Irradiation A
Significant
Risk Factor for Carotid Atherosclerosis
Robert S. Feehs, MD; W. Frederick McGuirt, MD; M. Gene Bond, PhD; Harriet L. Timothy E. Craven, MSPH; Jeffrey B. Hiltbrand, MD \s=b\ Radiation exacerbates the development of atherosclerosis in the large arteries of animals and is postulated to do likewise in human beings. To study this relationship, we used high-resolution B-mode ultrasonography to measure carotid artery wall thickness in 29 previously irradiated head and neck cancer patients and compared the results with those of nine epidemiologically similar but nonirradiated head and neck cancer patients. Maximal intima-media thickness was greater in the study group (mean, 1.28 \m=+-\SE 0.06 mm) than in the control group (mean, 0.90 \m=+-\SE 0.05 mm). Even after the effects of age, hypertension, and tobacco consumption were controlled, these differences remained statistically significant. This study suggests that irradiation may contribute to the development of more severe and extensive carotid atherosclerosis in head and neck cancer patients who receive radiation therapy. (Arch Otolaryngol Head Neck Surg.
1991;117:1135-1137) Accepted for publication March 13,1991. From the Department of Otolaryngology (Drs Feehs, McGuirt, and Hiltbrand), Neurobiology and Anatomy (Drs Bond and Strickland), and Public Health Sciences (Dr Craven), The Bowman Gray School of Medicine of Wake Forest University,
Winston-Salem, NC.
Presented at the American Society of Head and Neck Surgery, April 30-May 1, 1990, Palm Beach, Fla. Reprint requests to the Department of Otolaryngology, The Bowman Gray School of Medicine, 300 S Hawthorne Rd, Winston-Salem, NC 27103 (Dr Feehs)
Strickland, DVM;
Irradicarotid ation-iatherosclerosis nandduced acceleration has been hy¬
of
numerous studies of carotid atherosclerosis follow¬ ing radiation therapy support this hy¬ pothesis. Previous studies have only indirectly assessed carotid atheroscle¬ rosis using blood flow methods, and thereby inferred but did not define anatomic changes. We undertook this study to evaluate directly the anatomic extent and severity of carotid athero¬ sclerosis in asymptomatic, previously irradiated head and neck cancer pa¬ tients and to determine what role irra¬ diation may play in the development of carotid atherosclerosis.
pothesized, severe
MATERIALS AND METHODS Patients who had undergone radiation for head and neck cancers at our institution were identified, and those at least
therapy
years' postirradiation were requested to participate in the study. Nonirradiated pa¬ tients with newly diagnosed head and neck cancer served as control patients. 3
Patients were interviewed and charts reviewed to determine age, sex, systol¬ ic blood pressure, tobacco consumption, total plasma cholesterol concentration, tumor cell type and location, irradiation dosage and treatment portals, and interval since comple¬ tion of radiation therapy. were
Downloaded From: by a UNIVERSITY OF ADELAIDE LIBRARY User on 05/14/2018
Participants underwent ultrasound exami¬ nation of the carotid arteries, using a highresolution B-mode imager, which features an 8-MHz transducer. For this examination, the carotid artery was divided into three seg¬ ments: the distal common carotid, the carotid bifurcation (bulb), and the proximal internal carotid. A standardized scanning protocol was used to ensure the valid and reliable identification of arterial segments and defini¬ tion of artery wall interfaces (Figs 1 and 2).1 The normal combined intima-media thick¬ ness ranges from 0.8 mm in the common and internal carotid arteries to 1.1 mm at the bifurcation.2 An atherosclerotic plaque is present when the intima-media thickness is greater than 1.3 mm and there is nonparallel displacement of the interfaces used to define the intima-media. Maximal near-wall and far-wall intima-media measurements were obtained for each arterial segment of both carotid arteries in each subject. The resulting near-wall and far-wall val¬ ues were averaged to yield a combined mean maximal value for each artery. These two single artery means were then averaged to yield one mean maximal score reflecting the patient's overall carotid intima-media thick¬ ening. The data were analyzed using the Stu¬ dent f test, analysis of covariance, and the Fisher's Exact Test for two-way contingency tables. RESULTS
Twenty-nine previously irradiated patients (20 men, nine women) en-
Table
1.—Histologie Classification of Tumors Irradiated Control Patients Patients
Cell Type
Squamous
(n
29)
=
(n
=
9)
cell
carcinoma
26
Lymphoma Rhabdomyosarcoma
9
1 1
Undifferentiated carcinoma
1
Table 2.—Tumor Location Irradiated Patients
Site
(n
Oropharynx Nasopharynx Larynx Other
Interfaces Near Wall 1 Periadventitia-adventitia 2 Adventitia-media 3 Intima-lumen
Far Wall 4 Lumen-intima 5 Media-adventitia 6 Adventitia-periadventitia
Fig 1 .—Schematic of high-resolution B-mode ultrasonograph of the right carotid artery with lesion In the bifurcation. Near-wall interfaces 1, 2, and 3, and far-wall interfaces 4,5, and 6 are identified.
