Skip to main content
SpringerLink
Log in

Progression rate of radiation-induced carotid stenosis in head and neck cancer survivors after statin treatment: a retrospective cohort study

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background and aims

Whether statin treatment is effective in retarding the progression of radiation-induced carotid stenosis (RICS) in head and neck cancer (HNC) survivors has not been well studied. The purpose of this study was to assess the association of statin treatment with RICS progression rate in HNC survivors after radiotherapy.

Methods

We conducted a retrospective cohort study at Sun Yat-sen Memorial Hospital, Sun Yat-sen University in Guangzhou, China. Between January 2010 and December 2021, we screened HNC survivors whose carotid ultrasound scans had shown stenosis of the common and/or internal carotid arteries. The primary outcome was the RICS progression rate. We compared eligible patients treated with statins with those who did not in multivariable Cox regression models.

Results

A total of 200 patients were included in this study, of whom 108 received statin treatment and 92 did not. Over a mean follow-up time of 1.5 years, 56 (28.0%) patients showed RICS progression, 24 (42.9%) and 32 (57.1%) in the statin and control groups, respectively. The statin group showed less RICS progression than the control group (adjusted-HR 0.49, 95% CI 0.30–0.80, P = 0.005). In the subgroup analysis, there was no significant interaction in the effect of statins on lowering RICS progression rate in the subgroups stratified by baseline low-density lipoprotein cholesterol (LDL-C) levels (P for interaction = 0.53) or baseline degrees of stenosis (P for interaction = 0.50).

Conclusions

Statin treatment was associated with a lower risk of RICS progression in patients with HNC after radiotherapy, regardless of baseline LDL-C level and baseline stenosis degrees.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Availability of data and materials

Data supporting the findings of the study are available on reasonable request after approval of a proposal from the corresponding author (YT, tangym@mail.sysu.edu.cn).

References

  1. Chow L (2020) Head and neck cancer. N Engl J Med 382:60–72

    Article  CAS  PubMed  Google Scholar 

  2. Alterio D, Marvaso G, Ferrari A, Volpe S, Orecchia R, Jereczek-Fossa BA (2019) Modern radiotherapy for head and neck cancer. Semin Oncol 46:233–245

    Article  CAS  PubMed  Google Scholar 

  3. Lam WW, Leung SF, So NM, Wong KS, Liu KH, Ku PK, Yuen HY, Metreweli C (2001) Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer 92:2357–2363

    Article  CAS  PubMed  Google Scholar 

  4. Abayomi OK (2004) Neck irradiation, carotid injury and its consequences. Oral Oncol 40:872–878

    Article  PubMed  Google Scholar 

  5. Dorresteijn LD, Kappelle AC, Boogerd W, Klokman WJ, Balm AJ, Keus RB, van Leeuwen FE, Bartelink H (2002) Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol 20:282–288

    Article  PubMed  Google Scholar 

  6. Howard D, Gaziano L, Rothwell PM (2021) Risk of stroke in relation to degree of asymptomatic carotid stenosis: a population-based cohort study, systematic review, and meta-analysis. Lancet Neurol 20:193–202

    Article  PubMed  PubMed Central  Google Scholar 

  7. Plummer C, Henderson RD, O’Sullivan JD, Read SJ (2011) Ischemic stroke and transient ischemic attack after head and neck radiotherapy: a review. Stroke 42:2410–2418

    Article  PubMed  Google Scholar 

  8. Swisher-Mcclure S, Mitra N, Lin A, Ahn P, Wan F, O’Malley B, Weinstein GS, Bekelman JE (2014) Risk of fatal cerebrovascular accidents after external beam radiation therapy for early-stage glottic laryngeal cancer. Head Neck J Sci Spec Head Neck 36:611–616

    Article  Google Scholar 

  9. Yu SC, Zou WX, Soo YO, Wang L, Hui JW, Chan AY, Lee KT, Ip VH, Fan FS, Chan AL et al (2014) Evaluation of carotid angioplasty and stenting for radiation-induced carotid stenosis. Stroke 45:1402–1407

    Article  PubMed  Google Scholar 

  10. Zheng Z, Zhao Q, Wei J, Wang B, Wang H, Meng L, Xin Y, Jiang X (2020) Medical prevention and treatment of radiation-induced carotid injury. Biomed Pharmacother 131:110664

