Citations

BACKGROUND AND OBJECTIVES: Despite standard of care with maximal safe resection and chemoradiation, glioblastoma (GBM) is the most common and aggressive type of primary brain cancer. Surgical resection provides a window of opportunity to locally treat gliomas while the patient is recovering and before initiating concomitant chemoradiation. The objective was to assess the safety and establish the maximum tolerated dose of adipose-derived mesenchymal stem cells (AMSCs) for the treatment of recurrent GBM. Secondary objectives were to assess the toxicity profile and long-term survival outcomes of patients enrolled in the trial. In addition, biospecimens will be collected to explore the local and systemic responses to this therapy. METHODS: We will conduct a phase 1, dose-escalated, nonrandomized, open-label, clinical trial of patients with GBM who are undergoing surgical resection for recurrence. Up to 18 patients will receive intracavitary application of AMSCs encapsulated in fibrin glue during surgical resection. All patients will be followed for up to 5 years for safety and survival data. Adverse events will be recorded using the CTCAE V5.0. EXPECTED OUTCOMES: This study will explore the maximum tolerated dose of AMSCs along with the toxicity profile of this therapy in patients with recurrent GBM. In addition, preliminary long-term survival and progression-free survival outcome analysis will be used to power further randomized studies. Finally, cerebrospinal fluid and blood will be obtained throughout the treatment period to investigate circulating molecular and inflammatory tumoral/stem cell markers and explore the mechanism of action of the therapeutic intervention. DISCUSSION: This prospective translational study will determine the initial safety and toxicity profile of local delivery of AMSCs for recurrent GBM. It will also provide additional survival metrics for future randomized trials.

AbstractObjectiveNeck metastases are a poor prognostic factor in olfactory neuroblastoma (ONB). Pathologic dural invasion (pathDI) may increase the risk of neck metastases due to invasion of dural lymphatics. We aim to evaluate the prognostic value of pathDI in predicting rates of neck metastases and recurrence using a large, multicenter database of ONB patients.Data sourcesRetrospective review of a prospective, multicenter database of electronic health records of all patients who presented with ONB between 2005 and 2021 at nine tertiary academic care centers within North America.Review methodsClinicopathologic features including modified Kadish staging systems, margin status, treatment modalities, Hyams grading, follow‐up time, and survival.ResultsOf 258 ONB patients, 189 patients met the inclusion criteria. The 10‐year neck recurrence‐free survival (neck‐RFS) rates were 85.7% (75.6‒97.3) and 61.8% (47.9‒79.8) for patients without and with pathDI, respectively (p = 0.018). Time‐to‐event multivariable regression analysis found pathDI to have an odds ratios of 9.7 (95% confidence interval [CI] 1.2–80.4, p = 0.04) for neck‐RFS and 9.5 for RFS at any site (95% CI 1.1–83.3, p = 0.04).ConclusionIn multivariable analysis, the presence of pathDI appears to be the strongest predictor of neck recurrence and recurrence at any site. Future studies exploring the benefit of elective neck dissection or radiation for patients with pathDI may impact disease management.

Skull base surgery has evolved remarkably since the pioneering techniques of early 20th-century surgeons, such as Schloffer and Cushing, who laid the foundation for transcranial and transnasal approaches [...]