| Stratification | Grade I recommendations | Grade II recommendations | Grade III recommendations |
|---|---|---|---|
| ECOG PS = 0‐1 |
• Concurrent chemoradiotherapy[Link], [Link], [Link], [Link], [Link] ,①③ (Evidence 1A) • Referral to MDT to assess the possibility of surgery after concurrent chemoradiotherapy. If complete resection can be achieved, surgery is recommended |
• Chemotherapy[Link], [Link], [Link], [Link] , ② (Evidence 2B) • Radiotherapyb‐d, f, g ,③ (Evidence 2B) • Referral to MDT to assess the possibility of surgery after concurrent chemoradiotherapy. If complete resection can be achieved, surgery is recommended |
|
| ECOG PS = 2 |
• Best supportive care or symptomatic treatment (Evidence 1A) • Bypass surgery, endoscopic treatment, stenting, and/or palliative radiotherapy are recommended if they may improve nutritional status, alleviate cancer‐related complications such as bleeding, pain, or obstruction. |
• Best supportive care or symptomatic treatment + chemotherapy ± radiotherapyb‐g (Evidence 2A) • After nutritional support, if the patient's conditions are suitable, can consider chemotherapy② alone or in combination with palliative radiotherapy |
Abbreviations: ECOG, Eastern Cooperative Oncology Group; PS, performance score; MDT, multidisciplinary team;
①Concurrent chemoradiotherapy regimen:
− Carboplatin + paclitaxel (Evidence 1A) [107]
− Cisplatin + 5‐FU or capecitabine or tegafur (Evidence 1A) [108]
− Oxaliplatin + 5‐FU or capecitabine or tegafur (Evidence 2B) [109]
− 5‐FU (Evidence 1a) [115]
②Chemotherapy regimen: refer to section Chemotherapy regimen for late‐stage metastatic gastric cancer
③Radiotherapy: 3D conformal radiotherapy/intensity‐modulated radiotherapy
Notes
Gastric adenocarcinomas are considered unresectable if: (1) presence of tumor‐related factors: the primary tumor shows extensive invasion to adjacent structures and cannot be separated from the surrounding normal tissues or has encased major vascular structures; the regional lymph nodes are fixed and fused into clusters, or presence of metastatic lymph nodes outside the scope of surgery; presence of distant metastasis or intraperitoneal implantation (including positive peritoneal lavage fluid cytology), etc.; (2) contraindications to surgery or refusal of surgical intervention due to poor general condition, malnutrition, and severe hypoproteinemia, anemia or other underlying causes.
aFor patients with unresectable tumor and good general conditions, if the tumor is localized and radiotherapy can be provided, concurrent chemoradiotherapy is recommended. Studies have confirmed that concurrent chemoradiotherapy was superior to chemotherapy alone or radiotherapy alone in terms of tumor downstaging and pathological remission rate [116, 117]. If the tumor responds well after treatment, the possibility of radical resection should be evaluated. Some studies have shown that if a patient is fit for surgery, radical or palliative resection could both provide survival benefits [116, 117]. Retrospective studies have shown that for unresectable patients, chemoradiotherapy was associated with superior survival benefits than chemotherapy alone [118, 119].
bFor patients with extensive tumor invasion or lymph node metastasis, wide irradiation fields could lead to intolerance to concurrent chemoradiotherapy, and for such cases, chemotherapy alone or radiotherapy alone could be considered as an alternative. For patients with favorable responses after treatment, referral to an MDT is recommended to judge the potential for surgical resection. If the tumor is still found unresectable, chemotherapy with sequential or concurrent radiotherapy may be considered, and tumor resectability should be re‐evaluated after the treatment.
cRadiologists should perform a comprehensive evaluation based on the patients’ physical condition and the scope of the irradiation field before performing sequential or concurrent chemoradiotherapy. In general, concurrent chemoradiotherapy is superior to radiotherapy alone [120]. For concurrent chemoradiotherapy, the choice of chemotherapy regimen should be based on the tumor location (i.e., the EGJ or stomach), and radiotherapy alone can be considered if the patient cannot tolerate concurrent chemoradiotherapy. However, patients who had prior chemotherapy may have poor tolerance to radiotherapy, and a double‐drug regimen with concurrent chemoradiotherapy may reduce the completion rate of radiotherapy. For such cases, single‐drug chemotherapy using 5‐FU with concurrent chemoradiotherapy can be considered [71, 111‐114].
dConsideration for radiotherapy. For patients with potentially resectable tumors, in addition to the visible lesions (primary/metastatic tumors or lymph nodes) confirmed by imaging examinations, expansion of the irradiation field to include high‐risk regions of lymphatic drainage can be considered. The recommended radiotherapy dose of tumor (DT) is 45‐50.4 Gy. After treatment, the tumor should be re‐assessed to judge whether the patient can undergo surgery or continue the systemic treatment. For unresectable tumors, radical radiotherapy at a dose of DT 50‐60 Gy can be considered. For frail patients or those with extensive non‐resectable cancer, the irradiation field should only include the visible tumor, avoid inclusion of the regional lymph nodes. The recommended dose for palliative radiotherapy is DT 30‐40 Gy (10‐20 cycles). The dosage and scope of irradiation should be based on the patient's general condition, the size of the irradiation field, expected lifespan, and possible irradiation damage to surrounding normal tissues and organs.
eCompared to best supportive care, chemotherapy can prolong the survival of metastatic or late‐stage gastric cancer patients [121]. As such, for patients presenting with severe gastrointestinal obstruction, bleeding, or obstructive jaundice, it is recommended to first provide feeding gastrostomy tube, stent implantation, gastrointestinal bypass surgery, local palliative radiotherapy, proton pump inhibitors, and analgesia, based on the patient's condition, preferentially within the first 2‐4 weeks of presentation as longer waiting time could result in tumor progression. After amelioration of the patient's general condition, chemotherapy can then be considered. If not, best supportive care can be continued. The main chemotherapy drug regimens could be 5‐FU‐based, platinum‐based, taxanes‐based, and irinotecan regimen. Combination chemotherapy is recommended as it has been associated with a response rate of 30%‐54% and a median OS (mOS) of 8‐13 months [122]. For those who cannot tolerate combined chemotherapy, single‐drug chemotherapy such as 5‐FU alone can be considered.
fRadiotherapy can significantly alleviate some clinical symptoms of late‐stage gastric cancer, such as hemorrhage, severe cancer pain, dysphagia and obstruction, and can improve the patients’ general condition and quality of life [123, 124, 125]. Palliative radiotherapy may be considered for patients of old age, with advanced disease, decreased cardiopulmonary functions, multiple underlying diseases, and difficulty sustaining surgical intervention.
gThree‐dimensional conformal radiotherapy (3D‐CRT) and intensity‐modulated radiotherapy (IMRT) are recommended as related studies have demonstrated that, compared with conventional two‐dimensional radiotherapy, 3D‐CRT or IMRT was superior in targeting the dose distribution area and protecting normal organ tissue, especially in the gastrointestinal tract, liver, and kidneys, against adverse events from irradiation [126, 127].