CTVp is defined as the GTVp with 2–4 cm expansion proximally and distally along the length of the esophagus. The intent is to extend the margin along the length of the esophagus to provide a margin for coverage of submucosal extension of the tumor. One pathological analysis of 34 surgical specimens of ESCC showed the mean microscopic spread beyond the gross tumor was 10.5 ± 13.5 mm proximally and 10.6 ± 8.1 mm distally, and placement of a 3 cm margin proximally and distally on the primary tumor would cover microscopic disease extension in 94 % of cases [11].

CTVn is defined as the GTVn with 0–0.5 cm margin in all directions.

The regional lymph nodes are defined as CTV subclinical (CTVs) for each primary site in the treatment of elective nodal irradiation. Several pathological analyses of surgical specimens of ESCC reported that the rate of positive lymph nodes per number of cases was 47–70 % and patterns of involved nodal spread were different from each primary site [12–14] (Fig. 13.2). Retrospective analysis from Japan showed that elective nodal irradiation was effective for regional lymph node failure [15]. Guidelines 2012 for the treatment of esophageal cancer in Japan shows the inclusion of regional lymph nodes in CTVs for each primary site (Table 13.1) (Fig. 13.3a–d). Typically, the regional lymph nodes include bilateral supraclavicular fossae, superior mediastinal, and subcarinal lymph nodes for carcinoma of the cervical esophagus and upper thoracic esophagus (Fig. 13.4a). Mid-jugular lymph nodes are also included for carcinoma of the cervical esophagus. And the regional lymph nodes include superior mediastinal, subcarinal, middle mediastinal, lower mediastinal, and perigastric lymph nodes for carcinoma of the middle or lower thoracic esophagus (Fig. 13.4b). Celiac axis lymph nodes are also included for carcinoma of the lower thoracic esophagus. There is no consensus about inclusion of regional lymph nodes in CTVs for carcinoma of the middle thoracic esophagus.

PTV is defined as CTV with 1–2 cm margin in craniocaudal direction and 0.5–1 cm margin in the lateral direction to account for respiratory organ motion and daily setup error. Report of evaluating the respiratory motion of distal esophageal tumor using 4D-CT showed that a radical margin of 0.8 cm and axial margin of ±1.8 cm would provide tumor motion coverage for 95 % of the cases [16].

In the treatment of target to the primary tumor and involved lymph nodes only, beam arrangement in 3D-CRT uses a multi-field technique such as a three- to six-field arrangement (Fig. 13.1b). By contrast in the treatment including the elective nodal irradiation, anteroposterior (AP)/posteroanterior (PA) fields are used up to 40–45 Gy followed by off-cord boost fields. For cervical esophageal tumor, right anterior oblique (RAO) and left anterior oblique (LAO) with wedged pairs are usually used as off-cord boost fields. For upper, middle, and lower esophageal tumor, RAO and left posterior oblique (LPO) are usually used as off-cord boost fields. At the beginning of initial treatment for a middle or lower thoracic esophagus tumor, a multi-field technique such as a four-field arrangement (AP/PA/RAO/LPO) is recommended considering the cardiac toxicity (Fig. 13.5). However, it is necessary to minimize the volume of irradiated lung (beam weight; AP/PA ≫ obliques) as to the lung toxicity. In the case of existence of hot spot such as >110 % of the prescribed radiation dose, field-in-field technique is considered to improve the conformity of the dose distribution. More recently, intensity-modulated radiotherapy (IMRT) has been considered, particularly cervical lesions. IMRT can further improve the conformity of the dose distribution by sparing the adjacent normal strictures such as spinal cord to help meet dose constraints (Fig. 13.6). Diametric comparisons of IMRT versus 3D conformal therapy in cervical esophageal cancer have demonstrated superior target volume coverage and conformality with decreased normal-tissue dose [17]. A potential disadvantage of IMRT is the possibility of delivering low doses of radiation therapy to normal-tissue areas. The influence of this on toxicity (low-dose pulmonary irradiation and development of lung toxicity) remains uncertain.

Conventional daily dosing at 1.8–2.0 Gy fraction is standard. In the treatment of radiotherapy alone, 60–70 Gy at 1.8–2 Gy per fraction is standard radiation dose. In the treatment of chemoradiotherapy, based on the result of a randomized trial intergroup (INT) 0123 demonstrated that no significant difference in overall survival and local/regional control between the 50.4 Gy arm and the 64.8 Gy arm among patients (85 % SCC) treated with concurrent 5-FU and cisplatin chemotherapy for nonsurgical therapy [18], standard dose of radiotherapy for esophageal cancer is usually 50–50.4 Gy at 1.8–2 Gy per fraction in the definitive setting. In addition pattern care of study reported that median total dose of external radiotherapy was 60 Gy for definitive chemoradiotherapy patients in Japan [19]. In the neoadjuvant setting, 40–50.4 Gy at 1.8–2 Gy per fraction is the standard radiation dose.

