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Are radiation-induced cavernomas clinically relevant findings? Results from long-term follow-up with brain magnetic resonance imaging of childhood cancer survivors

Lucas Becker
Lucas Becker
, 
Judith Gebauer
Judith Gebauer
, 
Jan Küchler
Jan Küchler
, 
Christian Staackmann
Christian Staackmann
, 
Hannes Schacht
Hannes Schacht
, 
Melchior Lauten
Melchior Lauten
, 
Ulf Jensen-Kondering
Ulf Jensen-Kondering
, 
Peter Schramm
Peter Schramm
, 
Thorsten Langer
Thorsten Langer
 und 
Alexander Neumann
Alexander Neumann
   | 10. Aug. 2021
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Article Category: Research Article
Online veröffentlicht: 10. Aug. 2021
Seitenbereich: 274 - 283
Eingereicht: 25. Jan. 2021
Akzeptiert: 20. Juni 2021
DOI: https://doi.org/10.2478/raon-2021-0032
© 2021 Lucas Becker, Judith Gebauer, Jan Küchler, Christian Staackmann, Hannes Schacht, Melchior Lauten, Ulf Jensen-Kondering, Peter Schramm, Thorsten Langer, Alexander Neumann, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Flowchart of the patient selection process.* = craniopharyngeoma, ependymoma, germinoma, medulloblastoma; ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia; CR = cranial radiotherapy; LTFU = long-term follow-u; MRI = magnetic resonance imaging; TBI = total body irradiation
Flowchart of the patient selection process.* = craniopharyngeoma, ependymoma, germinoma, medulloblastoma; ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia; CR = cranial radiotherapy; LTFU = long-term follow-u; MRI = magnetic resonance imaging; TBI = total body irradiation

Figure 2

Examples of radiation-induced cavernomas with a type II lesion (A, B) and multiple type IV lesions (C) according to the Zabramski classification. Radiation-induced meningioma (D) and leukoencephalopathy with brain atrophy (E).
Examples of radiation-induced cavernomas with a type II lesion (A, B) and multiple type IV lesions (C) according to the Zabramski classification. Radiation-induced meningioma (D) and leukoencephalopathy with brain atrophy (E).

Patient characteristics, therapy data, findings of radiation-induced cavernomas and other comorbidities

