Guidelines for Radiotherapy of Esophageal Carcinoma (2020 Edition)
2021; Wiley; Volume: 5; Issue: 2 Linguagem: Inglês
10.1002/pro6.1119
ISSN2398-7324
Autores Tópico(s)Esophageal and GI Pathology
ResumoEsophageal carcinoma is a high-incidence malignant tumor in China, ranking sixth and fourth highest in morbidity and mortality, respectively. Radiotherapy plays an important role in the comprehensive treatment of esophageal carcinoma. Standardized diagnosis and treatment based on the suggestions of a multidisciplinary team (MDT) form its foundation. For operable esophageal carcinoma, surgery after neoadjuvant chemoradiotherapy is the standard treatment; contrarily, for inoperable esophageal carcinoma, radical chemoradiotherapy is the only treatment option, and postoperative adjuvant radiotherapy can improve local control and survival rates in selected cases. Owing to the rapid technological development in radiotherapy, three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and image guidance technology are widely used in the treatment of esophageal carcinoma. Though drugs for treating cancer have been developed rapidly, we need to explore their optimal combination with radiotherapy, including chemotherapy, targeted or immune, and radiosensitizers. Esophageal carcinoma in China differs greatly from that in European and American countries in terms of etiology, pathological type, high-incidence site, etc. Therefore, the European and American guidelines on radiotherapy for esophageal carcinoma cannot be applied in clinical practice in China. This gap was addressed when the 2019 edition of the Chinese Guidelines for Radiotherapy of Esophageal Carcinoma was formulated. In combination with suggestions for the clinical application and the latest research, the 2020 edition was launched with the hope of benefiting most patients with esophageal carcinoma. Early symptoms of esophageal carcinoma are indiscernible. There is often a sense of a foreign body in the esophagus. When swallowing hard food, there is a sense of stagnation, choking, posterior sternal burning, pinprick, or traction rubbing pain. These symptoms can be mild or severe. Typical symptoms include progressive dysphagia and the production of mucoid sputum. Persistent chest pain or back pain often suggests that the tumor has invaded the extraesophageal tissue. Invasion of the tumor into the recurrent laryngeal nerve may cause hoarseness and choking on drinking water. The compression of the cervical sympathetic ganglion may lead to Horner syndrome. Similarly, its invasion into the trachea and bronchus may cause the formation of esophagotracheal or esophagobronchial fistula, respectively; this may result in severe choking during swallowing, respiratory infection, formation of esophagomediastinal fistula, or fever. If distant metastasis occurs, then the affected organs may exhibit symptoms. Most patients with esophageal carcinoma display no obvious positive signs on physical examination. Special attention should be paid to the signs of distant metastasis, such as enlarged lymph nodes in the neck or supraclavicular region, liver masses, pleural effusion, and peritoneal effusion. including blood routine, liver function and kidney function, viral serology, electrolyte, blood glucose, coagulation function, urine routine, fecal routine, etc. including cytokeratin 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC), etc. High expression of EGFR is an independent risk factor for the poor prognosis of esophageal carcinoma; thus, the detection of tissue EGFR expression is recommended. Immunotherapy is used as the second-line and above treatment for advanced esophageal carcinoma and first-line combined chemotherapy or postoperative adjuvant therapy; eligible patients should be tested for programmed death protein ligand 1 (PD-L1) and its combined positive score (CPS), tumor mutation coincidence (TMB), microsatellite instability (MSI), and mismatch repair protein loss (dMMR). An important method for the diagnosis and evaluation of the curative effect on esophageal carcinoma, and low-tension double-contrast radiography is recommended. Patients who are scheduled to undergo radiotherapy should be checked for contraindications to radiotherapy, such as presence of deep ulcers. Chest and upper abdomen