VRAAG 2: RESECTIE VERSUS WATCHFUL WAITING
Systematic reviews
Study ID
Method
Patient characteristics
Intervention(s)
Results
Critical appraisal of review
quality
Veeravagu
2013




 Eligibility criteria:
Patients with a
suspected intracranial
LGG receiving biopsy or
resection
 Patient characteristics:
o No patients
Biopsy, surgical
resection
Biopsy vs. surgical resection
Overall survival (critical): no data available
Level of evidence: -
SR
Funding/CoI: None
Search date: 11/2012
Databases: Cochrane
Central Register of
Controlled Trials,
MEDLINE, EMBASE
 Study designs: RCTs
(or CCTs)
 N included studies: 0
Quality of life (critical): no data available
Symptom-free survival (important): no data available
 This SR fulfils high
standards of quality;
however, no study was
identified meeting all
required inclusion criteria
Progression-free survival (important): no data available
Morbidity (important): no data available
Primaire studies
Study ID
Method
Patient characteristics
Interventions
Results
Bianco 2013
 Design: retrospective
study
 Funding/CoI: declared
no CoI
 Setting: Hospital das
Clínicas de São Paulo
and Hospital de Câncer
de Barretos Pio XII,
Brazil
 Sample size: N=82
 Duration: >8 years
o Median follow-up: 4.8
years
 Eligibility criteria: adult patients
with hemispheric low-grade
astrocytoma
 A priori patient characteristics:
o % males: 57%
o Median age: 37y (range 1869y)
o KPS at diagnosis: 90-100%:
N=58; 70-80%: N=16;
50-60%: N=8
o Postoperative radiotherapy:
N=61
o Postoperative chemotherapy:
N=12
GTR/STR (N=56)
Overall survival (critical):
 GTR/STR vs. biopsy:
o tumours in non-eloquent brain areas: 4.7 vs.
1.9y, p=0.013
o tumours in eloquent areas: 4.5 vs. 2.1y,
p=0.33
Jakola 2013
Jakola 2012a
Jakola 2012b
 Design: retrospective
parallel cohort study
 Funding/CoI: one author
has approximately 0.3%
of the stocks in
Sonowand, the
 Eligibility criteria: 18 years or
older, histologically verified
supratentorial WHO grade II
tumours; diffuse LGG
 A priori patient characteristics:
o % males: 42%
vs.
Biopsy (N=26)
Critical appraisal of study
quality
Level of evidence: high risk of
bias
 Unclear if populations are
comparable, blinding
unlikely
Quality of life (critical): Not reported
Symptom-free survival (important): Not reported
Progression-free survival (important): Not
reported
Biopsy and watchful
waiting (N=66)
vs.
Early resection
Morbidity (important):
 Permanent new neurological deficit due to
surgical procedure: N=4 (5%)
 Surgical infection: N=2 (2%)
 No operative mortality
Overall survival (critical):
 HR = 1.0 (95%CI 0.5-2.0) (Cox regression
including actual treatment, Pignatti scores and
treating centre)
 1y-survival: 89% each
 3y-survival: 70% vs. 80%
Level of evidence: high risk of
bias
 Unclear bias, potentially
with respect to selection
bias, blinding, confounders
1
Study ID
Method
company making the
3D-ultrasound–based
intraoperative imaging
system (SonoWand)
used in the resections at
hospital B. The other
authors report no
disclosures
 Setting: 2 Norwegian
university hospitals
 Sample size: N=153
 Duration: 12-year
o Inclusion period: 1998
- 2009
o Median follow-up:H1
7.0y (IQR 4.5-10.9);
H2 7.1y (IQR 4.2-9.9)
o Follow-up until 4/2011
Sahgal 2013
Schomas 2009
 Design: retrospective
study
 Funding/CoI: supported
by the Brain Tumour
Foundation of Canada;
CoI not reported
 Setting: University
hospital, Ontario,
Canada
 Sample size: N=182
 Duration:
o Inclusion period: 1992
- 1996
o Mean/median followup: not reported
 Design: retrospective
study
Patient characteristics
o Mean age: 44.4y
o Preoperative KPS ≥80:
79.7%
o Radiotherapy: 66%
o Chemotherapy: 51%
Interventions
Results
(N=87)
 5y-survival: 60% vs. 74%
 7y-survival: 44% vs. 68%
Quality of life (critical):
 Only reported with respect to local area of
tumours (eloquent/non-eloquent), but not with
respect to biopsy vs. resection
Critical appraisal of study
quality
 One author is stock-holder
of the company producing
some of the surgical
equipment used for the
resections
Symptom-free survival (important): Not reported
Progression-free survival (important): Not
reported
Morbidity (important):
All patients (N=153)
 Surgical complications: 9% vs. 8%, p=0.82
 New or worsened neurological deficits (in
postoperative period, 30 days): 18% vs. 21%,
p=0.7
 30-day mortality: 2% vs. 0%, p=0.25
 Malignant transformation: 56% vs. 37%, p=0.02
 Eligibility criteria: adult patients
diagnosed with low-grade
astrocytoma; at least one
confirmatory histopathology
report
 A priori patient characteristics:
o % males: 56%
o Mean age: 50 y
o Not specified astrocytoma
78%, protoplasmic
astrocytoma 2.2%,
gemistocytic astrocytoma
11.5%, fibrillary astrocytoma
8.2%
Biopsy (N=98)
 Eligibility criteria: adult patients
(>=55 years) diagnosed as
having nonpilocytic LGG;
GTR + rSTR + STR:
(N=1+1+14=16)
vs.