29)
=
Oral cavity
9 1
Control Patients
(n
=
9)
3
4
1
13 2
5
ages ranged from 33 to 75 years (mean, 58.7 ±13.8 years). Systolic blood pres¬ sures ranged from 90 to 150 mm Hg (mean, 128.3 ±20.7 mm Hg); tobacco consumption ranged from 0 to 90 pack years (mean, 50.5 ±32.0 pack years). Age, systolic blood pressure, and to¬ bacco consumption were not signifi¬ cantly different between the two groups (P=.40, .21, and =.32, respectively). No patient in either group had hypercholesterolemia. Tables 1 and 2 show tumor histolog¬ ie findings and location for the two groups. The applied dose of radiation ranged from 40 to 87.2 Gy (mean, 60.36 Gy) in the irradiated group. Time since completion of irradiation ranged from 3 to 17 years (mean, 8.5 years). =
Fig 2. —High-resolution B-mode ultrasonograph of left carotid artery showing the bifurcation. Nearwall interfaces 1, 2, and 3, and far-wall interfaces 4, 5, and 6 are identified. Note site of intima-media thickening on the near wall and acoustical shadowing across the opposite far wall. tered the study. Their ages ranged from 20 to 87 years (mean, 62.6 ±11.6 years). Systolic blood pressures ranged from 110 to 190 mm Hg (mean, 138.6 ± 18.5 mm Hg). Ten patients had adequately controlled hypertension.
Tobacco consumption ranged from 0 to 120 pack years (mean, 42.9 ±28.7 pack
years).
Nine nonirradiated head and neck patients (six men, three wom¬ en) served as control patients. Their cancer
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The mean maximal intima-media thicknesses ranged from 0.55 to 1.97 mm (mean, 1.28 ±0.06 mm) in the irra¬ diated group and from 0.70 to 1.13 mm (mean, 0.90 ±0.05 mm) in the control patients. These values were statistical¬ ly different (P=.003) and remained different after analysis of covariance was used to control for the effects of age, blood pressure, and tobacco
consumption. Arterial plaque (intima-media
>1.3
present in 27 (93%) of the 29 irradiated patients and in six (67%) of mm)
was
the nine control patients. Plaques oc¬ curred at multiple sites in 24 (81%)
irradiated patients, with 10 (33%) pa¬ tients having plaque in all segments. In contrast, plaque in control patients was found only at the bifurcation, indi¬ cating a significant difference in the two groups (P=.0007, Fisher's Exact
Test).