CT examination is needed before radiotherapy and during follow-up. A contrast-enhanced CT is also recommended. The scanning range can be increased according to the location (e.g., the supraclavicular area and neck) and range of lesions. Can effectively complement CT in the diagnosis and evaluation of the curative effect on esophageal carcinoma. The diagnostic value of lymph node metastasis is similar or superior to that of contrast-enhanced CT. Functional MRI techniques such as diffusion-weighted imaging are helpful in the evaluation of the curative effect and prognosis. Mainly used for diagnosing pleural effusion, metastasis to abdominal organs, and metastasis to abdominal and cervical lymph nodes. Not recommended as a routine primary screening method for the diagnosis of bone metastasis; a positive bone scan should be confirmed by X-ray, CT, MRI, or PET/CT. Recommended only if necessary or conditional but not as a routine screening method. Upper gastrointestinal endoscopy is an important method for the qualitative and localized diagnosis and treatment of esophageal carcinoma. Endoscopic biopsy is the gold standard for the diagnosis of esophageal carcinoma. Pigmented endoscopy and endoscopic ultrasonography can confirm the morphology and extent of lesions and assist in determining the clinical T and N stages. Endoscopic metal clips mark the upper and lower edges of early lesions, which can accurately assist in target localization for radiotherapy. Helps screen for arrhythmias and history of myocardial infarction. Helps screen for lung volume, lung ventilation, and diffusion function. When the aforementioned tests cannot determine the patient's cardiopulmonary capacity to tolerate radiotherapy, an exercise cardiopulmonary function test is recommended for further assessment. Recommended for patients with a previous history of heart disease to determine any structural changes and the functional status of the heart. Esophageal angiography reveals localized thickening of the esophageal mucosa, stiffness of the local wall, filling defect, or niche shadow. Chest CT, MRI, and PET/CT show thickening of the esophageal wall, or PET/CT displays high uptake of fluorodeoxyglucose (FDG). Upper gastrointestinal endoscopy reveals early lesions such as localized erosion of the mucosa, rough and small granular sensation, local mucosal congestion with unclear borders, small nodules, small ulcers, and small plaques. The middle- and late-stage lesions mainly exhibit nodular or cauliflower-like masses, mucosal congestion, edema, erosion or pale stiffness, easy bleeding when touched, ulcers, or varying degrees of stenosis. The clinical diagnosis of esophageal carcinoma requires further pathological examination. Esophageal carcinoma includes two main types—SCC and adenocarcinoma—along with other rare types. Early esophageal carcinoma: Protuberant, superficial, and depressed (ulcer) type. Advanced esophageal carcinoma: Medullary, umbrella, ulcerative, constrictive, and intraluminal type. The World Health Organization classification of esophageal carcinoma (2010 edition) was used (see Appendix 1). Verrucous carcinoma: Though this tumor is well differentiated and does not have the ability to metastasize, its occurrence in the esophagus is associated with a higher mortality rate. Spindle cell SCCs (sarcomatoid carcinomas and carcinosarcomas): Most of these show pleomorphic or spindle cell (sarcomatoid) manifestations, occasionally exhibiting focal cartilage, bone, or rhabdomyogenic differentiation. These sarcomatoid components are of epithelial origin and share the same clonal origin as that of cancer components. Basal cell-like SCC: Has a highly aggressive biological behavior, and its degree of malignancy is higher than that of common esophageal SCC. More common in the lower one-third of the esophagus and occasionally originates from the ectopic gastric mucosa or the glands distributed in the lamina propria mucosae in the middle and upper esophagus. Originates in the submucosal gland in the esophagus and is similar to the mucoepidermoid carcinoma of the oral cavity in morphological characteristics and biological behavior. Classification and diagnostic criteria are the same as those for gastrointestinal pancreatic neuroendocrine tumors. These include gastrointestinal