# Radiation Oncology/Toxicity/Carotid artery

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Carotid Artery Radiation Toxicity

## Cavernous Sinus Meningioma

* Mayo Clinic, 2005 PMID 16029803 -- "Results of stereotactic radiosurgery for patients with imaging defined cavernous sinus meningiomas." (Pollock BE, Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1427-31.)
** In text authors note they documented 4 cases of internal carotid stenosis (cavernous sinus meningioma n=2, pituitary adenoma n=2) at their institution; however, they don't say how many patients were treated. In this series, there were 49 cavernous sinus meningiomas reported, with mean margin dose 15.9 Gy
* Marseille, 2000 (France)(1992-1998) PMID 11143266 -- "Gamma knife radiosurgery in the management of cavernous sinus meningiomas." (Roche PH, J Neurosurg. 2000 Dec;93 Suppl 3:68-73.)
** Retrospective. 80 patients, 50 primary and 30 adjuvant. Mean prescription dose 28 Gy, with median peripheral isodose 50%.
** One temporary intracavernous carotid artery occlusion at 3 months. Estimated carotid dose was 36 Gy

## Head & Neck
### Carotid Artery Blowout Syndrome

* Complication of aggressive management of H&N cancer
* Typically presents as significant, difficult to control oronasal bleeding
* Predisposing factors: RT, radical surgery and surgical complications (flap necrosis, wound infections, pharyngocutaneous fistula), persistent/recurrent tumor
* Results from destruction or damage to vessel adventitia
* Most occur in the petrous segment of internal carotid artery, possibly due to associated osteonecrosis after high dose RT
* Mean dose in Taipei series of patients who developed it was 73 Gy (range 54-110)
* Latency varies between <1 year to >20 years
* Management of bleeding can be via endovascular approaches
* Taipei
** 2008 (1997-2006) PMID 18164999 -- "Radiation carotid blowout syndrome in nasopharyngeal carcinoma: Angiographic features and endovascular management." (Luo CB, Otolaryngol Head Neck Surg. 2008 Jan;138(1):86-91.)
*** Retrospective. 14 patients with nasopharyngeal carcinoma with 15 carotid blowout syndromes, initially treated by RT alone. All presented with oronasal bleeding. Location was internal carotid (n=10), external carotid (n=4), or common carotid (n=1)
*** RT info: mean dose 73 Gy (54 - 110 Gy); mean latency 33 months (8 - 70 months)
*** Management: Endovascular embolization.
** 2006 PMID 16538509 -- "Radiation acute carotid blowout syndromes of the ascending pharyngeal and internal carotid arteries in nasopharyngeal carcinoma." (Luo CB, Eur Arch Otorhinolaryngol. 2006 Jul;263(7):644-6. Epub 2006 Mar 15.)
*** Case report. NPC patient with radiation-induced acute carotid blowout syndrome in cervical internal carotid artery

