Authors
Year
No. of patients
Technique
Dose (Gy)
FU (months)
Tumor control (%)
Late toxicity (%)
Carella et al. [9]
1982
57
EBRT
55–60
NA
95
NA
Forbes and Goldberg [10]
1984
31
EBRT
53
45
72 at 4 years
13
Barbaro et al. [7]
1987
54
EBRT
52.5
78
68
0
Miralbell et al. [14]
1992
36
EBRT
45–64
88
84 at 8 years
16
Goldsmith et al. [3]
1994
117
EBRT
54
40
89 at 5 years; 77 at 10 years
3.6
Maire et al. [11]
1995
91
EBRT
52
40
94
6.5
Peele et al. [16]
1996
42
EBRT
55
48
100
5
Condra et al. [18]
1997
28
EBRT
53.3
98
87 at 15 years
24
Connell et al. [19]
1999
54
EBRT
54
55
76 at 5 years
19
Maguire et al. [20]
1999
26
EBRT
53
41
81 at 8 years
8
Nutting et al. [15]
1999
82
EBRT
55–60
41
92 at 5 and 83 at 10 years
14
Vendrely et al. [17]
1999
156
EBRT
50
40
79 at 5 years
11.5
Dufour et al. [21]
2001
21
EBRT
52
73
93 at 5 and 10 years
3.2
Pourel et al. [22]
2001
38
EBRT
56
30
95 at 5 years
4
Mendenhall et al. [23]
2003
101
EBRT
54
64
95 at 5, 92 at 10, and 15 years
8
Buglione et al. [24]
2014
18
EBRT
46–66
42
52.6 at 5 and 40 at 8 years
0
Debus et al. [25]
2001
189
FSRT
56.8
35
97 at 5 and 96 at 10 years
12
Jalali et al. [26]
2002
41
FSRT
55
21
100
12.1
Lo et al. [27]
2002
18
FSRT
54
30.5
93.3
5
Torres et al. [28]
2003
77
FSRT
48.4
24
97.2
5.2
Selch et al. [29]
2004
45
FSRT
56
36
100 at 3 years
0
Metellus et al. [12]
2005
38
FSRT
53
88.6
94.7
2.6
Milker-Zabel et al. [13]
2005
317
FSRT
57.6
67
90.5 at 5 and 89 at 10 years
8.2
Henzel et al. [30]
2006
84
FSRT
56
30
100
NA
Brell et al. [8]
2006
30
FSRT
52
50
93 at 4 years
6.6
Hamm et al. [31]
2008
183
FSRT
56
36
97 at 5 years
8.2
Minniti et al. [32]
2011
52
FSRT
50
42
93 at 5 years
5.5
Solda et al. [33]
2013
222
FSRT
50–55
43
93 at 5 years and 86 at 10 years
5
Fokas et al. [34]
2014
253
FSRT
50–55.8
50
92.9 at 5 years
3
Kaul et al. [35]
2014
179
FSRT
57
35
92.7 at 5 years and 85.8 at 10 years
0.7
Combs et al. [36]
2013
507
376 SRT/131 IMRT
57.6
107
91 at 10 years
NA
Uy et al. [37]
2002
40
IMRT
50.4
30
93 at 5 years
5
Pirzkall et al. [38]
2003
20
IMRT
57
36
100
0
Sajja et al. [39]
2005
35
IMRT
50.4
19.1
97 at 3 years
0
Milker-Zabel et al. [40]
2007
94
IMRT
57.6
52
93.6
4
Wenkel et al. [41]
2000
46
Prot/Phot
59
53
100 at 5 and 88 at 10 years
16
Vernimmen et al. [42]
2001
23
Protons
20.6
38
87
13
Weber et al. [43]
2004
16
Protons
56
34.1
91.7 at 3 years
24
Noel et al. [44]
2005
51
Prot/Phot
60.6
21
98 at 4 years
4
Slater et al. [45]
2012
72
Protons
59
74
99 at 5 years
8.3
Combs et al. [46]
2013
107
Protons
57.6
12
100 (grade I) and 33 (grades II–III) at 2 years
0
After the advent of CT planning, Goldsmith and coworkers [3] showed that local control using radiotherapy could rival that of surgical resection. They suggested that 5-year progression-free survival (PFS) in the post-1980 era with the aid of more modern techniques was 98 % compared with 77 % in patients treated before 1980 (p = 0.002).
