Jonathan Klein PGY3 Radiation Oncology University of Toronto Case 1 Mr A 64M presents to ER with two weeks of dizziness and things on my left side look funny Feels he veers to the left side when walking ID: 735606
Download Presentation The PPT/PDF document "High Grade Gliomas : Case Presentation..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
High Grade Gliomas: Case Presentation and Summary of Evidence for Radiation Therapy Management
Jonathan Klein
PGY3,
Radiation
Oncology
University of TorontoSlide2
Case #1Mr. A64M presents to ER with two weeks of dizziness and “things on my left side look funny”.
Feels he veers to the left side when walking.Slide3
WorkupHistory
PhysicalSlide4
WorkupHistoryCharacterize symptoms: OPQRSTGeneral: headache, seizures, N/V, syncope, cognitive
Δ
Focal: weakness, sensory loss, aphasia, visual
Δ
Family history
PMHx
/Meds/allergies
PhysicalSlide5
WorkupHistory
Characterize symptoms - OPQRST
General: headache, seizures, N/V, syncope, cognitive
Δ
Focal: weakness, sensory loss, aphasia, visual
Δ
Family history
PMHx
/Meds/allergies
Physical
CNS: GCS, CNII-XII, gait, strength, DTRs,
Babinski
Screening CVS, lung, abdomen examSlide6
ImagingMRI with gadolinium is preferred modalityRelevant imaging findings for contouring
T1 with gadolinium: enhancing cavity
T2/FLAIR: edema and enhancementSlide7
WorkupSlide8
ImagingSlide9
Histology4 criteria (AMEN) :nuclear Atypia Mitosis
Endothelial proliferation
Necrosis
# Criteria 0 1* 2 3-4
Grade I II III IV
*1 criterion = atypia for Grade II Slide10
StagingAJCC TNM Staging System not usedSlide11
Staging
GBM can be primary or secondary (10%)Slide12
PrognosisPrognosis by classification
Oligodendroglial component is positive prognostic factorSlide13
PrognosisCurran, JNCI, 1993
Recursive partitioning analysis
to retrospectively analyze 1578 patients with high grade
glioma
3 RTOG studies testing RT +/- Chemo
Results
<50yo: histology most important prognostic factor
>50yo: KPS most important prognostic factor
Mental status
differentitated
poor KPS group
Conclusion: Older and poor KPS do worse
Curran et al. J
Natl
Cancer Inst. 1993 May 5;85(9):704-10.Slide14
Lamont ED, Christakis NA. Survival estimates in advanced cancer.
In
:
UpToDate
,
Basow
, DS (Ed),
UpToDate
,
Waltham
, MA, 2013. Slide15
PrognosisBy recursive partitioning analysis (RPA)
Curran et al. J
Natl
Cancer Inst. 1993 May 5;85(9):704-10.Slide16
ManagementReferred to NeurosurgeryWhat should they do?Slide17
SurgeryNO RCTs have studied Surgery vs not
Total vs subtotal resection
Standard: Attempt at gross resection
Not always possible
Location
Critical structuresSlide18
SurgerySimpson,
Int
J
Radiat
Oncol
Biol
Phys, 1993
Review of 3 RTOG trials: 643 patients with GBM
Improved survival with more resection
Surgery: Biopsy Partial Total
% of patients: 17% 64% 19%
MS (months): 6.6 10.4
11.3
Simpson JR et al.
