High Grade Gliomas: Case Presentation and Discussion of

Report
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.
Workup
 History
 Physical
Workup
 History
 Characterize symptoms: OPQRST
 General: headache, seizures, N/V, syncope, cognitive Δ
 Focal: weakness, sensory loss, aphasia, visual Δ
 Family history
 PMHx/Meds/allergies
 Physical
Workup
 History
 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 exam
Imaging
 MRI with gadolinium is preferred modality
Relevant imaging findings for contouring


T1 with gadolinium: enhancing cavity
T2/FLAIR: edema and enhancement
Workup
Imaging
Histology
 4 criteria (AMEN) :
 nuclear Atypia
 Mitosis
 Endothelial proliferation
 Necrosis
# Criteria
Grade
0
I
1*
II
*1 criterion = atypia for Grade II
2
III
3-4
IV
Staging
 AJCC TNM Staging System not used
Staging
 GBM can be primary or secondary (10%)
Prognosis
 Prognosis by classification
 Oligodendroglial component is positive prognostic
factor
Prognosis
 Curran, 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.
Lamont ED, Christakis NA. Survival estimates in advanced cancer.
In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013.
Prognosis
 By recursive partitioning analysis (RPA)
Curran et al. J Natl Cancer Inst. 1993 May 5;85(9):704-10.
Management
 Referred to Neurosurgery
 What should they do?
Surgery
 NO RCTs have studied


Surgery vs not
Total vs subtotal resection
 Standard: Attempt at gross resection
 Not always possible
 Location
 Critical structures
Surgery
 Simpson, Int J Radiat Oncol Biol Phys, 1993
 Review of 3 RTOG trials: 643 patients with GBM
 Improved survival with more resection
Surgery:
% of patients:
MS (months):
Biopsy Partial Total
17%
64%
6.6
10.4
Simpson JR et al. Int J Radiat Oncol Biol Phys. 1993 May 20;26(2):239-44.
19%
11.3
Surgery
 Lacroix, J Neurosurg, 2001
 Retrospective review, 416 patients with GBM
 Improved survival with total resection (>98%)
Surgery
MS (months)
Partial (<98%)
8.8
Total (>98%)
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.
Back to Case
 Patient taken to OR
 Resection attempted, but 2.4cm segment of tumour
remains
Management
 Referred to Radiation Oncology
 What should we do?
Radiation
 Walker, J Neurosurg, 1978
 Phase III, 303 patients with anaplastic glioma
 Surgery then randomized to:
MS (mo)
RT vs BCNU vs
8.1
4.2
RT+BCNU vs Obs
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.
Radiation
 Walker, Int J Radiat Oncol Biol Phys, 1979
 Meta-analysis of 3 RCTs
 621 patients with Gr. III/IV glioma
 Surgery then:
MS (mo)
Obs vs 45Gy vs 50Gy vs 55Gy vs 60Gy
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.
Radiation
 Walker, NEJM, 1980
 Phase 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.
Radiation
 Kristiansen, Cancer, 1981
 Phase III, 118 patients with Gr III/IV astrocytoma
 Surgery then randomized to:
MS (mo)
RT vs RT+Bleomycin vs Obs
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.
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.
Radiation
 So RT is good…
 What dose should we give?
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.
Radiation
 Bleehen, BJC, 1991
 474 patients with Gr III/IV astrocytoma
 Surgery, no chemo, then randomized to:
MS (mo)
45/20* vs 40/20+20/10**
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.
Radiation
 Scott, Int J Radiat Oncol Biol Phys, 1998 RTOG 9006
 712 patients with Gr III/IV glioma
 Randomized to carmustine + :
MS (mo)
60/30 vs 72/60 (1.2 Gy/# BID)
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.
Radiation
 Should we use SRS?
?SRS?
 Early series showed promising survival w/SRS

