Patient number
Sex/Age (years)
Pathological diagnosis
Side/Location
Primary treatment
RT dose/fraction number
Total RT time (days)
Chemotherapy
Time to progression (months)
Preoperative KPS
Treatment for RN
Follow-up (months)
1
M/41
glioma
L/temporal
Surgery
50 Gy/25 fr
38
/
24
80
Surgery
36
2
F/49
Cavernous angioma
L/frontal
Gamma Knife
60 Gy/30 fr
46
/
18
90
Surgery
36
3
M/64
Glioma
L/temporal
Surgery
50 Gy/25 fr
37
TMZ
8
70
Surgery
19
4
M/59
Glioma
L/temporal
Surgery
60 Gy/30 fr
44
TMZ
13
70
Surgery
14
5
F/67
GBM
R/frontal
Surgery
60 Gy/30 fr
48
TMZ
15
90
Medical
9
6
F/73
GBM
R/parietal
Surgery
60 Gy/30 fr
50
TMZ
14
90
Medical
15
7
M/57
GBM
L/parietal
Surgery
60 Gy/30 fr
40
TMZ
28
80
Surgery
14
8
M/57
Glioma
L/fronto-temporal
Surgery
60 Gy/30 fr
50
/
26
70
Surgery
12
9
M/48
Glioma
L/occipital
Surgery
50 Gy/25 fr
38
/
14
80
Surgery
4
10
M/55
Glioma
R/fronto-temporal
Surgery
60 Gy/30 fr
48
TMZ
14
80
Surgery
22
11
F/53
Glioma
R/parietal
Surgery
50 Gy/25 fr
39
TMZ
12
90
Medical
18
12
F/47
Glioma
R/parietal-occipital
Surgery
45 Gy/20 fr
34
/
33
70
Surgery
6
Magnetic resonance imaging (MRI) was performed at 3- to 6-month intervals after completion of the radiation therapy. When clinical deterioration occurred, MRI was performed. All the patients, including the one with cavernous angioma, developed a newly formed lesion mimicking tumor recurrence (Fig. 1). The mean time between the administration of radiation therapy and the appearance of the newly formed lesion was 18 months (range 8–33 months). Nine patients underwent surgical resection of the lesion to alleviate the severe symptoms, while three patients received only medical treatment after stereotactic biopsy, as they had relatively mild symptoms. Pathological study of the specimens showed RN (Fig. 2). MRI or computed tomography (CT) scans of the brain were then performed at 3- to6 -month intervals during the follow-up. The mean duration of follow-up was 16 months (range 4–36 months) (Table 1).
Fig. 1
(a, b) Axial magnetic resonance (MR) images of patient with primary glioma. The solid portion of radionecrosis and the perilesional edema in the left temporal lobe have low signal intensity on axial T1-MRI and high signal intensity on axial T2-MRI (c, d) axial MR images of patient with primary cavernous angioma. The solid portion of radionecrosis and the perilesional edema in the frontal lobe show iso-to-hypointense signal intensity on T1 Fluid attenuated inversion recovery (FLAIR) image; the lesion was irregularly enhancement. Hyperintense signal with patches of a hypointense signal area are shown on T2-MR image
Fig. 2
Pathological section of radionecrosis shows proliferation of surrounding gliocytes, coagulative necrosis of large areas, formation of a glial scar, and infiltration of inflammatory cells around the blood vessels
Results
In our series the median preoperative Karnofsky performance score (KPS) was 80. Apparent total surgical removal of the lesion was performed in nine patients, all of whom had a significant reduction in intracranial pressure within a few days postoperatively. No major complications occurred.
Two patients presented with a severe motor deficit of the left arm and two had postoperative seizures. Transient dysphasia was observed in two more patients. After surgery, brain edema progressively resolved in all the patients within 3 weeks, allowing a reduction or suspension of corticosteroid therapy by that time.
Three patients developed mild neurological symptoms a few weeks postoperatively. MRI showed a worsening of cerebral edema, which recovered after corticosteroid administration.
Discussion
The treatment of brain tumors remains challenging, although neurosurgery, radiotherapy, and chemotherapy are the current options, and they can be integrated. However, prolongation of survival can be accompanied by the appearance of new features, such as RN, which has increased in incidence since radiotherapy started to be considered an outstanding treatment opportunity for brain tumors, arteriovenous malformations, and some head and neck cancers [7].
The primary goal of brain radiotherapy is to deliver a therapeutic dose of radiation, sparing the surrounding normal brain tissue; in fact, irradiation occasionally affects the normal tissue, damaging normal brain tissue near the tumor site [13, 36]. The tolerance of normal tissue has been a limiting factor in the radiation therapy of cerebral pathologies. Patients vary in their individual responses to radiotherapy: some may develop severe adverse reactions, while others receiving comparable radiation doses for similar pathologies in similar locations do not. The exact reason for this variability in response remains unclear, although several researchers have tried to address the issues of intrinsic tissue sensitivity over the past two decades [1, 9, 20, 28, 33], and a median dose of 20 Gy in a single fraction has been advocated to obtain an optimal balance between therapeutic efficacy and the risk of complications [17, 23].
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