Int
J
Radiat
Oncol
Biol
Phys. 1993 May 20;26(2):239-44.Slide19
Surgery
Lacroix
, J
Neurosurg
, 2001
Retrospective review, 416 patients with GBM
Improved survival with total resection (>98%)
Surgery Partial (<98%) Total (>98%)
MS (months) 8.8
13
Predictors of survival
Age, KPS, extent of resection, degree of necrosis, pre-op MRI enhancement
Lacroix M, et al. J Neurosurg. 2001 Aug;95(2):190-8.Slide20
Back to CasePatient taken to ORResection attempted, but 2.4cm segment of tumour remainsSlide21
ManagementReferred to Radiation OncologyWhat should we do?Slide22
RadiationWalker, J Neurosurg
, 1978
Phase III, 303 patients with
anaplastic
glioma
Surgery then randomized to:
RT
vs
BCNU
vs
RT+BCNU
vs
Obs
MS (mo)
8.1
4.2
8
3.2
Showed
no benefit
from chemo
RT = 50Gy WBRT + 10
Gy
boost
BCNU =
carmustine
80mg/m2 x days 1-3 every 6-8 weeks
Walker MD et al. J Neurosurg. 1978 Sep;49(3):333-43.Slide23
RadiationWalker, Int J
Radiat
Oncol
Biol
Phys, 1979
Meta-analysis of 3 RCTs
621 patients with Gr. III/IV
glioma
Surgery then:
Obs
vs
45Gy
vs
50Gy
vs
55Gy
vs
60Gy
MS (mo) 4 3 7 9
10
Showed
benefit
for RT and
dose-response
relationship
Walker MD, et
al.Int
J
Radiat
Oncol
Biol
Phys. 1979 Oct;5(10):1725-31.Slide24
RadiationWalker, NEJM, 1980Phase III, 358 patients with
anaplastic
glioma
Surgery then randomized to
RT
vs
RT+BCNU
vs
RT+Semus
vs
Semus
Results
No arm significant difference between arms
Conclusion: RT alone remains standard
Walker MD et al. N
Engl
J Med. 1980 Dec 4;303(23):1323-9.Slide25
RadiationKristiansen, Cancer, 1981
Phase III, 118 patients with
Gr
III/IV
astrocytoma
Surgery then randomized to:
RT
vs
RT+Bleomycin
vs
Obs
MS (mo)
10.8
10.8
5.2
Showed
no benefit
from chemo
RT = 45Gy WBRT
Bleomycin
=
carmustine
180mg 3/week, 1hr prior to RT, weeks 1,2,4,5
Kristiansen K et al. Cancer. 1981 Feb 15;47(4):649-52.Slide26
Radiation
Laperriere
,
Radiother
apy
+ Oncology, 2002
Systematic review of 6 RCTs
Confirmed benefit from post-op RT
Recommended:
Young (< 70
yo
)
Treat enhancing
tumour
+ margin (e.g. 2 cm)
Dose: 50-60
Gy
in 1.8-2Gy per fraction
Older with good KPS
Can use short course RT
Older with poor KPS
Can consider supportive care alone
This review
did not
recommend addition of chemo
Laperierre
N et al.
Radiother
Oncol
. 2002 Sep;64(3):259-73.Slide27
RadiationSo RT is good…What dose should we give?Slide28
Radiation
Nelson, NCI
Monog
., 1988
RTOG 74-01
626 patients with Gr III/IV astrocytoma
Randomized to:
60Gy*
vs
60+10
vs
60+B**
vs
60+C+D***
Median survival:
60Gy: 9.3 months
vs
60+10Gy: 8.2 months
Subsets:
>60
yo
:
RT+chemo
did not
improve survival
40-60
yo
: RT+BCNU =
23% 2 year survival
vs
RT alone =
8%
*60
Gy
WBRT
**60
Gy
+
carmustine
(=BCNU)
***60
Gy
+
semustine
+
dacarbazine
Nelson DF et al. NCI
Monogr
.
1988;(6):279-84.Slide29
Radiation
Bleehen
, BJC, 1991
474 patients with Gr III/IV astrocytoma
Surgery,
no
chemo, then randomized to:
45/20*
vs
40/20+20/10**
MS (mo) 9
12
60/30 improved survival with similar toxicity
*=45/20 to “all known and potential
tumour
”
**=40/20 as above, then 20/10 to “defined
tumour
volume
together with a 1 cm margin around it.”
Bleehen
NM,
Stenning
SP. Br J Cancer. 1991 Oct;64(4):769-74.Slide30
RadiationScott,
Int
J
Radiat
Oncol
Biol
Phys, 1998
RTOG 9006
712 patients with Gr III/IV
glioma
Randomized to
carmustine
+ :
60/30
vs
72/60
(1.2
Gy
/# BID)
MS (
mo
)
13.2
11.2
72/60 not better for any subgroup
60/30 was better for
all patients < 50
yo
Scott CB et al.
Int
J
Radiat
Oncol
Biol
Phys. 1998 Jan 1;40(1):51-5.Slide31
RadiationShould we use SRS?Slide32
?SRS?Early series showed promising survival w/SRSBuatti et al., 1995
Int
J
Radiat
Oncol
Biol
Phys. 1995 Apr 30;32(1):205-10.
Int
J
Radiat
Oncol
Biol
Phys. 1995 Jul 15;32(4):1161-6.
Gannett et al., 1995
Int
J
Radiat
Oncol
Biol
Phys. 1995 Sep 30;33(2):461-8.
