 pts treated with identical RT + cisplatinumcisplatinum ( POG 9239) ( POG 9239)

�Identical cohort, non�Identical cohort, non--randomised�randomised�

No difference in outcomeNo difference in outcome

Freeman IJORBP 2000, 47(3).

RadiotherapyRadiotherapy

FS a little generous as kids FS a little generous as kids

could be uncooperativecould be uncooperative

Conventional Cobalt/6 MVConventional Cobalt/6 MV

No great benefit of hiNo great benefit of hi--fi fi

techniquestechniques

Beneficial in focal tumours Beneficial in focal tumours

(conformal/stereotactic/IMRT)(conformal/stereotactic/IMRT)

5454--60 Gy/30#60 Gy/30#

Recurrent brain stem gliomasRecurrent brain stem gliomas

�� Individualise, symptomatic care/Individualise, symptomatic care/steriodssteriods

�� ReRe--irradiation rarely ever possible/helpfulirradiation rarely ever possible/helpful

�� Chemo largely ineffectiveChemo largely ineffective

�� Temozolomide, Temozolomide, TamoxifenTamoxifen, , interferonsinterferons, , IressaIressa, etc , etc ��

several small phase II studies several small phase II studies -- investigationalinvestigational

Large study material Large study material �� learnt what does not worklearnt what does not work

Something very original/innovative neededSomething very original/innovative needed

10% of all childhood CNS tumours10% of all childhood CNS tumours

90% are intracranial; 2/3 within the posterior fossa90% are intracranial; 2/3 within the posterior fossa

50% of pts are < 5yrs old, 25% are less than 250% of pts are < 5yrs old, 25% are less than 2

Difficult to treat, perplexing tumoursDifficult to treat, perplexing tumours

HaemorrhageHaemorrhage, calcification, calcification

Cellular, with Cellular, with

rosettes/rosettes/pseudorosettespseudorosettes

Anaplastic: 10Anaplastic: 10--30%30%

Spinal Spinal metsmets: 10: 10--15%15%

EpendymoblastomaEpendymoblastoma (PNET)(PNET)

Spinal MRI/CSF for post Spinal MRI/CSF for post

fossa/anaplastic tumoursfossa/anaplastic tumours

EpendymomaEpendymoma

Surgery treatment of choice and the most important prognostic faSurgery treatment of choice and the most important prognostic factorctor

Gross tumour resection (GTR) Gross tumour resection (GTR) -- 5050--75% long term control75% long term control

Subtotal resection (STR) Subtotal resection (STR) -- 00--30% GTR possible in only 50% cases, 30% GTR possible in only 50% cases,

aggressive debulking/2aggressive debulking/2ndnd looklook

Van Van VeelanVeelan JNS 2002JNS 2002

SchildSchild IJROBP 1998IJROBP 1998

RadiotherapyRadiotherapy

�� No randomised trial of RT No randomised trial of RT vsvs no RT, but large data about no RT, but large data about

efficacy of RTefficacy of RT

�� CSI CSI -- in 1970�s and 80�s, but does not influence local in 1970�s and 80�s, but does not influence local

control/survivalcontrol/survival

�� Present recommendationsPresent recommendations-- local RT (even in anaplastic)local RT (even in anaplastic)

�� CSI CSI �� if spinal if spinal metsmets (CSF or MRI)(CSF or MRI)

�� Unresolved questions Unresolved questions �� a) RT in completely resected tumoursa) RT in completely resected tumours

b) can we avoid RT in very young childrenb) can we avoid RT in very young children

Merchant IJROBP 2002;53:51Merchant IJROBP 2002;53:51--77

VanuytselVanuytsel IJROBP 1992;23:313IJROBP 1992;23:313--99

RadiotherapyRadiotherapy

�� Traditionally post fossa irradiation, Traditionally post fossa irradiation,

cover inferiorly cover inferiorly uptoupto C3C3--C4C4

�� Local RT= GTV + margin (2 Local RT= GTV + margin (2 cmscms))

�� Conformal (3D CRT, Stereotactic Conformal (3D CRT, Stereotactic

RT with lesser margins)RT with lesser margins)

Stereotactic conformal RTStereotactic conformal RT attractive option attractive option

minimise treatment related toxicity; dose escalationminimise treatment related toxicity; dose escalation

6 field 6 field noncoplanarnoncoplanar technique the most optimaltechnique the most optimal

-20-10

0102030405060708090

B/l +vertex obl + vertex 3 field NCP 6 field

95%80%50%

Murthy Murthy RadiothRadioth.& .& OncolOncol 2003;67:1912003;67:191--88

ChemotherapyChemotherapy

�� Role unknownRole unknown

�� Randomised trial of RT Vs RT + Randomised trial of RT Vs RT + adjadj V, CCNU & P V, CCNU & P ��

no benefit (no benefit (MPOMPO 1996;27:81996;27:8--1414))

