BAIRDA: a novelin vitrosetup to quantify radiobiological parameters for cervical cancer brachytherapy dose...

Objective. Brachytherapy (BT) dose prescriptions for locally advanced cervical cancer are made with account for the radiobiological parameters,α/βratio and halftime of repair (T). However, a wide range of parameter values has been reported which can challenge commonly held equivalencies between dose prescriptions. This is the first reported study that aims to develop anin vitroexperimental technique using clinical high-dose-rate (HDR) and pulsed-dose-rate (PDR) Ir-192 brachytherapy afterloaders to quantify these parametersin vitroand to contextualize findings within contemporary practice.Approach. To efficiently quantifyα/βandT,in vitroexperiments more reflective of clinical BT practice than traditional clonogenic survival assays were developed and applied to four squamous cell carcinoma cell lines (CaSki, C-33A, SiHa, and SW756). Radiation was delivered using single acute and fractionated dose treatments with a conventional irradiator and clinical HDR and PDR BT afterloaders. For the latter, a novelbrachytherapyafterloaderradiationdeliveryapparatus (BAIRDA) was developed.Main Results. Theα/βandTvalues determined using BAIRDA and the conventional irradiator showed close agreement, validating the novel apparatus and technique. For CaSki, C-33A, SiHa, and SW756, the BAIRDA-measuredα/βratios (5.2 [4.6-5.8], 5.6 [4.5-6.6], 6.3 [4.9-7.7], and 5.3 [4.7-6.0] Gy, respectively) were consistently smaller, while theT(3.3 [2.7-3.9], 2.7 [2.0-3.3], 2.8 (2.4-3.1], and 4.8 [4.1-5.4] hours) larger, than the widely accepted values in clinical practice (α/β= 10 Gy;T = 1.5 h).Significance.In vitroexperiments using BAIRDA provided evidence for differences between the conventionally selected and experimentally determinedα/βratio andT. Treatment regimens using HDR-BT and PDR-BT, designed to deliver equivalent radiobiological doses based on conventional values, were shown to differ by up to 27 Gy EQD2 - an effect that could impact treatment outcomes in cervical cancer. Furthermore, with BAIRDA, we have developed a novel method for radiobiological research in BT.