Masciopinto
et al., 1995
J
Neurosurg
. 1995 Apr;82(4):530-5.Slide33
?SRS?RTOG 9305 Souhami,
Int
J
Radiat
Oncol
Biol
Phys, 2004
RCT, 203 GBM pts
all
received 60Gy EBRT +
carmustine
Randomized to upfront SRS
vs
no SRS (15-24Gy)
Median survival not different: 13.5 v 13.6 months
SRS not currently standard for GBM
Souhami
et al.
Int
J
Radiat
Oncol
Biol
Phys 2004;60:853-860.Slide34
ManagementReferred to Medical OncologyShould the patient have chemotherapy?Slide35
ChemotherapyStewart, Lancet, 2002
Metanalysis
, 12 RCTs, 3004 patients
Hazard ratio for death = 0.85
Chemotherapy group did
better
Stewart LA. Lancet. 2002 Mar 23;359(9311):1011-8. Review.Slide36
Chemotherapy
Stewart LA. Lancet. 2002 Mar 23;359(9311):1011-8. Review.Slide37
ChemotherapyStupp
, JCO, 2002
Phase II, 64 patients with primary GBM
RT
+
Temozolomide
RT: 60Gy/30
TMZ: 75 mg/m
2
/d x 42d then 200 mg/m
2
/d for 5d q28d x6 cycles
Median survival = 16 months
OS: 1
yr
= 58% ; 2
yr
= 31%
Grade ≥3 toxicity = 6
%
Good prognosis subsets:
≤50
years old
patients
who
had
debulking
surgery
Stupp
R et al.
Clin
Oncol
. 2002 Mar 1;20(5):1375-82.Slide38
WAKE UP!!!!Important Study AlertSlide39
EORTC 26981
Stupp
, NEJM, 2005 (2009 Lancet
Oncology
update)
Phase III, 573 patients <70
yo
with primary GBM
Randomized to
RT alone
vs
Stupp
Phase II protocol:
RT: 60Gy/30
TMZ
: 75 mg/m
2
/d x 42d then 200 mg/m
2
/d for 5d q28d x6 cycles
Stupp R et al. N Engl J Med. 2005 Mar 10;352(10):987-96.Slide40
EORTC 2698188% of patients received full course ChemoRT40% of patients completed adjuvant Chemo
Grade ≥3 toxicity = 4%
Slide41
EORTC 26981
RT ChemoRT
MS (med) 12.1 mo 14.6 mo
PFS (med) 5 mo 6.9 mo
OS: 2 yr 10% 26%
4 yr 3% 12%
5 yr 2% 10%Slide42
Overall survival curve
EORTC 26981
Stupp R et al. N Engl J Med. 2005 Mar 10;352(10):987-96.Slide43
EORTC 26981Subgroups:
Methylated
MGMT
Unmethylated
Stupp R et al. N Engl J Med. 2005 Mar 10;352(10):987-96.Slide44
EORTC 26981Improved response for patients with methylated MGMT gene
Epigenetic silencing of MGMT (O6-methylguanine-DNA
methyltransferase
) DNA-repair gene by promoter
methylation
compromises DNA repair and has been associated with longer survival in patients with
glioblastoma
who receive
alkylating
agents.
Hegi ME et al. N Engl J Med. 2005 Mar 10;352(10):997-1003.Slide45
MGMT MethylationHegi
, NEJM, 2005
206 patients from EORTC 26891 trial assessed for MGMT
methylation
status
MethylMGMT
found in 45%
Results
MethylMGMT
was a
favorable
prognostic factor: HR =0.45
For
methylMGMT
TMZ better than RT: 21.7
vs
15.3 months
For
unmethylMGMT
,
no
statistically significant difference
Conclusions
GBM with
methylMGMT
benefited from TMZ, but
unmethylMGMT
promoter did not benefit
Hegi ME et al. N Engl J Med. 2005 Mar 10;352(10):997-1003.Slide46
Hegi ME et al. N Engl J Med. 2005 Mar 10;352(10):997-1003.Slide47
RTOG 0525
Gilbert, ASCO, 2011
RCT, 833
pts
> 60
yo
with GBM/
Gliosarcoma
Test dose-dense TMZ regimen
Randomized to
EORTC 26981 RT+TMZ protocol
vs
60Gy/30 + daily TMZ followed by 21d adjuvant chemo
Gilbert MR et al. Journal of Clinical Oncology, 2011 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol
29, No 15_suppl (May 20 Supplement), 2011: 2006Slide48
RTOG 0525
Gilbert MR et al. Journal of Clinical Oncology, 2011 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol
29, No 15_suppl (May 20 Supplement), 2011: 2006Slide49
RTOG 0525
Gilbert MR et al. Journal of Clinical Oncology, 2011 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol
29, No 15_suppl (May 20 Supplement), 2011: 2006Slide50
RTOG 0525Improved response for patients with methylated MGMT continuedNo difference in PFS or OS between study arms for either methylated or non-methylated subgroups
Slide51
Ongoing StudiesWhat is being tested now? Biologic agentsSlide52
Ongoing StudiesRTOG 0837Phase IIIRT+TMZ
vs
RT+TMZ+bevacizumab
Bevacizumab (Avastin) shown effect in RCC,NSCLC,CRC
RTOG 0825
Phase III
RT+TMZ
vs
RT+TMZ+cediranibSlide53
Back to casePatient receives concurrent 60Gy/30 RT Planned for continuing adjuvant monthly TMZPatient returns to clinic 1 month after treatment with MRI
Scan shows increased enchancement of treated tumour cavity
…Now what?