stromal tumor, leiomyosarcoma, malignant melanoma, lymphoma, rhabdomyosarcoma, and synovial sarcoma. In their 8th edition of the 2017 TNM staging of esophageal and esophagogastric junction (EGJ) cancer, the American Joint Committee on Cancer (AJCC) and the International Union against Cancer (UICC) jointly defined the tumor location as the midpoint of the primary lesion. Bordered superiorly by the hypopharynx and inferiorly by the thoracic inlet, which lies at the level of the sternal notch. Its endoscopic tumor length measured from the incisors is 15–20 cm. Bordered superiorly by the thoracic inlet and inferiorly by the lower border of the azygos vein. Its endoscopic tumor length from the incisors is 20–25 cm. Spans from the lower edge of the azygos arch to the level of the inferior pulmonary vein. Its endoscopic tumor length from the incisors is 25–30 cm. Bordered superiorly by the lower border of the azygos vein and inferiorly by the inferior pulmonary veins. Its endoscopic tumor length from the incisors is 25–30 cm. Endoscopic EGJ is usually defined as the first appearance of gastric folds, a theoretical landmark. Histologically, EGJ can be accurately defined as the junction of the esophageal columnar epithelium and squamous epithelium. If the midpoint of the tumor is within 2 cm of the proximal stomach, whether it invades the lower esophagus or EGJ, the tumor is staged according to the classification for esophageal carcinoma. If the tumor is beyond 2 cm of the proximal stomach, then it is staged according to the classification for gastric cancer. The 8th edition (2017) of AJCC/UICC staging (see Appendix 2) was used, including clinical staging (cTNM), postoperative pathological staging (pTNM), and post-neoadjuvant treatment staging (ypTNM). Based on adequate assessment of patients and tumors, the principle of comprehensive treatment based on the suggestions of MDT is recommended for reasonable application of the existing treatment methods to maximize survival rates, reduce adverse reactions, and improve quality of life. For patients with pTis-T1aN0, endoscopic mucosal resection, endoscopic submucosal dissection (grade I recommendation), or combined radiofrequency ablation (grade II recommendation) is recommended. Resection of esophageal cancer is also feasible. Endoscopic resection combined with radiotherapy can aid in achieving a radical cure (grade II recommendation, class 2B evidence). Surgical resection is recommended for patients with a non-cervical segment of the pT1b-2N0 stage (grade I recommendation). Radical concurrent chemoradiotherapy is also feasible for stage I SCC. For patients with locally advanced stage and resectable esophageal cancer, surgery remains the cornerstone of treatment. For patients with cT1b-2N+ or cT3-4aN0/N+, the treatment principles of SCC and adenocarcinoma are different. For patients with adenocarcinoma, neoadjuvant chemoradiotherapy is recommended (class 1A evidence) neoadjuvant chemotherapy is also feasible; for patients with adenocarcinoma who refuse surgery or have surgical contraindications, radical concurrent chemoradiotherapy (grade II recommendation) is recommended. For patients with SCC, neoadjuvant chemoradiotherapy is recommended (class 1A evidence), whereas radical concurrent chemoradiotherapy is recommended for tumors in the cervical segment and for patients who refuse surgery (class 1A evidence). The operative timing was 6–8 weeks after neoadjuvant chemoradiotherapy or 3–6 weeks after neoadjuvant chemotherapy. For patients with locally advanced stages such as cT4bN0/N+, radical concurrent chemoradiotherapy (grade I recommendation, class 1A evidence) is recommended if the performance status (PS) score is 0–1. Radiotherapy should be carefully selected for patients with esophageal perforation or a tendency for massive hemorrhage. Radiotherapy alone is recommended for patients who cannot tolerate concurrent chemoradiotherapy. Patients with a PS score of 2 are recommended the best supportive care or symptomatic treatment (grade I recommendation), chemotherapy alone, or palliative radiotherapy (class 2B evidence). Regardless of whether patients with SCC received neoadjuvant chemoradiotherapy, postoperative adjuvant therapy for patients with R0 resection is controversial, and regular