No. Gender (F=female; M=male) Initial tumor diagnosis Age at diagnosis (years) Cumulative radiation dose to the brain (Gy) Total number of brain MRI Detection of RIC Latency between CR and RIC (years) Zabramski classification RIC localization (1=supratentorial; 2=infratentorial; 3=both) RIC dynamic Other benign tumors in follow-up brain MRI Leukoencephalopathy (mild; moderate; extensive) Brain atrophy (mild; mode-rate; severe) Other comorbidities in the long term Period of follow-up (years)
1 F ALL 17 24 9 Meningioma moderate - COPD, hyperparathyroidism, hypercholesterolemia, migraine 44
2 F ALL 1 12 2 mild - Lipedema, fibroepithelioma 26
3 F ALL 3 12 2 - - Class I obesity 22
4 F ALL 7 8 2 mild - CRF, class II obesity, hypercholesterolemia, hypopituitarism, thyroid nodules 37
5 F ALL 3 24 4 + 40 II 3 + Meningioma extensive mild Hypercholesterolemia, class I obesity, thyroid nodules, scoliosis, myoma uteri 44
6 F ALL 21 24 2 + 10 IV 1 mild - Reduced left ventricular ejection fraction, class III obesity, multiple vein thrombosis 13
7 M ALL 5 12 2 - - Hypercholesterolemia 19
8 F ALL 9 12 2 mild - Hypercholesterolemia 28
9 M ALL 11 30 9 mild - Hypogonadism, hypercholesterolemia, 13
10 F ALL 7 30.6 3 + 29 IV 1 Meningioma moderate - Basalioma, hyperparathyroidism, class II obesity, thyroid nodules 33
11 F ALL 5 39 6 Vestibular schwannoma, DD aneurysmal bone cyst mild - Diabetes mellitus type 2, hypercholesterolemia, steatosis hepatis, congestive heart failure, restrictive lung disease, thyroid nodules, deep vein thrombosis, basalioma, CRF, vestibular schwannoma 39
12 M ALL 2 30 2 moderate - Thyroid Nodules, hypopituitarism, diabetes mellitus type 2, CRF, steatosis hepatis, cataract 35
13 F ALL 2 12 4 moderate - Intellectual disabiliy 17
14 F AML 14 12 2 + 21 IV 1 mild - Thyroid nodules, hypercholesterolemia, hypertension, spondyloarthritis 26
15 M AML 15 12 2 - - Thyroid nodules, restrictive lung type disease, 1, hypogonadism, diabetes mellitus hypercholesterolemia 31
16 F AML 16 12 3 + 28 IV 3 moderate - Thyroiditis 18
17 F AML 2 15 2 + 21 IV 3 - - Cataract, hypercholesterolemia, depression 24
18 F AML 8 12 3 - - CRF, class ii obesity, chronic pain, visual impairment 14
19 M PA 1 54 28 + 23 IV 3 moderate moderate Hypopituitarism, stroke, epilepsia, hearing loss, hypercholesterolemia, gallstones 29
20 M PA 17 50.4 24 moderate - Hypercholesterolemia 11
21 M Germinoma 17 40 16 mild - Hypopituitarism, chronic renal failure 5
22 M Germinoma 14 24 20 mild - Hypopituitarism, class I obesity, depression, hypercholesterolemia 9
23 M Germinoma 10 40 21 + 5 IV 1 moderate - Depression, hypercholesterolemia, hypopituitarism 12
24 M CP 17 n.a. 15 mild - Hypopituitarism, class I obesity, hypercholesterolemia, autoimmune polyendocrine syndrome type 2 with diabetes mellitus type 1, vitiligo, thyroiditis 13
25 F Medulloblastoma 7 55 3 + 27 IV 2 Meningioma - mild Hypothyroidism, thyroid nodules, hearing loss,asthma 28
26 M Medulloblastoma 8 54 25 + 5 IV 3 + mild - Hypopituitarism, hearing loss 14
27 M Medulloblastoma 8 54 21 + 2 I 3 + moderate moderate Hypopituitarism, hearing loss 10
28 M Medulloblastoma 13 54 24 + 5 IV 2 + moderate - Hypopituitarism, loss, class I obesity, epilepsy, tetraparesis hearing 10
29 M Medulloblastoma 11 68.6 24 + 2 IV 3 + - mild Spinal hygroma, hypothyrodism, growth hormone deficiency 14
30 M Medulloblastoma 6 68.6 18 + 7 IV 3 + - - Hypopituitarism, hearing loss, intellectual disability 19
31 M Medulloblastoma 9 60 3 + 29 II 2 mild - Basalioma, hearing loss, intellectual disability 30
32 F Medulloblastoma 25 60 6 + 18 IV 3 extensive moderate Coxarthrosis with total endoprothesis, gonarthrosis 18
33 M Medullo- blastoma 2 60 13 + 7 IV 3 moderate mild Visual Impairment, groth hormone deficiency, hypothyroidism, intelectual disability, hearing loss, steatosis hepatis 17
34 F Ependy-moma 12 68 31 + 13 IV 3 moderate mild Hypopituitarism, chronic renal failure 13
35 F Ependy-moma 6 72 28 extensive - - 13
36 F Ependy-moma 7 68 10 mild - Asthma bronchiale 13

MRI classification of cerebral cavernomas according to Zabramski et al.: type I, type II and an additionally proposed new type V are associated with higher prospective hemorrhage rates, as published by Nikoubashman et al. in connection with non-radiation induced cavernomas13,14

Lesion type MRI signal characteristics Pathological characteristics
Type I T1: hyperintense coreT2: hyper- or hypointense core with surrounding hypointense rim Subacute hemorrhage, surrounded by a rim of hemosiderinstained macrophages and gliotic brain
Type II T1: reticulated mixed-signal core hypointense rim Loculated areas of hemorrhage and thrombosis of varying ages, surrounded by gliotic, hemosiderin-stained brain; in large lesions, areas of calcification may be seen
T2: reticulated mixed-signal core with surrounding
Type III T1: iso- or hypointense core Chronic resolved hemorrhage, with hemosiderin staining within and around the lesion
T2: hypointense with a hypointense rim that magnifies the size of the lesion
GE: hypointense with greater magnification than T2
Type IV T1: poorly seen or not visualized at allT2: poorly seen or not visualized at all GE: punctate hypointense lesions Two lesions in the category were pathologically documented as telangiectasias
Type V T1 and T2: visible parts in the center of the actual cavernoma; the cavernoma is not fully distinguishable from hemorrhage

Cranial radiotherapy according to treatment protocols

Tumor entity Dose/day Number of fractions
ALL 1.5 Gy 8, 12, 16, 20 or 26
AML 1.5 Gy 8 or 10
Pilocytic Astrocytoma 1.8 Gy 28 or 30
Germinoma 1.6 Gy 15 or 25
1.8 Gy 30 or 34
Medulloblastoma 2 x 1.0 Gy (hyperfractionated) 30 or 34
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