JONT Journal

1.       Introduction

Esophageal Carcinoma (EC) is one of the most common cancers with the highest rates of cancer-related death [1]. In Korea, there were 2136 and 2245 persons diagnosed with EC, and 1406 and 1507 persons death at 2009 and 2011 respectively [2,3]. There were a higher morbidity and mortality rates of EC in China [4,5]. The morbidity and mortality rates of EC were 7.74% and 21.88%, and 9.29% and 15.85% in China at 2009 and 2010 respectively [6,7].

Dysphagia is the most common complaint of patients with EC, which not only impacts prognosis, but is also the main factor impacting health-related Quality of Life (QOL); therefore, the relief of dysphagia was an important method to improve the prognosis and QOL of locally advanced EC patients [7,8]. Esophageal stenting was the most commonly used and most effective method to relieve dysphagia compared to the other methods, because which can improve early dysphagia [8].

Radiation therapy played an important role in the comprehensive treatment of esophageal cancer [9], but many controversies existed on the treatment strategy and optimal radiation dose [10]. Three-Dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulation Radiation Therapy (IMRT) were the most common radiotherapy techniques for EC [11]. There are short of optimal dosimetry study of target areas and Organs at Risk (OARs) between 3DCRT and IMRT for locally advanced EC inserted metal stent. The purpose of this study was to analyze the optimal radiation dose distribution of the target areas and OARs received in patients inserted metal stent treated using 3DCRT and IMRT for locally advanced EC.

2.       Material and Methods

2.1.  Patient Characteristics

A total of 5 adult cases (4 males, 1females, mean age 57 years, range 48～65 years) who were confirmed to have inoperable locally advanced EC by pathology and imageology from January to may 2016 (Table 1). A metal stent (MICRO-TECH Nanjing, China) made of Ni-Ti alloy (nitinol single reticulate metal stent with a diameter of 18 mm and a length of 100 mm) was inserted due to grade Ⅲ/Ⅳ dysphagia. All patients underwent esophageal barium swallow examination, contrast-enhanced Computed Tomography (CT) of the thoracic region and 18-F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) scans.

2.2.  Simulation CT Scanning

All cases were scanned by a contrast-enhanced simulation CT (Sim-CT, GE Corporation, America, scanning parameters 120 kV and 200 mA, 2.5 mm/layer) after intravenous injection of 98 ml Omnipaque (Schering AG, Germany, speed 3 ml/s). The region of Sim-CT scan was from the crico-thyroid membrane to the level of the adrenal gland, and the image of Sim-CT was transmitted to the CMS plan system (4.3, CMS Corporation, America).

2.3.  Delineation of Target Areas

The target areas were delineated by a veteran radiotherapist according to the International Commission on Radiation Units and Measurements (ICRU)-62 report [12] and literature report [13] based on the results of the esophageal barium swallow examination in the CMS treatment plan system (CMS TPS). The target areas were affirmed by three persons, including two radiotherapists and a radio-physicist. For this study, the Gross Tumor Volume (GTV) was defined by the fusion of Sim-CT and PET and clinical information. The Clinical Target Volume (CTV) was defined as 3 cm proximal and distal to the GTV and 0.5 cm lateral to the GTV. The Planned Treatment Volume (PTV) was defined as 1 cm proximal and distal to the CTV and 0.5 cm lateral to the CTV (Figure 1).

2.4.  Delineation of OARs

The delineation of the OARs included the whole lungs (right and left lung separately), heart, and spinal cord (extending 2 cm proximal and distal to the PTV).

2.5.  Design of Radiation Plans

Both IMRT (0^°/50^°/100^°/150^°/210^°/260^°/310^°, 6MV photons) and 3DCRT (0^°/30^°/130^°/210^°/330^°, 6MV photons) plans were designed by means of the CMS TPS. The prescription doses of PTVs were 60Gy (30 fractions at 2 Gy per fraction). The requirements of the affirmation plan were the isodose curve of PTV D95% ≥ 56 Gy, a maximum dose of ≤ 110%, and a minimum dose of ≥ 93%. V20Gy ≤ 30% for both lungs, V30 Gy ≤ 40% for the heart, and D1cc < 45 Gy for the spinal cord. The conformity index (CI, ≥ 0.70) and homogeneity index (HI, ≤ 1.20) were calculated in accordance with the literatures [14,15] (Figure 1).

2.6.  Evaluation Parameters

The evaluation parameters of the target areas included minimum, maximum, mean dose, D95%, D90%, D85% and D80% for GTV, CTV and PTV, while OARs included minimum, maximum, mean dose, V5Gy, V10Gy, V20Gy and V30Gy for both lungs; V20Gy, V30Gy, V40Gy and V50Gy for heart, and minimum, maximum, mean dose, D1cc and D5cc for the spinal cord.

2.7.  Statistical Analysis

SPSS 17.0 statistical analysis software was used for the statistical analysis. A paired t-test was used to count data in accordance with Gaussian distribution, or else by rank sum test. A significance of p< 0.05 was used.

3.       Results

3.1.  Dosimetry of Target Areas

The CI and HI of the target areas were slightly different between 3DCRT and IMRT (0.76±0.03 and 0.78±0.01, 1.24±0.02 and 1.18±0.01 respectively), but there were not significant differences (P>0.05). The doses of target areas using IMRT were generally higher compared to the doses using 3DCRT, but only the doses of GTV had differences (P<0.05) (Table 2).

3.2.  Dosimetry of OARs

For the lungs, in addition to minimum and mean doses, the other doses using IMRT were lower compared to the doses using 3DCRT, there were significant differences for the V5Gy, V10Gy and V20Gy of right lung and V5Gy and V10Gy of left lung(P<0.05); the others had no significant differences (P>0.05) (Table 3).