monitoring is required. Adjuvant radiotherapy or chemoradiotherapy may be considered for high-risk postoperative patients who have not received neoadjuvant therapy (lymph node positivity and/or stage pT3-4aN0). For patients with adenocarcinoma who have received neoadjuvant chemoradiotherapy, postoperative observation or postoperative chemotherapy is recommended. For patients without neoadjuvant therapy and with negative lymph nodes, regular monitoring can be considered; however, fluorouracil-based chemoradiotherapy is feasible for high-risk pT2 (poorly differentiated, intravascular cancer emboli, nerve invasion, age <50 years) and pT3-4a stages. For lymph node-positive patients, fluorouracil-based postoperative chemotherapy (class 1A evidence) or chemoradiotherapy (class 2B evidence) is recommended. Patients who have received R1/R2 resection but not neoadjuvant chemoradiotherapy are recommended to undergo adjuvant concurrent chemoradiotherapy (class 1A evidence), sequential chemoradiotherapy (for those who cannot tolerate concurrent chemoradiotherapy, grade II recommendation, class 2B evidence), or adjuvant chemotherapy (grade III recommendation, class 3 evidence). SCC patients who received neoadjuvant chemoradiotherapy are recommended to undergo chemotherapy, optimal supportive treatment/symptomatic management, or observation (class 2B evidence). Patients with adenocarcinoma are recommended for reoperation or observation (class 2B evidence). Chemotherapy-based combination therapy is recommended for small cell carcinomas (class 2B evidence). Radical surgery is recommended as the primary treatment for sarcomatoid carcinoma (class 2B evidence). Surgical resection is preferred for malignant melanomas (class 2B evidence). Accurate staging and evaluation of each tumor determine the treatment choice for multiple primary cancers. For patients with local recurrence and metastasis after radiotherapy, salvage surgery or secondary chemoradiotherapy can be considered after comprehensive assessment. Radical resection of esophageal carcinoma is suitable for patients with stage I, stage II, and partial stage III (except for the cervical segment). Patients with locally advanced disease stages are recommended to undergo neoadjuvant therapy. Salvage surgery for esophageal cancer is suitable for patients with local recurrence after radiotherapy, no distant metastasis, resectable tumors after assessment, and for those who can tolerate surgery in general. Primarily suitable for patients with stage cT1b-2N+ or cT3–4aN0/N+. Neoadjuvant chemoradiotherapy is grade I recommendation for patients with adenocarcinoma and non-cervical esophageal SCC. Patients with cT1b-2N+ or cT3-4aN0/N+ cervical esophageal SCC or those with non-cervical esophageal carcinoma who refused surgery. Patients with cT4bN0/N+. Patients with thoracic esophageal carcinoma with supraclavicular or retroperitoneal lymph node metastasis only. Patients who cannot tolerate surgery after preoperative chemoradiotherapy or radiotherapy evaluation. Patients with contraindications or at high risk of operation owing to old age and severe cardiopulmonary disease. Patients who underwent R1 or R2 resection and did not receive preoperative chemoradiotherapy. Patients with adenocarcinoma who did not receive preoperative chemoradiotherapy and had N+ or high-risk pT2 N0 and pT3–4a N0 after R0 resection. Patients with SCC who did not receive preoperative chemoradiotherapy and had N+ or pT3–4a N0 after R0 resection. After chemotherapy, the metastatic foci of patients with advanced disease are reduced or stable, and radiotherapy for primary lesions should be considered. Patients with extensive multistation lymph node metastasis who cannot receive radical radiotherapy. Patients with clinical symptoms caused by distant metastasis. To alleviate obstruction and improve the nutritional status of advanced stage patients. Patients with partially uncontrolled regional recurrence after radical treatment. Poor general condition or cachexia. Poor cardiopulmonary function or severe complications with diseases of vital organs and systems, making it difficult to tolerate radiotherapy. Massive esophageal bleeding or signs of massive hemorrhage. Esophageal fistula complicated by severe infection Conformal, intensity-modulated, and