Reconsidering the Role of Radiotherapy for Inoperable Gastric Cancer: A Systematic Review of Gastric Radiotherapy Given With Definitive and Palliative Intent.

Aims: The role of radiotherapy (RT) for inoperable gastric cancer (IGC) is commonly low-dose, given reactively for symptoms (e.g. bleeding), in contrast to the oesophagus, where high quality evidence exists for higher doses of RT. This systematic review aims to evaluate the use of, and evidence for, definitive and high-dose palliative RT for IGC and whether a change in practice is warranted.

Materials And Methods: Following registration with PROSPERO (CRD42022297080), MEDLINE, EMBASE and The Cochrane Library were searched in accordance with PRISMA standards for studies evaluating definitive (non-metastatic disease, BED10 >45Gy) or high-dose palliative RT (for symptom/local control, minimum BED10 >30Gy). A manual search of meeting proceedings and clinical trial registries was also performed.

Results: 31 studies were selected for analysis. 10 definitive studies totalling n = 354 patients receiving RT with 45-50.4Gy/25-28#, showed median overall survival ranging between 11 and 26.4 months, clinical complete response range 12%-45%, G3 gastrointestinal toxicity 0-31% (range) and RT completion rates ranging from 81% to 100%. 21 high-dose palliative studies (n = 955) mostly evaluated haemostatic control and reported 38 different RT regimens (most commonly 30Gy/10#). Bleeding response rate (RR) was 59.6%-90%, pain RR 45.5-100%, obstruction RR 52.9%-100%, G3 gastrointestinal toxicity <5% and RT completion 68%-100%. An additional American National Cancer Database review >4700 non metastatic IGC patients which combined both definitive and palliative doses found significant benefit to RT in addition to chemotherapy. Evidence regarding a dose-response relationship is conflicting, limited by retrospective data. Two studies report high quality -of-life (QOL) scores following gastric RT.

Conclusion: There is a body of mainly non-randomised, observational evidence showing high-dose RT is efficacious, safe and may maintain QOL for patients with IGC. A change in practice will require a prospective randomised controlled trial, which should explore the role of prophylactic, high-BED RT combined with optimal systemic therapy using modern IMRT techniques and RT quality assurance.