To Explore the Dose Distribution of Semi-field Radiotherapy Options in Radiotherapy of Upper & Middle Esophageal Cancer

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1 Med One To Explore the Dose Distribution of Semi-field Radiotherapy Options in Radiotherapy of Upper & Middle Esophageal Cancer Biao Zeng 1 2, Jiutang Zhang 1 2, Jianhui Liu 3, Hui Wang 1 2*, Qianxi Ni Department of Radiation Oncology, Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya Medicine, Central South University, Changsha , Hunan, P.R. China; 2 Key Laboratory of Translational Radiation Oncology, Changsha , Hunan, P.R. China; 3 Department of Information, Hunan Hospital of Armed Police Forces, Changsha , Hunan, P.R. China First Author: Biao Zeng, radiotherapy physicist of Hunan Cancer Hospital; Research Interests: radiotherapy physics and radiotherapy technology. zengbiao008@163. com; * Correspondence: Hui Wang, doctoral supervisor in Thoracic Radiotherapy Department I of Hunan Cancer Hospital. wanghui710327@163.com. ABSTRACT DOI: /mo Received: May 8, 2016 Accepted: July 3, 2016 Published: Copyright: 2016 Cain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective: To explore an adequate treatment method and provide a better irradiation mode for the radiotherapy of upper & mid esophageal carcinoma through the comparison of the dose distributions in six different semi-field radiotherapy options. Methods: Twenty patients with upper & mid esophagus carcinoma were selected for six treatment options: Option A for the conventional 5-field three-dimensional conformal radiation therapy (3D-CRT), Option B for conventional 5-field intensity modulated radiation therapy (IMRT), Option C for conventional 3-field IMRT. Semi-field irradiation is also divided into three types, Option D for 5-field IMRT in the upper target and 3-field conformal radiation therapy in the lower target area, Option E for 5-field IMRT in the upper target and 3-field IMRT in the lower target area, and Option F for 5-field IMRT in the upper target and 5-field IMRT in the lower target area. Dose distribution of the target area and dose distribution in normal tissue were compared in the six options. Results: The target coverage in the three programs with the semi-field technique was effective via the comparison of six options, of which, the lowdose area of lung and the mean lung dose (MLD) were lower in Options D and E. The conformal index in Option E is higher than that in Option D. Conclusion: It may be concluded that options D and E are two relatively advantageous options because they allow effectively to deliver the prescribed dose to the target volumes, while minimize the exposure of lung tissues to low doses. Key Words: dose; IMRT; semi-field; esophageal cancer MED ONE 2016,1(4);1 mo@qingres.com 1

2 INTRODUCTION The radiotherapy target of upper & middle esophageal carcinoma spans the thoracic inlet. Due to its anatomical characteristics, the target depth varied significantly, resulting in an uneven target dose distribution in the radiotherapy and an excessive exposure dose in normal tissues, especially the lungs. It is difficult for threedimension -conformal radiotherapy (3D-CRT) to avoid the vital organs of the patients while improving the target dose, such as, spinal cord, lung tissues, etc. Highly conformal radiotherapy techniques can improve the target dose, but they can cause excessive irradiation of pulmonary tissues of the patients with low doses. Therefore, to decrease the exposed area of lung to low dose has become one of the primary considerations for the physicists to develop the radiotherapy plan. This study attempted to decrease the exposed area of lung tissues to low dose and reduce the incidence of radiation pneumonitis by using the semi-field IMRT technique, a new technique for the treatment of esophageal cancer that has never been described in the literature, namely semi-field intensity-modulated mode for upper half segment, and 3-field 3D-CRT or semi-field intensitymodulated mode for lower half segment. The aim is to lay a theoretical foundation for the application of monoisocenter upper and lower semi-field technique via the dose comparison of different radiotherapy planning techniques. MATERIALS AND METHODS 1. Clinical Data Twenty patients with upper and mid esophagus cancer were selected, including 15 male and 5 female patients, aged years old, with a mean age of 45 years old. Selection criteria: the target ranged in esophagus tumor and lymphatic drainage area of thoracic upper and middle segments [2]. 