Effect of fractionated irradiation prior to conservative and radical surgery on therapeutic gain in a spontaneous fibrosarcoma of the C3H mouse.

The efficacy of fractionated irradiation given preoperatively was examined using early generation isotransplants of a spontaneous fibrosarcoma (FSaII) growing in the right leg of syngeneic C3Hf/Sed mice and employing as endpoints local tumor control probability, normal tissue damage (5 mm leg shortening), and distant metastasis. Complete dose response assays have been performed on small (4-5 mm) and large (8 mm) tumors. TCD50s (the dose that on average would be expected to control half the irradiated tumors) for radiation given in five equal doses (1 day between treatments) were 93.6 and 111.8 Gy for the 4-5 and 8-mm tumors, respectively. Surgery was performed under a dissecting (8X) microscope at 5-6 days after the completion of irradiation. For small tumors, radical (en bloc) and conservative (local) resection alone achieved 69.8 (30/43) and 21.9% (7/32) tumor control, respectively. The corresponding figures for large tumors were 25 (8/32) and 6.1% (2/33), respectively. Preoperative irradiation increased tumor control rate up to 100% at dose levels much lower than TCD50 for radiation alone. Enhancement ratios (ER) were computed for preoperative radiation as follows: TCD50 for radiation alone/TCD50 for radiation and surgery. ERs were computed for local and en bloc resection for tumor control and for leg shortening. From these ER values, therapeutic gain factors (TGF) were then computed for local and en bloc resection for tumor control and for leg shortening. From these ER values, therapeutic gain factors (TGF) were then computed as ER tumor response/ER leg shortening. In small tumors, the TGFs (TCD80 and leg shortening of 5 mm) were 2.1 and 2.0 for conservative and radical resection, respectively. Corresponding figures for large tumors were 1.5 and 1.5. In this experimental system for small and large tumors, radiation treatment prior to conservative surgery achieved a comparable therapeutic gain to that by combining radiation with radical surgery. No effect of preoperative fractionation on the frequency of distant metastasis was observed.