ABSTRACT: brain tumor of adults. Among all gliomas it

 

ABSTRACT:

BACKGROUND AND OBJECTIVES:

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GBM also known as glioblastoma multiforma (GBM) is  a WHO grade IV, most common aggressive
malignant brain tumor of adults with high fatality rate.1With the
well known poor survival in this tumor, understanding  clinical and treatment related prognostic
factors can help in tailored treatment. Hence this retrospective analysis was
undertaken to know the influence
of prognostic factors on survival in cases treated in our institute.

METHODS:

All GBM patients treated in our hospital during
2010-2015(n=70) were screened and 46 were included in analysis and divided into
groups based on prognostic factors including age, sex, preoperative seizure as
symptom of presentation, location of tumor, side, lobe involved, ECOG
performance status, antiepileptic drug, type of surgery, gap between surgery
and radiation, usage of concurrent temozolomide, number of cycles of adjuvant temozolomide.
Overall survival(OS) and
disease free survival(DFS) were compared, effect of prognostic factors
was analysed with Kaplan meier method.

RESULTS:

Age at
presentation less than or 45 years and adjuvant chemotherapy with 6 cycles or
more temozolomide improved OS and DFS (P value 0.015, 0.0001; 0.015,
0.0001).Multivariate analysis retained the statistically significant positive
impact of usage of adjuvant temozolomide chemotherapy on OS and DFS (P value
0.0001, 0.0005).

Use of
Levetiracetam had a statistically significant improvement of DFS (P value
0.027)

INTERPRETATION AND CONCLUSION:

Among various clinical and treatment related
prognostic factors evaluated younger age at presentation and addition of
temozolomide chemotherapy to radiation had shown improvement in OS and DFS. Use
of antiepileptic drug levetiracetam had an impact on DFS.

Key words: GBM, prognostic factors, adjuvant
temozolomide

 

INTRODUCTION:

GBM also known as glioblastoma multiforma (GBM), is the
most common malignant brain tumor of adults. Among all gliomas it is the most
aggressive type, with high fatality rate and according to WHO classification it
is grade 4 tumor.1

Symptoms of presentation are headache, vomiting,
drowsiness (non site specific) and site specific symptoms like seizures and
neurological deficits. Rate of symptom onset and extent of nonspecific symptoms
will help in understanding aggression of disease.2 Standard
treatment protocol is maximum safe resection followed by adjuvant concurrent
chemoradiotherapy followed by adjuvant chemotherapy with 6 cycles of temozolomide.
This standard of treatment led to improved survival of patients compared to
historical controls, but most of the patients develop recurrent disease early in
the course of treatment due to multifocal stem cell niche like progenitor cells
and succumb to illness in less than two years.2

Recurrent disease is treated with salvage surgery or
chemotherapy commonly six more cycles of temozolomide once in four weeks. Although
survival is less than two years for majority of patients, long-term survivals (greater
than 3 years) have been published , though long term survival is rare it is
still seen, with less than 10% of patients surviving at least 5 years
post-diagnosis, suggesting heterogenous nature of disease and pretreatment
prognostic factor may help in predicting long term survivor.

Further advances are progressing towards molecular
genetics and prognostic factors at gene level to assess treatment response and improve
survival but day to day practice may not be feasible at genetic level
especially in low income patient population hence clinical factors like age at
presentation, symptom duration, performance status may be handy in
prognostication of patient before treatment. Several clinical studies have
identified factors affecting clinical outcome.3

Identification of clinical and treatment related
prognostic factors helps in tailored treatment.

With this background we have conducted a retrospective
analysis to know the impact of various prognostic factors affecting overall and
disease free survival in GBM patients treated at our institute.

MATERIALS AND METHODS:

All GBM
patients treated in sri
venkateswara institute of medical sciences, a tertiary care institute in
South India during 2010-2015 were included in analysis.

In our hospital all GBM cases were preoperatively evaluated
with complete history and physical examination including presenting symptoms,
performance status, drug usage and were analysed with computed
tomography(CT)/magnetic resonance tomography(MRI) brain scan for tumor site,
location and then maximum possible resection was attempted and
histopathologically confirmed cases of GBM were subjected to  post operative MRI brain scan and patients were
treated with adjuvant radiation of 60 gray(Gy) in 30 fractions at a dose of 2
Gy per fraction 5 fractions per week with 3dimensional conformal radiotherapy(3DCRT).

Concurrent chemotherapy was provided with oral alkylating
agent temozolomide @ 75 mg/m2 body surface area(BSA) for 5 days a week half an
hour before radiation for six weeks and adjuvant chemotherapy was continued
with temozolomide @ 150 mg/m2 BSA once a day for 5 days once  in 4 weeks for 6 cycles and repeat MRI brain study was
done and if residual/recurrent disease not amenable for repeat surgery
was identified then six more four weekly cycles of temozolomide were continued
as institutional protocol. All patients received prophylaxis for pneumocystis
carinii pneumonia with trimethoprim-sulfamethoxazole-160 + 800 mg (one DS
tablet) orally, daily during chemotherapy.

Retrospective
analysis was started after getting institutional ethics committee approval.

Totally 70
patients were screened and patients with incomplete data like preoperative
clinical, surgery details , defaulters for radiation, death during radiation
were excluded and remaining 46 cases were included in analysis.

For analysis we considered various prognostic
factors and grouped them under following categories. (Table 1)

Overall survival(OS): OS was calculated from the day of surgery
till date of death or last follow-up.

Disease free surviva(DFS)l: DFS was calculated from the date of surgery
to date of recurrence or death.

Survival curves were estimated using the
Kaplan-Meier method and are used to compare 
age, sex, preoperative seizure as symptom of presentation, location of
tumor, side of lesion, lobe involved, Eastern
Cooperative Oncology Group(ECOG) performance status on the day of surgery, antiepileptic drug,
type of surgery, gap between surgery and radiation, usage of concurrent temozolomide
drug , number of cycles of adjuvant temozolomide. 95% confidence intervals for
the median survival time of the groups were constructed and log-rank test was
employed to determine if there is statistical evidence of differences between
the survival curves of the groups. 
Finally, the Cox proportional hazard model was used in a multivariate
analysis. Statistical significance was set at a P value

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