Atherosclerosis: Open Access
Open Access

Radiation therapy; Tumors, Cancer, Atherosclerosis; Carotid artery; Vascular stenosis

Introduction

Radiation therapy has been widely used to treat malignant tumours in recent years, and it is a very essential treatment in breast cancer. To far, research on RIAI as a consequence of radiation therapy have been done; nevertheless, there have been few instances of such damage to the arteries of the upper limbs, and the clinical aspects of this syndrome are not entirely known. As a result, we want to look at and discuss the clinical characteristics, effective diagnostic tools, and successful treatment strategies for RIAI in the upper limbs. Thomas [1] described RIAI as a disorder in which radiation treatment produces stenosis and blockage of the major arteries. Radiation-induced sub clavian artery stenosis: incidence and prevalence. Until date, it has been assumed that RIAI is uncommon following radiation therapy. Yet, as imaging technology has evolved and doctors have become more aware of the notion of RIAI, reports of RIAI have grown. Lam [2] studied newly diagnosed patients with nasopharyngeal cancer patients before and after they had radiation therapy and found that artery stenosis was more prevalent in the irradiated area of the post-radiation group (56/71 vs. 11/51). Additionally, 50% or greater artery stenosis was exclusively detected after radiation treatment. Moreover, Elerding [3] estimates that the risk of carotid stenosis of 70% or higher following radiation therapy is 6.3%, whereas Cheng estimates it to be 11.7%- 16%. It has also been noted that the symptom of vascular stenosis develops in 14.6% of instances [4].The carotid artery is the focus of the majority of RIAI reports [5-11]. Nevertheless, there have been few cases of RIAI in the upper limb arteries, such as the axillary and sub clavian arteries. From 1974 to 2015, there were 13 reports of 21 RIAI in the upper limbs, including axillary artery and sub clavian artery instances, according to our review of the literature [12-22]. Breast cancer is the most frequent non-dermatological cancer in women in the United States, accounting for an estimated 60,290 noninvasive (in situ) tumours, 231,840 newly diagnosed invasive tumours, and 40,290 fatal cases in 2015. Furthermore, in 1997, the results of two randomised controlled trials from Denmark and Canada suggested that post-mastectomy radiation therapy (PMRT) combined with systemic chemotherapy for breast cancer not only reduced the rate of localised recurrence but also improved survival in the high-risk group. A comprehensive evaluation published in 2005 by the Early Breast Cancer Trialists’ Collaborative Group indicated that in the high-risk group with lymph node metastases, PMRT not only improved the rate of local control but also enhanced survival. Additionally, post-operative irradiation enhanced rates of local control and survival following breast preservation surgery, regardless of axillary lymph node metastases. As a result, the significance of radiation therapy for breast cancer has grown in recent years. According to the “Japanese Structure Survey of Radiation Oncology in 2009 (first report)” by the Japanese Society for Radiation Oncology (JASTRO) database committee, breast cancer was the most common cancer type (23.3%) based on the primary lesion in new patients who underwent radiation therapy. The mechanisms of onset of RIAI in the carotid artery and RIAI in the sub clavian to axillary arteries must be the same. As a result, given the amount of case reports, we believe that many people go undiagnosed, and we suggest that practitioners should be better aware of this issue. The overall mechanism of action is separated into three parts. To begin, it is thought that irradiation produces endothelium dysfunction. Endothelial cell injury causes vascular permeability to increase, and serum mucopolysaccharide deposits on the endothelium, resulting in intimal hyperplasia. Moreover, radiation exposure has been linked to the activation of nuclear factor-kappa B, as well as inflammation caused by oxidative stress. It has been observed that inflammatory markers can rise quickly after radiation exposure and may be helpful predictors of angiostenosis induced by RIAI; however, more research is needed to confirm this discovery. Second, vasa vasorum injury results in localised necrosis of the media, which leads to fibrosis, adventitial chronic inflammation, and other complications. These alterations eventually promote arteriosclerosis, resulting in stenosis and blockage. RIAI has the following clinical characteristics: The irradiation and lesion sites overlap, lesions can develop with relatively low radiation doses of 40-80 Gy, several years may pass between irradiation and the emergence of symptoms, and the lesions pathologically seem to be the same as arteriosclerotic lesions. The duration between irradiation and the emergence of symptoms has been reported to range from 3 to 24 years, with a mean of 14.7 years. Furthermore, angiographic findings reveal poor collateral circulation development, which is attributed to the possible impact of dissecting tissue in the area extending from the subclavian to axillary arteries, such as the pectoral muscle and axillary blood vessels, during breast cancer surgery. Moreover, peripheral ischemia symptoms might be more severe than those associated with typical arteriosclerosis, which should be addressed. Fatigability of the arms, numbness, and coldness are common symptoms of artery stenosis. The reason for the scarcity of reports on RIAI in the arteries of the upper limbs is that the symptoms of stenosis, such as weariness and numbness of the upper limb, are similar to the symptoms of lymphedema and nerve diseases that typically arise after mastectomy. Hence, we believe, may impede detection of RIAI in the upper limbs. RIAI is frequently difficult to distinguish from atherosclerosis. RIAI, on the other hand, essentially fits the lesion exposed radiation. As a result, it is critical to determine whether the patient has previously had radiation therapy. The presence of numbness, coldness, and fatigability of the upper limbs, as well as an absent or weak pulse, confirms the diagnosis. The bilateral difference in upper limb blood pressure is measured. Ultrasonography and contrast-enhanced computed tomography or angiography are beneficial in the event of a bilateral disparity in blood pressure. The ankle-brachial index is another noninvasive technique that may be used. Bypass surgery is the most often described revascularization procedure. Mellièr studied the results of bypass surgery for sub clavian or axillary artery stenosis caused by RIAI in four individuals and found that the procedure was effective in all four patients. All of the papers we reviewed had similar satisfactory surgical results. Only one patient was allegedly able to make significant progress with solely medical treatment and exercise. Nevertheless, it has not been established if medical therapy from an early stage is useful in preventing the advancement of RIAI. As a result, we should think about medical therapy for RIAI in the future.

