METHODS
Total of 101 patients with radiologically or pathologically GBM were included in this study. Data of
patient age, sex, tumor dimensions, and preoperative peritumoral edema were analyzed.
RESULTS
While average survival was 16.67±3.99 months (95% confidence interval [CI]: 8.85-24.49 months)
and 1- and 3-year survival rates were 50% and 16.7%, respectively, for patients without edema, average
survival was 13.74±1.95 months (95% CI: 9.91-17.58 months) and 1- and 3-year survival rates were
35.6% and 8.5%, respectively, for patients with edema. No statistical difference between them was found
(p=0.297).
CONCLUSION
Prognostic value of edema for survival could not be determined in this retrospective analysis of homogeneous
group of patients with isolated GBM.
Keywords: Glioblastoma multiforme; peritumoral edema; survival
GBM's standart treatment is surgical. The main aim
of surgical treatment is a complete surgical excision which has a direct relationship with disease-free survival
and overall survival.[
In high grade tumors age, KPS, histology, resection
width, duration of symtomes, neurological-functional
mental state and tumor's crossover to the opposite lobe
are defined prognostic factors.[
Treatment
Computer tomography scans were done for RT applicaton.
The mass or mass loge was fusioned with MRG
which has had before surgical treatment. Brainstem,
lenses, optical nerrves, pituitary gland and optical chiasm
were contoured as critical organs.
The 3 dimensional conformal radiotherapy (3DRT) or intensity modulated radiotherapy (IMRT) techniques were used. In RT planning, if there wasn't an edema, the mass or mass bed was described as the GTV2 in terms of gross tumor volume (GTV), if there was an edema, it is described as the GTV1 including that. The clinical tumor volume (CTV) was forged with 2 cm margins given to the GTV1 or GTV2. The CTV was excluded from anatomic barriers if there was not an extension. The planned target volume (PTV) was forged with 0.5 cm margins given to the CTV. 2 Gy each for 23 fractions total 46 Gy were given to the PTV1, 2Gy/7 fractions total 14 Gy were given to the PTV2 and grand total tumor dose reached to 60 Gy. Everyday orally 75mg/m2 TMZ was applied as simultaneously CT. After RT, once in 28 days, 5 days long 150–200mg/m2 TMZ was applied for 5 cures.
Follow-up
After RT, clinical examination, complete blood test and
MRG controls were done with 2 months periods. The
overall survival was accepted as the time between diagnosis
and last control or death date.
Statistical methods
The obtained data was loaded to the SPSS 13.0 softwere.
The Kaplan-Meier test was used for survival times. The
prognostic factors were calculated with the long-rank
test. P<0.05 was accepted as significant.
The average tumor size was 4.03±1.46 cm (1.5–8.0) and at 59 (58%) patients ≤4 cm and at 42 (42%) of them >4 cm. Because they were medical inoperable at 23 (23%) patients diagnosis was made by radiologically. 23 (23%) of the 78 (77%) patients who were operated, only biopsy was applied. Subtotal excision was made to 21 (21%) patients and total excision was made to 34 (33%) of them. The drawn volumes at the RT planning; the mass was 92.03±107.58 (13.65–721.21) cm3, PTV 0–46 544.88±240.19 (50.91–1257.85) cm3 and PTV 46–60 319.45±172.32 (19.81–899.96) cm3. If it was evaluated based on sex; while the average survival at females was 13.45±2.13 (95% CI: 9.28–17.63) months, and 1 and 3 years survival rates were 33.6% and 5.7% respectively, the average survival at males was 13.95±2.06 (95% CI: 9.91–17.98) months and 1 and 3 years survival rates were 37.7% and 9%, and there were no statistically difference between them. If the survival was evaluated based on age; while the average survival was 24.83±3.01 (95% CI: 18.91–30.75) months, 1 and 3 years survival rates were 79% and 15% respectively at the patients below 50 years old, the average survival was 11.44±1.56 (95% CI: 8.38–14.50) months, 1 and 3 years survival rates were 28.7% and 5.6% respectively and, there was a statistically significant difference between them (p=0.001). If the survival was evaluated by tumor size; while at the patients ≤4 cm the average survival was 8.13±2.24 (95% CI: 3.72–12.53) months, 1 and 3 years survival rates were 35.9% and 14% respectively, at the patients >4 cm survival was 11.49±1.62 (95% CI: 8.32–14.67) months, 1 and 3 years survival rates were 39.5% and 0%. A significant relation between tumor size and survival couldn't be found (p=0.0404). While the average survival at the patients who were treated without surgical operation was 9.50±2.05 (95% CI: 5.46–13.53) months, 1 and 3 years survival rates 24.8% and 0% respectively, the average survival at the patients who were applied biopsy and subtotal excision was 11.88±1.62 (95% CI: 8.38–14.50) months, 1 and 3 years survival rates were 39.1% and 3.3% respectively, the average survival at the patients who were applied total excision was 19.62±3.82 (95% CI: 12.13–27.12) months, 1 and 3 years survival rates were 39.3% and 23.9% respectively and, a statistically significant relation between them couldn't be found (p=0.099).
