I. Principles of surgery
1.Preoperative examination and evaluation
(1) Clinical staging based on chest and abdominal CT, whole body PET (PET-CT is recommended) and endoscopic ultrasound to assess resectability; the esophageal surgeon will assess the physiological tolerance of the patient for esophagectomy, and generally choose patients with suitable physiological condition and resectable esophageal cancer (more than 5 cm from the epiglottis).
(2) Cervical esophageal cancer
(2) Radical radiotherapy is preferred for cervical esophageal cancer or upper thoracic esophageal cancer not more than 5 cm from the epiglottis.
2. Resectable esophageal cancer
(1) Tis/Tla stage (tumor invades the mucosa but does not reach the submucosa): endoscopic mucosal resection (EMR) or esophagectomy can be considered.
(2) Tumors located in the submucosa (Tlb stage) or deeper: perform esophagectomy.
(3) Stage Tl.T3, including those with regional lymph node metastasis (Nl).
(4) Stage T4 tumors invading solely the pericardium, pleura or diaphragm.
(5) Stage IVA lesions located in the distal esophagus with resectable abdominal lymph nodes and no involvement of the abdominal artery, aorta or other organs.
(6) For patients with Tis/Tla or TlbNO/NX stage (non-cervical segment) esophageal cancer, esophageal cancer resection is preferred; while for patients with T, any N Mla (stage IVA) esophageal cancer, neoadjuvant chemotherapy plus surgery (only for adenocarcinoma of lower esophagus or cardia) is recommended, or preoperative radiotherapy and then decide whether to perform surgery according to the efficacy, or directly choose radical radiotherapy.
3.Unresectable esophageal cancer
(1) Stage T4: The tumor involves the heart, large blood vessels, trachea or adjacent organs, including liver, pancreas, lung and spleen, etc.
(2) Stage IVA: Tumor located in distal esophagus with unresectable abdominal lymph nodes and involvement of abdominal artery, aorta or other organs including liver, pancreas, lung and spleen.
(3) Stage IVB: distant metastasis or non-regional lymph node metastasis.
II. Principles of chemotherapy
For focal esophageal cancer, the listed treatment regimens include some of the preferred regimens from participating institutions in phase II trials, which may not be superior to those with level 1 evidence; for esophageal cancer with distant metastases, phase III trials have not been conducted for many years, and some of the listed regimens are from the gastric adenocarcinoma phase III trial, which also included patients with lower segment esophageal and/or cardia cancer; for complete resection (RO resection) after esophageal
It is recommended that the function and condition of each organ should be checked for appropriate requirements before chemotherapy, that the course, toxicity and efficacy of chemotherapy should be communicated in detail to patients and their families, and that preventive and treatment measures to reduce the severity and duration of complications should also be advised; that complications should be closely observed and managed during chemotherapy, and that appropriate blood products should be prepared. Assess the patient’s response after chemotherapy and monitor various long-term complications.
1. Pre- and post-operative chemotherapy (only for lower esophageal or cardia adenocarcinoma).
(1) ECF (epirubicin, cisplatin and 5-Fu).
(2) ECF adjustment regimen.
2.Preoperative radiotherapy
(1) Cisplatin plus fluorouracil-based.
(2) Irinotecan plus cisplatin.
(3) paclitaxel plus cisplatin or carboplatin.
(4) Doxorubicin plus cisplatin.
(5) doxorubicin or paclitaxel plus fluorouracil analogs (5-Fu or capecitabine)
(6) Oxaliplatin plus fluorouracil class (5-Fu or capecitabine).
3.Radical radiotherapy
(1) cisplatin plus 5-Fu
(2) Irinotecan plus cisplatin.
(3) paclitaxel plus cisplatin or carboplatin.
(4) Doxorubicin plus cisplatin.
(5) doxorubicin or paclitaxel plus fluorouracil analogs (5-Fu or capecitabine)
(6) Oxaliplatin plus fluorouracil class (5-Fu or capecitabine).
4.Postoperative radiotherapy: only for esophageal gland or cardia cancer, fluorouracil class 5-Fu or capecitabine.
5.Metastatic cancer or locally advanced cancer
(1) DCF (doxorubicin, cisplatin and 5.Fu).
(2) ECF.
(3) EC-adjusted regimen.
(4) Irinotecan plus cisplatin.
(5) Oxaliplatin plus fluorouracil-based (5-Fu or capecitabine).
(6) DCF-adjusted regimens.
(7) Irinotecan plus fluorouracil analogs (5-Fu or capecitabine).
