PO61

Abstract

Purpose In the conventional fractionation schemes of high-dose-rate (HDR) brachytherapy, the intra-fractional and inter-fractional DNA damage repair and repopulation of tumor cells are neglected in calculating the biologically effective dose (BED). This may result in inaccurate model prediction of the theoretical tumor control probability (TCP). Notwithstanding, current prostate brachytherapy prescriptions may still be large enough to theoretically overcome these effects, among others. The purpose of this study was to recalculate the theoretical TCP, accounting for intrafraction DNA damage repair and 192Ir source decay for prostate cancer treated using HDR brachytherapy as the monotherapy, compared against common 1-, 2-, and 9-fraction prescription schemes. Materials and Methods We incorporated the Lea-Catcheside dose protraction factor g, the effective tumor doubling time Td, the total elapsed time of the treatment course T, and the onset or lag time of cell repopulation Tk, into the full-form BED calculation, in contrast to the simple form BED which only includes the total dose, dose per fraction and α/β. The Poisson model relating the surviving fraction and the number of tumor clonogens (K) was used to calculate TCP. The parameter set α = 0.15 Gy-1, α/β = 3.1 Gy, τ = 0.27 h (DNA damage repair half time), Td = 42 days, and Tk = 0 was used for the full-form BED calculation. K = 1.1 × 107 from the high-risk group was used in the TCP calculation. The new 192Ir source (40,700 U, 10 Ci, 1.27 Gy/min) and the 90-day source (17,470 U, 4.3 Ci, 0.55 Gy/min) were used to investigate the source decay effect on TCP. Three different fractionation schemes n = 1, 2, and 9 fraction(s) were studied. Simple BED, full-form BED (both 10 Ci and 4.3 Ci), TCP50 (total dose at TCP = 50%), and TCP90 (total dose at TCP = 90%) were calculated for each setup. 1 x 21 Gy, 2 x 13.5 Gy, and 9 x 6 Gy prescriptions were selected to evaluate the robustness of different fractionation schemes on TCP impacted by DNA damage repair and source decay. Results TCP50 and TCP90 using the simple BED, the full-form BED at 10 Ci and 4.3 Ci were calculated. In the single-fraction group, TCP50 = 17.0, 18.6, and 21.2 Gy, and TCP90 = 18.0, 19.9, and 22.8 Gy. In the 2-fraction group, TCP50 = 23.3, 24.7, and 26.8 Gy, and TCP90 = 24.7, 26.3, and 28.7 Gy. In the 9-fraction group, TCP50 = 43.3, 44.3, and 45.6 Gy, and TCP90 = 46.3, 47.4, and 48.9 Gy. For 1 × 21 Gy, the simple BED and full-form BED (10 Ci and 4.3 Ci) = 163.3, 134.8, and 109.0 Gy, and TCP = 99.9%, 98.2%, and 41.9%. For 2 × 13.5 Gy, the simple BED and full-from BED (10 Ci and 4.3 Ci) = 144.6, 128.5, and 112.0 Gy, and TCP = 99.6%, 95.4%, and 57.4%. For 9 × 6 Gy, the simple BED and full-from BED (10 Ci and 4.3 Ci) = 158.5, 151.4, and 143.4 Gy, and TCP = 99.9%, 99.9%, and 99.5%. In general, we have observed: (1) using the simple BED overestimated the TCP compared to the full-form BED, (2) with the source decay, a higher total dose was needed to achieve the same level of TCP, (3) using the hypo-fractionation saved total dose and total irradiation time to achieve the same TCP, but (4) using the hyper-fractionation can dampen the effects of DNA damage repair and source decay on TCP. Conclusions The changes in BED introduced by the Lea-Catcheside dose protraction factor into our TCP model were most significant for deliveries with a long treatment time and/or a decayed source. Current prescriptions for 1, 2, and 9 fraction(s) are adequate to reach TCP of