…Did treatment fail?Slide54
PseudoprogressionSanghera, Can J Neurol
Sci
, 2010
Retrospective, 111 patients
GBM or Gr.III with GBM-like radiographic features
Used
Stupp
RT+TMZ protocol
Pseudoprogression
(
psP
) = no further radiographic progression, without salvage therapy, within 6 months after TMZ+RT
Represent transient increase in vessel permeability and damaged
peritumoural
BBB
Sanghera
P. Can J
Neirol
Sci. 2010 Jan;37(1):36-42.Slide55
PseudoprogressionResults
psP
group had stable
dexamethasone
dose
25% had evidence of early progression, with 32% of these representing
psP
Median OS : whole cohort = 56.7 weeks
psP
= 125 weeks
true early progression = 36 weeks
Conclusion: Maintenance TMZ should
not
be stopped on the basis of seemingly discouraging imaging features within first three months after RT/TMZ.Slide56
Pseudoprogression
Sanghera
P. Can J
Neirol
Sci. 2010 Jan;37(1):36-42.Slide57
PseudoprogressionBrandes, JCO, 2008Cohort, 103 patients with MGMT status
Treated with
Stupp
TMZ+RT protocol
Results
psP
occurs in 91% of
methylMGMT
+
ve
GBM
vs
41% -
ve
+
ve
methylMGMT
and
psP
each improved survival
Patients more sensitive to treatment more likely to get
psP
Brandes
AA. J
Clin
Oncol
. 2008 May 1;26(13):2192-7.Slide58
PseudoprogressionSanghera, Clin Oncol
, 2012
Expert consensus on
psP
Poor efficacy 2
nd
line
Tx
so need to minimize inappropriate withdrawal of adjuvant TMZ
psP
unlikely if radiographic progression over 2 mo within 6 mo post-
Tx
Sanghera
P.
Clin
Oncol
(R
Coll
Radiol
). 2012 Apr;24(3):216-27.Slide59
Pseudoprogression
Sanghera
P.
Clin
Oncol
(R
Coll
Radiol
). 2012 Apr;24(3):216-27.Slide60
Sanghera
P.
Clin
Oncol
(R
Coll
Radiol
). 2012 Apr;24(3):216-27.Slide61
Back to casePatient continues on monthly adjuvant TMZReturns for 6 month post-RT appointment and has another MRIScan shows clearly increased size of disease
…Now what?Slide62
Recurrent GBM - RTMedian time to recurrence is ~7 monthsRe-irradiation trialsOver 300 patients reported
Combs 2005; Nieder 2008; Fogh 2010
Results
6 month PFS: 28-39%
1 year median OS: 26% (range 18-46%)
Source: RTOG 0125 protocol.
May be accessed at: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1205Slide63
Recurrent GBM - RTFogh
, JCO, 2010
147 patients with recurrent GBM
Treated with stereotactic RT 35/10
Cox analysis performed
Survival improved with:
Younger age
Smaller GTV
Shorter time between diagnosis and recurrence
High RT dose (≥35Gy) showed
trend
to significance (p = .07).
Survival not improved by:
Surgical resection
Chemotherapy
Source
: RTOG 0125 protocol.
May
be accessed at: http://
www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1205
Fogh SE et al. J Clin Oncol. 2010 Jun 20;28(18):3048-53Slide64
Recurrent GBM - ChemoPhase II chemo trials
Wong ET
et
al. J
Clin
Oncol
. 1999 Aug;17(8):2572-8.
