2292 - Radiotherapy plus Chemoimmunotherapy Followed by Surgery for Gastric Cancer with Limited Lymph Node Metastases: Preliminary Results from the MIRACLE-G Study

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 26

POSTER

Presenter(s)

Fan Xia, MD, PhD - Fudan University Shanghai Cancer Center, Shanghai, Shanghai

M. L. Zhou¹, J. Guo², W. Yang¹, H. Zhang¹, Y. Wang¹, Y. Chen¹, J. Wang¹, L. Shen¹, Y. Wang¹, J. Wan¹, S. Zhou¹, R. Wu¹, Z. Zhang¹, H. Pan², B. Sun², Y. Duan², J. Gao², H. Cai², G. Zhao², D. Xu², F. Xia¹, and Z. Zhang¹; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

Purpose/Objective(s):

Systemic therapy remains the standard of care for metastatic gastric cancer (GC). However, select patients with limited metastases may benefit from the addition of surgical resection. Building upon chemoimmunotherapy, the addition of radiotherapy may further enhance treatment efficacy through synergistic interactions. The phase II trial (MIRACLE-G) evaluated the efficacy and safety of radiotherapy combined with chemoimmunotherapy, followed by surgery, in GC patients with limited lymph node metastases (LLNM).

Materials/Methods:

In this prospective, single-arm, investigator-initiated phase II study, we enrolled GC patients with LLNM, defined as retroperitoneal lymph node metastases (RPLM) alone or in combination with extra-abdominal lymph node metastases (e.g., supraclavicular). Eligible patients received hypofractionated radiotherapy to the primary tumor and metastatic lesions, followed by SOX/FOLFOX chemotherapy and a PD-1 inhibitor (with trastuzumab added for HER2-positive cases). Response was assessed every eight weeks. Patients achieving resectable status underwent radical gastrectomy with regional lymphadenectomy; those with unresectable disease continued systemic therapy until progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included R0 resection rate, objective response rate (ORR), pathological complete response (pCR) rate, progression-free survival (PFS), and safety.

Results:

As of January 31, 2026, efficacy data were available for 14 patients. The majority were male (n=10, 71.4%), with a median age of 67 years (range: 48–75). Nine patients presented with RPLM alone, and five with RPLM plus extra-abdominal lymph node metastases. All tumors were adenocarcinoma and microsatellite stable, including one HER2-positive and one EBER-positive case. The ORR was 92.9% (13/14). Among the 10 patients who underwent radical surgery, the R0 resection rate was 100% (10/10), and the pCR rate was 60.0% (6/10). At last follow-up, nine patients had no evidence of disease (NED), while one had experienced recurrence (peritoneal seeding). With a median follow-up of 12.9 months (95% CI: 3.4–22.4), no deaths were reported. Median PFS and OS were not reached. No grade 5 treatment-related adverse events (TRAEs) occurred. The most common all-grade TRAEs were lymphocytopenia (100.0%), hypoalbuminemia (85.7%), and thrombocytopenia (78.6%). The most frequent grade 3/4 TRAEs were lymphocytopenia (28.6%), thrombocytopenia (14.3%) and anemia (7.1%).

Conclusion:

In patients with GC and LLNM, the combination of radiotherapy and chemoimmunotherapy followed by surgery demonstrated promising efficacy and a manageable safety profile. Continued patient accrual and longer follow-up are warranted to assess long-term outcomes.