title: Radiation administered as a large single dose or in a fractionated schedule: Role of the tumour vasculature as a target for influencing response.
abstract: This study was designed to demonstrate a differential tumour response to radiation given as a large single dose or fractionated, and to investigate the postulated role of the tumour vasculature as a target for this difference. A C3H mammary carcinoma grown in the right rear foot of female CDF1 mice was used when at 200 mm3. Radiation (240 kV x-rays) was given locally to the tumour bearing foot either as 1 x 20 Gy or 10 x 2 Gy (2 fractions/day). Tumour response was assessed by calculating tumour growth time (TGT; time to grow to 3 times treatment volume). Vascular effects were monitored by performing dynamic contrast enhanced-magnetic resonance imaging using a 3-Tesla magnet and the contrast agent gadolinium (Gd)-DTPA. The endpoint was the initial area under the concentration curve (IAUC) following Gd-DTPA. The mean (+/-1 S.E.) TGT for control mice was 4.0 days (+/-0.2). This was significantly (Student's t-test; p < 0.05) increased to 12.9 (+/-0.6) and 19.8 (+/-0.7) days, by 10 x 2 and 1 x 20 Gy, respectively. The mean (+/-1 S.E.) of the median IAUC values for control tumours was 8.4 mMs (+/-0.5). This was non-significantly increased to 9.4 mMs (+/-0.4) 6-hours after 1 x 20 Gy, but then significantly decreased to a nadir of 6.8 mMs (+/-0.5) after 48-hours. IAUC recovered at longer time intervals. With 10 x 2 Gy, IAUC significantly decreased during irradiation, reaching 6.7 (+/-0.3) and 5.6 (+/-0.3) mMs at the mid-point and end of the irradiation period, respectively. IAUC recovered 24-hours after irradiating before significantly decreasing to 4.4 mMs (+/-0.3) at 48-hours. Our results confirm that radiation given in a large single dose is superior to the same dose given in a more conventional fractionated schedule, but vascular-mediated effects did not account for this difference in radiation sensitivity.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark. mike@oncology.dk
authors.forename: Michael R
authors.initials: MR
authors.lastname: Horsman
authors.forename: Thomas
authors.initials: T
authors.lastname: Nielsen
authors.forename: Leif
authors.initials: L
authors.lastname: Østergaard
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002277:Carcinoma / Q000098:blood supply / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008833:Microcirculation / Q000502:physiology* / Q000528:radiation effects*; D011829:Radiation Dosage; D047368:Tumor Burden / Q000528:radiation effects