spiral tomographic intensity-modulated techniques can be employed for esophageal cancer radiotherapy. Generally, 6–8-MV X-rays are used for conformal radiotherapy, with four to five shooting fields. Anterior and posterior fields were mainly used to reduce radiation exposure to the lungs, while the lateral field avoids exposure to the spinal cord. X-ray at a dose of 6 MV is recommended for intensity adjustment of the fixed field. Generally, five to seven fields should be set up, and both shoulders should be avoided as far as possible. In general, X-ray at a dose of 6 MV and 2-arc isocentric coplanar irradiation are used in the spiral tomographic intensity-modulated technique. To reduce the radiation dose, especially the low-dose radiation volume for the lungs, two incomplete arcs can be considered, that is, transverse penetration of the lung tissue should be avoided. The spiral tomographic intensity-modulated technique can set the shielding angle at the target level to avoid transverse radiation from both sides of the lungs. Pre-radiotherapy image guidance for esophageal cancer includes two- and three-dimensional online images. The online images should be collected before the first three to five treatments and then once a week. As bed subsidence will be introduced again after the setup of spiral tomography, it is suggested to improve the frequency of image guidance and conduct megavoltage CT (MVCT) scanning at different layers for the middle and lower segments during esophageal cancer radiotherapy. This will reduce the additional radiation dose received by a certain segment of the anatomical structure. CT simulation location of esophageal cancer: The patient can be placed in the supine position on the fixed frame of the CT scanning bed, and the cervical and upper thoracic esophageal cancer can be fixed using a head-neck-and-shoulder integrated thermoplastic mask, with the arms parallel to the sides of the body. The middle and lower thoracic esophageal cancers can be fixed with a vacuum negative-pressure bag, with both hands holding the elbows in front of the forehead, legs close together, and the whole body relaxed. The scanning condition can be set as axial scanning with a layer thickness of 3 mm, and the scanning range can be set according to the lesion location and range. To manage respiratory movement, CT can be combined with technologies such as active respiratory control, four-dimensional CT, and respiratory gating. The markers of cervical and upper thoracic esophageal cancer can be placed at the mandibular level, and for middle and lower thoracic esophageal cancers they can be placed on the flat chest surface. The cross-marker line of the front part of the pelvic cavity can be added to correct the left–right deviation of the trunk when set up before treatment. MRI simulation location of esophageal cancer: Ensuring the safety of the device and patient, the location of MRI simulation should avoid contact between the coil and the body, consistently retaining body position, mark, and scanning layer thickness during the CT location process. The position verification after the first course of radiotherapy is generally approximately 40 Gy. (1) Radical radiotherapy Gross tumor volume (GTV): This includes primary tumors (GTVp) and metastatic lymph nodes (GTVn). GTVp is a visible esophageal lesion that can be determined using a combination of imaging techniques (e.g., esophagography, contrast-enhanced CT, MRI, and/or PET/CT) and endoscopy (e.g., electronic upper gastrointestinal endoscopy and/or intravascular ultrasound). GTVn refers to metastatic lymph nodes with a diameter of ≥10 mm (paraesophageal, tracheoesophageal groove ≥5 mm) as observed on CT and/or MRI or a high SUV (except inflammatory lymph nodes) as observed on PET/CT. Even if the lymph node characteristics are under these standards, those with evident necrosis, circular enhancement, enhancement to a similar degree as that of the primary lesion, and eccentric calcification are also considered as GTVn (class 2 B evidence). Cervical esophageal carcinoma: bilateral 101, 102, 104, 105, and 106 rec groups Upper thoracic esophageal carcinoma: bilateral 101, 104, 105, and 106 and partial 108 groups Middle thoracic esophageal carcinoma: bilateral 101, 104, and 105, 106, 107, and 