Loss of radiobiological effect of imaging dose in image guided radiotherapy due to prolonged imaging-to-treatment times.

PURPOSE Increased use of cone beam CT guidance in image guided radiotherapy has prompted the inclusion of the imaging dose in treatment plans, thus using imaging beams to treat tumors. Sublethal radiation damage repair during tau(d), the time between imaging and treatment, could reduce the effectiveness of the imaging dose, resulting in tumor underdosage. The theoretical magnitude of this effect was quantified using radiobiological modeling. METHODS The therapeutic effective dose (TED), which, if delivered using only therapeutic beams, would result in the same tumor cell survival as for both the imaging and therapeutic beams, was derived using the generalized linear-quadratic model. The correction factor P(d) by which therapeutic dose can be scaled to compensate for sublethal damage repair was also derived. TED and P(d) are dependent on alpha/beta, sublethal damage repair half-time (T(r)), imaging dose (D(I)) and dose rate (D(I)), therapeutic dose (D(T)) and dose rate (D(T)), and tau(d). TED and P(d) were calculated as a function of tau(d), and each parameter was varied independently while holding the remaining parameters at their reference values. The reference values were based on prostate cancer cells and were D(p) = D(I)+D(T) = 1.8 Gy, D(I)/D(p) = 5%, D(I) = 0.33 Gy/min, D(T) = 1.0 Gy/min, alpha/beta = 3.1 Gy, T(r) = 16 min, and tau(d) = 0 min. Estimates of the expected values of TED and P(d), (TED) and (P(d)), were calculated using tau(d) and D(T) distributions from a few thousand prostate treatment fractions. RESULTS For a typical tau(d) value of 5.0 min and all other parameters set to their reference values, TED was 0.5% lower than the prescription dose D(p). For tau(d) = 20 min and all other parameters at reference conditions, TED dropped by 5% relative to D(p) when D(I)/D(p) was 20% and by 2% relative to D(p) when alpha/beta = 1 Gy or T(r) = 5 min. TED/D(p) varied more with D(T) than D(I) when tau(d) < or = 20 min, varying by up to 1% over 0.05 < or = D(T) < or = 10 Gy/min and by less than 0.1% over 0.05 < or = D(I) < or = 2.0 Gy/min. Under the reference conditions, (TED) was lower than D(p) by 0.5%. For the extreme D(I)/D(p) = 20% and all other parameters at their reference values, setting alpha/beta = 1 Gy resulted in (TED) dropping below D(p) by 2.5% and setting T(r) = 5 min resulted in (TED) dropping below D(p) by 4%. For tumors with a T(r) of 16 min or greater and alpha/beta of 11 Gy, (TED) dropped below D(p) by 0.2% or less. CONCLUSIONS For prostate tumors receiving a reasonable percentage of 5% of their total dose from imaging beams, the theoretical drop in (TED) relative to D(p) was 0.5%. This loss could be accounted for during treatment planning by scaling the therapeutic dose by the expected sublethal damage repair factor (P(d)). For nonprostate tumors with alpha/beta values of 11 Gy, the theoretical drop in (TED) relative to the reference TED was low at 0.2%.