Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis

Hirokazu Makishima, Hitoshi Ishikawa, Toshiyuki Terunuma, Takayuki Hashimoto, Koichi Yamanashi, Takao Sekiguchi, Masashi Mizumoto, Toshiyuki Okumura, Takeji Sakae, Hideyuki Sakurai, Hirokazu Makishima, Hitoshi Ishikawa, Toshiyuki Terunuma, Takayuki Hashimoto, Koichi Yamanashi, Takao Sekiguchi, Masashi Mizumoto, Toshiyuki Okumura, Takeji Sakae, Hideyuki Sakurai

Abstract

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.

Keywords: DVH analysis; concurrent chemoradiotherapy; deformation adaptation; esophageal cancer; proton beam therapy.

© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Figures

Fig. 1.
Fig. 1.
Typical dose distributions and dose–volume histograms in treatment of esophageal cancer in (A) X-ray 3D-CRT and (B) PBT. In 3D-CRT, 20 Gy is delivered widely to the lung, 30 Gy is delivered to most of the heart, and 60 Gy is also delivered widely to the heart. (C) Typical dose–volume histograms of the lung and heart. PBT results in lower irradiation doses in both OARs.
Fig. 2.
Fig. 2.
Parameters in patients with and without adverse events of Grade ≥2. All parameters were significantly higher in patients with late adverse events of Grade ≥2. Bars show the median and 95% CI. Horizontal bars show cut-off lines calculated from ROC curves.
Fig. 3.
Fig. 3.
Differences in parameters in the lung and heart in actual treatment plans and experimental plans. All dose parameters were significantly lower in PBT (P < 0.001 by paired t-test). Horizontal bars show median values and vertical bars show the 95% CI.
Fig. 4.
Fig. 4.
Potential changes in parameters in patients with adverse effects of Grade ≥2 in the X-ray group and in patients with adverse effects of Grade ≤1 in the proton group. Horizontal bars show cut-off lines calculated from ROC curves.
Fig. 5.
Fig. 5.
Normal tissue complication probability (NTCP) changes between plans in the X-ray and proton groups.

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