�� CCG trial CCG trial �� V, CCNU, P Vs 8V, CCNU, P Vs 8--inin--1 chemo: no 1 chemo: no

difference (difference (JNS 1999;88:695JNS 1999;88:695--0303))

�� Could consider for children < 5 years with 40% not Could consider for children < 5 years with 40% not

requiring RT for 2 years (requiring RT for 2 years (JCO 2001JCO 2001))

�� Role needs to be crystallised Role needs to be crystallised

Benign/lowBenign/low--grade with indolent behaviourgrade with indolent behaviour

Surgery treatment of choiceSurgery treatment of choice

completely excised/small residual completely excised/small residual -- observe observe

excellent cure ratesexcellent cure rates

Fernandez Fernandez NeurosurgNeurosurg 2003;53:5442003;53:544

PilocyticPilocytic astrocytomaastrocytoma

�� Chemotherapy (baby brain protocol, Chemotherapy (baby brain protocol, CarboplatinCarboplatin + +

VCR) for very young children to avoid/defer RTVCR) for very young children to avoid/defer RT

�� RT RT �� only for large residual, near brain stem or only for large residual, near brain stem or

progressiveprogressive

�� Local RT (preferably with conformal RT to 50Local RT (preferably with conformal RT to 50--54 54

Gy/30 #) Gy/30 #)

Packer JCO 1993;11:850Packer JCO 1993;11:850--77

Conformal therapyConformal therapy

phase II data phase II data

�� 102 children (64 EP, 38 LGA)102 children (64 EP, 38 LGA)

�� PTV= GTV + 1.0 cm CTV + 0.5 PTV= GTV + 1.0 cm CTV + 0.5 cmscms

�� Localised fields with conformal RT to 54 Localised fields with conformal RT to 54 �� 59 Gy59 Gy

�� median follow up of 17 months (3 median follow up of 17 months (3 -- 43)43)

�� 92 patients controlled92 patients controlled

�� 6 pts with EP failed (5 local, 1 disseminated)6 pts with EP failed (5 local, 1 disseminated)

�� 4 pts with LGA failed (3 within CTV)4 pts with LGA failed (3 within CTV)

�� Encouraging prelim results with narrow marginsEncouraging prelim results with narrow margins

Merchant IJROBP 2002;52:325Merchant IJROBP 2002;52:325--3232

�� 26 children (benign and low26 children (benign and low--grade brain tumours)grade brain tumours)

�� Localised fields with conformal RT to 54 GyLocalised fields with conformal RT to 54 Gy

�� median follow up of 25 months (12 median follow up of 25 months (12 -- 47)47)

�� 25 patients controlled; Cognition 25 patients controlled; Cognition maintainedmaintained

Baseline score of Full Scale IQ for patients treated Baseline score of Full Scale IQ for patients treated

with SCRT (n=20)with SCRT (n=20)

ClassClass IQ LimitsIQ Limits Number of Patients Number of Patients

DefectiveDefective 69 & below69 & below 44 (20%)(20%)

BorderlineBorderline 7070--7979 55 (25%)(25%)

DullDull--normalnormal 8080--8989 55 (25%)(25%)

AverageAverage 9090--109109 5 (25%)5 (25%)

BrightBright--normalnormal 110110--119119 0 (0%)0 (0%)

SuperiorSuperior 120120--129129 1 (5%)1 (5%)

Very SuperiorVery Superior 130 & above130 & above 0 (0%)0 (0%)

14/20 patients have below 14/20 patients have below avgavg IQIQ

Jalali IJROBP 2006 (Jalali IJROBP 2006 (IinIin press)press)

Neuropsychological profile in children treated with SCRTNeuropsychological profile in children treated with SCRT

HighHigh--grade hemispheric gliomasgrade hemispheric gliomas

Relatively rareRelatively rare

Somewhat better outcome than Somewhat better outcome than

adults but longadults but long--term cure still rareterm cure still rare

OverexpOverexp of p53 strong prognostic of p53 strong prognostic

factor (factor (NEJM 2002NEJM 2002))

Surgery, Surgery, convconv RT std of care as in RT std of care as in

adultsadults

Role of chemo not fully evolvedRole of chemo not fully evolved

HighHigh--grade hemispheric gliomasgrade hemispheric gliomas

�� Randomised trial of RT + Randomised trial of RT + adjadj pCVpCV Vs RT alone (n=58): 5yr Vs RT alone (n=58): 5yr

DFS of 46% Vs 18% (CCG 943)DFS of 46% Vs 18% (CCG 943)

�� Results never duplicated (38 % slides reviewed were not Results never duplicated (38 % slides reviewed were not

highhigh--grade, grade, BoyettBoyett 19981998))

�� Intensive/pre irradiation chemo: no major impactIntensive/pre irradiation chemo: no major impact

�� Currently several regimens being tested (TMZ, Currently several regimens being tested (TMZ,

thalidomide, thalidomide, carboplatincarboplatin, , topetecantopetecan, etc), etc)

SpostoSposto J J NeuroOncolNeuroOncol 19891989