    Article  CAS  PubMed  Google Scholar 

  11. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP (2014) The strengthening the reporting of observational studies in epidemiology (strobe) statement: guidelines for reporting observational studies. Int J Surg 12:1495–1499

    Article  Google Scholar 

  12. Blackshear WJ, Phillips DJ, Thiele BL, Hirsch JH, Chikos PM, Marinelli MR, Ward KJ, Strandness DJ (1979) Detection of carotid occlusive disease by ultrasonic imaging and pulsed doppler spectrum analysis. Surgery 86:698–706

    PubMed  Google Scholar 

  13. von Reutern GM, Goertler MW, Bornstein NM, Del SM, Evans DH, Hetzel A, Kaps M, Perren F, Razumovky A, von Reutern M et al (2012) Grading carotid stenosis using ultrasonic methods. Stroke 43:916–921

    Article  Google Scholar 

  14. Oates CP, Naylor AR, Hartshorne T, Charles SM, Fail T, Humphries K, Aslam M, Khodabakhsh P (2009) Joint recommendations for reporting carotid ultrasound investigations in the united kingdom. Eur J Vasc Endovasc Surg 37:251–261

    Article  CAS  PubMed  Google Scholar 

  15. Beach KW, Bergelin RO, Leotta DF, Primozich JF, Sevareid PM, Stutzman ET, Zierler RE (2010) Standardized ultrasound evaluation of carotid stenosis for clinical trials: university of washington ultrasound reading center. Cardiovasc Ultrasound 8:39

    Article  PubMed  PubMed Central  Google Scholar 

  16. Columbo JA, Zwolak RM, Arous EJ, Goodney PP, Lilly MP, Welch HG (2020) Variation in ultrasound diagnostic thresholds for carotid stenosis in the united states. Circulation 141:946–953

    Article  PubMed  Google Scholar 

  17. Liapis C, Kakisis J, Papavassiliou V, Ntanou A, Kontopoulou S, Kaperonis E, Koumakis K, Gogas J (2000) Internal carotid artery stenosis: rate of progression. Eur J Vasc Endovasc Surg 19:111–117

    Article  CAS  PubMed  Google Scholar 

  18. Giannopoulos S, Texakalidis P, Jonnalagadda AK, Karasavvidis T, Giannopoulos S, Kokkinidis DG (2018) Revascularization of radiation-induced carotid artery stenosis with carotid endarterectomy vs Carotid artery stenting: a systematic review and meta-analysis. Cardiovasc Revascularization Med 19:638–644

    Article  Google Scholar 

  19. Rothwell PM, Eliasziw M, Gutnikov SA, Fox AJ, Taylor DW, Mayberg MR, Warlow CP, Barnett HJ (2003) Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 361:107–116

    Article  CAS  PubMed  Google Scholar 

  20. Boulet J, Pena J, Hulten EA, Neilan TG, Dragomir A, Freeman C, Lambert C, Hijal T, Nadeau L, Brophy JM et al (2019) Statin use and risk of vascular events among cancer patients after radiotherapy to the thorax, head, and neck. J Am Heart Assoc 8:e5996

    Article  Google Scholar 

  21. Addison D, Lawler PR, Emami H, Janjua SA, Staziaki PV, Hallett TR, Hennessy O, Lee H, Szilveszter B, Lu M et al (2018) Incidental statin use and the risk of stroke or transient ischemic attack after radiotherapy for head and neck cancer. J Stroke 20:71–79

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fernandez-Alvarez V, Lopez F, Suarez C, Strojan P, Eisbruch A, Silver CE, Mendenhall WM, Langendijk JA, Rinaldo A, Lee A et al (2018) Radiation-induced carotid artery lesions. Strahlenther Onkol 194:699–710

    Article  PubMed  Google Scholar 

  23. Cheng SW, Ting AC, Ho P, Wu LL (2004) Accelerated progression of carotid stenosis in patients with previous external neck irradiation. J Vasc Surg 39:409–415

    Article  PubMed  Google Scholar 

  24. Ait-Aissa K, Leng LN, Lindsey NR, Guo X, Juhr D, Koval OM, Grumbach IM (2023) Mechanisms by which statins protect endothelial cells from radiation-induced injury in the carotid artery. Front Cardiovasc Med 10:1133315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gaugler MH, Vereycken-Holler V, Squiban C, Vandamme M, Vozenin-Brotons MC, Benderitter M (2005) Pravastatin limits endothelial activation after irradiation and decreases the resulting inflammatory and thrombotic responses. Radiat Res 163:479–487