On the other hand, there are limited accounts of revascularization utilising PTA rather than bypass surgery, and our literature search yielded just five instances. We described a case in which the calcification of the lesion was significant, appropriate dilatation with plain old balloon angioplasty (POBA) was challenging, and adequate dilatation could not be obtained. Interestingly, one of the four successful bypass surgery instances described by Mellièr was initially failed by PTA. Hans stated that symptoms resurfaced 3 years and 9 months after POBA and that recovery from bypass surgery was satisfactory. As a result, in RIAI-induced arteriosclerosis, significant calcification can make PTA revascularization exceedingly challenging, and favourable mid- to long-term results are unlikely. As a result, bypass surgery, which has seen many successful examples, should definitely be considered first. Successful treatment strategies should be investigated further in a bigger sample size.

Conclusion

Although radiation therapy is a popular cancer treatment, there is little question that it increases the risk of arteriosclerosis. Radiation combination therapy has increased cancer survival in recent years, enhancing the value of radiation therapy. We feel that it is critical that the RIAI be widely acknowledged. Further research with a bigger sample size is needed. Radiation therapy, particularly for breast cancer, induces occlusion in the sub clavian artery, with symptoms similar to lymphedema and neuropathy after breast cancer surgery, and requires careful investigation.

Acknowledgement

Not applicable.

Conflict of Interest

Author declares no conflict of interest.

1. Thomas E, Forbus WD (1959) Irradiation injury to the aorta and the lung. A.M.A. Arch Pathol 67:256-263.

Indexed at, Google Scholar                

2. Lam WW, Leung SF, So NM, Wong KS, Liu KH, et al. (2001) Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer 92:2357-2363.

Indexed at, Google Scholar, Crossref

3. Elerding SC, Fernandez RN, Grotta JC, Lindberg RD, Causay LC, et al. (1981) Carotidartery disease following external cervical irradiation. Ann Surg 194:609-615.

Indexed at, Google Scholar, Crossref

4. Cheng SWK, Ting ACW, Lam LKL, Wei WI (2000) Carotid stenosis after radiotherapy for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 126:517-521.

Indexed at, Google Scholar, Crossref

5. Ahuja A, Blatt GL, Guterman LR, Hopkins LN (1995) Angioplasty for Symptomatic Radiation? Induced Extracranial Carotid Artery. Neurosurgery 36:399-403.