COMMENT The development of carotid athero¬ sclerosis following irradiation was ini¬ tially reported by Heidenberg et al3 in 1966; numerous cases have since been published.4"13 Studies characterizing ir¬ radiation-induced atherosclerosis indi¬ cate that the disease begins at a youn¬ ger age, involves only vessels within the irradiated field, affects arterial segments normally not prone to devel¬ op atherosclerosis, and is associated with less coronary and peripheral vas¬ cular disease when compared with nat¬ urally occurring atherosclerosis." The irradiation dosage delivered does not seem to correlate with the severity of disease,1415 and the interval from treat¬ ment to the appearance of symptoms of cerebral vascular insufficiency has been from 1 to 34 years.5,16 Carotid atherosclerosis generally re¬ mains undetected until symptoms re¬ lated to arterial stenosis or occlusion occur. Scholz et al,1' using sonography, found a 19% incidence of carotid steno¬ sis in 37 irradiated patients compared with 2.7% in 556 control subjects. Elerding et al18 performed noninvasive indirect carotid evaluations in 118 pre¬ viously irradiated patients and detect¬ ed hemodynamically significant lesions in 25%. Neither of these studies direct¬ ly evaluated anatomically defined ca¬ rotid atherosclerosis. Our evaluation using high-resolution B-mode ultrasound imaging of 29 asymptomatic, previously irradiated patients demonstrated that this popu-
lation had a significant increase in overall carotid intima-media thickness compared with control patients. Plaques were more numerous and more widespread in the irradiated group, but were present only at the carotid bifurcation in control patients. Age, blood pressure, and tobacco con¬ sumption were similar between the groups; although each is known to in¬ fluence the development and progres¬ sion of carotid artery atherosclerosis, none could be used to account for the observed differences between these two groups.
Despite
small numbers of control all differences were statisti¬ patients, cally significant. Additional factors not addressed in this study that need fur¬ ther examination because they may have contributed to the observed dif¬ ferences include previous surgery, type and technique of irradiation, and qi other unknown risk factors for ca¬ rotid atherosclerosis. Patients having received neck irra¬ diation had more severe and extensive carotid atherosclerosis than did control patients. Other known risk factors for carotid atherosclerosis were present but could not account for these differ¬ ences. These findings support and strengthen the hypothesis that neck irradiation may be a significant risk factor for the development and/or pro¬ gression of carotid atherosclerosis. We
acknowledge
the expertise of the sonographs and readers in the Division of Vascular Ultrasound Research, The Bowman Gray School of Medicine, Winston-Salem, NC: Anne W. Safrit, Rita M. Phillips, Lori E. Szostak, and Gina L. Enevold.
References 1. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imag-
ing. Circulation. 1986;74:1399-1406. 2. Bond MG, Strickland HL, Wilmoth SK, Sha-
Downloaded From: by a UNIVERSITY OF ADELAIDE LIBRARY User on 05/14/2018
frit AW, Phillips RM, Szostak LE. Interventional clinical trials using noninvasive ultrasound end points: the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS). J Cardiovasc Pharma-
col. 1990;15(suppl 1):S30-S33. 3. Heidenberg WJ, Lupovitch A, Tarr N. 'Pulseless disease' complicating Hodgkin's disease: a case apparently caused by radiotherapy. JAMA.
1966;195:488-491.
4. Glick B. Bilateral carotid occlusive disease irradiation for carcinoma of the vocal cords. Arch Pathol. 1972;93:352-355. 5. Levinson SA, Close MB, Ehrenfeld WK, Stoney RJ. Carotid artery occlusive disease following external cervical irradiation. Arch Surg.
following
1973;107:395-397. 6. Silverberg GD, Britt RH, Goffinet DR. Radiation-induced carotid artery disease. Cancer. 1978;41:130-137. 7. Atkinson JLD, Sundt TM Jr, Dale AJD, Cascino TL, Nichols DA. Radiation-associated atheromatous disease of the cervical carotid artery: report
of seven cases and review of the literature. Neurosurgery. 1989;24:171-178. 8. Eisenberg RL, Hedgcock MW, Wara WM, Jeffrey RB. Radiation-induced disease of the carotid artery. West JMed. 1978;129:500-503. 9. Nardelli E, Fiaschi A, Ferrari G. Delayed cerebrovascular consequences of radiation to the neck: a clinicopathologic study of a case. Arch Neurol. 1978;35:538-540. 10. Marty AT, Logan JA III. Radiation induced amaurosis fugax. Indiana Med. 1984;77:90-91. 11. Rotman M, Seidenberg B, Rubin I, Botstein C, Bosniak M. Aortic arch syndrome secondary to radiation in childhood. Arch Intern Med.
