Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment. We studied the expression of a handful of immune markers (CD3, CD8, CD68, PD-L1 and PD-1) in GBM tissues in 15 paired primary and recurrent GBM. In five selected patients, we used Nanostring Digital Spatial Profiling (DSP) to obtain simultaneous assessments of multiple biomarkers both within the tumor and the microenvironment in paired primary and recurrent GBM. Our results suggest that the evolution of the immune landscape between paired primary and recurrent GBM tumors is highly heterogeneous. However, our study identifies B3-H7 and HLA-DR as potential targets in primary and recurrent GBM. Spatial profiling of immune markers from matched primary and recurrent GBM shows a nonlinear complex evolution during the progression of cancer. Nonetheless, our study demonstrated a global increase in macrophages, and revealed differential localization of some markers, such as B7-H3 and HLA-DR, between GBM and its TME.

BACKGROUND AND OBJECTIVES: In skull base neurosurgery, the pterional approach is of particular importance for many indications. These approaches are challenging for young inexperienced neurosurgeon. That is why training on realistic model is a true added value. We aimed to develop and pedagogically evaluate a revascularized cadaveric model combining pulsatile arterial perfusion with restoration of cerebrospinal fluid pressure. The model was designed to simulate a frontopterional approach, subarachnoid dissection, and exposure of the circle of Willis. It also aimed to reproduce the management of an intracranial carotid artery injury. METHODS: Sixteen neurosurgical residents completed 3 simulation using freshly preserved cadavers perfused with the SIMLIFE system (synthetic blood perfusion through common carotid arteries) and intracranial pressure restauration through cerebrospinal fluid perfusion. The model was assessed using Kirkpatrick's framework: Realism (level 1), Self-reported confidence (level 2), and Objective technical performance including blinded video analysis, bleeding duration and volume, and nontechnical skills such as communication and stress management (level 3). RESULTS: Anatomic and physiological realism were rated highly. Significant improvement in self-confidence was observed for most surgical steps. Blinded video analysis did not demonstrate a statistically significant global improvement, largely because of substantial intercadaver variability affecting brain consistency and vascular patency. CONCLUSION: This revascularized cadaveric model provides a high-fidelity simulation strongly appreciated by trainees. It significantly enhances confidence in performing a complex skull base and vascular approaches. Optimization of cerebral fixation and vascular consistency could improve reproducibility and enable more accurate measurement of technical progress.

A solitary bone plasmacytoma is a rare tumor. Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma. We present the case of a 48-year-old female patient who consulted for recent back pain, with a final diagnosis of T10 solitary plasmacytoma and synchronous intrahepatic cholangiocarcinoma. Imaging suggested cholangiocarcinoma with bone metastasis. The patient underwent neurosurgical management with laminectomy, arthrodesis, and arthrectomy, with biopsies revealing monotypic kappa plasmacytic proliferation. Liver biopsies revealed an adenocarcinoma with expression of cytokeratin 19, cytokeratin 7, N-cadherin, and high expression of carbonic anydrase IX. The plasmacytoma was treated with external radiotherapy. The cholangiocarcinoma was treated with selective internal radiation therapy and concomitant systemic treatment with combinations of cisplatin and durvalumab, with capecitabine during radiotherapy, switched for gemcitabine after completion of irradiation. One year after initial management, imaging revealed a partial metabolic response of the intrahepatic cholangiocarcinoma, and a complete metabolic response of the plasmacytoma. This case illustrates the importance of not ignoring two primary tumors and the management of two concomitant treatments exploiting potential therapeutic synergies and limiting expected toxicities.