BSLD-10 CLOSED-LOOP, RECIRCULATING INTRAVENTRICULAR CHEMOTHERAPY DELIVERY FOR LEPTOMENINGEAL DISEASE TREATMENT
Beverly Petusseau, Kevin Kalish, Armin Tavakkoli, Marcie Glicksman, Anthony DePasqua, Enresto Ruiz, Caleb Stewart, Linton EvansAbstract
Background
Leptomeningeal disease (LMD) is a devastating complication of metastatic cancer characterized by dissemination of malignant cells throughout the cerebrospinal fluid (CSF) and leptomeninges. Prognosis remains poor, with no established standard-of-care that reliably prolongs survival or preserves neurologic function. Existing therapies are limited by inadequate CSF drug penetration and systemic toxicity. We evaluated a novel closed-loop, recirculating intraventricular delivery system designed to enhance CSF drug distribution through controlled, programmable flow.
Methods
U87 gliomas were induced in immunosuppressed Yucatan mini-pigs to model central nervous system malignancy. Following tumor establishment, animals underwent placement of bilateral ventricular catheters connected to subcutaneous reservoirs to allow repeated intraventricular access. Pigs were assigned to one of two groups. The control group received standard intraventricular topotecan (0.1 mg) administered twice weekly for two weeks. The experimental group received identical dosing followed by 2 hours of closed-loop CSF recirculation using the EnClear EnTrega system, enabling continuous drug circulation and oscillatory CSF flow. After completion of treatment, MRI was performed to evaluate tumor progression. Brain tissue was analyzed using matrix-assisted laser desorption/ionization (MALDI) and liquid chromatography-mass spectrometry (LC-MS) to assess drug distribution.
Results
All animals demonstrated successful tumor engraftment prior to treatment initiation. Bilateral catheter placement and closed-loop CSF circulation were well tolerated, with no procedural complications. To date, 12 treatment sessions have been completed in the experimental group without technical failures or adverse events. Preliminary findings support the feasibility and safety of the recirculating delivery platform. Quantitative analyses of drug distribution and therapeutic response are ongoing.
Conclusions
Closed-loop, recirculating intraventricular chemotherapy delivery is feasible and well tolerated in a large animal model. This approach has the potential to improve CSF drug distribution and therapeutic efficacy in LMD. Further studies are underway to evaluate pharmacokinetics and treatment outcomes with first in human studies planned for Q12027.