1969;124:87-90. 12. Hayward RH. Arteriosclerosis induced by radiation. Surg Clin North Am. 1972;52:359-366. 13. Louis EL, McLoughlin MJ, Wortzman G. Chronic damage to medium and large arteries following irradiation. Can Assoc Radiol J. 1974;25:94\x=req-\ 104. 14.
Marcial-Rojas RA, Castro JR. Irradiation injury to elastic arteries in the course of treatment for neoplastic disease. Ann Oto Rhinol Laryngol. 1962;71:945-958. 15. Jones TR, Frusha JD. Carotid revasculari-
zation after cervical irradiation. South Med J.
1986;79:1517-1520. 16. Conomy JP, Kellermeyer RW. Delayed cerebrovascular consequences of therapeutic radiation: a clinicopathologic study of a stroke associated with radiation-related carotid arteriopathy. Can-
1975;36:1702-1708. E, Diener HC, Voss AC. Gef\l=a"\ssver\l=a"\nderungender extrakraniellen Arterien nach Strahlentherapie von Kopf-Hals-Tumoren (with English abstract). Strahlentherapie. 1982;158:290\x=req-\ cer.
17. Scholz
297. 18.
Elerding SC, Fernandez RN, Grotta JC, LingbergRD, Causay LC, McMurtrey MJ. Carotid artery disease following external cervical irradiation. Ann Surg. 981;194:609-615.
Significant
Risk Factor for Carotid Atherosclerosis
Robert S. Feehs, MD; W. Frederick McGuirt, MD; M. Gene Bond, PhD; Harriet L. Timothy E. Craven, MSPH; Jeffrey B. Hiltbrand, MD \s=b\ Radiation exacerbates the development of atherosclerosis in the large arteries of animals and is postulated to do likewise in human beings. To study this relationship, we used high-resolution B-mode ultrasonography to measure carotid artery wall thickness in 29 previously irradiated head and neck cancer patients and compared the results with those of nine epidemiologically similar but nonirradiated head and neck cancer patients. Maximal intima-media thickness was greater in the study group (mean, 1.28 \m=+-\SE 0.06 mm) than in the control group (mean, 0.90 \m=+-\SE 0.05 mm). Even after the effects of age, hypertension, and tobacco consumption were controlled, these differences remained statistically significant. This study suggests that irradiation may contribute to the development of more severe and extensive carotid atherosclerosis in head and neck cancer patients who receive radiation therapy. (Arch Otolaryngol Head Neck Surg.
1991;117:1135-1137) Accepted for publication March 13,1991. From the Department of Otolaryngology (Drs Feehs, McGuirt, and Hiltbrand), Neurobiology and Anatomy (Drs Bond and Strickland), and Public Health Sciences (Dr Craven), The Bowman Gray School of Medicine of Wake Forest University,
Winston-Salem, NC.
