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

Becker, Lucas; Gebauer, Judith; Küchler, Jan; Staackmann, Christian; Schacht, Hannes; Lauten, Melchior; Jensen-Kondering, Ulf; Schramm, Peter; Langer, Thorsten; Neumann, Alexander

doi:10.2478/raon-2021-0032

Figures & Tables

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

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
Type II	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

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

Figures & Tables

Figure 1

Figure 2

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

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

Cranial radiotherapy according to treatment protocols

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