Stratification	Grade I recommendations	Grade II recommendations	Grade III recommendations
ECOG PS = 0‐1	Concurrent chemoradiotherapy a , b , c , e , f 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 b , c , g ② (Evidence 2B) Radiotherapy b , c , e , f , g , h ③ (Evidence 2B) Referral to MDT to assess the possibility of surgery after concurrent chemoradiotherapy. If complete resection can be achieved, surgery is recommended	Chemotherapy ② + radiotherapy b , c , d , e , f , g , h or concurrent chemoradiotherapy a , b , c , d , e , f , ①③ (Evidence 3) 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 ± radiotherapy b , c , d , e , f , g , h (Evidence 2A) After nutritional support, if the patient 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; 3D, three dimension; 5‐FU, 5‐fluorouracil.

① Concurrent chemoradiotherapy regimen:

Carboplatin + paclitaxel [126] (Evidence 1A)

Cisplatin + 5‐FU or capecitabine or tegafur [127] (Evidence 1A)

Oxaliplatin + 5‐FU or capecitabine or tegafur [128] (Evidence 2B)

Paclitaxel + 5‐FU or capecitabine or tegafur [129, 130] (Evidence 2B)

Capecitabine [131] (Evidence 2B)

S‐1 [132, 133, 134] (Evidence 2B)

5‐FU [135] (Evidence 1A)

② Systemic regimen: refer to section “2.2 Treatment of advanced or metastatic gastric cancer”

③ Radiotherapy: 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 have 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.

^a For patients with an 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 [136, 137]. If the tumor responds well after treatment, the possibility of radical resection should be evaluated. Some studies have shown that if a patient is suitable for surgery, radical or palliative resection could both provide survival benefits [136, 137]. Retrospective studies have shown that even in patients who cannot undergo surgical resection, chemoradiotherapy can provide survival benefits compared to chemotherapy alone, with a few patients able to achieve long‐term DFS [138, 139].

^b For patients with locally advanced tumors or extensive lymph node involvement, radiation oncologists should evaluate the treatment approach based on MDT recommendations to assess the feasibility of irradiation target volumes. When the irradiation target volume is deemed excessively large and could potentially make patients intolerant to concurrent chemoradiotherapy, options such as chemotherapy alone or radiotherapy alone may be considered [140]. Following chemotherapy or radiotherapy, patients are presented to the MDT for further evaluation. Surgery may be an option for a selected group of patients who are sensitive to chemotherapy, aiming for curative resection. If complete tumor removal is not achievable, a sequential approach of chemotherapy followed by radiotherapy or concurrent chemoradiotherapy may be considered, with the possibility of reevaluating the feasibility of surgery after completing radiotherapy.

^c For concurrent chemoradiotherapy, the choice between sequential chemotherapy plus chemoradiotherapy or primary concurrent chemoradiotherapy should be based on the comprehensive assessment by radiation oncologists in conjunction with the MDT consultation recommendations, taking into account the patient's physical condition and the required extent of irradiation. In general, concurrent chemoradiotherapy is preferred over radiotherapy alone [141], except in cases where patients cannot tolerate concurrent chemoradiotherapy. The selection of chemotherapy regimens during concurrent chemoradiotherapy depends on the tumor's location (the EGJ or stomach) and specific clinical trial protocols. Limited courses of induction chemotherapy may also be considered to screen for chemosensitivity. Patients who have undergone chemotherapy may have reduced tolerance to radiotherapy, and strategies to enhance tolerability, such as acid suppression, nutritional support, dose reduction or consideration of single‐agent fluoropyrimidine‐based chemotherapy regimens during concurrent chemoradiotherapy, may be considered [131, 132, 133, 134].

^d Combining immune checkpoint inhibitors (ICIs) with chemotherapy is becoming more common in advanced or recurrent gastric cancer. There is a growing body of research exploring concurrent chemoradiotherapy with immunotherapy for locally advanced gastric cancer. Published phase II clinical trials [142, 143, 144, 145] have shown promise for this approach, both in salvage therapy for unresectable advanced or recurrent gastric cancer after standard chemotherapy failure and in neoadjuvant treatment for locally advanced EGJ and/or gastric adenocarcinoma. These trials reported favorable tumor response rates, with MPR rates ranging from 48.7% to 73.7% and pCR ranging from 22.6% to 42.1%. Treatment‐related toxicities were manageable. Additional data on optimal chemotherapeutic agents, irradiation target volumes and dose fractionation in combination therapy are still needed.

^e Radiotherapy is recommended to employ precise techniques such as three‐dimensional conformal and intensity‐modulated radiotherapy (IMRT). Several studies have reported that compared to conventional two‐dimensional radiotherapy techniques, three‐dimensional conformal or IMRT techniques offer superior advantages in terms of target dose distribution and the protection of normal tissues and organs, which is particularly evident in protecting the gastrointestinal, renal or hepatic structures, leading to a reduction in radiation‐related adverse reactions [146, 147].

^f Consideration for radiotherapy planning. 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 radiation 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 at pretreatment evaluation, 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 and avoid the inclusion of the regional lymph nodes. The recommended dose for palliative radiotherapy is DT 30‐40 Gy for 10‐20 cycles. The dosage and scope of irradiation should be based on the patient's general condition, the irradiation target volume, expected lifespan, and possible irradiation damage to surrounding normal tissues and organs.

^g Compared to best supportive care, effective systemic therapy can prolong the survival of patients with advanced or metastatic gastric cancer [148]. 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, targeted therapy and immunotherapy can then be considered. If not, best supportive care can be continued. The main chemotherapy regimens could be 5‐FU‐based, platinum‐based, taxanes‐based, and irinotecan regimens. 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 [149]. For those who cannot tolerate combined chemotherapy, single‐drug chemotherapy, such as 5‐FU alone, can be considered.

^h Radiotherapy 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 [150, 151, 152]. Palliative radiotherapy may be considered for patients of old age, with advanced disease, decreased cardiopulmonary functions, multiple underlying diseases, and difficulty sustaining surgical intervention.