at least 41.9%, 57.4%, and 99.5%. In the conventional fractionation schemes of high-dose-rate (HDR) brachytherapy, the intra-fractional and inter-fractional DNA damage repair and repopulation of tumor cells are neglected in calculating the biologically effective dose (BED). This may result in inaccurate model prediction of the theoretical tumor control probability (TCP). Notwithstanding, current prostate brachytherapy prescriptions may still be large enough to theoretically overcome these effects, among others. The purpose of this study was to recalculate the theoretical TCP, accounting for intrafraction DNA damage repair and 192Ir source decay for prostate cancer treated using HDR brachytherapy as the monotherapy, compared against common 1-, 2-, and 9-fraction prescription schemes. We incorporated the Lea-Catcheside dose protraction factor g, the effective tumor doubling time Td, the total elapsed time of the treatment course T, and the onset or lag time of cell repopulation Tk, into the full-form BED calculation, in contrast to the simple form BED which only includes the total dose, dose per fraction and α/β. The Poisson model relating the surviving fraction and the number of tumor clonogens (K) was used to calculate TCP. The parameter set α = 0.15 Gy-1, α/β = 3.1 Gy, τ = 0.27 h (DNA damage repair half time), Td = 42 days, and Tk = 0 was used for the full-form BED calculation. K = 1.1 × 107 from the high-risk group was used in the TCP calculation. The new 192Ir source (40,700 U, 10 Ci, 1.27 Gy/min) and the 90-day source (17,470 U, 4.3 Ci, 0.55 Gy/min) were used to investigate the source decay effect on TCP. Three different fractionation schemes n = 1, 2, and 9 fraction(s) were studied. Simple BED, full-form BED (both 10 Ci and 4.3 Ci), TCP50 (total dose at TCP = 50%), and TCP90 (total dose at TCP = 90%) were calculated for each setup. 1 x 21 Gy, 2 x 13.5 Gy, and 9 x 6 Gy prescriptions were selected to evaluate the robustness of different fractionation schemes on TCP impacted by DNA damage repair and source decay. TCP50 and TCP90 using the simple BED, the full-form BED at 10 Ci and 4.3 Ci were calculated. In the single-fraction group, TCP50 = 17.0, 18.6, and 21.2 Gy, and TCP90 = 18.0, 19.9, and 22.8 Gy. In the 2-fraction group, TCP50 = 23.3, 24.7, and 26.8 Gy, and TCP90 = 24.7, 26.3, and 28.7 Gy. In the 9-fraction group, TCP50 = 43.3, 44.3, and 45.6 Gy, and TCP90 = 46.3, 47.4, and 48.9 Gy. For 1 × 21 Gy, the simple BED and full-form BED (10 Ci and 4.3 Ci) = 163.3, 134.8, and 109.0 Gy, and TCP = 99.9%, 98.2%, and 41.9%. For 2 × 13.5 Gy, the simple BED and full-from BED (10 Ci and 4.3 Ci) = 144.6, 128.5, and 112.0 Gy, and TCP = 99.6%, 95.4%, and 57.4%. For 9 × 6 Gy, the simple BED and full-from BED (10 Ci and 4.3 Ci) = 158.5, 151.4, and 143.4 Gy, and TCP = 99.9%, 99.9%, and 99.5%. In general, we have observed: (1) using the simple BED overestimated the TCP compared to the full-form BED, (2) with the source decay, a higher total dose was needed to achieve the same level of TCP, (3) using the hypo-fractionation saved total dose and total irradiation time to achieve the same TCP, but (4) using the hyper-fractionation can dampen the effects of DNA damage repair and source decay on TCP. The changes in BED introduced by the Lea-Catcheside dose protraction factor into our TCP model were most significant for deliveries with a long treatment time and/or a decayed source. Current prescriptions for 1, 2, and 9 fraction(s) are adequate to reach TCP of at least 41.9%, 57.4%, and 99.5%.