title: Novel insights into pathological changes in muscular arteries of radiotherapy patients.
abstract: OBJECTIVE
  Vascular disease is increased after radiotherapy and is an important determinant of late treatment-induced morbidity and excess mortality. This study evaluates the nature of underlying pathologic changes occurring in medium-sized muscular arteries following irradiation.
  
  
  METHODS
  Biopsies of irradiated medium-sized arteries and unirradiated control arteries were taken from 147 patients undergoing reconstructive surgery with a vascularised free flap following treatment for head and neck (H&N) or breast cancer (BC). Relative intimal thickening was derived from the ratio of the thickness of the intima to the thickness of the media (IMR) on histological sections. Proteoglycan, collagen and inflammatory cell content were also scored.
  
  
  RESULTS
  Intimal thickness was significantly increased in irradiated vessels: in the H&N group the IMR was 1.5-fold greater without correction for the control artery (p=0.018); in the BC group the IMR increased 1.4-fold after correction for the control artery (p=0.056) at a mean of 4 years following irradiation. There was an increase in the proteoglycan content of the intima of the irradiated IMA vessels, from 65% to 73% (p=0.024). Inflammatory cell content was increased in the intima of the irradiated H&N vessels (p=0.014).
  
  
  CONCLUSIONS
  Radiation-induced vascular pathology differs quantitatively and qualitatively from age-related atherosclerosis.
authors.affiliation: Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands. n.russell@nki.nl
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Russell
authors.forename: Saske
authors.initials: S
authors.lastname: Hoving
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: J Joris
authors.initials: JJ
authors.lastname: Hage
authors.forename: Leonie A E
authors.initials: LA
authors.lastname: Woerdeman
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
authors.forename: Peter J F M
authors.initials: PJ
authors.lastname: Lohuis
authors.forename: Ludi
authors.initials: L
authors.lastname: Smeele
authors.forename: Jack
authors.initials: J
authors.lastname: Cleutjens
authors.forename: Addy
authors.initials: A
authors.lastname: Valenkamp
authors.forename: Lucille D A
authors.initials: LD
authors.lastname: Dorresteijn
authors.forename: Otilia
authors.initials: O
authors.lastname: Dalesio
authors.forename: Mat J
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Stewart
mesh_terms: D000328:Adult; D001158:Arteries / Q000473:pathology* / Q000528:radiation effects*; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016022:Case-Control Studies; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply; D011336:Probability; D011832:Radiation Injuries / Q000473:pathology*; D011879:Radiotherapy Dosage; D019651:Plastic Surgery Procedures / Q000379:methods; D012016:Reference Values; D018570:Risk Assessment; D013524:Surgical Flaps / Q000098:blood supply; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology / Q000528:radiation effects