Use of fractional dose-volume histograms to model risk of acute rectal toxicity among patients treated on RTOG 94-06

Abstract

Background and purpose: For toxicities occurring during the course of radiotherapy, it is conceptually inaccurate to perform normal-tissue complication probability analyses using the complete dose-volume histogram. The goal of this study was to analyze acute rectal toxicity using a novel approach in which the fit of the Lyman-Kutcher-Burman (LKB) model is based on the fractional rectal dose-volume histogram (DVH).

Materials and methods: Grade ≥2 acute rectal toxicity was analyzed in 509 patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06. These patients had no field reductions or treatment-plan revisions during therapy, allowing the fractional rectal DVH to be estimated from the complete rectal DVH based on the total number of dose fractions delivered.

Results: The majority of patients experiencing Grade ≥2 acute rectal toxicity did so before completion of radiotherapy (70/80=88%). Acute rectal toxicity depends on fractional mean rectal dose, with no significant improvement in the LKB model fit when the volume parameter differs from n=1. The incidence of toxicity was significantly lower for patients who received hormone therapy (P=0.024).

Conclusions: Variations in fractional mean dose explain the differences in incidence of acute rectal toxicity, with no detectable effect seen here for differences in numbers of dose fractions delivered.

Figure 1

Histogram of times at which Grade ≥2 acute rectal toxicity occurred.

Figure 2

Incidence of Grade ≥2 acute rectal toxicity in each of 10 subgroups of 50–51 patients. Points are plotted at the average (mean) value of fractional mean dose per subgroup. Horizontal error bars show ±1 standard deviation; vertical error bars show ±1 standard error computed using binomial statistics. The solid curve illustrates the fit of the Lyman-Kutcher-Burman model using fractional rectal DVHs.

Figure 3

Incidence of Grade ≥2 acute rectal toxicity as a function of fractional mean dose in subgroups of patients treated with (6 groups, 24–25 patients each) or without (7 groups, 51–52 patients each) neoadjuvant hormone therapy. Points and error bars are as in Figure 2. Solid curves show the fit of the Lyman-Kutcher-Burman model with hormone therapy included as a dose-modifying factor on the fractional TD₅₀ value.

Figure 4

Correlation between overall mean rectal dose and fractional mean dose to rectum in the study cohort. The Pearson correlation coefficient (r) and significance level (P) are shown.