Abstract
To analyze published biochemical control data for different fractionation schemes obtained using high-dose-rate brachytherapy as monotherapy for prostate cancer and to determine optimal dose per fraction by including the effect of intrafraction DNA repair. A meta-analysis was conducted on 31 studies, published between 2009-2017, which estimated biochemical control using Kaplan-Meier (KM) method for 3692 patients: 1413 low-risk (LR), 1161 intermediate-risk (IR), and 470 high risk (HR) (648 unspecified). In these studies, risk was classified using NCCN standards and biochemical control was defined using the Phoenix definition. We compared reported biochemical control as a function of biologically effective dose (BED) calculated using various methods. To account for intrafraction repair, BED was calculated with and without the Lea-Catcheside dose protraction factor for a range of source activities and dose rates. Clinical data suggests prostate cancer has a fast rate of repair which is on the same order of magnitude of delivery time, especially for single fractions. Biologically optimal dose per fraction for a given number of fractionation schemes was determined based on BED. Reported biochemical control rates were ≥ 85% for LR patients in nearly all studies, with the notable exception of a 1-fraction study with biochemical control rates of 66% at a KM projection of 6 years. Among the 31 studies, fractionations ranged from 1 to 9 fractions with BEDs of 180-299 Gy (α/β=1.5 Gy) and 108-167 Gy (α/β=3 Gy). BED was reduced by up to 31.9% (α/β=1.5 Gy) and 29.5% (α/β=3 Gy) for 1-fraction delivery when including corrections for intrafraction repair. The poor biochemical control seen with single fractions may be attributed to underestimating the effect of intrafraction repair. Table 1 shows calculated prescription doses required to match a BED of 207 Gy (α/β=1.5 Gy) including intrafraction repair for the 6x7 Gy scheme (biochemical control of 94% at 8 years). To achieve this BED, a 1-fraction delivery may require 21 (α/β=1.5 Gy) or 22.3 Gy (α/β=3 Gy). Prescription doses may need to be even higher for single fractions as the effects of tumor hypoxia and reoxygenation are neglected. In general, excellent clinical outcomes are achievable with HDR brachytherapy as monotherapy for prostate cancer patients – this study focused on LR. The relatively poor biochemical control rates observed for single fractions suggests multi-fraction HDR brachytherapy may be more clinically effective. If single fractions are used, cautious dose escalation should be considered to improve biochemical control.Abstract 3482# of FxClinically Used [Gy/Fx]Reported Biochemical Control Rates for Low-Risk (LR) Prostate Cancer PatientsRecommended Rx Doses [Gy/Fx]11966% @ 6 y21212-13.592% @ 5 y13.5310-11.585% @ 5 y10.548.5-9.594% @ 5 y966-7.594% @ 8 y776.5N/A [IR patients only]6.586N/A [IR patients only]69685% @ 5 y5.5 Open table in a new tab
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