Surgical excision
(N=84)
Astrocytoma only (N=117)
 Neurological complications (in postoperative
period, 30 days): 13% vs. 21% (p=0.272):
o New/worsened dysphasia: 0 vs. 2
o New/worsened paresis: 3 vs. 6
o New/worsened visual function: 0 vs. 2
o Impaired consciousness: 1 vs. 0
o Cognitive deterioration: 3 vs. 2
o Other: 0 vs. 1
Overall survival (critical):
 Mean survival time: biopsy 3.4y (SD 0.5) vs.
excision 5.5y (SD 0.6)
Quality of life (critical): Not reported
Level of evidence: high risk of
bias
 Unclear if populations are
comparable, confounders;
blinding unlikely
Symptom-free survival (important):Not reported
Progression-free survival (important): Not
reported
Morbidity (important): Not reported
Overall survival (critical):
 Median: GTR/rSTR/STR 3.0y vs. biopsy 2.2y
(p=0.57)
Level of evidence: high risk of
bias
2
Study ID
Method
Patient characteristics
Interventions
Results
 Funding/CoI: Grant
Number 1 UL1
RR024150-01* from the
National Center for
Research Resources
(NCRR)
 Setting: Mayo Clinic,
Rochester, Minnesota,
 Sample size: N=32
 Duration:
o Inclusion period: 1960
- 1992
o Median follow-up:
17.3 years
Critical appraisal of study
quality
 Unclear if populations are
comparable, patients not
giving consent to analyse
their data; blinding unlikely
detailed operative report ,
vs.
 5y-survival: GTR/rSTR/STR 31% vs. biopsy
biopsy confirmation ,
31%
pathologic review; only patients Biopsy (N=16)
 10y-survival: GTR/rSTR/STR 19% vs. biopsy
who allowed their data to be
17%
used
 A priori patient characteristics:
Quality of life (critical): Not reported
o % males: 59%
o Median age: 61y (range 55Symptom-free survival (important): Not reported
74)
o Astrocytoma 69%, mixed
Progression-free survival (important):
oligoastrocytoma 22%,
 Median: GTR/rSTR/STR 3.0y vs. biopsy 1.5y
oligodendroglioma 9%
(p=0.93)
o Postoperative radiotherapy
 5y-survival: GTR/rSTR/STR 19% vs. biopsy
72%
25%
o Postoperative chemotherapy
3%
Morbidity (important): Not reported
Abbreviations: 95%CI: 95% confidence interval; CCT: controlled clinical trial; CoI: conflicts of interest; GTR: gross total resection; HR: hazard ratio; IQR: interquartile range; KPS: Karnofsky performance
score; LGG: low-grade glioma; RCT: randomized controlled trial; rSTR: radical subtotal resection; SD: standard deviation; SR: systematic review; STR: subtotal resection; WHO: World Health Organization
References
Bianco AdM, Miura FK, Clara C, Almeida JRW, Silva CCd, Teixeira MJ, et al. Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas. Arq
Neuropsiquiatr. 2013;71(1):31-4.
Jakola AS, Myrmel KS, Kloster R, Torp SH, Lindal S, Unsgard G, et al. Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade
gliomas. JAMA. 2012a;308(18):1881-8.
Jakola AS, Unsgard G, Myrmel KS, Kloster R, Torp SH, Lindal S, et al. Low grade gliomas in eloquent locations - implications for surgical strategy, survival and long term quality of life.
PLoS ONE. 2012b;7(12):e51450.
Jakola AS, Unsgard G, Myrmel KS, Kloster R, Torp SH, Losvik OK, et al. Surgical strategy in grade II astrocytoma: a population-based analysis of survival and morbidity with a
strategy of early resection as compared to watchful waiting. Acta Neurochir. 2013:1-9.
Sahgal A, Ironside SA, Perry J, Mainprize T, Keith JL, Laperriere N, et al. Factors Influencing Overall Survival Specific to Adult Low-grade Astrocytoma: A Population-based Study. Clin
Oncol. 2013;25(7):394-9.
Schomas DA, Laack NN, Brown PD. Low-grade gliomas in older patients: Long-term follow-up from Mayo Clinic. Cancer. 2009;115(17):3969-78.
Veeravagu A, Jiang B, Ludwig C, Chang SD, Black KL, Patil CG. Biopsy versus resection for the management of low-grade gliomas. Cochrane Database Syst. Rev. 2013(4).
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