Patients with isolated para-aortic (station 16) lymph node metastases from gastric adenocarcinoma will receive first-line systemic conversion therapy based on PD-L1 combined positive score (CPS).

* CPS ≥1: 3 cycles of SOX (S-1 plus oxaliplatin) plus a PD-1 inhibitor (every 3 weeks).
* CPS \<1: 3 cycles of SOX alone. After \~8 weeks, patients with non-progressive disease (CR/PR/SD) undergo D2 radical gastrectomy, followed by 5 cycles of adjuvant SOX.

Subsequently, patients receive elective intensity-modulated radiotherapy (IMRT) to the para-aortic (station 16) nodal basin (45-50 Gy/25 fractions; positive nodes 56-60 Gy/25 fractions) with concurrent oral capecitabine or S-1.

For CPS ≥1 patients, maintenance PD-1 inhibitor therapy continues for up to 1 year.

The SOX regimen consists of oxaliplatin 130 mg/m² IV on day 1 plus oral S-1 (tegafur/gimeracil/oteracil) 40-60 mg twice daily, taken on days 1-14 followed by 7 days off, in a 21-day cycle.

Experimental arm: 3 cycles before surgery, 5 cycles after surgery. Control arm: up to 8 cycles as standard systemic therapy.

SOX regimen

A PD-1 inhibitor is administered intravenously at a fixed dose of 200 mg every 3 weeks.

It is combined with SOX in the experimental arm (CPS ≥1 patients) during conversion and adjuvant phases, and with CAPEOX or SOX in the control arm (CPS ≥1 patients).

Maintenance PD-1 inhibitor continues for up to 1 year or until disease progression or unacceptable toxicity.

PD-1 inhibitor

Intensity-modulated radiotherapy (IMRT) is delivered postoperatively to the para-aortic (station 16) nodal basin.

Elective nodal basin: 45-50 Gy in 25 fractions Positive nodes: 56-60 Gy in 25 fractions Radiotherapy is given concurrently with oral capecitabine or S-1 as radiosensitizers.

Para-aortic lymph node radiotherapy (IMRT to station 16)

During para-aortic IMRT, patients receive concurrent oral capecitabine 825 mg/m² twice daily on radiation days, or oral S-1 dosed according to body surface area.

These agents are used as radiosensitizers during postoperative radiotherapy.

Capecitabine / S-1 (radiosensitizer during IMRT)

Patients in this arm will receive systemic therapy without surgery or radiotherapy.

* CPS ≥1: CAPEOX or SOX chemotherapy combined with a PD-1 inhibitor, followed by PD-1 inhibitor maintenance for up to 1 year.
* CPS \<1: CAPEOX or SOX chemotherapy alone. Systemic therapy continues until disease progression, unacceptable toxicity, or completion of 8 planned cycles.

The CAPEOX regimen consists of oxaliplatin 130 mg/m² IV on day 1 plus oral capecitabine 1000 mg/m² twice daily on days 1-14, repeated every 3 weeks (q3w), up to 8 cycles.

Used as a standard chemotherapy option in the control arm, with or without PD-1 inhibitor according to PD-L1 CPS score.

SOX 요법, CAPEOX 요법, PD-1 억제제, 대동맥 주위 림프절 방사선 치료(16번 스테이션까지 IMRT), 카페시타빈/S-1(IMRT 중 방사선 증감제)