Influence of dose per fraction and overall treatment time on the response of pulmonary micrometastases of the R1H-tumour to fractionated irradiation

Background and purpose: Macroscopic subcutaneously growing R1H-tumours have been shown to respond almost independently of the dose per fraction when treated under ambient conditions. In addition decelerated repopulation during fractionated irradiation has been shown for this experimental tumour. The aim of the present study was to investigate whether this is also the case for pulmonary micrometastases which are assumed to be fully oxygenated or whether differences in the oxygenation status of the tumour possibly alters its response to fractionation. The influence of the dose per fraction and overall treatment time on the response of micrometastases to fractionated irradiation was studied. Materials and methods: Pulmonary metastases were induced by i.v. injection of viable tumour cells. Treatment was started 14 days later, when metastases reached an average size of four cells. Total doses of 16 to 28 Gy were administered within an overall treatment time of 11 or 25 days, using doses per fraction of 1, 2, or 4 Gy. Tumour response was quantified by metastatic control (MCD37%) Results: Fractionation had a significant influence on local control (P = 0.009). After application of 1, 2, or 4 Gy and an overall treatment time of 11 days the MCD37% was 25.4 (95% C.I.: 21.5-32.0) Gy, 20.7 (17.0-24.0) Gy, and 18.5 (14.9-21.6) Gy, respectively. When overall treatment time was prolonged to 25 days the MCD,,, increased to 25.5 (21.3-33.5) Gy when fractions of 2 Gy where applied, but this difference was not significant (P = 0.13). The doubling time of 12.8 days determined for the metastatic clonogenic tumour cells during fractionated irradiation was significantly longer than the 4.1 days observed for untreated metastases (P = 0.006). Conclusions: The results show a strong influence of fractionation on treatment outcome and a decelerated repopulation during fractionated irradiation treatment for well oxygenated pulmonary metastases of the R1H-tumour. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.