Presented at the American Society of Head and Neck Surgery, April 30-May 1, 1990, Palm Beach, Fla. Reprint requests to the Department of Otolaryngology, The Bowman Gray School of Medicine, 300 S Hawthorne Rd, Winston-Salem, NC 27103 (Dr Feehs)
Strickland, DVM;
Irradicarotid ation-iatherosclerosis nandduced acceleration has been hy¬
of
numerous studies of carotid atherosclerosis follow¬ ing radiation therapy support this hy¬ pothesis. Previous studies have only indirectly assessed carotid atheroscle¬ rosis using blood flow methods, and thereby inferred but did not define anatomic changes. We undertook this study to evaluate directly the anatomic extent and severity of carotid athero¬ sclerosis in asymptomatic, previously irradiated head and neck cancer pa¬ tients and to determine what role irra¬ diation may play in the development of carotid atherosclerosis.
pothesized, severe
MATERIALS AND METHODS Patients who had undergone radiation for head and neck cancers at our institution were identified, and those at least
therapy
years' postirradiation were requested to participate in the study. Nonirradiated pa¬ tients with newly diagnosed head and neck cancer served as control patients. 3
Patients were interviewed and charts reviewed to determine age, sex, systol¬ ic blood pressure, tobacco consumption, total plasma cholesterol concentration, tumor cell type and location, irradiation dosage and treatment portals, and interval since comple¬ tion of radiation therapy. were
Downloaded From: by a UNIVERSITY OF ADELAIDE LIBRARY User on 05/14/2018
Participants underwent ultrasound exami¬ nation of the carotid arteries, using a highresolution B-mode imager, which features an 8-MHz transducer. For this examination, the carotid artery was divided into three seg¬ ments: the distal common carotid, the carotid bifurcation (bulb), and the proximal internal carotid. A standardized scanning protocol was used to ensure the valid and reliable identification of arterial segments and defini¬ tion of artery wall interfaces (Figs 1 and 2).1 The normal combined intima-media thick¬ ness ranges from 0.8 mm in the common and internal carotid arteries to 1.1 mm at the bifurcation.2 An atherosclerotic plaque is present when the intima-media thickness is greater than 1.3 mm and there is nonparallel displacement of the interfaces used to define the intima-media. Maximal near-wall and far-wall intima-media measurements were obtained for each arterial segment of both carotid arteries in each subject. The resulting near-wall and far-wall val¬ ues were averaged to yield a combined mean maximal value for each artery. These two single artery means were then averaged to yield one mean maximal score reflecting the patient's overall carotid intima-media thick¬ ening. The data were analyzed using the Stu¬ dent f test, analysis of covariance, and the Fisher's Exact Test for two-way contingency tables. RESULTS
Twenty-nine previously irradiated patients (20 men, nine women) en-
Table
1.—Histologie Classification of Tumors Irradiated Control Patients Patients
Cell Type
Squamous
(n
29)
=
(n
=
9)
cell
carcinoma
26
Lymphoma Rhabdomyosarcoma
9
1 1
Undifferentiated carcinoma
1
Table 2.—Tumor Location Irradiated Patients
Site
(n
Oropharynx Nasopharynx Larynx Other
Interfaces Near Wall 1 Periadventitia-adventitia 2 Adventitia-media 3 Intima-lumen
Far Wall 4 Lumen-intima 5 Media-adventitia 6 Adventitia-periadventitia
Fig 1 .—Schematic of high-resolution B-mode ultrasonograph of the right carotid artery with lesion In the bifurcation. Near-wall interfaces 1, 2, and 3, and far-wall interfaces 4,5, and 6 are identified.
29)
=
Oral cavity
9 1
Control Patients
(n
=
9)
3
4
1
13 2
5
ages ranged from 33 to 75 years (mean, 58.7 ±13.8 years). Systolic blood pres¬ sures ranged from 90 to 150 mm Hg (mean, 128.3 ±20.7 mm Hg); tobacco consumption ranged from 0 to 90 pack years (mean, 50.5 ±32.0 pack years). Age, systolic blood pressure, and to¬ bacco consumption were not signifi¬ cantly different between the two groups (P=.40, .21, and =.32, respectively). No patient in either group had hypercholesterolemia. Tables 1 and 2 show tumor histolog¬ ie findings and location for the two groups. The applied dose of radiation ranged from 40 to 87.2 Gy (mean, 60.36 Gy) in the irradiated group. Time since completion of irradiation ranged from 3 to 17 years (mean, 8.5 years). =
Fig 2. —High-resolution B-mode ultrasonograph of left carotid artery showing the bifurcation. Nearwall interfaces 1, 2, and 3, and far-wall interfaces 4, 5, and 6 are identified. Note site of intima-media thickening on the near wall and acoustical shadowing across the opposite far wall. tered the study. Their ages ranged from 20 to 87 years (mean, 62.6 ±11.6 years). Systolic blood pressures ranged from 110 to 190 mm Hg (mean, 138.6 ± 18.5 mm Hg). Ten patients had adequately controlled hypertension.