Carson KA et al.
J Clin Oncol. 2007 Jun 20;25(18):2601-6.
6 month PFS: 15%; Median OS: 6 months
Bevacizumab
/other monoclonal Abs studied in ph. II trials
Vredenburgh
JJ et al. J
Clin
Oncol
. 2007 Oct 20;25(30):4722-9.
32 pts given
bevacizumab
+
irinotecan
6 month PFS: 38%; MS for GBM patients: 9.2 months
Kreisl
TN et al.
J Clin Oncol 2009 Feb 10;27(5):740-5.
48 recurrent
glioblastoma
patients received
bevacizumab
alone
Response rate: 25%; Median PFS: 16 weeks; 6-month
PFS:
29
Other trials have added
bevacizumab
to other chemo agents such as low dose TMZ,
etoposide
,
erlotinib
,
nitrosurea
No improvement
in survival shown, but worse toxicity
Source: RTOG 0125 protocol.
May be accessed at: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1205Slide65
Recurrent GBM - ChemoFriedman HS et al.
J
Clin
Oncol
. 2009 Oct 1;27(28):4733-40.
RCT, 167 patients with recurrent GBM in 1
st
or 2
nd
relapse
Randomized to
bevacizumab
alone 10 mg/kg q2weeks
vs
bevacizumab
+
irinotecan
(82 patients)
Results
not
significant:
Beva
alone
Beva+irino
6-month PFS: 42.6%; 50.3%
Median survival: 9.2 months 9.7 months
Conclusion: No increase in efficacy with
irinotecan
, but increase toxicity
Source: RTOG 0125 protocol.
May be accessed at: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1205Slide66
Recurrent GBM - ChemoSalvage chemotherapy post-bevacizumab failure has 6-month PFS of 2% (Quant 2009).
Recurrent GBM patients should be enrolled on trial whenever possible
Ongoing trials include
RTOG 1205:
Randomized Phase II for recurrent GBM
Bevacizumab + RT
vs
bevacizumab alone
Source: RTOG 0125 protocol.
May be accessed at: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1205Slide67
Case #2Mr. B.80M2 weeks persistent headache and malaise
Refractory to OTC analgesia
Diagnosed with GBM on imaging
Referred to
NeuroSx
Taken to OR for biopsy
Platelets decreasing so procedure abandonedSlide68
Mr. Z.Referred to Rad Onc for managementWork upHistory
Physical
ImagingSlide69Slide70
Mr. Z.What to do?No biopsy, so no tissue diagnosisTreated as presumed GBMSlide71
ManagementCurran, JNCI, 1993Recursive partitioning analysis to retrospectively analyze 1578 patients with high grade
glioma
3 RTOG studies testing RT +/- Chemo
Results
<50yo: histology most important prognostic factor
>50yo: KPS most important prognostic factor
Mental status
differentitated
poor KPS group
Conclusion: Older and poor KPS do worse
Curran et al. J
Natl
Cancer Inst. 1993 May 5;85(9):704-10.Slide72
Management
Bauman,
Int
J
Radiat
Oncol
Biol
Phys, 1994
Prospective, 29 patients with GBM
Treated with 30Gy/10 WBRT
Compared with historical radical and supportive care controls
Results
Overall median survival 6 months
Median survival: RT = 10
mos
; Supp. care = 1 mo
Improved survival for radical dose if KPS>50
Conclusion: 30/10 reasonable for older patients with poor KPS
Bauman GS et al.
