Solid tumor models for the assessment of different treatment modalities: XXVI. Estimates of cell survival from tumor growth delay after alternating radiotherapy and chemotherapy.
The doubling time (Td) for hepatoma 3924A in ACI rats is relatively constant between different treatments when growth resumes after treatment with either chemotherapy or radiotherapy. Advantage was taken of this to estimate the fraction of surviving cells (SF) from in vivo growth delay (GD) data using the expression SF = 1/2GD/Td. Survival curves were constructed for several recently published treatment schedules which employed alternating radiotherapy and chemotherapy, and for both daily and multiple fractions per day (MFD) radiation schedules. A doubling time of 5.2 days was assumed, in the range observed for control and regrowing treated tumors, which yields one surviving cell at the TCD37 (3650 cGy single dose). The single fraction, multi-target, single hit model, SF = 1 - (1 - e-D/D0)n with D0 = 406 cGy and n = 1.63 is a reasonable representation of the data over the dose range 375-2250 cGy. The D0 of 406 cGy should be considered as a relative, not absolute value which is dependent on the radiosensitivity of the tumor cells and the accuracy of the doubling time, but is useful in relating the single dose data to more complex radiation schedules. Using D0 = 406 cGy, n = 1.63, and f = number of fractions, the multi-fraction, multi-target, single hit model SF = (1 - [1 - e-D/D0]n)f closely fits our data for 30 daily fractions given at 100 to 375 cGy/day for total radiation doses of 3000 to 11,250 cGy. The fraction of surviving cells for daily radiation alternated with three courses of cyclophosphamide (CP) was in good agreement with an additive effect of the two modalities at radiation doses of 3000 to 5640 cGy. Multiple fractions per day radiation given as 250 cGy fractions was more effective than predicted by the model both when given alone or alternately with cyclophosphamide.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D051381:Rats
D003520:Cyclophosphamide