Stomach cancer is one of the malignant tumors with the highest incidence and mortality rate. China is a high incidence area of gastric cancer, and the incidence rate and mortality rate are in the top 3 of malignant tumors. Although the detection rate of early gastric cancer has been improved by the primary and secondary prevention and treatment of gastric cancer in recent years, patients with intermediate and advanced stages still account for about 70%. The 5-year survival rate of middle and advanced gastric cancer is low, ranging from 1% to 18% for stage III gastric cancer and <5% for stage IV gastric cancer.
I. Diagnostic points
(I) Clinical manifestations
There are often no special symptoms in the early stage, but with the progress of tumor, various symptoms can appear, often similar to the symptoms of gastritis, ulcer disease and other chronic diseases of stomach.
1. Upper abdominal discomfort and pain: It is the earliest and most common symptom. At the beginning, the symptoms are often epigastric discomfort, fullness and vague pain in the middle and upper abdomen, without a certain pattern, which may be temporarily relieved by taking acid-suppressing and antispasmodic drugs, but the effect cannot last. As the disease progresses, the pain turns into persistent.
2. Nausea and vomiting: In the early stage, there may be only post-food fullness and mild nausea. In the late stage, obstructive symptoms may appear. The lesion at the cardia can cause dysphagia, and in severe cases, dysphagia and food reflux. When pyloric obstruction caused by pyloric lesion causes nausea and vomiting, the vomiting volume is large and the vomit is mostly rotten food.
3.Bleeding and black stool: When the tumor erupts and breaks down, it is accompanied by gastrointestinal bleeding. The chance of occurrence is about 30%. When a small amount of bleeding occurs, there is only fecal occult blood (+). When the tumor invades larger blood vessels and the bleeding is larger, there can be black stool or vomiting blood.
4. Other symptoms and signs: weakness, emaciation, loss of appetite and anemia can exist in different degrees in all stages of the disease. When distant metastasis of gastric cancer occurs, there may be enlarged left supraclavicular lymph nodes, rectal and bladder indentation masses, and ovarian masses.
(II) Examination means
1.Laboratory examination: early stage blood test is mostly normal, while middle and late stage may have different degrees of anemia and positive fecal occult blood test, about 20% for early stage gastric cancer and up to 80% for middle and late stage
2.X-ray examination: Barium meal examination of stomach is widely used and simple, but early lesions still need to be combined with gastroscopy. The main X-ray signs include niche shadow, filling defect, mucosal fold change, peristaltic abnormality and obstructive change.
3.CT: Enhanced CT can clearly show the extent of gastric cancer involving the stomach wall, the relationship with surrounding tissues, and the presence of abdominopelvic metastasis. Other imaging examinations such as color ultrasound, MRI and PET-CT also have certain significance.
4.Gastroscopy: Upper gastrointestinal endoscopy and endoscopic pathological biopsy are important for the diagnosis of gastric cancer. Gastroscopy can detect early gastric cancer, distinguish benign and malignant ulcers, and determine the type of gastric cancer and the scope of lesions.
5.Endoscopic ultrasound: it can measure the extent of lesions and help preoperative clinical staging in order to determine the method of neoadjuvant therapy and its efficacy.
6.Tumor markers: There are no tumor markers with strong specificity for gastric cancer diagnosis, but continuous testing of CEA, CA50, CA724 and other markers is of certain value to determine the efficacy and prognosis of gastric cancer.
7.Physical examination: When gastric cancer is suspected, attention should be paid to the examination of supraclavicular lymph nodes and rectal finger examination during the physical examination.