108; partial 110; and abdominal 1, 2, 3, and 7 groups Lower thoracic esophageal carcinoma: 107, 108, and 110, abdominal 1, 2, 3, and 7 groups Upper crossing middle esophageal carcinoma: bilateral 101, 104, 105, 106, 107, and 108 groups Middle crossing upper esophageal carcinoma: 105, 106, 107, and 108 and partial 110 groups Middle crossing lower esophageal carcinoma: partial 105, 106, 107, 108, and 110 and abdominal 1, 2, 3, and 7 groups Lower crossing middle esophageal carcinoma: 107, 108, and 110 and abdominal 1, 2, 3, and 7 groups Planned target area (PTV): This includes CTV with a 5-mm expansion in all directions; longitudinal expansion can be up to 8 mm, and the actual margin can be determined according to the quality control data of each center. Selective lymph node irradiation usually requires repeated localization after the first dose of prophylaxis is administered. If there is no new lesion, then only the involved field irradiation needs to be performed for radical cure during follow-up. Simultaneous integrated boost has also been studied and applied clinically and is noteworthy. (2) Neoadjuvant radiotherapy At present, there is no specific target area regulation for neoadjuvant chemoradiotherapy globally; hence, it is suggested that the principle of radical radiotherapy involving random radiation should be followed. When delineating the target area, the location of anastomotic stoma during subsequent surgical resection should be considered, and it should be avoided in the irradiation field to reduce the incidence of anastomotic fistula. The 2020 NCCN guidelines do not recommend adjuvant treatment after radical resection of esophageal SCC. However, global large-scale research, prospective stratification studies, and retrospective analyses have demonstrated that the recurrence rates of lymph node positivity and/or pT3–4a N0 stage and high-risk pT2 N0 adenocarcinoma were consistent; these results revealed that the survival rate of postoperative radiotherapy was higher than that reported in single-surgery group studies and that the recurrence rate of the radiotherapy field was significantly reduced. Therefore, postoperative radiotherapy or chemotherapy is recommended. CTV: The bilateral supraclavicular area and superior mediastinum area include the 104, 105, 106, and 107 groups. If the lesion is in the lower esophagus with the number of lymph node metastases being ≥3 and radiotherapy alone is used, then it is recommended to include the following lymph node areas: 104, 105, 106, 107 and abdominal groups 1, 2, 3, and 7. In case of a upper thoracic esophageal carcinoma or upper resection margin ≤3 cm, anastomotic stoma should be included (class 2B evidence). The conformal radiotherapy plan field should follow four principles: (1) the distance from the incident plane to the center of the target area should be short; (2) avoid organs at risk; (3) the side of the beam should be parallel to the longest side of the target area; and (4) the angle between adjacent radiation beams should generally be no less than 40° (except for the supplementary small beam). In addition, the isocenter of the radiation field can generally be placed at the center of the tumor and can be slightly adjusted by considering the actual irradiation position. Cervical and upper thoracic esophageal cancers (Figure 1): The neck, thoracic entrance, and upper thoracic esophagus largely differ in their thickness, and the depth of the esophagus is different from the body surface. If the anatomical position is deeper, then the target area dose is insufficient, and a supplementary beam should be added. Conformal plan radiation beam distribution and the relative position of the tumor and spinal cord shown in the beam eye view for cervical esophageal cancer Note: A is a schematic diagram of the four fields of coplanar conformal radiation for cervical esophageal cancer. B–E are the relative positions of the tumor and spinal cord in the beam eye view of the four irradiation beams as well as the settings of the multi-leaf grating and collimator Middle and lower thoracic esophageal cancer (Figure 2): This is divided into four fields: anterior, posterior, left, and right; five fields: left anterior, right posterior, right anterior, left posterior, and anterior; or on this basis in