Leptomeningeal carcinomatosis in pancreatic cancer: Clinical presentation, management, and outcomes—A systematic review.

Abstract

e16431 Background: Leptomeningeal carcinomatosis (LMC) is a rare and devastating complication of advanced malignancies, occurring in fewer than 1% of patients with pancreatic cancer. Owing to its rarity, the clinical presentation, diagnostic approaches, management strategies, and outcomes remain poorly defined. We conducted a systematic review to characterize the clinical features, diagnostic modalities, treatments, and survival outcomes of pancreatic cancer–associated LMC. Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and conference proceedings from January 2001 through December 2025 to identify reported cases of pancreatic cancer complicated by leptomeningeal carcinomatosis (LMC). Eligible cases included histologically confirmed pancreatic adenocarcinoma, neuroendocrine tumor, or mucinous neoplasm with leptomeningeal involvement confirmed by neuroimaging, cerebrospinal fluid analysis, or autopsy, and sufficient clinical detail. Data extracted included demographics, tumor characteristics, diagnostic modalities, treatments, and outcomes. Results: Twenty-five cases of pancreatic cancer–associated leptomeningeal carcinomatosis (LMC) were identified. Median age at pancreatic cancer diagnosis was 57 years (IQR, 45–72), and 60% were male. Histology was predominantly pancreatic ductal adenocarcinoma (84%). LMC developed a median of 11 months after cancer diagnosis. Common neurologic presentations included headache (80%), cranial nerve deficits (40%), confusion or encephalopathy (36%), seizures (32%), and gait ataxia (28%). Diagnosis relied primarily on contrast-enhanced brain MRI (92%), while CSF cytology was positive in only 40% of cases despite abnormal findings. Management was largely palliative, including whole-brain radiotherapy (44%), intrathecal chemotherapy (20%), systemic therapy continuation (32%), and supportive care alone (28%). Median survival following LMC diagnosis was 14 days. Conclusions: Leptomeningeal carcinomatosis in pancreatic cancer is a terminal complication with severe neurologic morbidity and poor survival. Early recognition and prompt MRI evaluation are critical in symptomatic patients. Current therapies offer limited benefit, emphasizing the need for improved diagnostics and CNS-penetrant treatments to advance patient-centered care. Baseline characteristics of patients with pancreatic cancer–associated leptomeningeal carcinomatosis (N = 25). Characteristic Value Sex (M/F) 60% / 40% Age PC dx, yrs 57 (45–72) Age LMC dx, yrs 57 (45–80) Tumor site Head 36%, Tail 28%, Body 24% Histology PDAC 84%, Mucinous 8%, NET 4% Stage IV 36% CA 19-9, U/mL 533 (1–22,700) Smoking known 20% Pathogenic mutation 20% Values are N (%) or median (IQR/range). PC = pancreatic cancer; LMC = leptomeningeal carcinomatosis; PDAC = pancreatic ductal adenocarcinoma; NET = neuroendocrine tumor.