(III) TNM staging
TX Unable to assess primary tumor
NX cannot evaluate regional lymph nodes
MX Unable to evaluate distant metastasis
Tis carcinoma in situ, intraepithelial tumor
N0 No regional lymph node metastasis
M0 No distant metastasis found
T1 Tumor infiltrating mucosa or submucosa
N1 1~6 regional lymph node metastases
M1 distant metastasis
T2 Tumor infiltrates into the muscular layer or subplasma layer
N2 7~15 regional lymph node metastases
T3 Tumor penetrated the plasma membrane layer and did not invade adjacent tissues and organs
N3 >15 regional lymph node metastases
T4 Tumor invades adjacent tissues and organs
II. Treatment principles
According to the stage of gastric cancer, the integrated treatment mode of surgery, chemotherapy, radiotherapy, biological therapy and Chinese medicine therapy can improve the treatment effect, prolong the survival period and improve the survival quality of patients with gastric cancer.
For early stage radical gastric cancer surgery, T1N0 patients do not need adjuvant therapy and only need regular follow-up; T2N0 patients without high-risk factors also need regular follow-up, but if there are high-risk factors (poorly differentiated tumor cells, high grade, invasion of lymphatic vessels and blood vessels, age <50 years), they need to receive adjuvant therapy.
Patients with intermediate or advanced disease need to receive adjuvant therapy after radical surgery or dividend surgery.
Adjuvant therapy includes various methods such as chemotherapy, radiotherapy, and biologic therapy, including preoperative, intraoperative, and postoperative chemotherapy and/or radiotherapy.
Advanced gastric cancer in poor general condition or with distant metastasis should be treated with salvage therapy. The salvage treatment includes the best supportive treatment and chemotherapy.
III. Treatment strategies
(i) Neoadjuvant chemotherapy
Preoperative chemotherapy is used for locally advanced gastric cancer where radical resection is estimated to be difficult or impossible and has the tendency of distant metastasis. The purpose is to reduce tumor load, improve surgical resection rate and prolong survival time. Most neoadjuvant chemotherapy is given for 2~3 courses preoperatively.
1.ECF regimen
Epirubicin 50mg/m2 iv gtt d1
Cisplatin 60mg/m2 iv gtt d1
Fluorouracil 200mg/m2 iv gtt with 21d
Repeat every 4 weeks
2.CF regimen
Calcium folinic acid 200 mg/m2 iv gtt d1~5
Fluorouracil 200 mg/m2 iv gtt d1~5
Repeat every 3 weeks
(II) Adjuvant chemotherapy
Adjuvant chemotherapy is a part of comprehensive treatment, which aims to prevent recurrence and metastasis of tiny residual tumors after radical surgery and prolong survival time. The prognosis of gastric cancer depends largely on the stage of the disease at the time of diagnosis. The 5-year survival rate of early gastric cancer (Tis, T1 N0 M0, T2 N0 M0) treated by surgery alone is 90%, and adjuvant chemotherapy is not needed after surgery. However, in locally advanced stage without lymph node metastasis (T3 N0 M0), the 5-year survival rate is only 50% even after radical surgery. Therefore, except for early stage patients, systemic and rational combination therapy should be applied early, but there is no standardization of chemotherapy regimen and duration.
1.CF regimen See neoadjuvant chemotherapy.
2.ECF regimen See neoadjuvant chemotherapy.
3.FOLFOX regimen Repeat once every 2 weeks.
FOLFOX4 regimen
Oxaliplatin 85 mg/m2 iv gtt (2h) d1
Calcium folinic acid 200 mg/m2 iv gtt d1, d2
Fluorouracil 400 mg/m2 iv d1, d2
Fluorouracil 600 mg/m2 iv gtt (22h continuous) d1, d2
mFOLFOX6 regimen
Oxaliplatin 100 mg/m2 iv gtt (2h) d1
Calcium folinic acid 400 mg/m2 iv gtt d1
Fluorouracil 400 mg/m2 iv d1
Fluorouracil 2400~3000 mg/m2 iv gtt (46h continuous) d1
4.XELOX regimen
Oxaliplatin 130 mg/m2 iv gtt (2h) d1
Capecitabine (Xeloda) 850~1000 mg/m2 bid po d1~14
Repeat 1 time in 3 weeks.
