Oxygen tension in transplanted mouse osteosarcomas during fractionated high-LET- and low-LET radiotherapy - Predictive aspects for choosing beam quality?

Purpose: The lower OER of high-LET radiations, compared to conventional (lo w-LET) radiations, has often been put forward as an argument for using high -LET radiotherapy in the management of hypoxic tumours. Among the different neutron beams used in therapy, the reactor fission neutrons have the lowes t OER. The aim of the present study is to follow the variations of tumour o xygenation status during fractionated irradiation with different radiation qualities. Little information is available so far after fractionated high-L ET irradiation. In addition, the RBE of reactor fission neutrons for effect s on tumours and on normal tissues are compared. Material and Methods: Murine OTS 64 - osteosarcomas were tranplanted in 102 balb-C mice and irradiated by 36 Gy of photons in fractions of 3 Gy five t imes a week (group P-36/3) or by 12 Gy of reactor fission neutrons in fract ions of 2 Gy two times a week (group N-12/2). Irradiations started at a tum or volume of 500 to 600 mm(3). A third group received no radiotherapy, but all investigations (group CG). Tumor volume and tumor oxygenation were meas ured once a week under therapy and during three weeks after therapy. For in vivo-evaluation of oxygen status a computerized polarographic needle elect rode system (KIMOC pO(2) histograph, Eppendorf) was used. The median pO(2) and the hypoxic fraction (pO(2) values <5 mm Hg) of single tumors and of to tal groups were calculated from pooled histograms and from row data as well . Results: In correlation with the increase of tumor volume, from day 1 to da y 42 of follow-up the median pO(2) decreased from 20 mm to 8 mm Hg and the hypoxic fraction increased from 7% to 31%. After fractionated photon therap y a growth delay of three weeks was observed. Six weeks after beginning of the irradiation the median tumor volume had been doubled again. After fissi on neutron therapy growth delay continued until the end of the follow-up pe riod. In both of the irradiated groups a significant decrease of median pO( 2) values and an increase of the hypoxic fraction were observed under radio therapy. Hypoxia was more intensive after neutrons with a decrease of the m edian pO(2) from 20 mm Hg to 1 mm Hg vs. 10 mm Hg after photon therapy and with an increase of the hypoxic fraction from 7% to 78% vs. 36% respectivel y. Two weeks after the end of therapy the median pO(2) and the hypoxic frac tion of both treated groups reached the levels prior to irradiation indicat ing a complete reoxygenation. Conclusion: During fractionated irradiation of murine osteosarcomas weith p hotons: and reactor fission neutrons, a marked hypoxia was observed for bot h radiation qualities, but hypoxia was more intense during fractionated neu tron irradiation. After irradiation, a complete reoxygenation occured in bo th groups independently of the degree of hypoxia observed during the treatm ent. The RBE of reactor fission neutrons, after fractionated irradiation, w as much higher for effects on murine osteosarcomas compared to their RBE ob served for normal tissues in previous experiments. present data are in agre ement with our clinical observations on more than 300 patients treated with reactor fission neutrons for advanced and hypoxic tumours with various his tologies.