Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a 'liquid gold' biopsy.

BACKGROUND: Biomarkers that reflect glioblastoma tumour activity and treatment response are urgently needed to help guide clinical management, particularly for recurrent disease. As the urinary system is a major clearance route of circulating extracellular vesicles (EVs; 30-1000 nm nanoparticles) we explored whether sampling urinary-EVs could serve as a simple and non-invasive liquid biopsy approach for measuring glioblastoma-associated biomarkers. METHODS: Fifty urine specimens (15-60 ml) were collected from 24 catheterised glioblastoma patients immediately prior to primary (n = 17) and recurrence (n = 7) surgeries, following gross total resection (n = 9), and from age/gender-matched healthy participants (n = 14). EVs isolated by differential ultracentrifugation were characterised and extracted proteomes were analysed by high-resolution data-independent acquisition liquid chromatography tandem mass spectrometry (DIA-LC-MS/MS). RESULTS: Overall, 6857 proteins were confidently identified in urinary-EVs (q-value ≤ 0.01), including 94 EV marker proteins. Glioblastoma-specific proteomic signatures were determined, and putative urinary-EV biomarkers corresponding to tumour burden and recurrence were identified (FC ≥ | 2 | , adjust p-val≤0.05, AUC > 0.9). CONCLUSION: In-depth DIA-LC-MS/MS characterisation of urinary-EVs substantiates urine as a viable source of glioblastoma biomarkers. The promising 'liquid gold' biomarker panels described here warrant further investigation.

Predictors of Clinical Failure after Endoscopic Lumbar Spine Surgery During the Initial Learning Curve.

OBJECTIVE: This study aims to identify clinical factors that may predict failed endoscopic lumbar spine surgery to guide surgeons with patient selection during the initial learning curve. METHODS: This is an Australasian prospective analysis of the first 105 patients to undergo lumbar endoscopic spine decompression by 3 surgeons. Modified MacNab outcomes, visual analog scale (VAS) and Oswestry Disability Index (ODI) scores were utilized to evaluate clinical outcomes at 6 months postoperatively. Descriptive statistics and ANOVA t tests were performed to measure statistically significant (P < 0.05) associations between variables using GraphPad Prism v10. RESULTS: Patients undergoing endoscopic lumbar surgery via an interlaminar or transforaminal approach have overall good/excellent modified MacNab outcomes and a significant reduction in postoperative VAS and ODI scores. Regardless of the anatomic location of disc herniations, good/excellent modified MacNab outcomes and significant reductions in VAS and ODI were reported post-operatively, however, not in patients with calcified disc herniations. Patients with central and foraminal stenosis overall reported poor/fair modified MacNab outcomes, however, there were significant reductions in VAS and ODI scores postoperatively. Patients with subarticular stenosis or an associated spondylolisthesis reported good/excellent modified MacNab outcomes and significant reductions in VAS and ODI scores postoperatively. Patients with disc herniation and concurrent degenerative stenosis had generally poor/fair modified MacNab outcomes. CONCLUSIONS: The outcomes of endoscopic spine surgery are encouraging with low complication and reoperation rates. However, patients with calcified disc herniations, central canal stenosis, or disc herniation with concurrent degenerative stenosis present challenges during the initial learning curve and may benefit from traditional open or other minimally invasive techniques.

Biphenotypic Sinonasal Sarcoma: A Case Report and Review of Literature.

OBJECTIVES: Biphenotypic sinonasal sarcoma (BSNS), previously low-grade sinonasal sarcoma with neural and myogenic features, is a rare tumor of the sinonasal tract first described in 2012. Due to its rarity, limited literature is available in providing clinicians with a standardized treatment regimen, particularly in cases of positive surgical margins. This article aims to provide a clinical review of the currently available reported cases of BSNS, as well as presenting clinical, radiologic, and pathologic details of 2 novel cases. METHODS: Online electronic databases include PubMed and Embase where queried for reports of biphenotypic sinonasal sarcoma or low-grade sinonasal sarcoma with neural and myogenic features. Two previously unpublished cases were included in the results. Data including clinical presentation, epidemiologic data, radiologic evaluation, intraoperative details, histopathology, treatment modality, and postoperative follow-up information were included. RESULTS: A total of 100 previously published cases were identified in 12 prior articles. Mean age at presentation was 52.9 years. Extrasinonasal extension was observed in 27.4% of cases with most common site of extension being cribriform plate. Forty-seven cases included treatment details with surgical excision being the most common modality. Recurrence rates were identical for both surgical excision alone and surgical excision with adjuvant radiotherapy (33.3%). CONCLUSIONS: Biphenotypic sinonasal sarcoma is a slow-growing tumor that is amenable to surgical resection. Recurrence rates are similar between surgical excision and surgical excision with adjuvant radiation therapy, but limited data in reported cases preclude a determination of treatment superiority.

Combination of palbociclib and radiotherapy for glioblastoma.

The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib (with and without RT). Overall survival was measured. Palbociclib treatment resulted in a significant increase in the percentage of cells in the G1 cell cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib combined with RT acted synergistically with the significant impediment of colony formation. The oral treatment of mice with palbociclib did not show any significant survival advantage when compared to control mice, however when combined with RT, a survival advantage of 8 days was observed. Our results support the use of palbociclib as an adjuvant treatment to RT and warrant translation to the clinic.