(iii) Treatment of advanced/recurrent gastric cancer
In the 1980s, the FAM regimen consisting of fluorouracil, doxorubicin, and mitomycin was widely used as the gold standard in the treatment of advanced gastric cancer. In recent years, several clinical trials have confirmed the efficacy of the combination of oxaliplatin and fluorouracil in the treatment of advanced gastric cancer. The single-agent effectiveness of paclitaxel and doxorubicin in advanced gastric cancer is 20-33% and 17-24%, respectively. In recent years, the number of studies of paclitaxel analogues combined with fluorouracil and cisplatin has increased, and several studies have proved that TCF regimen is significantly better than CF regimen, but it is not suitable for elderly gastric cancer patients >65 years old. The standardized and standard chemotherapy regimen for advanced gastric cancer still cannot be determined, and the choice of chemotherapy regimen in clinical practice needs to be based on the general condition of patients, treatment tolerance and personal experience of physicians.
1.ECF regimen See neoadjuvant chemotherapy.
2.FOLFOX regimen See adjuvant chemotherapy.
3.ELF regimen
Etoposide 120 mg/m2 iv gtt (50min) d1~3
Calcium folinic acid 300 mg/m2 iv gtt d1~3
Fluorouracil 500 mg/m2 iv gtt d1~3
Repeat every 3~4 weeks
4.EOX regimen
Epirubicin 50mg/m2 iv gtt d1
Oxaliplatin 130 mg/m2 iv gtt (2h) d1
Capecitabine (Xiloda) 825 mg/m2 bid po d1~14
Repeat every 3 weeks
5.TCF regimen
Doxorubicin 75 mg/m2 iv gtt d1
Cisplatin 60 mg/m2 iv gtt d1
Fluorouracil 200mg/m2 iv gtt d1~21
Repeat every 4 weeks
6.S1 regimen
In Japan, tegeo was approved for the treatment of advanced gastric cancer in 1999, head and neck cancer in 2001, colorectal cancer in 2003, and non-small cell lung cancer in 2004. Years of clinical application have proven that Tegeo is a safe and effective anti-cancer drug. According to statistics, over 80% of cases of chemotherapy for advanced gastric cancer in Japan are currently treated with Tegeo, with a treatment efficiency (CR + PR) of 44.6%. At present, there are two main dosage forms of S1 in China, namely Aiswan (imported original research: Dapeng Pharmaceutical Industry Co., Ltd.) and Vikandar (domestic: Shandong New Era).
S1 alone (Tegeo capsules) 80 mg/m2/d po divided into 2 doses 28 days off 14 days 1 course every 6 weeks
SP regimen
S1 (Tegeo capsules) 80 mg/m2/d po in 2 doses for 14 days with a 7-day break
Cisplatin (DDP) 60mg/m2 iv gtt d8
1 course of treatment every 3 weeks
7.Molecular targeted drug therapy
Compared with the three traditional treatments of surgery, radiotherapy and chemotherapy, molecular targeted therapy has molecular specificity and selectivity, which can efficiently and selectively kill tumor cells and reduce the damage to normal tissues of human body, and is the new direction of gastric cancer treatment, and will have a broader prospect in the comprehensive treatment of gastric cancer. The occurrence, development and regression of gastric cancer, like most other solid tumors, are the result of multi-target and multi-link regulation. Currently, most targeted drugs can only target one target, and the signaling mechanism in cells is a complex and multi-factor intersection network system. Most of the targeted drugs are non-cytotoxic drugs. Combining with cytotoxic drugs in a reasonable and effective way will bring better effects.
Commonly used targeted drugs
Gefitinib (ERSA) 250 mg po qd
Cetuximab (Abirater) 400 mg/m iv gtt week 1 and then 250 mg/m2 iv gtt once a week
Bevacizumab (Avastin) 5 mg/kg iv every 2 weeks