Radiotherapy + Chemoimmunotherapy Followed by Surgery in Patients With Limited Metastatic Gastric or GEJ Cancer

5 to 7 fractions of short course hypofractionated radiotherapy (HFRT) targeted to the primary lesion.

Hypofractionated radiotherapy (HFRT) or stereotactic body radiotherapy (SBRT) targeted to metastatic lesions. The target dose will be adjusted based on the lesion's site and diameter and organs at risk, with high-dose irradiation of 4-8 fractions. All metastatic lesions should be irradiated as much as possible, and partial lesion irradiation should be allowed when technically impractical.

The anti-PD-1 mAb is used on day 1 along with each cycle of chemotherapy. There are no restrictions on the choice of anti-PD-1 mAb. Patients can choose commonly used accessible monoclonal antibodies based on their personal preferences and financial status. The commonly used anti-PD-1 mAb usages are as follows: Nivolumab/Toripalimab 240mg solution intravenously once daily, Q2W. OR Nivolumab/Toripalimab 360mg solution intravenously once daily, Q3W; OR Pembrolizumab/Tislelizumab/Sintilimab/Camrelizumab, 200mg solution intravenously once daily, Q3W.

For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. The 3-weekly schedule of trastuzumab starts with a loading dose of trastuzumab of 8 mg/kg, followed by 6 mg/kg trastuzumab every 21 days.

The investigator's choice of chemotherapy regimens included SOX, XELOX or FOLFOX. Their usages are as follows: SOX: S-1 twice a day, days 1-14, the dose of S-1 is accorded to body-surface area (BSA): patients with a BSA of less than 1.25 m2 receive 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 receive 100 mg daily; and those with a BSA of 1.5 m2 or more receive 120 mg daily; and oxaliplatin 130 mg/m2, day 1, every 3 weeks; XELOX: Capecitabine 1000 mg/m2 twice a day, days 1-14 and oxaliplatin 130 mg/m2, day 1, every 3 weeks; FOLFOX: Leucovorin 400 mg/m2, day 1, fluorouracil 400 mg/m2, day 1 and 1200 mg/m2, days 1-2, and oxaliplatin 85 mg/m2, day 1, every 2 weeks.

For patients with a good response to preoperative treatment, surgical resection of primary and metastatic lesions is recommended. For primary lesions, gastrectomy with standard D2 lymphadenectomy is commonly used. The type of gastrectomy performed depends on the location and extent of the primary lesion. For GEJ or upper-third tumors, a 3 cm esophageal margin is recommended, and a total gastrectomy or esophagogastrectomy is performed. For middle-third tumors, the gastric margin is recommended to be more than 5 cm, and total gastrectomy is performed. For lower-third tumors, a 2 cm duodenal margin is recommended, and subtotal or total gastrectomy is performed. Billroth I or Roux-en-Y gastrojejunostomy is performed for distal gastrectomy patients. Roux-en-Y esophagojejunostomy is performed for patients receiving total gastrectomy.

For patients with a good response to preoperative treatment, surgical resection of primary and metastatic lesions is recommended. For metastatic lesions, the surgical procedure and resection range are determined by the surgeon.

Local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) achieve high rates of complete tumor eradication of small metastases, and can be seen as alternatives if a widely invasive surgical approach is required or patient is inoperable.