### Carotid Artery Stenosis

* After RT, carotid narrowing occurs in ~50% of vessels receiving >40 Gy
* Multiple other studies document accelerated atherosclerotic disease
* Duplex ultrasound screening may be warranted
* Carotid-sparing IMRT feasible for T1-2 glottic cancer, but long-term disease control and carotid outcomes not yet available PMID 19679406
* Mayo Clinic; 2005 (1974-1999) PMID 16169673 -- "A historical prospective cohort study of carotid artery stenosis after radiotherapy for head and neck malignancies." (Brown PD, Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1361-7. Epub 2005 Sep 19.)
** Retrospective. 44 H&N patients treated with unilater RT. Bilateral carotid duplex ultrasound screening performed
** Outcome: Significant stenosis RT-side 18% vs. contralateral 7% (NS), events increased with time
** Conclusion: Ultrasound carotid artery screening should be considered
* Fort Lewis, WA; 2004 PMID 15135672 -- "Focused high-risk population screening for carotid arterial stenosis after radiation therapy for head and neck cancer." (Steele SR, Am J Surg. 2004 May;187(5):594-8.)
** Retrospective. 40 patients treated with high dose (>55 Gy, mean 64 Gy) H&N RT. Mean F/U 10 years
** Outcome: Significant carotid artery stenosis 40%; no difference in terms of age, RT dose, tobacco, time from RT, or comorbidities. Unilateral complete occlusion 15%. CVA in 8%
** Conclusion: Prevalence of carotid artery disease is clinical significant, and warrants aggressive screening
* Prince of Wales Hospital; 2001 (Hong Kong) PMID 11745291 -- "Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy." (Lam WW, Cancer. 2001 Nov 1;92(9):2357-63.)
** Retrospective. 71 carotid arteries examined with Doppler U/S in nasopharyngeal patients after RT. Compared with control group of 51 newly diagnosed NPC patients
** Outcome: Arterial stenosis RT group 79% vs. pre-RT group 22% (SS); significant stenosis (>50%) only in post-RT group 51%
** Conclusion: RT can cause significant carotid stenosis
* Queen Mary Hospital; 1999 PMID 10587192 -- "Irradiation-induced extracranial carotid stenosis in patients with head and neck malignancies." (Cheng SW, Am J Surg. 1999 Oct;178(4):323-8.)
** Comparative cross-sectional study. Duplex U/S 240 patients with H&N EBRT. Mean interval 6 years after RT
** Outcome: Significant (>70%) ICA/CCA disease in 12%
** Predictors for significant narrowing: age (>60), cerebrovascular symptoms, RT interval (>5 years), location (nasopharynx or larynx)
** Conclusion: Significant risk of carotid stenosis after RT; recommend routine ultrasound screening
* VA Washington DC; 1999 (1993-1998) PMID 10587388 -- "Accelerated carotid artery disease after high-dose head and neck radiotherapy: is there a role for routine carotid duplex surveillance?" (Carmody BJ, J Vasc Surg. 1999 Dec;30(6):1045-51.)
** Case control. 23 patients with RT and 46 age-matched controls. Mean RT dose 60.6 Gy. Average interval to screening 6.5 years
** Outcome: Advanced carotid disease RT group 22% vs. control 4% (SS); 16/23 RT patients underwent 2nd U/S and had further progression
** Conclusion: High dose RT significant risk factor for accelerated atherosclerosis, may warrant routine ultrasound screening
* Seoul; 1994 PMID 8040432 -- "MRI of carotid angiopathy after therapeutic radiation." (Chung TS, J Comput Assist Tomogr. 1994 Jul-Aug;18(4):533-8.)
** Retrospective. 16 patients, pre and post RT (>40 Gy) MRI scans reviewed blindly by 2 readers
** Outcome: Interval narrowing of carotid artery lumen (common, internal, or external) seen in 56%; difference in lumen was statistically significant. 3/16 patients had new critical stenosis; 7/16 patients had diffuse obliteration of carotid planes
** Conclusion: Incidence of accelerated atherosclerosis after RT may be greater than expected

## Breast Cancer

* MD Anderson; 2008 PMID 18000801 -- "Prospective analysis of carotid artery flow in breast cancer patients treated with supraclavicular irradiation 8 or more years previously: no increase in ipsilateral carotid stenosis after radiation noted." (Woodward WA, Cancer. 2008 Jan 15;112(2):268-73.)
** Retrospective. 46 breast cancer patients, adjuvant RT to SCV. Median dose 50 Gy. Bilateral Doppler ultrasound of carotid artery. Minimum F/U 8 years, median F/U 14.6 years
** Outcome: asymptomatic carotid stenosis 9%, but only 2% (1 patient) irradiated carotid artery only, 2% (1 patient) had bilateral, and 4% (2 patients) had contralateral stenosis. No difference between sides on peak systolic flow
** Conclusion: No evidence of late, clinically relevant carotid artery stenosis