Thermal dose fractionation affects tumour physiological response.
OBJECTIVE
It is unknown whether a thermal dose should be administered using a few large fractions with higher temperatures or a larger number of fractions with lower temperatures. To evaluate this we assessed the effect of administering the same total thermal dose, approximately 30 CEM43T(90), in one versus three to four fractions per week, over 5 weeks.


METHODS
Canine sarcomas were randomised to receive one of the hyperthermia fractionation schemes along with fractionated radiotherapy. Tumour response was based on changes in tumour volume, oxygenation, water diffusion quantified using MRI, and a panel of histological and immunohistochemical end points.


RESULTS
There was a greater reduction in tumour volume and water diffusion at the end of therapy in tumours receiving one hyperthermia fraction per week. There was a weak but significant association between improved tumour oxygenation 24 h after the first hyperthermia treatment and extent of volume reduction at the end of therapy. Finally, the direction of change of HIF-1α and CA-IX immunoreactivity after the first hyperthermia fraction was similar and there was an inverse relationship between temperature and the direction of change of CA-IX. There were no significant changes in interstitial fluid pressure, VEGF, vWF, apoptosis or necrosis as a function of treatment group or temperature.


CONCLUSIONS
We did not identify an advantage to a three to four per week hyperthermia prescription, and response data pointed to a one per week prescription being superior.
College of Veterinary Medicine, North Carolina State University, Raleigh, USA.
Donald E
DE
Thrall
Paolo
P
Maccarini
Paul
P
Stauffer
James
J
Macfall
Marlene
M
Hauck
Stacey
S
Snyder
Beth
B
Case
Keith
K
Linder
Lan
L
Lan
Linda
L
McCall
Mark W
MW
Dewhirst
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004285:Dogs; D006979:Hyperthermia, Induced; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000951:Antigens, Neoplasm; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D053148:Caspase 3; D002256:Carbonic Anhydrases