In Vitro α/β Ratio Variations in Cervical Cancer, with Consequent Effects on Equivalent Dose in 2 Gy Fraction in High-Dose-Rate Brachytherapy

Purpose: To determine the distributions of published α/β values measured in vitro and the resulting uncertainties in the equivalent dose in 2 Gy fractions (EQD₂) when applied to high-dose-rate brachytherapy (HDR-BT) for cervical cancer. Methods and Materials: An analysis of 98 published α/β values from 31 papers was conducted, spanning 23 cervical cancer cell lines. Values were further divided into squamous cell carcinoma and adenocarcinoma histologies. Probability distributions were fit to histograms using the bootstrapped Kolmogorov-Smirnov goodness-of-fit test. Both average and most probable α/β values for cervical cancer were determined. The probability distributions were then applied to three representative external beam therapy (EBT) plus HDR brachytherapy prescriptions to determine the potential impact they would have on the equivalent dose in 2 Gy fractions (EQD₂) for each prescription. Results: Published results of α/β values ranged from 1.06 to 34.3 Gy. A right-skewed log-normal distribution was shown to be the best fit for overall α/β values as well as for squamous cell carcinoma and adenocarcinoma subtypes. Average α/β values were determined to be 8.05, 8.47, and 6.60 Gy for the total, squamous cell carcinoma, and adenocarcinoma groups, respectively. The most probable values were 4.25, 4.34, and 4.22 Gy, respectively. The variations in α/β values led to uncertainties of −8.0 to 46.4 Gy in EQD₂. Average α/β values resulted in EQD₂ deviations of up to 4.3 Gy for the 83.9 Gy EQD₂ prescription, whereas most probable values resulted in disparities as significant as 10 Gy. We used our α/β value distributions to create uncertainty distributions for EQD₂ and discovered that the 83.9 Gy prescription in EQD₂ had average variations of up to 8% from the intended dose. Conclusion: There was large variation in in vitro α/β values which presented as a right-skewed log-normal distribution with a most probable value of ∼4.3 Gy for cervical cancer. Adenocarcinoma showed somewhat lower average α/β values compared with squamous cell carcinoma, but the difference was not substantial enough to draw definitive conclusions. Lower α/β values resulted in higher EQD₂ for HDR-BT compared with α/β values at 10 Gy. This suggests that more accurate and potentially lower α/β values should be used for cervical cancer.