2. Methods 2.1 Delineation of Targets Gross tumor volume (GTV) on computed tomography (CT) planning is defined as the tumor extension (GTVt) and lymphadenopathies (GTVnd) that can be seen via the diagnosis and staging imagiology and endoscopy. Clinical target volume (CTV) includes GTVt and GTVnd plus the lymphatic drainage area of subclinical risk, planning a margin of 1 cm around the GTVt and GTVnd, and 4 cm at vertical direction of GTVt or 2 cm at CT level with a lymphatic metastasis (GTVnd), and meanwhile, it includes the lymphatic drainage area with a higher lymphatic metastasis rate. The CTV was edited to exclude structures such as vertebrae, without subclinical risk. Posteriorly, it was defined the planning target volume (PTV) by adding a margin of 0.5 cm to CTV. 2.2 Treatment Planing CT scanning was performed to both chest and neck by the immobilization in CT simulator. The CT scanning images were transmitted via the local area network for the physicians to outline the tumor target areas. XiO (Elekta Ltd.) treatment planning system, Varian 600CD linear accelerator (Varian Medical Systems, Inc. ) and 6 MV X rays were used. Six treatment options were developed for each patient, three conventional total-field versus three semi-field plans. The conventional total-field options were: Option A for the conventional 5-field 3D-CRT, Option B for conventional 5-field intensity modulated radiation therapy (IMRT), and Option C for conventional 3-field IMRT. The mono-isocenter semi-field plan options were: Option D for 5 semi-field IMRT in the upper target and 3 semi-field 3D-CRT in the lower target area, Option E for 5 semi-field IMRT in the upper target and 3 semifield IMRT in the lower target area, and Option F for 5 semi-field IMRT in both the upper and lower target areas. The conformal plans used the coplanar design, and the IMRT plans used the step and shoot delivery. All the 5- and 3-field IMRT plans employed the equivalent split field technique. The prescription dose to PTV was 60 Gy in 30 fractions. The PTV was required to reach 100 % of 60 Gy, and this prescription dose should cover 95 % of the PTV, with a maximum dose of 110 %. The prescription dose greater than 110 % could not exist in any place out of the target area, there was no cold spot in the PTV and there was no hot spot in the esophagus wall included in the PTV. The maximum dose to spinal cord was less than 42 Gy, lung s V20 (lung volume receiving 20 Gy) was less than 28 %, and their doses were all calculated using the superposition/convolution algorithm. 3. Program Evaluation The dose volume histograms were used to count the dose to organs at risk and the dose indicators of PTV: D90 (dose delivered to 90% of the PTV), D95, D100, maximum dose, V100 (percent of the PTV receiving 100% of the prescribed dose), V110, homogeneity index (HI), and conformity index (CI). CI[2]=, where V100(Target) is the PTV covered by the isodose of 100%, the V100(Body) is the body volume covered by the isodose of 100%, and the V(Target) is the PTV. HI was defined by D2/D98. A greater HI value indicates a poorer homogeneity. The closer to 1 is the CI value, the better the conformation of the plan will be. A CI greater than 1 indicates that the irradiated volume (IV) is greater than the target volume (PTV) and includes healthy tissues. If the CI is less than 1, the target volume is only partially irradiated. After trying to meet the dose constraints to the organs at risk, the lung volumes V5, V10, V20, and V30, and the mean lung dose (MLD) were compared among the six planes of treatment. 4. Data Analysis The one-way analysis of variance was performed to compare the mean values of the six options using the International Business Machines Corporation software SPSS (Statistical Package for the Social Sciences) If P < 0.05, it would be of a statistical significance. MED ONE 2016,1(4);1 mo@qingres.com 2

3 RESULTS 1. Comparison of Various PTV Parameters Comparison of Various PTV Parameters The data analysis shows that D100, D95 and D90 in conventional conformal Option A were all lower than that of the other five options, and the coverage of target area was poorer, while there was no difference among the other five options. The HI studies showed that the homogeneity of the conventional 5- (Option B) and 3-field IMRT (Option C) options was better than that of the conventional 3D-CRT option (Option A) and the three single-isocenter upper/mid semi-field radiotherapy options (Options D, E, and F). The studies of CI showed that the Options B, E and F, respectively, conventional 5-field IMRT, mono-isocenter upper 5 semi-field and lower 3 semi-field IMRT, and 5 semi-field IMRT in both the upper and lower target area, had better conformation than that of the other three options. The IV studies of the six options