Background: Leptomeningeal carcinomatosis (LMC) from gastric cancer is rare but carries a poor prognosis, and its risk factors and clinical presentation remain unclear.
Methods: Among 3850 patients treated with palliative chemotherapy, those with pathologically or cytologically confirmed LMC were included. Responsiveness to intrathecal methotrexate (IT-MTX) was defined as a malignant cell count < 1/μL on ≥ 2 consecutive cerebrospinal fluid analyses. Survival outcomes were compared across subgroups with different clinical presentations.
Results: During a median follow-up of 13.7 months, LMC was diagnosed in 0.8% (32/3850) of patients. At the time of LMC diagnosis, 27 patients were undergoing palliative systemic chemotherapy, 4 were diagnosed with recurrence following curative surgery, and 1 was diagnosed with the initial presentation of metastatic gastric cancer. Multivariate logistic regression analysis revealed that signet ring cell carcinoma (SRC) and/or poorly differentiated adenocarcinoma (PD) was the most relevant risk factor for LMC (adjusted odds ratio 4.78; p = 0.036). Thirty patients received IT-MTX, with responders (n = 23) showing longer overall survival (OS) than non-responders (n = 7) (p = 0.004). Among the 29 patients with available data on extracranial disease control, those with controlled extracranial disease at LMC diagnosis (n = 19) demonstrated significantly better OS following IT-MTX than those with progressive extracranial disease (n = 10) (p = 0.023).
Conclusions: SRC and/or PD is a key risk factor for LMC, which often arises despite controlled extracranial disease, necessitating early evaluation for neurologic symptoms. Survival outcomes depend on IT-MTX response and the status of extracranial disease.
Keywords: Gastric cancer; Leptomeningeal carcinomatosis; Risk factor.
© 2026. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.