Malignant gliomas are among the most devastating of
cancers, commonly producing profound and progressive
disability and leading to death in most cases. They are
difficult to diagnose and challenging to treat. Incidence
peaks in children and at age 50–60 years.
1
These tumours
are therefore a major cause of mortality in a young
population, and improvement of survival by even a
moderate amount could potentially result in many years of
life saved. The infiltrating nature of high-grade glioma
makes complete resection virtually impossible, even when
possible resection can be associated with severe neurological
damage. Thus, standard treatment generally consists of
cytoreductive surgery followed by radiotherapy. However,
prognosis remains poor, with a median survival time of 9
months and only 5–10% of patients surviving to 2 years.
2
Over a period of almost 30 years, several randomised trials
have explored the use of adjuvant chemotherapy, with
research mostly focusing on nitrosoureas, which are used
because they are lipid soluble and cross the blood-brain
barrier. Most of these trials have been small, and many have
randomised multiple treatments within the trial. Not
surprisingly, therefore, most have shown inconclusive
results and there is consequently no international consensus
on the value of chemotherapy in this setting.
Combination of the results of trials in a meta-analysis
increases statistical power and may provide sufficient
information to show any survival benefit more reliably. Two
meta-analyses based on summary data extracted from trial
reports have been published.
3,4
However, these have several
limitations and potential biases. Each identified only a
proportion of currently relevant trials and included some
that used pseudo-random methods of allocation, which are
liable to bias.
5
The meta-analyses were limited to published
trials, thereby being susceptible to publication bias,
6
and
many of the trials excluded substantial proportions of
patients (on average 10–15%) from their published
analyses, potentially introducing further bias. There is
strong evidence that meta-analyses based on data extracted
from published reports can give different results from those
based on updated data on individual patients.
7,8
We therefore initiated a systematic review and a metaanalysis based on individual patient data to collect, validate,
and reanalyse trial data on all randomised patients from all
relevant trials. This approach has many advantages.
9
In
particular, it permits time-to-event analyses, which are
extremely important in a disease such as malignant glioma,
for which prolongation of survival rather than cure is
expected. It also allows analyses to assess whether
chemotherapy may be more or less effective in different
subgroups of patients. The meta-analysis was initiated and
coordinated by the UK Medical Research Council Clinical
Trials Unit and done by the Glioma Meta-analysis Trialists
(GMT) group.
Malignant gliomas are among the most devastating ofcancers, commonly producing profound and progressivedisability and leading to death in most cases. They aredifficult to diagnose and challenging to treat. Incidencepeaks in children and at age 50–60 years.1These tumoursare therefore a major cause of mortality in a youngpopulation, and improvement of survival by even amoderate amount could potentially result in many years oflife saved. The infiltrating nature of high-grade gliomamakes complete resection virtually impossible, even whenpossible resection can be associated with severe neurologicaldamage. Thus, standard treatment generally consists ofcytoreductive surgery followed by radiotherapy. However,prognosis remains poor, with a median survival time of 9months and only 5–10% of patients surviving to 2 years.2Over a period of almost 30 years, several randomised trialshave explored the use of adjuvant chemotherapy, withresearch mostly focusing on nitrosoureas, which are usedbecause they are lipid soluble and cross the blood-brainbarrier. Most of these trials have been small, and many haverandomised multiple treatments within the trial. Notsurprisingly, therefore, most have shown inconclusiveresults and there is consequently no international consensuson the value of chemotherapy in this setting.Combination of the results of trials in a meta-analysisincreases statistical power and may provide sufficientinformation to show any survival benefit more reliably. Two
meta-analyses based on summary data extracted from trial
reports have been published.
3,4
However, these have several
limitations and potential biases. Each identified only a
proportion of currently relevant trials and included some
that used pseudo-random methods of allocation, which are
liable to bias.
5
The meta-analyses were limited to published
trials, thereby being susceptible to publication bias,
6
and
many of the trials excluded substantial proportions of
patients (on average 10–15%) from their published
analyses, potentially introducing further bias. There is
strong evidence that meta-analyses based on data extracted
from published reports can give different results from those
based on updated data on individual patients.
7,8
We therefore initiated a systematic review and a metaanalysis based on individual patient data to collect, validate,
and reanalyse trial data on all randomised patients from all
relevant trials. This approach has many advantages.
9
In
particular, it permits time-to-event analyses, which are
extremely important in a disease such as malignant glioma,
for which prolongation of survival rather than cure is
expected. It also allows analyses to assess whether
chemotherapy may be more or less effective in different
subgroups of patients. The meta-analysis was initiated and
coordinated by the UK Medical Research Council Clinical
Trials Unit and done by the Glioma Meta-analysis Trialists
(GMT) group.
การแปล กรุณารอสักครู่..