The assessment of response to therapy of bone metastases in breast cancer.

Serial bone scans, x-rays and records of bone pain were reviewed in order to determine the relative contributions of these parameters in the assessment of response of bone metastases to treatment. Twenty-seven patients with abnormal bone scans due to metastatic breast cancer were studied. Ten of the patients showed an early temporary flare on bone scan including five with apparent new lesions. Confirmation that such new lesions did not denote progressive disease was provided by subsequent improvement in symptoms and reduction in intensity and number of lesions on a follow-up bone scan, without any change in systemic therapy. Serial x-rays were found to be unreliable as a sole method for assessing response to therapy or disease progression, as in only seven of the 27 patients could a definitive radiological assessment of response be made. In only one patient did x-rays improve the accuracy of the scan by distinguishing between a healing flare and progressive disease. In contrast, this distinction was made in seven of the 10 patients on the basis of improvement in bone pain at the time of the flare. The other 3 patients had no bone pain prior to therapy or at the time of the flare. Tentative response criteria incorporating bone scan, x-ray and symptoms are suggested. The criteria incorporate recognition of the fact that new lesions appearing on a bone scan within six months of initiation of therapy may comprise part of a healing flare response.

The concentration maximum concept in intravenous cholangiography.

The excretion of ioglycamate in the bile of the rhesus monkey was measured at 5% and at 100% bile diversion following an intravenous bolus injection of ioglycamate. At 100% diversion the bile volume was reduced and the concentration of ioglycamate was increased, but the quantity excreted was unchanged. A similar study using iodipamide reported previously gave the same result. When the ioglycamate was given by intravenous infusion, the effect of 100% bile diversion was quite different. The concentration of ioglycamate in the bile was unchanged by the bile diversion but the excretion was reduced. These results indicate that the transport maximum for the excretion of ioglycamate in bile is not a constant and is reduced by interruption of the enterohepatic circulation of bile salts. The maximum concentration of ioglycamate in bile was constant and was independent of the reduction in bile salt output produced by 100% bile diversion. Following a single bolus injection however, the reduction in bile flow produced by 100% bile diversion increased the biliary concentration of ioglycamate. These results suggest that the excretion of ioglycamate is limited by a maximum concentration rather than a transport maximum. The maximum rate of transport (Tm) is dependent on two factors--the maximum concentration of ioglycamate in the bile and the rate of bile flow. The maximum concentration is achieved by an infusion technique and not by a single bolus injection and this supports the view that an infusion technique should be used for intravenous cholangiography.

Levels of ioglycamate (Biligram) in the bile of the rhesus monkey following intravenous infusion at different dose-rates.

The maximun rate of excretion of ioglycamate in the bile of the rhesus monkey was achieved when the rate of adminstration was at least twice the rate of excretion. A maximum concentration of ioglycamate in the bile was also established, and this is more important to the visualization of the bileducts than the quanity of ioglycamate excreted. The maximum concentration was obtained at the same rate of infusion as that which produced the maximum rate of excretion. The peak concentration was sustained longer with an infusion lasting two hours than with one lasting 36 minutes, althought the same quanity of ioglycamate had been administered. It is concluded that an infusion at a rate equal to twice the maximum excretory rate and continued for two hours or longer is a rational approach to intravenuous cholangiography particularly in those patients where there has been some diffculty in bile-duct visulization.