    Article  CAS  PubMed  Google Scholar 

  26. Sibley CT, Vavere AL, Gottlieb I, Cox C, Matheson M, Spooner A, Godoy G, Fernandes V, Wasserman BA, Bluemke DA et al (2013) Mri-measured regression of carotid atherosclerosis induced by statins with and without niacin in a randomised controlled trial: the nia plaque study. Heart 99:1675–1680

    Article  CAS  PubMed  Google Scholar 

  27. Liu Y, Hua Y, Liu R, Wang L, Duan C, Ling C, Wu X, Bruce O, Feng W (2018) Ultrasonographical features associated with progression of atherosclerosis in patients with moderate internal carotid artery stenosis. Transl Stroke Res 9:375–381

    Article  PubMed  Google Scholar 

  28. Noyes AM, Thompson PD (2014) A systematic review of the time course of atherosclerotic plaque regression. Atherosclerosis 234:75–84

    Article  CAS  PubMed  Google Scholar 

  29. Song P, Fang Z, Wang H, Cai Y, Rahimi K, Zhu Y, Fowkes F, Fowkes F, Rudan I (2020) Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study. Lancet Glob Health 8:e721–e729

    Article  PubMed  Google Scholar 

  30. Pereira EB, Gemignani T, Sposito AC, Matos-Souza JR, Nadruz WJ (2014) Low-density lipoprotein cholesterol and radiotherapy-induced carotid atherosclerosis in subjects with head and neck cancer. Radiat Oncol 9:134

    Article  PubMed  PubMed Central  Google Scholar 

  31. Toprak U, Aytas I, Ustuner E, Habiboglu R, Aslan N, Pasaoglu E, Karademir A (2012) Sonographic assessment of acute changes in plaque size and echogenicity and in intima-media thickness of carotid arteries after neck radiation therapy. J Clin Ultrasound 40:566–571

    Article  PubMed  Google Scholar 

  32. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115:459–467

    Article  PubMed  Google Scholar 

  33. Beckman JA, Liao JK, Hurley S, Garrett LA, Chui D, Mitra D, Creager MA (2004) Atorvastatin restores endothelial function in normocholesterolemic smokers independent of changes in low-density lipoprotein. Circ Res 95:217–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

None.

Funding

YT is supported by the National Natural Science Foundation of China (81925031 and 81820108026) and the Science and Technology Program of Guangzhou (202007030001). YL is supported by the National Natural Science Foundation of China (81872549) and the Key-Area Research and Development Program of Guangdong Province (2018B030340001). HL is supported by The National Natural Science Foundation of China (82003389). YX is supported by the Youth Program of the National Natural Science Foundation of China (81801229). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Author information

Author notes

  1. Yanting Chen and Yongteng Xu contributed equally to the study.

Authors and Affiliations

  1. Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Yanting Chen, Yongteng Xu, Honghong Li, Jinhua Cai, Yi Li, Qingyu Shen & Yamei Tang

  2. Department of Neurology, The Eighth Affiliated Hospital, SunYat-Sen University, Shenzhen, 528406, China

    Dong Pan

  3. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Yamei Tang

  4. Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510120, China

    Yamei Tang

Authors
  1. Yanting Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongteng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Honghong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jinhua Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qingyu Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yamei Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: YC, YL, QS and YT. Data curation: YC, YX, DP, HL and JC. Analysis and interpretation of data: YC, DP, YL, QS and YT. Writing—original draft: YC, YL, QS and YT. Writing, review and/or revision of the manuscript: All authors. Study supervision: YL, QS and YT.

Corresponding authors

Correspondence to Yi Li, Qingyu Shen or Yamei Tang.

Ethics declarations

Conflict of interests

All authors have declared that they had no competing interests.

Ethical approval and consent to participate

This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, and the requirement for informed consent was waived due to the retrospective design.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 151 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Xu, Y., Pan, D. et al. Progression rate of radiation-induced carotid stenosis in head and neck cancer survivors after statin treatment: a retrospective cohort study. J Neurol 271, 2573–2581 (2024). https://doi.org/10.1007/s00415-024-12197-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-024-12197-4

Keywords

Search

Navigation