BAIRDA: a novel in vitro setup to quantify radiobiological parameters for cervical cancer brachytherapy dose estimations

Abstract

Objective: Brachytherapy (BT) dose prescriptions for locally advanced cervical cancer are made with account for the radiobiological parameters, α/β ratio and halftime of repair (T1/2 ). 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 an in vitro using clinical high-dose-rate (HDR) and pulsed-dose-rate (PDR) Ir-192 brachytherapy afterloaders to quantify these parameters in vitro and to contextualize findings within contemporary practice. Approach: To efficiently quantify α/β and T1/2 , in vitro experiments 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 novel brachytherapy afterloader in vitro radiation delivery apparatus (BAIRDA) was developed. Main Results: The α/β and T1/2 values 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-measured α/β ratios (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 the T1/2 (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; T1/2 =1.5 hours). Significance: In vitro experiments using BAIRDA provided evidence for differences between the conventionally selected and experimentally determined α/β ratio and T1/2 . 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.

The influence of source decay on BED in2 high dose rate brachytherapy for cervical cancer : considering different tumor cell lines and normal tissues

“…Additionally, according to clinical trial for cervix carcinoma in stage I and II, parameters with α/β = 52.63 Gy and 10 Gy, with T 1/2 = 1.5 and 0.25 hour were reported, respectively [31]. In regards to cervical cell lines, Kelland L, et al [21] and Braden Chow, et al [20] discovered that the nine cell lines they studied possess unique α/β values and T 1/2 values. These parameters are summarized in Table 2.…”

“…It is well-known that cells have varying repair times for DNA damage. It is crucial in cervical cancer radiotherapy to explore the biological effects of various tumor cell subtypes on a clinical level [20,21]. In recent years, there has been growing interest among researchers in the radio biological effects of various cervical cancer cell lines.…”

“…These studies have revealed that various cell lines exhibit different sensitivities to radiation, leading to variable α/β values. For instance, Braden Chow et al [20] discovered that in cervical cancer cell lines such as CaSki, C33A, SiHa, and SW756, the measured α/β ratios were consistently lower (5.2, 5.6, 6.3, and 5.3 Gy, respectively) compared to the commonly accepted values in clinical practice (α/β = 10 Gy, T 1/2 = 1.5 hours ), while the T 1/2 values were higher (3.3, 2.7, 2.8, and 4.8 hours). However, in clinical practice, it has not been taken into account that different BEDs can arise due to varying sensitivities of cell lines to radiation.…”