While there was no peritumoral edema at 15 (15%)
patients, at 86 (85%) of them there was an edema and
the average volume of the edema was 145.71±133.92
(0.0–549.80) cm3. If the survival was evaluated for peritumoral
edema at the GBM patients; while the average
survival was 16.67±3.99 (95% CI: 8.85–24.49) months,
1 and 3 years survival rates were 50% and 16.7% respectively
at the patients without edema, the average survival
was 13.74±1.95 (95% CI: 9.91–17.58) months, 1 and
3 years survival rates were 35.6% and 8.5% respectively
at the patients with edema and, there wasn't a statistical
difference between them (p=0.297) (Figure
If the peritumoral edema was evaluated for sex; while there was no peritumoral edema at 5 female patients, at 34 of them there was an edema. The edema seen rate at females was 87%. The average survival of female patients without edema was 21.40±7.32 (95% CI: 7.04–35.75) months, 1 and 3 years survival rates were 50% and 25%, the average survival of female patients with edema was 11.44±1.91 (95% CI: 7.69–15.20) months, 1 and 3 years survival rates were 33.8% and 0% respectively. There was no statistical difference between two groups (p=0.145). While the edema wasn't observed at 10 male patients, at 52 of them it was observed. The edema rate at male patients was 83%. The average survival of male patients without edema was 13.79±4.18 (95% CI: 5.58–22.0) months, 1 and 3 years survival rates were 50% and 12.5%, the average survival of male patients with edema was 14.42±2.64 (95% CI: 9.23–19.61) months, 1 and 3 years survival rates were 34% and 10.4% respectively. There was no statistical difference between two groups (p=0.406). If all groups compared with each other, there was no statistical difference between them (p=0.619).
If the peritumoral edema was evaluated for age; while there was no peritumoral edema at 4 patients under ages of 50, at 11 of them there was an edema and, edema seen rate was 73%. The average survival was 26.99±4.63 (95% CI: 17.91–36.07) months, 1 and 3 years survival rates were 75% and 25% respectively at the patients under 50 years with no edema. The average survival rate was 23.91±4.10 (95% CI: 15.87–31.96) months, 1 and 3 years survival rates were 70.7% and 0% respectively at the patients under 50 years with edema. There was no statistical difference between two groups (p=0.800). The average survival rate was 12.15±4.49 (95% CI: 3.33–20.96) months, 1 and 3 years survival rates were 30% and 15% respectively at the patients 50 years old and over with no edema. The average survival rate was 11.04±1.53 (95% CI: 8.02–14.06) months, 1 and 3 years survival rates were 30.1% and 4.3% respectively at the patients 50 years old and over with edema. There was no statistical difference between two groups (p=0.918). But, if all groups were compared, there was a statistical difference (p=0.034).