Tobacco consumption ranged from 0 to 120 pack years (mean, 42.9 ±28.7 pack
years).
Nine nonirradiated head and neck patients (six men, three wom¬ en) served as control patients. Their cancer
Downloaded From: by a UNIVERSITY OF ADELAIDE LIBRARY User on 05/14/2018
The mean maximal intima-media thicknesses ranged from 0.55 to 1.97 mm (mean, 1.28 ±0.06 mm) in the irra¬ diated group and from 0.70 to 1.13 mm (mean, 0.90 ±0.05 mm) in the control patients. These values were statistical¬ ly different (P=.003) and remained different after analysis of covariance was used to control for the effects of age, blood pressure, and tobacco
consumption. Arterial plaque (intima-media
>1.3
present in 27 (93%) of the 29 irradiated patients and in six (67%) of mm)
was
the nine control patients. Plaques oc¬ curred at multiple sites in 24 (81%)
irradiated patients, with 10 (33%) pa¬ tients having plaque in all segments. In contrast, plaque in control patients was found only at the bifurcation, indi¬ cating a significant difference in the two groups (P=.0007, Fisher's Exact
Test).
COMMENT The development of carotid athero¬ sclerosis following irradiation was ini¬ tially reported by Heidenberg et al3 in 1966; numerous cases have since been published.4"13 Studies characterizing ir¬ radiation-induced atherosclerosis indi¬ cate that the disease begins at a youn¬ ger age, involves only vessels within the irradiated field, affects arterial segments normally not prone to devel¬ op atherosclerosis, and is associated with less coronary and peripheral vas¬ cular disease when compared with nat¬ urally occurring atherosclerosis." The irradiation dosage delivered does not seem to correlate with the severity of disease,1415 and the interval from treat¬ ment to the appearance of symptoms of cerebral vascular insufficiency has been from 1 to 34 years.5,16 Carotid atherosclerosis generally re¬ mains undetected until symptoms re¬ lated to arterial stenosis or occlusion occur. Scholz et al,1' using sonography, found a 19% incidence of carotid steno¬ sis in 37 irradiated patients compared with 2.7% in 556 control subjects. Elerding et al18 performed noninvasive indirect carotid evaluations in 118 pre¬ viously irradiated patients and detect¬ ed hemodynamically significant lesions in 25%. Neither of these studies direct¬ ly evaluated anatomically defined ca¬ rotid atherosclerosis. Our evaluation using high-resolution B-mode ultrasound imaging of 29 asymptomatic, previously irradiated patients demonstrated that this popu-
lation had a significant increase in overall carotid intima-media thickness compared with control patients. Plaques were more numerous and more widespread in the irradiated group, but were present only at the carotid bifurcation in control patients. Age, blood pressure, and tobacco con¬ sumption were similar between the groups; although each is known to in¬ fluence the development and progres¬ sion of carotid artery atherosclerosis, none could be used to account for the observed differences between these two groups.