In radiotherapy treatment planning of esophageal cancer, normal-tissue tolerance should always be considered. Accurate delineation of adjacent organs, including the lungs, spinal cord, heart, kidneys, and liver, is important. And it is necessary to evaluate the dose-volume histogram (DVH) analyses for each organ (Fig. 13.7). Max dose of the spinal cord is generally limited to 45 Gy using 1.8 Gy fractions. Several studies have demonstrated that dosimetric parameters derived from DVH are associated with organ toxicity after treatment of esophageal cancer [20–26]. In the treatment of esophageal cancer using neoadjuvant regimen of 45 Gy with concurrent chemoradiotherapy, a lung V10 (a percentage of lung volume receiving at least 10 Gy) of 40 % or greater, and a V15 of 30 % or greater, was shown to be predictive of significantly greater pulmonary complications (pneumonia and acute respiratory distress syndrome [ARDS]) [20]. Investigators from United States reported that the volume of the lung spared from doses of 5 Gy or higher (VS5) was the factor most strongly associated with postoperative pulmonary complications (pneumonia and ARDS) for esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery [21]. In the treatment of esophageal cancer using definitive regimen of 60 Gy with concurrent chemoradiotherapy, investigators from Japan reported that the optimal V20 threshold to predict symptomatic radiation pneumonitis (grade 2) was 30.5 % [22]. Konski and colleagues proposed thresholds for symptomatic cardiac toxicities (pericardial effusion, myocardial infarction, and sick sinus syndrome) for whole-heart V20 of 70 %, V30 of 65 %, and V40 of 60 % [23]. Wei and colleagues performed an analysis of pericardial effusion risk from DVH parameters among patients treated with definitive chemoradiotherapy [24]. Their data showed that the risk of pericardial effusion increased significantly with a mean pericardial dose of 26.1 Gy (p = 0.002) and pericardium V30 greater than 46 % (p = 0.001). Fukada and colleagues reported that mean pericardial doses of 36.5 Gy and V45 of 58 % were selected as optimal cutoff values for predicting symptomatic pericardial effusion [25]. For lower esophageal cancers, it is recommended that mean liver dose should be limited to less than 28 Gy, and mean dose of bilateral whole kidneys should be limited to less than 15–18 Gy [27].

Brachytherapy permits treatment of a localized area of the esophagus to high radiation doses with relative sparing of surrounding structures. This technique may be used alone or in combination with external beam radiotherapy with or without chemotherapy. The indication of brachytherapy is the treatment of superficial esophageal cancer for curative intent in Japan (local control rate: 79–85 %) [28–34]; on the other hand, it is used to relieve symptom such as dysphagia for palliative intent in the treatment of advanced esophageal cancer in Western countries [35, 36]. Brachytherapy involves intraluminal placement of a radioactive source into the esophagus with an intraorally or intranasally inserted applicator. Brachytherapy can be administered by two general methods: low-dose rate (LDR) brachytherapy and high-dose rate (HDR) brachytherapy. Modern HDR brachytherapy equipment delivers radiation much faster than 12 Gy/h, permitting the delivery of a planned dose within minutes compared with LDR sources, which require many hours or days. As a general rule of HDR brachytherapy, the diameter of the balloon applicator should be 15–20 mm. The whole length of tumor and 2 cm above and below the lesion are included in the target volume. The reference dose point is set at a depth of 5 mm of the esophageal submucosa (5 mm beyond the wall of the balloon surface). There is no definite consensus about the optimal dose of intraluminal brachytherapy for esophageal cancer. In Japan, 50–60 Gy external beam radiotherapy followed by 8–12 Gy in 2–4 fractions (3–4 Gy per fraction) HDR brachytherapy is generally used. It was reported that higher dose per fraction is associated with the risk of esophageal ulcer and perforation [29]. Dose of 4 Gy or less per fraction by HDR brachytherapy and dose of 6 Gy or less per fraction by LDR brachytherapy once or twice a week is recommended in Japan [32]. The American brachytherapy society (ABS) recommends an HDR dose of 10 Gy in two fractions, prescribed at 1 cm from the source, to boost 50 Gy EBRT [37]. Figure 13.8 illustrates the dose distribution and 3D view in the treatment planning of HDR brachytherapy.