showed that the IV of patients with more than 3000 cm 3 in Option C conventional 3-field IMRT option was the highest. The detailed data are shown in Table 1. Table 1 Comparison of PTV Parameters among Six Different Treatment Options Treatment Option D100 (cgy) D95 (cgy) D90 (cgy) CI HI IV (cm3) Option A 5440± ± ± ± ± ±290 Option B 5590± ± ± ± ± ±280 Option C 5562± ± ± ± ± ±260 Option D 5566± ± ± ± ± ±292 Option E 5514± ± ± ± ± ±260 Option F 5522± ± ± ± ± ±289 F Value P Value Notes: CI: conformity index; Dx: dose delivered to x% of the PTV; F Value: variance of the group of means; HI: homogeneity index; IV: irradiated volume; PTV: planning target volume; P Value: calculated probability to determine the statistical significance in the hypothesis test. 2. Comparison of Radiation Dose of Lung Tissues In Options A, B, and F, respective ly, 5-field 3D-CRT, 5-field IMRT, and upper/lower mono-isocenter 5 semifield IMRT options, the volume of low-dose area received by lung tissues was large, while V20 and V30 did not increase with the increase of the number of fields. There was no statistical difference between the options. The detailed data are given in Table 2. The coronal dose distribution of Options D, F, and C receiving 500 cgy is shown in Fig. 1. Table 2 Comparison of Radiation Dose of Lung Tissues among Six Different Treatment Options Treatment Option V30 (%) V20 (%) V10 (%) V5 (%) MLD(Gy) Option A 11.2± ± ± ± ±2.1 Option B 12.8± ± ± ± ±2.1 Option C 18.1± ± ± ± ±2.1 Option D 13.3± ± ± ± ±2.1 Option E 13.8± ± ± ± ±2.0 Option F 13.2± ± ± ± ±2.1 F Value P Value Notes: F Value: variance of the group of means; MLD: mean lung dose; PTV: planning target volume; P Value: calculated probability to determine the statistical significance in the hypothesis test; Vx: lung volume receiving x Gy. MED ONE 2016,1(4);1 mo@qingres.com 3

4 Fig. 1 Coronal Dose Distribution of Options D, F and C in Lung Received 500cGy 3. Comparison of Segment Number and Treatment Monitor Unit (Mu) in Six Treatment Options The number of segments and the treatment MU of Options E and F were significantly greater than that of the other options, while the number of segments was little and its MU was the shortest. The number of segments of Option C was less than that of Options B, D, E, and F. However, there was no statistical difference between Option C and Options B and D regarding the MU. DISCUSSION The radiotherapy of upper and middle thoracic esophageal carcinoma aims to maximally increase the dose of the target area to kill the tumor cells so as to ensure less or no necessary radiation dose for the surrounding normal tissues or organs [3]. Many doctors and medical physicists have done various dosimetry comparisons. The studies showed that, compared to the conventional radiotherapy option, the 3D-CRT technique has the advantages of increasing the dose of target areas and protecting the spinal cord and lung tissues. The IMRT technique could provide more conformal and more even dose distribution to the tumor target areas and the V20 of lung was also significantly better (lower) than with the 3D-CRT, while the V5 of lung (a low-dose area) was higher than with 3D-CRT [4]. Chen et al [5] compared and researched the intensity modulated arc therapy (IMAT) and IMRT in the esophageal carcinoma and concluded that the IMAT could reach the dosimetry requirements similar to IMRT, but it had no advantage in the protection of lung tissues. For this reason, the application of mono-isocenter upper and lower semi-field radiotherapy in the upper and middle esophageal carcinoma was researched concerning the aspects of target area coverage, conformation, homogeneity, treatment time, and protection the normal tissues, especially the lung tissues, by using the monoisocenter 5 semi-field IMRT technique for the upper segment and the 3 semi-field 3D-CRT or the 3 or 5 semifield IMRT technique for lower segment of thoracic esophagus. The research results showed that the three treatment options using mono-isocenter upper & lower semifield radiotherapy got a good results in the coverage of target area, which could meet the clinical requirements. Its conformation was also good and the homogeneity is slightly poor, however, it could well protect the normal tissues, especially the lung tissues. Lung is an organ relatively sensitive to the radiation. The acute radiation pneumonitis and pulmonary fibrosis are the most common lung complications of radiotherapy of upper and middle thoracic esophageal carcinoma and they are important factors affecting the quality of life of these patients. The doses received by the lungs are also the main restrictive factors that affect the