Abstract

BackgroundBetter knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy. The conventional dose-toxicity model is based on the dose volume histogram, which is the parameter lacking spatial dose information. To overcome this limit, we explore a comprehensive rectal dose-toxicity model based on both dose volume histogram and dose map features for accurate radiation toxicity prediction.MethodsForty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively studied, including 12 with Grade ≥ 2 rectum toxicity and 30 patients with Grade 0–1 toxicity (non-toxicity patients). The cumulative equivalent 2-Gy rectal surface dose was deformably summed using the deformation vector fields obtained through a recent developed local topology preserved non-rigid point matching algorithm. The cumulative three-dimensional (3D) dose was flattened and mapped to a two-dimensional (2D) plane to obtain the rectum surface dose map (RSDM). The dose volume parameters (DVPs) were calculated from the 3D rectum surface, while the texture features and the dose geometric parameters (DGPs) were extracted from the 2D RSDM. Representative features further computed from DVPs, textures and DGPs by principle component analysis (PCA) and statistical analysis were respectively fed into a support vector machine equipped with a sequential feature selection procedure. The predictive powers of the representative features were compared with the GEC-ESTRO dosimetric parameters D0.1/1/2cm3.ResultsSatisfactory predictive accuracy of sensitivity 74.75 and 84.75%, specificity 72.67 and 79.87%, and area under the receiver operating characteristic curve (AUC) 0.82 and 0.91 were respectively achieved by the PCA features and statistical significant features, which were superior to the D0.1/1/2cm3 (AUC 0.71). The relative area in dose levels of 64Gy, 67Gy, 68Gy, 87Gy, 88Gy and 89Gy, perimeters in dose levels of 89Gy, as well as two texture features were ranked as the important factors that were closely correlated with rectal toxicity.ConclusionsOur extensive experimental results have demonstrated the feasibility of the proposed scheme. A future large patient cohort study is still needed for model validation.

Highlights

  • Better knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy

  • Representative features further computed from dose volume parameters (DVPs), textures and dose geometric parameters (DGPs) by principle component analysis (PCA) and statistical analysis were respectively feed into a support vector machine (SVM) equipped with a sequential feature selection (SFS) procedure

  • Significant improvements were achieved after topology preserved nonrigid registration point matching algorithm (TOP-DIR) point matching, with the median of Dice’s coefficient (DC) increased from 0.71 to 0.86 (p < 0.001), the median of percent error (PE), vertex to vertex distance (VVD) and Hausdorff distance (HD) decreased from 0.60, 1.53 mm and 6.52 mm to 0.26 (p < 0.001), 0.74 mm (p < 0.001) and 4.06 mm (p < 0.001), respectively

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Summary

Introduction

Better knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy. Buettner et al [6] analyzed the RSDM and found significant correlation between the subjective sphincter control and the dose delivered to the anal sphincter region Another issue with current D0.1/1/2cm evaluation procedure is that the cumulative dose is summed with an assumption that the hotspot regions are stationary throughout the entire fractional treatments [13, 14]. Promising advancements have been reported by Moulton et al who investigated the associations between RSDM and gastrointestinal toxicities after deformably registering each phase of a combined EBRT-BT prostate cancer treatment [18] These limited but inspiring studies shed light on the possibility of revealing more accurate dose-toxicity relationship by exploring the spatial dose distribution patterns on the deformable accumulated dose

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