Tumour temperature heterogeneity during hyperthermia has been attributed to irregular tumour vascular perfusion. We have compared temperature distributions in human tumours subjected to superficial hyperthermia under conditions of normal and occluded blood flow. Three patients with recurrent malignant melanoma on the leg were treated with radiation followed by hyperthermia 60-90 min later on days 1, 8 and 22. Heating (15-30 min) with normal blood flow was followed by 15 min of heating with tourniquet occlusion, although the tourniquet had to be intermittently released when the patients complained of discomfort. Hyperthermia was delivered using either a 1.4 MHz ultrasound or 915 MHz microwave applicator. Temperatures were monitored using superficial and interstitial thermometers in tumour and normal tissues. When the tourniquet was applied, the amount of power required to maintain peak temperatures was decreased by a factor of 3-10. With normal blood flow, there was a significant degree of temperature heterogeneity within the treatment volume, both within normal and tumour tissues, which improved with tourniquet application. The T90 and T50 indices increased both in normal tissues and tumour following the tourniquet occlusion, with the temperature increments being greater for normal tissues. Temperatures at depth were increased despite the reduction in applied power and the temperature profiles were smoother when the tourniquet was applied. No cutaneous, vascular or neuromuscular side effects were observed amongst these three subjects either acutely or at 1 month follow-up. These studies demonstrate directly that the temperature heterogeneity which exists in human tumours subjected to external heating can be reduced by occluding the blood supply.

Aged↗

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The potential role of HSP70 as an indicator of response to radiation and hyperthermia treatments for recurrent breast cancer.

Twenty-three patients with recurrent breast cancer participating in a Phase III trial evaluating radiotherapy (XRT) with or without hyperthermia (HT) were included in a parallel study of heat shock protein (hsp) expression. The patients had core biopsies and/or fine needle aspirates (FNA) performed on their tumours, before and after treatment. These were analysed for hsp content using immunohistochemical staining with a monoclonal antibody to the inducible form of hsp 70. The proportion of samples containing identifiable cancer cells was greater for the core biopsy specimens (80%) than with FNA (60%). Staining intensity was analysed using either the majority score, i.e. the staining intensity (on a relative scale from 0 to 3) for the largest proportion of tumour cells, or the arithmetic score, which is the sum of the product of percentage of tumour cells and their staining intensity. The staining intensity for hsp's after treatment correlated inversely with the probability of attaining a complete response (CR). Specifically, the median and maximum scores for the biopsy specimens were significantly inversely related to the probability of attaining CR. The results suggest that this technique may be useful in predicting for thermotolerance development, though more data is needed to confirm the utility of the technique. Results from this study corroborate data from other clinical studies which suggest that tumours with elevated hsp levels may demonstrate resistant biologic behaviour.

Biopsy↗

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Assessment of palliation in women with recurrent breast cancer.

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Breast Neoplasms↗

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Effect of 3-methylcholanthrene treatment on phenacetin O-dealkylation in several inbred mouse strains.

An increase in the metabolism of phenacetin to N-acetyl-p-aminophenol is correlated with benzo[a]pyrene hydroxylase induction by 3-methylcholanthrene among several inbred mouse strains. While the magnitude of induction of phenacetin O-dealkylation is considerably less than that of benzo[a]pyrene hydroxylation, the data indicate that in mice, the metabolism of these two substrates is under similar regulatory control.

Animals↗

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