The first issue in the treatment of a benign meningioma, using a standard fractionation scheme (1.8–2 Gy/day), concerns the dose to be delivered. Most of published series showed no significant difference on tumor control with the use of doses ranging between 50 and 60 Gy with a 2 Gy daily fraction. However, a dose <50 Gy is associated with higher recurrence rates [14, 17]. Goldsmith et al. [3] reported that doses greater than 52 Gy resulted in a 10-year local control of 93 % compared with 65 % using lower doses, although the dose was not an independent predictor at multivariate analysis.
Size and tumor site have been suggested as a possible predictor of tumor control. Connell et al. [19] reported a 5-year control of 93 % for 54 patients with skull base meningiomas of <5 cm and 40 % for tumors >5 cm.
Late toxicity of EBRT is relatively low, ranging from 0 to 24 % (Table 23.1), and includes neurological deficits, especially optic neuropathy, cerebral radionecrosis, cognitive deficits, and pituitary function deficits.
Cerebral radionecrosis is a severe and potentially fatal complication of RT; however it remains exceptional when doses less than 60 Gy and 3-D planning system are used. Goldsmith et al. [3] identified complications in five out of 140 patients (3.6 %) attributable to EBRT. Authors described retinopathy in two patients, optic neuropathy in one patient, and cerebral necrosis in two patients [3]. Generally, optic complications are quite rare with doses lower than 54 Gy, particularly with fractional doses of 2.0 Gy or less [14, 38, 47]. Goldsmith et al. generated a radiobiology model to predict optic nerve tolerance and recommended a maximum dose of 890 optic ret (corresponding to 890 cGy in single fraction or 54 Gy in 30 fractions) to be delivered at the optic nerve [48].
Patients with parasellar meningiomas are at risk to develop late hypopituitarism and should be carefully assessed long life after RT. Neurocognitive dysfunction is a recognized consequence of large-volume RT for brain tumors [49] and has been occasionally reported in irradiated patients with meningiomas, especially impairment of short-term memory [11, 20, 21].
High-dose radiation may be associated with the development of a second brain tumor. In a large series of 426 patients with pituitary adenomas who received conventional RT at the Royal Marsden Hospital between 1962 and 1994, Minniti et al. reported that the risk of second brain tumors was 2.0 % at 10 years and 2.4 % at 20 years, measured from the date of RT [50].
23.3 Fractionated Stereotactic Conformal Radiotherapy (FSRT)
FSRT uses conventional fractionation schemes using modern high-precision image-guided radiotherapy (IGRT) approaches allowing for significantly improved precision over older radiotherapy paradigms. FSRT leads to a reduction in the volume of normal brain irradiated at high doses. Thus, the principal aims of radiosensitive structures sparing are to reduce the long-term toxicity of radiotherapy and to increase the precision of treatment maintaining or possibly increasing its effectiveness.
Toxicity is reported to be less than 0–12 % of patients in series reporting results on the use of FSRT in benign meningiomas (Table 23.1), including cranial deficits (leading especially to visual problems), hypopituitarism, and impairment of neurocognitive function. Reduced volume of normal brain receiving radiation doses may decrease the risk of radiation-induced tumors.
23.4 Intensity-Modulated Radiotherapy (IMRT)
Intensity-modulated radiotherapy (IMRT) is an advanced mode of 3D conformal radiotherapy that uses computer-controlled linear accelerators to deliver precise radiation doses to a malignant tumor or specific areas within the tumor. IMRT combines two advanced concepts to deliver 3D conformal radiotherapy: (A) inverse treatment planning with optimization by computer and (B) computer-controlled intensity modulation of the radiation beam during treatment. IMRT for meningiomas could result in greater conformality and better target coverage than 3D CRT [51].