delivery of high doses to target area in radiotherapy. With the growth of incidence of esophageal carcinoma and the extensive development of the radiotherapy, increasing importance has been dedicated to the radio-pulmonary lesion. Graham et al [6] argued that the incidence and severity of radiation pneumonitis is closely associated with the radiation volume and dose of the lung tissues. Upon the multivariate analysis, MLD, V20 and V30 were the proven parameters closely related to the radiation-induced lung injury [6]. Furthermore, Wang et al [7] further pointed out that V5 might be the most valuable indicator to predict the radiation-induced lung injury. As V5 > 55%, the incidence of grade 2 or more radiation-induced lung injury might significantly increase [7]. Recent studies have also shown that the incidence of radiation pneumonitis increase with the increase of V10 [8]. The IMRT studies of lung showed that, the more the number of radiation fields was, the higher the V5 and V10 in lung would be [9]. In summary, Options D (5 semifield IMRT in the upper and 3 semi-field 3D-CRT in the lower target area) and E (5 semi-field IMRT in the upper and 3 semi-field IMRT in the lower target area) are the advantageous options and they are as effective as the other techniques to deliver the dose to target area and meanwhile minimize the exposure of the normal tissues to low doses, especially with better V5, V10, and V20 in the Option D, and a lower MLD in both Options D and E. However, the treatment time of Option D is much shorter than that of option E. In addition, according to the analysis of six treatment options, the homogeneity of Options D and E is poorer than that of other options. But, Junqi Wang, et al. believed that the dose homogeneity of target area in the radiotherapy was one of the major indices for the radiotherapists to evaluate various treatment options. However, as to the tumor of upper & middle esophageal carcinoma with a lower viability and poor prognosis, the main complication of radiotherapy radiation pneumonitis is the key issue that shall be firstly taken into consideration [10]. MED ONE 2016,1(4);1 mo@qingres.com 4

5 Acknowledgement The author thanks Jiutang Zhang, Hui Wang and Qianxi Ni (Department of Radiotherapy, Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya Medicine, Central South University, Changsha , Hunan, P.R. China) and Jianhui Liu (Department of Information, Hunan Hospital of Armed Police Forces, Changsha , Hunan, P.R. China) for the advises, assistance and technical support in sample collection and data acquisition. Financial Support This work was supported by a grant from Science & Technology Program of Hunan Provincial Science and Technology Department (program number: 2014SK3086) and National Key Clinical Specialty(Oncology Department)(National Health and Family Planning Commission of the P.R. China 2013/544). REFERENCES 1. Nianji Cui, Taixiang Lu, Xiaowu Deng. Practical and clinical radiation oncology. Guangzhou: Sun Yat-sen University Press Biao Zeng Xuwei Lu. The clinical application of intensity-modulated radiotherapy plan systemof oncentra masterplan. Medical Equipment, 2010, 23 (005): Hu Yimin Hu,Hongzhi Zhang, Jiangrong Dai. Tumor radiation physics. Beijing: Atomic Energy Press, Jing Xian, Ling Zhang, Xiaokai Li, et al. Comparison between IMRT and 3D-CRT in the Therapy of Midthoracic Esophageal Cancer. Journal of Military Surgeon in Southwest China, 2011, 4: Jinhu Chen, Yong Yin, et al. Application of IMAT versus fixed-gantry IMRT in cervical esophageal cancer: A comparison in dosimetry and implementation. Chinese Journal of Radiation Oncology. 2010, 12 (5): Graham M V, Purdy J A, Emami B, et al. Clinical dose volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). International Journal of Radiation Oncology Biology Physics, 1999, 45(2): Lan Wang, Chun Han, Xin Zhang, et al. The observation of three dimensional conformal radiotherapy curative effect. Chinese Journal of Clinical Oncology, 2008,35 (8): Schallenkamp JM, Miller RC, Brinkmann DH, et al. Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates. IntJ Radiat Onco BiolPhys, 2007,67(2): Available at: dx.doi.org/ /j.ijrobp Guo Xiaomao, MeiXin Zhu Guopei, et al. Comparison of conventional and conformal radiotherapy and different irradiation technique by 3D-TPS for esophageal carcinoma: a dosimetric study [J]. Chinese Oncology. 2005,15 (5): Junqi Wang, Long-gen Li, Zhiyong Xu, et al. Application of dose heterogeneity in the target volume in intensity-modulated radiation therapy of esophageal cancer. Chinese Journal of Radiological Medicine and Protection, 2011, 31 (4) : MED ONE 2016,1(4);1 mo@qingres.com 5