Despite
small numbers of control all differences were statisti¬ patients, cally significant. Additional factors not addressed in this study that need fur¬ ther examination because they may have contributed to the observed dif¬ ferences include previous surgery, type and technique of irradiation, and qi other unknown risk factors for ca¬ rotid atherosclerosis. Patients having received neck irra¬ diation had more severe and extensive carotid atherosclerosis than did control patients. Other known risk factors for carotid atherosclerosis were present but could not account for these differ¬ ences. These findings support and strengthen the hypothesis that neck irradiation may be a significant risk factor for the development and/or pro¬ gression of carotid atherosclerosis. We
acknowledge
the expertise of the sonographs and readers in the Division of Vascular Ultrasound Research, The Bowman Gray School of Medicine, Winston-Salem, NC: Anne W. Safrit, Rita M. Phillips, Lori E. Szostak, and Gina L. Enevold.
References 1. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imag-
ing. Circulation. 1986;74:1399-1406. 2. Bond MG, Strickland HL, Wilmoth SK, Sha-
Downloaded From: by a UNIVERSITY OF ADELAIDE LIBRARY User on 05/14/2018
frit AW, Phillips RM, Szostak LE. Interventional clinical trials using noninvasive ultrasound end points: the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS). J Cardiovasc Pharma-
col. 1990;15(suppl 1):S30-S33. 3. Heidenberg WJ, Lupovitch A, Tarr N. 'Pulseless disease' complicating Hodgkin's disease: a case apparently caused by radiotherapy. JAMA.
1966;195:488-491.
4. Glick B. Bilateral carotid occlusive disease irradiation for carcinoma of the vocal cords. Arch Pathol. 1972;93:352-355. 5. Levinson SA, Close MB, Ehrenfeld WK, Stoney RJ. Carotid artery occlusive disease following external cervical irradiation. Arch Surg.
following
1973;107:395-397. 6. Silverberg GD, Britt RH, Goffinet DR. Radiation-induced carotid artery disease. Cancer. 1978;41:130-137. 7. Atkinson JLD, Sundt TM Jr, Dale AJD, Cascino TL, Nichols DA. Radiation-associated atheromatous disease of the cervical carotid artery: report
of seven cases and review of the literature. Neurosurgery. 1989;24:171-178. 8. Eisenberg RL, Hedgcock MW, Wara WM, Jeffrey RB. Radiation-induced disease of the carotid artery. West JMed. 1978;129:500-503. 9. Nardelli E, Fiaschi A, Ferrari G. Delayed cerebrovascular consequences of radiation to the neck: a clinicopathologic study of a case. Arch Neurol. 1978;35:538-540. 10. Marty AT, Logan JA III. Radiation induced amaurosis fugax. Indiana Med. 1984;77:90-91. 11. Rotman M, Seidenberg B, Rubin I, Botstein C, Bosniak M. Aortic arch syndrome secondary to radiation in childhood. Arch Intern Med.
1969;124:87-90. 12. Hayward RH. Arteriosclerosis induced by radiation. Surg Clin North Am. 1972;52:359-366. 13. Louis EL, McLoughlin MJ, Wortzman G. Chronic damage to medium and large arteries following irradiation. Can Assoc Radiol J. 1974;25:94\x=req-\ 104. 14.
Marcial-Rojas RA, Castro JR. Irradiation injury to elastic arteries in the course of treatment for neoplastic disease. Ann Oto Rhinol Laryngol. 1962;71:945-958. 15. Jones TR, Frusha JD. Carotid revasculari-
zation after cervical irradiation. South Med J.
1986;79:1517-1520. 16. Conomy JP, Kellermeyer RW. Delayed cerebrovascular consequences of therapeutic radiation: a clinicopathologic study of a stroke associated with radiation-related carotid arteriopathy. Can-
1975;36:1702-1708. E, Diener HC, Voss AC. Gef\l=a"\ssver\l=a"\nderungender extrakraniellen Arterien nach Strahlentherapie von Kopf-Hals-Tumoren (with English abstract). Strahlentherapie. 1982;158:290\x=req-\ cer.
17. Scholz
297. 18.
Elerding SC, Fernandez RN, Grotta JC, LingbergRD, Causay LC, McMurtrey MJ. Carotid artery disease following external cervical irradiation. Ann Surg. 981;194:609-615.