Buatti et al., 1995



Gannett 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.
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.
?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.
Management
 Referred to Medical Oncology
 Should the patient have chemotherapy?
Chemotherapy
 Stewart, 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.
Chemotherapy
Stewart LA. Lancet. 2002 Mar 23;359(9311):1011-8. Review.
Chemotherapy
 Stupp, JCO, 2002
 Phase II, 64 patients with primary GBM
 RT + Temozolomide
RT: 60Gy/30
TMZ: 75 mg/m2/d x 42d then 200 mg/m2/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.
WAKE UP!!!!
Important Study Alert
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/m2/d x 42d then 200 mg/m2/d for 5d q28d x6
cycles
Stupp R et al. N Engl J Med. 2005 Mar 10;352(10):987-96.
EORTC 26981
 88% of patients received full course ChemoRT
 40% of patients completed adjuvant Chemo
 Grade ≥3 toxicity = 4%
EORTC 26981
MS (med)
PFS (med)
OS: 2 yr
4 yr
5 yr
RT
ChemoRT
12.1 mo
5 mo
10%
3%
2%
14.6 mo
6.9 mo
26%
12%
10%
EORTC 26981
 Overall survival curve
Stupp R et al. N Engl J Med. 2005 Mar 10;352(10):987-96.
EORTC 26981
Subgroups:
Methylated
MGMT
Unmethylated
Stupp R et al. N Engl J Med. 2005 Mar 10;352(10):987-96.
EORTC 26981
 Improved response for patients with methylated
MGMT gene
 Epigenetic silencing of MGMT (O6-methylguanineDNA 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.
MGMT Methylation
 Hegi, 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.
Hegi ME et al. N Engl J Med. 2005 Mar 10;352(10):997-1003.
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: 2006
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: 2006
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: 2006
RTOG 0525
 Improved response for patients with methylated
MGMT continued
 No difference in PFS or OS between study arms for
either methylated or non-methylated subgroups
Ongoing Studies
 What is being tested now?
Biologic agents
Ongoing Studies
 RTOG 0837
 Phase III
 RT+TMZ vs RT+TMZ+bevacizumab

Bevacizumab (Avastin) shown effect in RCC,NSCLC,CRC
 RTOG 0825
 Phase III
 RT+TMZ vs RT+TMZ+cediranib
Back to case
 Patient receives concurrent 60Gy/30 RT
 Planned for continuing adjuvant monthly TMZ
 Patient returns to clinic 1 month after treatment with
MRI
 Scan shows increased enchancement of treated
tumour cavity
…Now what?
…Did treatment fail?
Pseudoprogression
 Sanghera, 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.
Pseudoprogression
 Results
 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.
Pseudoprogression
Sanghera P. Can J Neirol Sci. 2010 Jan;37(1):36-42.
Pseudoprogression
 Brandes, JCO, 2008
 Cohort, 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.
Pseudoprogression
 Sanghera, Clin Oncol, 2012
 Expert consensus on psP
 Poor efficacy 2nd 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.
Pseudoprogression
Sanghera P. Clin Oncol (R Coll Radiol). 2012 Apr;24(3):216-27.
Sanghera P. Clin Oncol (R Coll Radiol). 2012 Apr;24(3):216-27.
Back to case
 Patient continues on monthly adjuvant TMZ
 Returns for 6 month post-RT appointment and has
another MRI
 Scan shows clearly increased size of disease
…Now what?
Recurrent GBM - RT
 Median time to recurrence is ~7 months
 Re-irradiation trials
 Over 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=1205
Recurrent GBM - RT
 Fogh, 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):3048-53
Recurrent GBM - Chemo
 Phase 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=1205
Recurrent GBM - Chemo
 Friedman HS et al. J Clin Oncol. 2009 Oct 1;27(28):4733-40.
 RCT, 167 patients with recurrent GBM in 1st or 2nd relapse
 Randomized to
bevacizumab alone 10 mg/kg q2weeks vs
bevacizumab +irinotecan (82 patients)
 Results not significant:


6-month PFS:
Median survival:
Beva alone
42.6%;
9.2 months
Beva+irino
50.3%
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=1205
Recurrent GBM - Chemo
 Salvage 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=1205
Case #2
 Mr. B.
 80M
 2 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 abandoned
Mr. Z.
 Referred to Rad Onc for management
 Work up
 History
 Physical
 Imaging
Mr. Z.
 What to do?
 No biopsy, so no tissue diagnosis
 Treated as presumed GBM
Management
 Curran, 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.
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.
Management
 Roa 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.
Management
Roa W et al. J Clin Oncol. 2004 May 1;22(9):1583-8.
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.
Management
OS
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/m2 x5d q28d
Median OS
6 mo OS
Median PFS
6 mo PFS
RT+TMZ
9.4 mos
95%
5.5 mos
45%
No TMZ
7.3 mos
78%
4.4 mos
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.
NOA-08
 Wick, 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/m2 x7d 1wk-on/1wk-off
Wick W et al. Lancet Oncol. 2012 Jul;13(7):707-15
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.
Wick W et al. Lancet Oncol. 2012 Jul;13(7):707-15
RT +/- TMZ
 Malmstrom, Lancet Oncol, 2012
 RCT, 291 patients with GBM ≥60 yo
 Randomization stratified by centre
 TMZ 200 mg/m2 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.
RT +/- TMZ
 Results
 Overall

TMZ 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=0·12
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 nonmethylated 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)
All patients
60-70 years
older than 70 years
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 .
Malmstrom A et al. Lancet Oncol. 2012 Sep;13(9):916-26.
Back to Case
 Mr. B treated with 40Gy/15 RT alone
 No chemo

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