Citations

Abstract Lead (Pb) poisoning is a significant threat to Aotearoa New Zealand's endangered kea ( Nestor notabilis ), an avian species important to Māori. Historically, exposure was thought to be from lead‐containing building materials; however, recent field observations suggest lead‐based ammunition as an additional source. We used stable lead isotopes to investigate the sources of lead to kea. Comparing 207 Pb/ 206 Pb ratios in kea blood ( n = 91) to both ammunition and building materials, we found approximately one‐third of exposed kea (blood lead > 10 µg/dL) had lead isotope ratios consistent with exposure to lead‐based ammunition. As lead ammunition is still used, including in government‐sponsored culling programs, our data indicate an urgent need to shift toward non‐lead ammunition use to prevent further poisoning and aid conservation efforts. Collaborating with tangata whenua /Māori guardians, we advocate for immediate policy changes to eliminate lead‐based ammunition in kea habitat to safeguard this endangered culturally treasured species from extinction.

Objective To evaluate the long-term changes in sporadic vestibular schwannoma (VS) disease-specific quality-of-life (QOL) outcomes. Study Design Prospective longitudinal study using the Penn Acoustic Neuroma Quality of Life (PANQOL) Scale. Setting National survey. Patients Patients with sporadic VS who completed a baseline survey before treatment and at least one follow-up survey recruited through the authors’ center and through the Acoustic Neuroma Association. Interventions Observation, microsurgery, radiosurgery. Main Outcome Measures Changes in PANQOL scores from baseline to most recent survey. Results Among 445 eligible patients the mean duration of follow-up was 4.4 (SD, 2.3) years, including 122, 218, and 105 in the observation, microsurgery, and radiosurgery groups, respectively. Patients managed with observation (p = 0.03) or microsurgery (p < 0.001) demonstrated improvement in anxiety scores. Changes in facial function scores differed significantly by management group (p = 0.01), with patients undergoing microsurgery demonstrating a mean decline of 10 points in facial function scores compared with mean declines of 3 for those managed with observation or radiosurgery. Hearing loss scores decreased similarly over time for all three groups (p = 0.3). There were minimal changes in total PANQOL scores over time across all management groups (p = 0.5). Conclusions Long-term changes in total QOL among VS management groups are not significantly different. Microsurgery may continue to confer an advantage regarding improvement in anxiety postoperatively, but with a greater decline in facial function when compared to observation or radiosurgery. Long-term declines in hearing loss scores were not statistically significantly different among groups.

Abstract BACKGROUND Glioblastoma (GBM) is the most common primary brain malignancy in adults. Standard of care (SOC) for suspected GBM begins with maximal safe resection followed by adjuvant radiotherapy and temozolomide, and maintenance temozolomide. Imvax has utilized its Goldspire™ platform to create IGV-001, an autologous biologic-device combination product for the treatment of newly diagnosed GBM (ndGBM). IGV-001 consists of autologous GBM tumor cells and an antisense oligonucleotide against IGF-1R mRNA (IMV-001), irradiated and administered via biodiffusion chambers implanted in the abdomen. Together, these components stimulate immunogenic cell death and antigen release. In a phase 1b study in patients with ndGBM, IGV-001 was well tolerated without unexpected adverse events. Multiple efficacy signals were also observed, including significant improvements in progression-free survival, overall survival, radiographic evidence of tumor response, and changes in immune response biomarkers. A phase 2b randomized, multicenter, double-blind, placebo-controlled study to assess the safety and efficacy of IGV-001 in patients with ndGBM (ClinicalTrials.gov identifier: NCT04485949) is ongoing. Here, we present the first safety data from the study. MATERIAL AND METHODS After surgical resection, patients are treated with IGV-001 or placebo followed by SOC. The study will enroll approximately 93 patients at 20 sites in the United States, with a 2:1 randomization favoring IGV-001. The primary outcome is progression-free survival, defined as the time from randomization to first progression, as determined by blinded central radiology review, or death. Secondary outcomes include overall survival, defined as the time from randomization to death due to any cause, and safety. RESULTS As of February 2, 2024, a total of 72 patients have been randomized and 69 have been implanted with IGV-001 or placebo plus SOC. The median age was 60.0 years (range, 24-70 years). Most randomized patients (76.4%) were 51-70 years of age, and the male:female ratio was 2.27. A total of 39/45 (86.7%) patients with enough follow-up time, initiated treatment with concurrent radiation and temozolomide. A total of 9/72 (12.5%) randomized patients discontinued treatment, including 7 patients who discontinued during the SOC treatment period. No patients discontinued treatment for adverse events, protocol deviations, or death. A total of 11/72 (15.3%) randomized patients discontinued the study after randomization. CONCLUSION To date, the review of blinded safety data did not show any emerging risk and supports that there is no change to the benefit-risk profile of treatment with IGV-001 versus placebo. The data will be updated before presentation.

Abstract BACKGROUND Myxopapillary ependymomas (MPE) are slow-growing tumors of the spine typically involving the medullary conus and cauda equina. MPE is regularly managed with surgical resection with radiation therapy reserved for cases where gross total resection cannot be achieved. Management of inoperable cases represents a clinical challenge. No systemic therapy is approved for treatment of MPE. Addition of chemotherapy may improve outcomes for cases not amenable to resection. MATERIAL AND METHODS We report feasibility and preliminary efficacy of combination treatment with proton beam radiation therapy and temozolomide chemotherapy for a patient with large, unresectable MPE. RESULTS A 19-year-old female presented with one year of gradually worsening hip and back pain despite treatment with physical therapy. MRI Lumbar spine identified a destructive and expansile T2-heterogenous and hyperintense intraosseous mass (14 x 12 x 13 cm) with extraosseous expansion involving the sacrum, coccyx, and left SI joint with abnormal soft tissue enhancement extending along the posterior spine. No additional lesions were identified on neuro-axis imaging. Biopsy of the mass was consistent with a WHO grade 2 myxopapillary ependymoma. Standard treatment of care would include complete surgical resection. Unfortunately, this would require a morbid procedure in an en block fashion with immediate and permanent loss of bowel, bladder, sexual, and ambulatory function in a young patient whose primary symptom was pain and mild weakness. It was therefore elected to treat the patient in an unconventional approach and begin with proton beam radiation therapy (59.4 Gy in 33 fractions) with concurrent temozolomide followed by 6 cycles of adjuvant temozolomide. Mild clinical improvement and significant radiographic response were achieved (size reduced to 8 x 7 x 11 cm). CONCLUSION This case suggests a potential role for use of proton radiation therapy with concurrent and adjuvant temozolomide for management of myxopapillary ependymoma not amenable to surgical resection.