Robin, Adam

ABSTRACTObjectiveIntrathecal fluorescein (IF) is effective for localizing nasal cerebrospinal fluid (CSF) leaks along the skull base during endoscopic exploration, with largest studies reporting sensitivities ranging from 66%–93%. Due to reports of intraoperative and postoperative neurologic complications such as seizures and paralysis, surgeons often dilute the fluorescein and inject it intrathecally slowly over a variable amount of time. However, no study has assessed whether rapid IF administration causes the aforementioned risks or whether it affects its accuracy in identifying CSF leaks intraoperatively.MethodsA prospective study was conducted from 2015 to 2024, where all patients undergoing endoscopic exploration and/or repair of CSF rhinorrhea had 0.1 mL of 10% fluorescein (10 mg) mixed with 3–5 mL of patients' CSF injected rapidly via the lumbar drain over a few seconds.ResultsOf the 82 included patients, the mean age was 53.8 ± 15.2 years, and 84% were female. Sixty‐nine patients underwent successful endoscopic CSF leak repairs, and 13 had negative endoscopic explorations. Rapid IF injection was 80% sensitive (20% false negative rate) and 100% specific for identifying CSF leaks, and it caused no seizures, paralysis, or other neurologic complications.ConclusionCompared to prior reports of slow low‐dose IF injection for CSF leak localization, rapid IF injection yielded similar efficacy (80% sensitivity) with no IF‐related complications. Rapid IF injection was safe and effective but should be corroborated by future studies.Level of Evidence4.

Abstract Standard of care (SOC) for ndGBM begins with maximal safe resection followed by adjuvant radiotherapy and temozolomide, and maintenance temozolomide. IGV-001 is an autologous biologic-device combination immunotherapy for the treatment of ndGBM that consists of autologous GBM tumor cells and an antisense oligonucleotide against IGF-1R mRNA, irradiated and administered via biodiffusion chambers implanted in the abdomen. In a phase 1b study, IGV-001 was well tolerated without unexpected adverse events in subjects with ndGBM. Multiple efficacy signals were observed, including significant improvements in progression-free survival (PFS), overall survival (OS), radiographic evidence of tumor response, and changes in immune response biomarkers. Here, we present early safety data from the phase 2b randomized, multicenter, double-blind, placebo-controlled study (NCT04485949) designed to assess efficacy and safety of IGV-001 in subjects with ndGBM across 20 sites in the United States. After surgical resection, subjects were randomized 2:1 and treated with IGV-001 or placebo followed by SOC. The primary outcome is PFS, defined as the time from randomization to first progression, as determined by blinded central radiology review, or death. Secondary outcomes include OS, defined as the time from randomization to death due to any cause, and safety. As of May 22, 2024, 99 subjects were randomized and 95 implanted with IGV-001 or placebo plus SOC. A total of 39/45 (86.7%) subjects had sufficient follow-up time after initiated treatment with concurrent radiation and temozolomide. Nine of 72 randomized (12.5%) discontinued treatment, including 7 who stopped during the SOC treatment period. None ceased treatment for adverse events, protocol deviations, or death. A total of 11/72 (15.3%) randomized subjects discontinued the study after randomization. A review of blinded safety data did not show any emerging risk and supports no change to the benefit-risk profile of IGV-001 versus placebo. Updated data will be presented.