addition to an overall conformal field with at least two beams completely avoiding the spinal cord. For patients undergoing postoperative radiotherapy, the shooting field through the thoracic stomach should be avoided. If it is unavoidable, then the weight of the beam should be minimized. Conformal plan radiation beam distribution and the relative position of the tumor and spinal cord shown in the beam eye view for thoracic esophageal cancer Note: A is the schematic diagram of the five fields of coplanar conformal radiation for middle and lower esophageal cancer. B–F are the relative positions of the gross tumor and spinal cord of the five irradiation fields in the beam eye view as well as the settings of the multi-leaf grating and collimator Intensity modulation scheme: Cervical and upper thoracic esophageal cancers can be distributed at equal angles. In the middle and lower thoracic esophageal cancer, the plan design is based on the principle of reducing the volume of lung irradiation, and butterfly-shaped fields along the midline of the body can be used with evenly distributed weights. Delineation of organs at risk: This mainly includes the spinal cord, lungs, heart, liver, trachea, main bronchus, and stomach. (1) The dose limits for the spinal cord, lungs, heart, and liver according to QUANTEC (2012) are as follows: The maximum doses for cervical and thoracic spinal cords are ≤45 Gy and ≤50 Gy. When V20 is ≤30% in both the lungs, the risk of symptomatic radiation pneumonia is <20%. When the mean lung doses (MLDs) are 7, 13, 20, 24, and 27 Gy, the rates of the risk of symptomatic radiation pneumonia are 5%, 10%, 20%, 30%, and 40%, respectively. The risk of pericarditis is less than 15% when the mean cardiac dose is <26 Gy. When the V30 of the heart is <46%, the risk of pericarditis is <15%. When V25 is <10%, the risk of long-term cardiogenic death is <1%. When the mean liver dose is <30–32 Gy, the risk of radiation-induced liver disease is <5% (in patients without previous liver diseases or hepatocellular carcinoma). When this dose is <28 Gy, the risk is <5% (in patients with previous liver diseases or hepatocellular carcinoma with Child–Pugh class A liver function; patients with hepatitis B virus reactivation are excluded). (2) The dose tolerance limits for the trachea, main bronchus, and stomach are as follows: Because of its proximity to the esophagus, despite the use of conformal intensity-modulated precise radiotherapy techniques, the trachea will inevitably receive high doses. There are few reports in the literature regarding a tolerable tracheal dose under routine segmentation. It is recommended that the maximum dose be <75 Gy, and the hot spot dose (≥110% of the prescribed dose) should be avoided from overlapping with the tracheal wall in the target area. When the stomach is irradiated, serious adverse reactions may occur, including ulcers and perforations. When the irradiated volume is one-third, two-thirds, and the whole stomach, TD5/5 values are 60, 55, and 50 Gy, respectively, and TD50/5 values are 70, 67, and 65 Gy, respectively. It is recommended that the stomach volume of 40 Gy should be <40%–50% of the entire thoracic stomach. The dose tolerance limit for the stomach according QUANTEC is D100% <45 Gy, corresponding to the gastric ulcer risk of <7%. Based on existing small-scale clinical research, it is recommended that qualified centers conduct relevant clinical research and treatments carefully when treating esophageal cancer with protons and heavy ions. Intensity-modulated proton therapy (IMPT) can reduce doses to the heart and liver better than the passive scattered proton therapy. The beam energy is 150–250 MeV, and the target delineation refers to the requirements of the relevant IMPT standards. The recommended dose of radical concurrent chemoradiation is 50.4 Gy (relative biological effectiveness; RBE) 28 times (five times/week, 36–63 Gy [RBE]). Proton therapy alone may appropriately increase the dose to 62–98 Gy (RBE). The doses to organs at risk were as follows: MLD is <20 Gy, the whole lung V20 is <30%, the heart V40 is <40%, the liver V30 is <30%, and the maximum dose to the spinal cord is <45 Gy. X-ray with proton beam irradiation can be used: X-ray dos
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