(8) paclitaxel-based regimens.
(9) Trastuzumab.
III. Principles of radiotherapy
1.General radiotherapy information
(1) Treatment recommendations must be formulated by multidisciplinary experts, including experts in oncologic surgery, oncologic radiotherapy, medical oncology, radiology, gastroenterology and pathology.
(2) Retrospective studies of CT scan, barium meal, ultrasound endoscopy, endoscopy and PET/PET-CT scan shall be performed by multidisciplinary experts when necessary to suggest treatment dose and range boundaries.
2. Simulation and treatment planning
(1) Simulated localization and 3D treatment under CT are encouraged.
(2) Under suitable conditions, intravenous and/or oral contrast agents may enhance CT simulation of the target area.
(3) Immobilization devices are highly recommended due to the repetitive nature of daily operations.
(4) The gross tumor area (GTV) should include the primary tumor and the involved regional lymph nodes confirmed by the planned scan and other examinations mentioned above; the clinical target area (CTV) should include areas at risk of microscopic residual lesions. The risk of lymph node metastasis in some specific areas mainly depends on the origin site of the primary tumor; the planned target area (PTV) should include the tumor and the edges of the upper and lower ends of 5 cm, and the radiation edges of 1.5-2 cm on both sides, and the error caused by respiratory motion should be taken into account.
3.Radiation field masking and dose routine radiation field masking is necessary to reduce unnecessary dose exposure to normal tissues including liver (60% liver <30Cy), kidney (at least 2/3 single kidney <20Gy), bone marrow (<45Gy), heart (1/3 heart <50Cy, to ensure the minimum amount of left ventricle exposure as possible) and lung. Radiation dose is generally 50-50.4Cy (1.8-2Cy/d)
IV. Precautions and best principles of supportive therapy
1. Precautions: For acute toxic effects that can be managed, avoid interrupting treatment or reducing the dose; patients should be closely observed and further supported during the interval; patients should be examined at least once a week during radiotherapy, including vital signs, body mass and blood cell count; antiemetics should be given prophylactically as appropriate, and acid control and antidiarrheal agents should be given when necessary; patients with estimated caloric intake <1500kcal/d should be considered for oral or enteral treatment. Consider oral or enteral hyper-nutrition and jejunostomy feeding if necessary; adequate enteral or intravenous hydration is necessary during radiotherapy and early recovery.
2. Best principles.
(1) Dysphagia: dysphagia caused by esophageal cancer often originates from obstruction, but it may also originate from tumor-induced esophageal motility disorder. Therefore, the extent of the lesion and the degree of swallowing impairment should be assessed [inability to swallow saliva, ability to swallow liquid, ability to swallow semi-liquid (same as infant food), ability to swallow solid food <18mm in diameter and chew adequately, ability to swallow solid food without special attention to size and chewing (dysphagia symptoms may be temporary)] and the etiology of dysphagia should be clarified.
(2) Obstruction.
a. Complete esophageal obstruction: endoscopic lumen reconstruction treatment is feasible; those who are not in a position to perform endoscopic treatment or endoscopic treatment fails should establish enteral nutrition access; intraoperative placement of jejunal nutrition tube (for those who intend to perform esophagectomy) or gastrostomy placement (for those who cannot perform esophagectomy), and retrograde endoscopic treatment through the gastrostomy can be attempted; brachytherapy can be considered instead of external radiation treatment; other methods include chemotherapy, surgery.
b. Severe esophageal obstruction: endoscopic lumen dilation; guidewire, balloon dilation; temporary application of removable small-diameter stents (8-16 mm) instead of large-diameter stents, but may lead to uncontrollable chest pain, bleeding and perforation; other measures mentioned above.
c. Moderate esophageal obstruction (can eat semi-liquid): intermittent endoscopic treatment is necessary, and the above measures can also be considered.
(3) Pain: see PAIN-1 section of NCCN guidelines for adult oncologic pain management for tumor-related pain; uncontrollable severe pain due to esophageal stent placement should be removed endoscopically immediately.
(4) Bleeding: Acute bleeding from esophageal cancer is often secondary to esophageal aortic fistula, which is mostly suggestive of middle to advanced stage of tumor; endoscopic examination and treatment may cause sudden hemorrhage and should be performed with caution; endoscopic electrocoagulation techniques such as bipolar and argon electric knife can be used for tumor surface bleeding: external radiation therapy is feasible for chronic blood loss caused by tumor.
(5) Nausea and vomiting: It is best to treat according to the antiemetic guidelines recommended by NCCN.