Biological Effectiveness of Fractionated Dose of Pions in Microscopic SCCVII Tumors: Comparison between Tumor Control Dose and Tumor Growth Time Assays

The relative biological effectiveness (RBE) of fractionated pions for tumor growth time (TGT) assay changes with the endpoints, so it is essential to determine the RBE for tumor control dose (TCD) assay. For this purpose, the TCD(50) of fractionated pions was compared with that of photons, and the RBEs for TGT and TCD assays were concurrently compared as a function of the effect level. A “convenient” RBE (cRBE) was substituted for the RBE when the comparison was made between similar fractionation schedules with different dose per fraction. SCCVII tumors (2 ×10(4) or 2 × 10(5) cells) were implanted into the feet of C3H mice and irradiated starting from 2 days after implantation at a total dose range of either 9.6–38.4 Gy pions (2.4–6.4 Gy per fraction) or 14.4–50.4 Gy photons (3.6–7.2 Gy per fraction) in 2–10 fractions over 5–6 days. The cRBE and the RBE at the iso‐effective level of 30 days TGT were 1.53–1.60 for 2.4–4.8 Gy pions and 1.50 for 4‐fracrionated pions, respectively: there were only small differences within these schedules used. However, the cRBE values decreased from 1.60 to 1.15 with increasing TGT from 30 to 75 days. In contrast, the cRBE values for TCD(50) increased from 1.08 to 1.40 (95% confidence limits [CL]; 1.18–1.63) with increasing evaluation time from 60 to 100 days: pions significantly inhibited late tumor appearance. The TCD(50) at 100 days was 28.7 Gy (CL; 25.0–32.5 Gy) for pions and 40.3 Gy (CL; 36.3–44.2 Gy) for photons. In conclusion, the RBE for TCD(50) was not predictable from the RBE for TGT assay. The cRBE value of 1.4 for microscopic tumor control was in close agreement with the reported values for skin reaction.