Few series are available on the use of IMRT in patients with meningiomas [37–40] (Table 23.1). Milker-Zabel et al. [40] reported data of 94 patients with complex-shaped meningiomas treated with IMRT with a median follow-up of 4.4 years. Overall local control was 93.6 %. Sixty-nine patients had stable disease, whereas 19 had a tumor volume reduction after IMRT. In 39.8 % of the patients, preexisting neurological deficits improved. Transient side effects such as headache were seen in 7 patients. Treatment-induced loss of vision was seen in 1 of 53 with a grade 3 meningioma, 9 months after retreatment with IMRT.
23.5 Proton Radiotherapy
Proton therapy is a type of external beam radiotherapy using a cyclotron to generate beams of protons. Due to their relatively large mass, protons have little lateral side scatter in the living tissue. Therefore, the beams can be highly focused on the tumor and deliver only low dose to surrounding tissue with a potentially lower risk of side effect.
At the Centre de Protonthérapie d’Orsay (CPO), Noel et al. [52] treated, between December 1995 and December 1999, 17 patients using a 201-MeV proton beam combining high-energy photons and protons for approximately 2/3 and 1/3 of the total dose. The median total dose delivered within gross tumor volume was 61 cobalt gray equivalent (CGE) (25–69). The 4-year local control and overall survival rates were 87.5 ± 12 % and 88.9 ± 11 %, respectively. Authors recorded 11 stable diseases (65 %) and five partial responses (29 %).
Wenkel et al. [41] reported data of 46 patients with partially resected or recurrent meningiomas treated between 1981 and 1996 with combined photon and 160-MeV proton beam therapy at the Massachusetts General Hospital (MGH). Overall survival at 5 and 10 years was 93 and 77 %, respectively. At a median follow-up of 53 months, 8 (17 %) of patients developed severe long-term toxicity from RT, including ophthalmologic, neurological, and otologic complications.
At a median follow-up of 40 months, a tumor control of 89 % has been reported by Vernimmen et al. [42] in 27 patients with large skull base meningiomas treated with stereotactic proton beam therapy. Permanent neurological deficits were reported in three patients.
23.6 Stereotactic Radiosurgery (SRS)
Single-fraction stereotactic focused irradiation (stereotactic radiosurgery; SRS) has been extensively employed in the treatment of skull base meningiomas as alternative treatment for lesions not amenable to surgical removal. Since its introduction into clinical practice in 1985 by Colombo et al. [53], the procedure has proved to be safe and reliable. Reported results, in terms of clinical stabilization and tumor growth control, seem to be relatively independent of the device (GammaKnife or modified linear accelerator [LINAC]). Most studies describe 5-year tumor control rates of about 90–95 %, with a low or very low treatment-related complication rate [54] (Table 23.2).
Table 23.2
Summary of results on main published studies on SRS of skull base meningiomas
Year | System | No. of patients | FU (months) | 5-year tumor control (%) | Late toxicity (%) | |
|---|---|---|---|---|---|---|
Roche et al. [55] | 2000 | GKS | 92 | 30 | 94 | 2 |
Nicolato et al. [56] | 2002 | GKS | 122 | 48 | 96 | 2.5 |
Kreil et al. [57] | 2005 | GKS | 200 | 94 | 98.5 | 4.5 |
Malik et al. [58] | 2005 | GKS | 309 | 96 | 87 | 3 |
Hasegawa et al. [59] | 2007 | GKS | 115 | 62 | 94 | 5.5 |
Kollovà et al. [60] | 2007 | GKS | 368 | 60 | 97.9 | 5.7 |
Kondziolka et al. [61] | 2008 | GKS | 972 | 48 | 97 | 7.7 |
Villavicencio et al. [62] | 2001 | LINAC | 56
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