Int
J
Radiat
Oncol
Biol
Phys. 1994 Jul 1;29(4):835-9.Slide73
ManagementRoa W, J Clin
Oncol
, 2004
RCT, 100 patients with GBM ≥ 60
yo
Randomized to radical RT 60/30
vs
short course RT 40/15
No chemo during
Tx
(some got for recurrence)
Results
Median survival: Radical= 5.1
mos
; Short= 5.6
mos
6 months survival: Radical= 44.7%; Short= 41.7%
Short course reduced steroid requirements
Conclusion: Short course reasonable to older patients
Roa
W et al. J
Clin
Oncol
. 2004 May 1;22(9):1583-8.Slide74
Management
Roa
W et al. J
Clin
Oncol
. 2004 May 1;22(9):1583-8.Slide75
Management
Keime-Guibert
, NEJM, 2007
RCT, 81 patients with Gr. III/IV
astrocytoma
All got surgery
Age ≥ 70
yo
and KPS ≥ 70
Randomized to RT 50
Gy
vs
supportive care alone
Results
Trial stopped early due to superiority
Median survival: RT= 29.1 wks; No RT= 16.9 wks
Survival benefit independent of extent of surgery
No effect on
HRQoL
or cognition from RT
Conclusion: RT is good for older, good KPS patients
Keime-Guibert
et al. N
Engl
J Med. 2007 Apr 12;356(15):1527-35.Slide76
Management
OSSlide77
Management
Muni,
Tumori
, 2010
Prospective comparison study 45 patients with GBM
Age ≥ 70
yo
OR
Age 50-70 and KPS < 70
1:1 split of 30Gy/6 ± TMZ 150-200 mg/m
2
x5d q28d
RT+TMZ
No TMZ
Median OS 9.4
mos
7.3
mos
6 mo OS 95% 78%
Median PFS 5.5
mos
4.4
mos
6 mo PFS 45% 22%
Minimal additional toxicity (≥
Gr
3 = 46%)
Conclusion:
RT+TMZ beneficial for older or poor KPS patients
Muni R et al.
Tumori
. 2010 Jan-Feb;96(1):60-4.Slide78
NOA-08Wick, Lancet Oncol
, 2012
RCT, 412 patients with
Gr
III/IV
astrocytoma
Age ≥ 65
yo
AND
KPS ≥70
Powered for non-inferiority
Randomized to:
RT 60Gy/30
vs
TMZ 100mg/m
2
x7d 1wk-on/1wk-off
Wick W et al. Lancet
Oncol
. 2012 Jul;13(7):707-15Slide79
NOA-08
Results
Median survival: RT=9.6 mo; TMZ=8.6 mo
P(non-inferiority)=0.033
Event-free survival: RT=4.7mo; TMZ=3.3mo
P(non-inferiority)=0.043
Subgroups
MGMT
methylation
cohort had
improved
survival
Median survival:
Methylated
=11.9mo;
Unmethylated
=8.2mo
Patients
with
MGMT
methylation
did better with
TMZ
EFS for +
ve
methMGMT
: RT=4.6 months; TMZ=8·4 months; RT=4·6 [4·2-5·0]),
Patients
without
MGMT
methylation
did better with
RT
EFS for –
ve
methMGMT
: RT=4.6 months; TMZ=3.3 months
Conclusion: TMZ alone is
not
inferior to RT for elderly, good KPS patients.
MGMT
methylation
status can aid decisions.Slide80
Wick W et al. Lancet
Oncol
. 2012 Jul;13(7):707-15Slide81
RT +/- TMZMalmstrom, Lancet Oncol, 2012
RCT, 291 patients with GBM ≥60
yo
Randomization stratified by centre
TMZ 200 mg/m
2
x5d q28d for 6 cycles
vs
hypo# RT: 34
Gy
/3-4
Gy
per fraction
vs
standard RT: 60Gy/30
Malmstrom A et al. Lancet Oncol. 2012 Sep;13(9):916-26. Slide82
RT +/- TMZResultsOverallTMZ better than standard 60Gy RT
median OS: TMZ=8.3 months; 60Gy RT=6.0 month
Standard 60 Gy RT
not
better than hypo# 34Gy RT
Median OS: 34Gy RT=7.5 mos; 60 Gy RT =6.0 mos
p=0.24
TMZ not better than hypo# 34Gy RT
Median OS: TMZO=8·4 mos; 34Gy RT= 7·4 mos
p=0·12Slide83
RT +/- TMZ
Subset results
Patients > 70 years old
TMZ better than standard RT
HR 0.35 p<0.0001
Hypo# 34Gy RT better than standard RT
HR 0.59 p=0.02
Patients receiving TMZ
Methylated
MGMT had better median overall survival
vs
non-
methylated
MGMT
MethylMGMT
= 9·7 months;
nonMethylMGMT
= 6·8 months p=0·02
Patients receiving RT
No difference
between
methylMGMT
and
unmethylMGMT
HR=0·97 p=0·81)Slide84
Figure 2 Kaplan-Meier analysis of overall survival in patients
randomised
across three treatment groups (A) All patients. (B) Patients aged 60?70 years. (C) Patients older than 70 years. TMZ=
temozolomide
. 34
Gy
=
hypofractionated
radiotherapy. 60
.
All patients
60-70 years
older than 70 years
Malmstrom A et al. Lancet Oncol. 2012 Sep;13(9):916-26. Slide85
Back to CaseMr. B treated with 40Gy/15 RT aloneNo chemo