If the peritumoral edema was evaluated for tumor size; while there was no edema at 6 patients with a tumor ≤4 cm, at 53 of them there was an edema. The edema seen rate was 90%. The average survival was 19.98±8.0 (95% CI: 4.30–35.66) months, 1 and 3 years survival rates were 40% and 40% respectively at patients with a ≤4 cm tumor without an edema. The average survival was 14.77±2.42 (95% CI: 10.02–19.51) months, 1 and 3 years survival rates were 35.5% and 10.2% respectively at patients with a ≤4 cm tumor and an edema. There was no statistical difference between two groups (p=0.426). While there was no edema at 9 patients with a tumor >4 cm, at 33 of them there was an edema. The edema seen rate was 79%. The average survival was 14.12±4.05 (95% CI: 6.16–22.08) months, 1 and 3 years survival rates were 55.6% and 0% respectively at patients with a >4 cm tumor without an edema. The average survival was 8.71±1.04 (95% CI: 6.65–10.76) months, 1 and 3 years survival rates were 34.3% and 0% respectively at patients with a >4 cm tumor and an edema. There was no statistical difference between two groups (p=0.141). If all groups compared with each other, there couldn't be found a statistical difference (p=0.259).
If it was evaluated for surgical operation; because 23
(23%) of the patients were accepted as medical inoperable,
the diagnosises were made radiologically. While
at 6 of these patients there was no edema, at 17 of them
there was an edema. The edema seen rate was 74%. The
average survival was 12.10±4.91 (95% CI: 2.47–21.73)
months, 1 and 3 years survival rates were 33.3% and
0% respectively at the group with no edema. The average
survival was 8.55±2.21 (95% CI: 4.21–12.89)
months, 1 and 3 years survival rates were 26.8% and
0% respectively at the group with an edema. There was
no statistical difference between two groups (p=0.571).
While at 6 of the patients who were applied biopsy and
subtotal excision there was no edema, at 38 of them
there was an edema. The edema seen rate was 86%. The
average survival was 12.60±5.98 (95% CI: 0.86–24.34)
months, 1 and 3 years survival rates were 40% and 20%
respectively at the group with no edema. The average
survival was 11.61±1.62 (95% CI: 8.42–14.80) months,
1 and 3 years survival rates were 34.5% and 0% respectively
at the group with an edema. There was no
statistical difference between two groups (p=0.588).
While at 4 of the patients who were applied total excision
there was no edema, at 30 of them there was an
edema. The edema seen rate was 88%. The average survival
was 31.93±6.83 (95% CI: 18.53–45.33) months, 1
and 3 years survival rates were 100% and 50% respectively
at the group with no edema. The average survival
was 18.18±3.88 (95% CI: 10.57–25.80) months, 1 and 3
years survival rates were 39.4% and 24.3% respectively
at the group with an edema. There was no statistical
difference between two groups (p=0.141). If all groups
compared with each other, there couldn't be found a
statistical difference (p=0.167). Table
It was come to a certain point at systemic treatment
as well as local treatment on GBM and it couldn't be
gone beyond Stupp's study.[
The necrosis MR is one of the pathognomonic factors
for GBM, too. Also, the peritumoral edema's being
wide situation at these tumors is a frequent situation at
diagnosis phase or at the patients not having stereoids.
It is being thought that the widespread edema at the diagnosis
phase is related with the tumor's biological behaviour.
Wu and his colleagues reported that at the retrospective
analysis which they examined 109 patients'
with malign glioma preoperative MR images, the edema
and necrosis were negative prognostic indicators
for overall survival. Also, they suggested these tumor
cells in the peritumoral edema area could be related to
the unresponsiveness to the treatment. It was indicated
that this peritumoral edema's effect was controversial in
the Liu and his colleagues' study.[
Wu CX and his colleagues[
The results of our study are inconclusive; the available
evidence does not certainly support or rule out an
association between pre-operative peritumoral edema
and overall survival (p=0.297). However, the patients
under 50 years with no edema had significant long
overall survival compared to patients 50 years old and
over with edema (p=0.034).
For a conclusion, the edema's prognostic value
couldn't be determined on the survival in the retrospective
analysis of our homogeneous group formed
from isolated GBM patients. There is a need for randomized
studies with higher patient numbers for researching
this subject.
Disclosure Statement
The authors declare no conflicts of interest.
