title: Thermal enhancement of low dose rate irradiation in a murine tumour system.
abstract: The effects of localized hyperthermia (HT) in combination with low dose rate irradiation (brachytherapy) have been investigated in vivo using a murine mammary adenocarcinoma. Flank tumours were grown to 0.45-0.70 cm3 in volume, at which time their treatment course was initiated. Tumours were locally heated in a water bath for 15 min at either 44 or 45 degrees C. For tumour irradiations a non-invasive cap was devised to permanently house three iodine-125 sealed sources located at 120 degree intervals around the circumference of the hemispherical cap. During treatment, mice were secured in a modified syringe tube allowing mobility while restricting access to the cap which was placed over the tumour. Calculated dose rates ranged from 15 to 40 cGy/h. Brachytherapy (BT) was delivered for 48 or 72 h to obtain a dose range of 830-2378 cGy. Mice were randomized into one of 10 treatment protocols: BT alone, HT-BT, BT-HT, HT-BT-HT, 1/2BT-HT-1/2BT, four control groups of HT alone and a sham treatment group. Normalized tumour doubling volume growth delays (GDDv) were used to calculate the thermal enhancement ratios (TER). In the 44 degrees C experiments, HT before BT (TER = 1.33 +/- 0.071) was more efficacious than HT after BT (TER = 1.07 +/- 0.042). Two HT treatments, one given before and one after BT (TER = 1.38 +/- 0.152), were not different from a single HT treatment given before BT. However, a single HT treatment given in the middle of an interrupted course of BT resulted in the greatest thermal enhancement (TER = 1.64 +/- 0.072) compared to any other treatment sequence. These data suggest that potentiation of low dose rate irradiation by a single heat treatment may be maximized if the HT is given either in the middle of, or simultaneously with, the BT.
authors.affiliation: Department of Medicine, Dartmouth-Hitchcock Medical Center, Hanover, NH 03756.
authors.forename: E L
authors.initials: EL
authors.lastname: Jones
authors.forename: B E
authors.initials: BE
authors.lastname: Lyons
authors.forename: E B
authors.initials: EB
authors.lastname: Douple
authors.forename: B J
authors.initials: BJ
authors.lastname: Dain
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy / Q000628:therapy; D000818:Animals; D001918:Brachytherapy; D003131:Combined Modality Therapy; D005260:Female; D006358:Hot Temperature / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H
chemical_list: D007457:Iodine Radioisotopes