The minimum and mean doses of the spinal cord using IMRT were higher compared to the doses using 3DCRT, but there were no significant differences (P>0.05). However, the other doses using IMRT were lower compared to the doses using 3DCRT, there were significant differences (P<0.05). (Table 4). For the heart, in addition to maximum doses, the other doses using IMRT were higher compared to the doses using 3DCRT; but there were no significant differences (P>0.05) (Table 4).

4.       Discussion

Dysphagia induced by EC has many different treatments, such as alcohol injection, argon plasma coagulation, YAG laser, radiotherapy, chemotherapy, surgery, stent and so on [8], but t radiotherapy and stent are the most effective and most commonly used methods. Radiotherapy has a longer time lag to efficacy and needs patient good fitness. Disadvantage of stent is tumor ingrowth and pain. Effective combination of both may be the best way to relieve dysphagia. Median overall survival is significantly higher, and mean dysphagia-free survival time is longer with the combination of stenting and radiotherapy compared to stenting alone (118.6±55.8 vs. 96.8±43.0 days) [14].

Esophageal stent is widely applied in EC patients with grade III/IV dysphagia [15]. The dose of radiotherapy is a very important factor, which relates to the effective control rate of carcinoma. According to the literatures, the total radiation dose of chemoradiotherapy is usually in the range of 54-70 Gy, and the incidence of radiation pneumonitis increases when the total dose exceeds 60 Gy; therefore, the common radiation dose is in the range of 54-60 Gy, as a total dose of 60 Gy is feasible and safe and does not increase overall toxicity and side effects [16-18]. To compare the dose distributions of the target areas and OARs with different radiation plans, PTV is often the main factor for dose calculation [19]. In our study, the radiation target areas had GTV, CTV and PTV in the two plans consisting with the literatures [20,21].

In our study, CI and HI were very similar between the two groups with no significant differences (P>0.05), which indicated that the dose distributions of the target areas had high uniformity using 3DCRT and IMRT. The doses of target areas using IMRT were generally higher compared to the doses using 3DCRT, but there were differences only for GTV (P<0.05), the other doses were no difference between 3DCRT and IMRT (P>0.05). The results of our study indicated that IMRT had the benefit to increase the doses of target areas compared to 3DCRT.

OARs are a major consideration when performing radiotherapy for the treatment of cancer. The lungs are one of critical OARs in radiotherapy for EC, as impaired lung function impacts patient QOL and hinders completion of the radiotherapy plan [17,22]. Doses of >V20Gy and [23-25]. Fakhrian K et al compared the exposure dose of the lungs for five different radiation techniques (3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB) with a radiotherapy plan based on 3DCRT in patients with locally advanced EC. The results showed that the mean lung doses were 13 Gy, 15 Gy, 12 Gy, 12 Gy and 13 Gy, V5 Gy doses were 71%, 74%, 79%, 75% and 73%, and V20 Gy doses were 20%, 25%, 16%, 18% and 19% for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB, respectively [21]. When V20Gy ≥ 31%, the incidence of radiation pneumonitis was 85% [23]. In our study, for the left and right lungs, the mean doses were 13.69±2.14 Gy and 18.66±1.36 Gy, the V5 Gy doses were 89.18±5.21% and 56.52±6.65 %, and the V20Gy were 43.52±4.57% and 29.24±4.26% using 3DCRT and IMRT respectively. The results of our study indicated that IMRT had the benefit to decrease the doses of lungs compared to 3DCRT.

The spinal cord is another important OAR and is extensively considered in the planning of radiotherapy; the spinal cord exposure dose must be severely restricted to prevent severe radiation myelopathy [26,27]. The spinal cord dose is <45 Gy [28]. In our study, the spinal cord doses using IMRT were lower compared to the doses using 3DCRT, the D1cc and maximum dose were <45 Gy using IMRT, while > 45 Gy using 3DCRT, there were differences (P<0.05). The results of our study indicated that IMRT had the benefit to decrease the spinal cord doses compared to 3DCRT.

Radiation induced cardiac disease is a complication of radiotherapy and has a higher incidence when the heart receives a high exposed dose, and it is the main cause of morbidity and mortality for radiotherapy of cancer [29,30]. Evaluation of the heart exposure dose, mean dose and volume percentage receiving a high dose level are important indicators [31]. In our study, the doses of heart using IMRT were higher compared to the doses using 3DCRT, but there were no differences (P>0.05). Mean dose, V30Gy, V40Gy and V50Gy of the heart were less than 30%. The results of our study indicated that the risk of radiation-induced heart disease had no differences between IMRT and 3DCRT.

5.       Conclusion

The results of our study indicated IMRT had the following dosimetry advantages compared to 3DCRT for locally advanced EC inserted metal stent:

·         Target areas had higher doses, especially GTV, which were benefit to increase the local control rate.

·         OARs had lower doses, which were benefit to protect preferably OARs. We suggested that IMRT would be the best option for locally advanced EC inserted metal stent, but the true results need to be further investigated.

Figure 1: Delineation of target areas (transection, coronal and anteroposterior axes. Red (GTV). Sky-blue (CTV). Purple (PTV)) (A). The isodose curve distributions using 3DCRT(B) and IMRT(C).

Table 1: Patient Characteristics.

Table 2: Comparison of dosiology features for target areas between 3DCRT and IMRT (n = 5, Gy.±s).

Table 3: Comparison of lungs doses between 3DCRT and IMRT (n =5.±s).

Table 4: Comparison of spinal cord and heart doses between 3DCRT and IMRT (n =5. ± s).

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