Indexed at, Google Scholar, Crossref

6. Ohta H, Sakai N, Nagata I, Sakai H, Higashi T, et al. (2001) Bilateral Carotid Stenting for Radiation-Induced Arterial Stenosis. No Shinkei Geka 29:559-563.

Indexed at, Google Scholar                

7. Mubarak NA, Roubin GS, Iyer SS, Gomez CR, Liu MW, et al. (2000) Carotid stenting for severe radiation-induced extracranial carotid artery occlusive disease. J Endovasc Ther 7:36-40.

Indexed at, Google Scholar, Crossref

8. Cohen JE, Rajz G, Lylyk P, Hur TB, Gomori JM, et al. (2005) Protected stent-assisted angioplasty in radiation-induced carotid artery stenosis. Neurol Res 27:69-72.

Indexed at, Google Scholar, Crossref

9. Kim PH, Kadkhodayan Y, Derdeyn CP, Moran CJ (2005) Outcome of carotid angioplasty and stenting for radiation associated stenosis. Am J Neuroradiol 26:1781-1788.

Indexed at, Google Scholar                

10. Houdart E, Mounayer C, Chapot R, Maurice JPS, Merland JJ (2001) Carotid stenting for radiation-induced stenosis. Stroke 32: 118-121.

Indexed at, Google Scholar, Crossref

11. Ting AC, Cheng SW, Yeung KM, Cheng PW, Lui WM, et al. (2004) Carotid stenting for radiation-induced extracranial carotid artery occlusive disease: efficacy and midterm outcomes. Endovasc Ther 11:53-59.

Indexed at, Google Scholar, Crossref

12. Thorleif E, Manfred H, Volker K (2013)  Subclavian-axillary graft plus graft-carotid interposition in symptomatic radiation-induced occlusion of bilateral subclavian and common carotid arteries. Vasa 42:223-226.

Indexed at, Google Scholar, Crossref

13. Hinchcliffe M, Ruttley MS, Rees GC (1995) Case report: percutaneous transluminal angioplasty of irradiation induced bilateral subclavian artery occlusions. Clin Radiol 50:804-807.

Indexed at, Google Scholar, Crossref

14. Stein JS, Jacobson JH (1993) Axillary-contralateral brachial artery bypass for radiation-induced occlusion of the subclavian artery. Cardiovasc Surg 1:146-148.

Indexed at, Google Scholar, Crossref

15. Becquemin JP, Gasparino LF, Etienne G (1994) Carotido-brachial artery bypass for radiation induced injury of the subclavian artery. The value of a lateral mid-arm approach. J Cardiovasc Surg 35:321-324.

Indexed at, Google Scholar                

16. Guthaner DF, Schmitz L (1982) Percutaneous transluminal angioplasty of radiation-induced arterial stenosis. Radiology 144:77-78.

Indexed at, Google Scholar, Crossref

17. Julius HJ, Murray GB (1974) Axillary-Contralateral Brachial Artery Bypass for Arm Ischemia. Ann Surg 179:827-829.

Indexed at, Google Scholar, Crossref

18. Kretschmer G, Niederle B, Polterauer P, Waneck R (1986) Irradiation-induced changes in the subclavian and axillary arteries after radiotherapy for carcinoma of the breast. Surgery 99:658-663.

Indexed at, Google Scholar, Crossref

19. Roche-Nagle G, Fitzgerald T, McNeaney P, Harte1 P (1997) Symptomatic Radiation-induced Upper Extremity Occlusive Arterial Disease. EJVES Extra 11:5-6.

Google Scholar, Crossref

20. Mellière D, Becquemin JP, Berrahal, Desgranges P, Cavillon (1997) Management of radiation-induced occlusive arterial disease: a reassessment. J Cardiovasc Surg 38:261-269.

Indexed at, Google Scholar                

21. Hans SS, Tuma (1989) Failure of Percutaneous Transluminal Angioplasty of Radiation-Induced Subclavian Artery Stenosis: Case Report. Vasc Endovasc Surg 23:235-239.

Google Scholar , Crossref

22. Yamanaka T, Fukatsu T, Satou H, Ichinohe Y, Komatsu H, et al. (2015) A case of radiation-induced subclavian artery stenosis treated with percutaneous transluminal angioplasty. J Cardiol Cases 12:61-64.

Indexed at, Google Scholar, Crossref