Radiobiological Modeling and Experimental Quantification of Radiobiological Parameters used in Cervical Cancer Brachytherapy Dose Calculation

• Author / Creator

  Chow, Braden K

• Cervical cancer is the fourth most common cancer worldwide, with an estimated 604,000 cases identified in 2020. The standard care for locally advanced cervical cancers is concurrent chemotherapy and external beam radiotherapy (EBRT) with a brachytherapy (BT) boost. Current guidelines recommend that the combined EBRT and BT doses be prescribed in units of radiobiological dose, which is calculated using radiobiological parameters α/β and T1/2. Though dose calculations are performed with conventional values of α/β (10 Gy for tumor and 3 Gy for organs at risk) and T1/2 (1.5 hours for both), a wide range of values have been reported in literature and their potential implications on current dose prescriptions have not been thoroughly investigated.

  This work presents the potential uncertainty that arises from the current body of reported parameter values and highlights pitfalls in estimating the clinical equivalency between two types of BT boosts: high-dose-rate (HDR) and pulsed-dose-rate (PDR). Variance in the α/β ratio and T1/2, within the ranges of values reported in the literature, can introduce over 10% variance in the calculated radiobiological tumor dose for PDR treatments, while changes in the α/β ratio can result in over 13% variance for HDR treatments. These significant variances highlight the need for further efforts to establish definitive radiobiological parameter values.

  Compared to the different radiation sources and treatment schedules used in previous experiments reported in literature, the in vitro experiments with cervical cancer cell lines performed in this study utilized clinical BT sources and clinically relevant treatment schedules. To do so, a first-in-kind brachytherapy afterloader in vitro radiation delivery apparatus (BAIRDA) was developed to deliver radiation to tissue culture plates. Parameter values (both α/β and T1/2) for seven cervical cancer cell lines (four squamous cell carcinoma and three adenocarcinoma) were determined using BAIRDA through single acute and fractionated hourly radiation schedules. Confirmatory experiments with a traditional irradiator yielded similar results for all cell lines, providing support for the novel BAIRDA methodology.

  Uncertainties influencing in vitro experiments using both irradiator and BAIRDA configurations, including those associated with measurements of cell survival and dose, were evaluated to refine the radiobiological parameters. Of the two, the dominant uncertainty was from cell survival measurements. The experimentally determined α/β and T1/2 values varied by a maximum of 0.5 Gy and 0.4 hours, respectively, when considering either all experimental uncertainties or limiting the analysis to including only the variance in the surviving fraction for an experiment triplicate, which has been the common approach. BAIRDA experiments had a larger overall uncertainty than those using established irradiator methodology, but it could be reduced to a comparable level with further refinements of the experimental setup. Regardless, a complete uncertainty analysis did not affect the study’s findings, and the radiobiological parameters estimated with BAIRDA and traditional irradiators remained similar. Therefore, the uncertainty investigation provides greater confidence in the BAIRDA methodology and findings utilizing it.

  The radiobiological parameters reported in this study indicate that α/β for both squamous cell carcinoma and adenocarcinoma may be lower than the current conventional assumption (10 Gy) for tumor, while T1/2 may be higher than the conventional assumption (1.5 hours) for squamous cell carcinoma and lower for adenocarcinoma. These results suggest the potential for personalizing BT boosts based on cancer type; a PDR BT boost might deliver a greater radiobiological dose than the conventionally equivalent HDR BT boost for squamous cells and vice versa for adenocarcinoma. Further research building upon the findings of this thesis is needed to translate the results to the improvements of cervical cancer BT. To determine if they hold clinically, further investigation of cervical cancer radiobiological parameter values is needed in more clinically relevant formats (e.g. in vivo or through patient outcomes studies).

• Subjects / Keywords

  • Brachytherapy
  • Radiobiology
  • Linear-Quadratic Model
  • Alpha/Beta
  • Cervical Cancer
  • Medical Physics
  • Clonogenic Assays

• Graduation date

  Spring 2022

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-34ty-q588

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.