Clinical Report: Combining Radiotherapy and Immunotherapy for Locally Advanced Gastric Cancer

Background

Gastric cancer and gastroesophageal junction adenocarcinoma are significant global health concerns, ranking as the 5th most common malignant tumors and a leading cause of cancer-related deaths.

Data Highlights

Current trials such as Neo-PLANET and SHARED have shown pathological complete response rates ranging from 22.6% to 38.2% with manageable toxicity profiles when combining neoadjuvant chemoradiotherapy and immune checkpoint inhibitors.

Key Findings

• Radiotherapy enhances antitumor immunity through mechanisms like immunogenic cell death and activation of the cGAS-STING pathway.
• Neoadjuvant chemoradiotherapy combined with ICIs has shown results, yet lacks long-term survival data.
• Predictive biomarkers such as PD-L1 expression and tumor mutational burden require further validation for effective patient stratification.
• Large-scale randomized controlled trials are needed to confirm survival benefits and establish standardized protocols for treatment.

Clinical Implications

Clinicians should consider the potential of combining radiotherapy with immunotherapy in treatment plans for locally advanced gastric cancer. Ongoing trials and emerging biomarkers may guide future therapeutic strategies and patient selection.

Conclusion

The combination of radiotherapy and immunotherapy presents a promising avenue for treating locally advanced gastric cancer, though further research is essential to validate findings and optimize treatment protocols.

Related Resources & Content

1. The ASCO Post, 2011 -- Despite Challenges, Combined-modality Therapy Warranted for Locally Recurrent Colorectal Cancer
2. Frontiers in Immunology, 2026 -- Unlocking the Potential: Current Landscape and Future Directions of Immunotherapy in Gastric Cancer
3. The ASCO Post, 2019 -- In Era of Immunotherapy, Radiation Therapy May Become Essential Component of Systemic Treatments of Cancer
4. New England Journal of Medicine -- Preoperative Chemoradiotherapy for Resectable Gastric Cancer
5. PMC, 2021 -- FDA Approval Summary: Nivolumab for the adjuvant treatment of adults with completely resected esophageal/gastroesophageal junction cancer and residual pathologic disease
6. Frontiers in Oncology — Feasibility and strategy analysis of radiotherapy consolidation following immunotherapy for stage IV esophageal squamous cell carcinoma
7. Perioperative Treatment With Durvalumab and FLOT Chemotherapy Can Reduce Risk of Recurrence for Some Patients With Gastric Cancers
8. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585)
9. Preoperative Chemoradiotherapy for Resectable Gastric Cancer | New England Journal of Medicine
10. FDA Approval Summary: Nivolumab for the adjuvant treatment of adults with completely resected esophageal/gastroesophageal junction cancer and residual pathologic disease - PMC
11. Trial Results: ECOG-ACRIN Research Round-Up - ASCO 2024 Highlights
12. Phase I/II Trial of Perioperative Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Junction Cancer - Uboha - 2025 - Journal of Surgical Oncology - Wiley Online Library
13. Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975) - NCI