RADIOBIOLOGICAL DETERMINATION OF GROWTH-KINETICS AND RADIOSENSITIVITYOF PULMONARY MICROMETASTASES OF THE R1H TUMOR

The aim of the study was to determine the radiosensitivity and the gro wth kinetics of pulmonary micrometastases of the R1H tumour of the rat . Lung metastases were induced by intravenous injection of viable tumo ur cells. At different time intervals (3-32 days) after injection, lun gs were locally irradiated with 200 kVp X-rays, using 1.5 Gy/fraction. Total doses of 6-33 Gy were administered within 11 days. Endpoints us ed were survival time, local control rate, and number of metastases in the lungs at autopsy. The data were evaluated using the multi-target model. Beginning in the fifth week after tumour cell inoculation the a nimals started to exhibit a pronounced dyspnoea and were sacrificed. S ections revealed an extensive metastatic infiltration of the lungs. Wi th increasing total dose a prolongation of survival time as well as an increase in cure rate was observed. The number of metastases found in the lungs decreased with increasing total dose. It is concluded that metastatic growth does not start earlier than 3 days after tumour cell inoculation and accelerates continuously. The doubling time of the tu mour cells in the micrometastases decreases continuously and from 5.2 to 1.2 days between day 3 and 40, whereas larger metastases containing more than 10(6) cells show gompertzian growth kinetics. The cell doub ling time in this stage of metastatic growth is longer than 5 days. Du ring the first 4 weeks of metastatic growth the radiosensitivity of me tastatic R1H cells in the lungs is the same as in vitro.