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Background: Primary skull base chondrosarcomas (SBCs) can severely affect patients’ quality of life. Surgical-resection and radiotherapy are feasible but may cause debilitating complications. We systematically reviewed the literature on primary SBCs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with primary SBCs. Clinical characteristics, management strategies, and treatment outcomes were analyzed. Results: We included 33 studies comprising 1307 patients. Primary SBCs mostly involved the middle-fossa (72.7%), infiltrating the cavernous-sinus in 42.4% of patients. Cranial-neuropathies were reported in 810 patients (62%). Surgical-resection (93.3%) was preferred over biopsy (6.6%). The most frequent open surgical approaches were frontotemporal-orbitozygomatic (17.6%) and pterional (11.9%), and 111 patients (21.3%) underwent endoscopic-endonasal resection. Post-surgical cerebrospinal-fluid leaks occurred in 36 patients (6.5%). Radiotherapy was delivered in 1018 patients (77.9%): photon-based (41.4%), proton-based (64.2%), and carbon-based (13.1%). Severe post-radiotherapy complications, mostly hypopituitarism (15.4%) and hearing loss (7.1%) were experienced by 251 patients (30.7%). Post-treatment symptom-improvement (46.7%) and reduced/stable tumor volumes (85.4%) showed no differences based on radiotherapy-protocols (p = 0.165; p = 0.062). Median follow-up was 67-months (range, 0.1–376). SBCs recurrences were reported in 211 cases (16.1%). The 5-year and 10-year progression-free survival rates were 84.3% and 67.4%, and overall survival rates were 94% and 84%. Conclusion: Surgical-resection and radiotherapy are effective treatments in primary SBCs, with acceptable complication rates and favorable local tumor control.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of the introduction of either wild-type or engineered viruses to the site of disease, where they exert an antitumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induces tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights the potential to integrate this therapeutic strategy into promising combinatory approaches.

Introduction: OS2966 is a first-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for the intratumoral, convection-enhanced delivery (CED) of OS2966. Gadolinium contrast will be added to OS2966 before each infusion, enabling the real-time visualization of therapeutic distribution via MRI. Subsequently, patients will undergo their clinically indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: (1) the latest CED technology, (2) 2-part design including neoadjuvant intratumoral administration, (3) a first-in-class investigational therapeutic, and (4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active.

Hyphal growth is essential for host colonization during Aspergillus infection. The transcription factor ZfpA regulates A. fumigatus hyphal development including branching, septation, and cell wall composition. However, how ZfpA affects fungal growth and susceptibility to host immunity during infection has not been investigated. Here, we use the larval zebrafish-Aspergillus infection model and primary human neutrophils to probe how ZfpA affects A. fumigatus pathogenesis and response to antifungal drugs in vivo. ZfpA deletion promotes fungal clearance and attenuates virulence in wild-type hosts and this virulence defect is abrogated in neutrophil-deficient zebrafish. ZfpA deletion also increases susceptibility to human neutrophils ex vivo while overexpression impairs fungal killing. Overexpression of ZfpA confers protection against the antifungal caspofungin by increasing chitin synthesis during hyphal development, while ZfpA deletion reduces cell wall chitin and increases caspofungin susceptibility in neutrophil-deficient zebrafish. These findings suggest a protective role for ZfpA activity in resistance to the innate immune response and antifungal treatment during A. fumigatus infection.