Radiobiological considerations in combining doses from external beam radiotherapy and brachytherapy for cervical cancer

Abstract

The recommended radio-therapeutic treatment for cervix cancer consists of a first phase of external beam radiotherapy (EBRT) plus a second phase of brachytherapy (BT), the combined treatment being delivered within 8 weeks. In order to assess a comprehensive dosimetry of the whole treatment, it is necessary to take into account that these two phases are characterized by different spatial and temporal dosimetric distributions, which complicates the task of the summation of the two contributions, EBRT and BT. Radiobiology allows to tackle this issue pragmatically by means of the LQ model and, in fact, this is the usual tool currently in use for this matter. In this work, we describe the rationale behind the summation of the dosimetric contributions of the two phases of the treatment, EBRT and BT, for cervix cancer, as carried out with the LQ model. Besides, we address, from a radiobiological point of view, several important considerations regarding the use of the LQ model for this task. One of them is the analysis of the effect of the overall treatment time in the result of the global treatment. Another important question considered is related to the fact that the capacity of LQ to predict the treatment outcomes is deteriorated when the dose per fraction of the radiotherapic scheme exceeds 6-10 Gy, which is a typical brachytherapy fractionation. Finally, we analyze the influence of the uncertainty and the variability of the main parameters utilized in the LQ model formulation in the assessment of the global dosimetry.

Keywords: Brachytherapy; Cervix cancer; Combined treatment; LQ model; Overall treatment time; Radiobiology.

Fig. 1

Representation of 7 different examples of radiotherapy schedules combining EBRT with HDR-BT. The red bars represent the days of EBRT; the long gray bars represent the weekends, in which there is not treatment; the short gray bars represent days in which there is not EBRT treatment, since it already finished; the black bars represent the days of HDR-BT; the blue line represent the recommended total treatment time limit of 8 weeks. The total treatment time, in days, is also displayed.

Fig. 2

Probability control data from the work of Huang et al. transformed to obtain the EQD2_39days equivalence and fits of the control probability model (16) to those data. Red squares correspond to κ = 1.0 Gy/day and black circles to κ = 0.5 Gy/day. The results of the fit of (16) to the data in Table 3 are also shown. The confidence interval is referred to as 95%.

Fig. 3

(a) Tumor control as a function of the increase in the total combined treatment time above 39 days. (b) Absolute loss of tumor control with respect to the treatment with duration of 39 days. The results for κ = 1.0 Gy/day are represented by the discontinuous red line and for κ = 0.5 Gy/day, by the continuous black line.

Fig. 4

(a) EQD2 distributions for the D₉₀ of the CTV_HR (black squares), EQD2_bladder and EQD2_rectum for D_2cc of the bladder (white circles) and the rectum (white squares). (b) Contribution of each treatment phase to the final EQD2 for the bladder. Uncertainties correspond to a confidence interval of 95%.

Fig. 5

Ratio between EQD2 computed with Eq. (17) and EQD2 computed with Eq. (15) considering fixed values for (α/β)_E equal to 3 Gy and 10 Gy for the normal tissue and the tumor, respectively, as a function of the difference between (α/β)_E and (α/β)_B. We have considered an EBRT schedule of 45 Gy in fractions of 1.8 Gy plus 4 fractions of 7 Gy of HDR-BT.