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Article ; Online: Radiomics Multifactorial in Silico Model for Spatial Prediction of Glioblastoma Progression and Recurrence: A Proof-of-Concept.

Luzzi, Sabino / Agosti, Abramo

2024 Volume 183, Page(s) e677–e686

Abstract: Background: Radiomics-based prediction of glioblastoma spatial progression and recurrence may improve personalized strategies. However, most prototypes are based on limited monofactorial Gompertzian models of tumor growth. The present study consists of ... ...

Abstract	Background: Radiomics-based prediction of glioblastoma spatial progression and recurrence may improve personalized strategies. However, most prototypes are based on limited monofactorial Gompertzian models of tumor growth. The present study consists of a proof of concept on the accuracy of a radiomics multifactorial in silico model in predicting short-term spatial growth and recurrence of glioblastoma. Methods: A radiomics-based biomathematical multifactorial in silico model was developed using magnetic resonance imaging (MRI) data from a 53-year-old patient with newly diagnosed glioblastoma of the right supramarginal gyrus. Raw and optimized models were derived from the MRI at diagnosis and matched to the preoperative MRI obtained 28 days after diagnosis to test the accuracy in predicting the short-term spatial growth of the tumor. An additional optimized model was derived from the early postoperative MRI and matched to the MRI documenting tumor recurrence to test spatial accuracy in predicting the location of recurrence. The spatial prediction accuracy of the model was reported as an average Jaccard index. Results: Optimized models yielded an average Jaccard index of 0.69 and 0.26 for short-term tumor growth and long-term recurrence site, respectively. Conclusions: The present radiomics-based multifactorial in silico model was feasible, reliable, and accurate for short-term spatial prediction of glioblastoma progression. The predictive value for the spatial location of recurrence was still low, and refinements in the description of tissue reorganization in the peritumoral and resected areas may be critical to optimize accuracy further.
MeSH term(s)	Humans ; Middle Aged ; Glioblastoma/diagnostic imaging ; Glioblastoma/surgery ; Glioblastoma/pathology ; Radiomics ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/surgery ; Brain Neoplasms/pathology ; Neoplasm Recurrence, Local/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Computer Simulation ; Retrospective Studies
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2024.01.002
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Article ; Online: In Reply to Letter to the Editor Regarding "Optic Foraminotomy versus Anterior Clinoidectomy for Small Superior-Projecting Paraclinoid Aneurysms: Visual and Angiographic Outcome Evaluation".

Luzzi, Sabino / Giotta Lucifero, Alice

World neurosurgery

2023 Volume 170, Page(s) 261

MeSH term(s)	Humans ; Foraminotomy ; Intracranial Aneurysm/diagnostic imaging ; Intracranial Aneurysm/surgery ; Angiography
Language	English
Publishing date	2023-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2022.12.021
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Article ; Online: Intraoperative Augmented Reality Fiber Tractography for Primary Motor Area Glioma Resection.

Luzzi, Sabino / Galzio, Renato

World neurosurgery

2023 Volume 180, Page(s) 111

Abstract: The implementation of intraoperative augmented reality fiber tractography (iAR-FT) into the surgical workflow for high-grade supratentorial gliomas has been shown to be effective and safe in maximizing the extent of resection and progression-free ... ...

Abstract	The implementation of intraoperative augmented reality fiber tractography (iAR-FT) into the surgical workflow for high-grade supratentorial gliomas has been shown to be effective and safe in maximizing the extent of resection and progression-free survival through the surgeon's enhanced 3-dimensional awareness of the spatial localization of fiber tracts.
MeSH term(s)	Humans ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/surgery ; Brain Neoplasms/pathology ; Motor Cortex/diagnostic imaging ; Motor Cortex/surgery ; Augmented Reality ; Diffusion Tensor Imaging/methods ; Glioma/diagnostic imaging ; Glioma/surgery ; Glioma/pathology ; Neuronavigation/methods ; Brain Mapping/methods
Language	English
Publishing date	2023-10-05
Publishing country	United States
Document type	Video-Audio Media
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2023.09.115
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Article ; Online: Microscope-based augmented reality with diffusion tensor imaging and fluorescein in insular glioma resection.

Luzzi, Sabino / Giotta Lucifero, Alice

Neurosurgical focus: Video

2022 Volume 6, Issue 1, Page(s) V10

Abstract: Maximal safe resection is the goal of insular glioma surgery. The combination of intraoperative augmented reality (AR) diffusion tensor imaging (DTI) fiber tracking with fluorescein dye (F) helps achieve this goal throughout a microscope-based ... ...

Abstract	Maximal safe resection is the goal of insular glioma surgery. The combination of intraoperative augmented reality (AR) diffusion tensor imaging (DTI) fiber tracking with fluorescein dye (F) helps achieve this goal throughout a microscope-based visualization of the tumor and white matter fiber tracts. The aim of the present video article was to show the technical key aspects of DTI-F microscope-based AR-assisted surgery during the gross-total resection of an insular Berger-Sanai type I+IV high-grade glioma in a 63-year-old patient, performed through a pterional transsylvian approach. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID2157.
Language	English
Publishing date	2022-01-01
Publishing country	United States
Document type	Journal Article
ISSN	2643-5217
ISSN (online)	2643-5217
DOI	10.3171/2021.10.FOCVID2157
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Article ; Online: Emerging immune-based technologies for high-grade gliomas.

Giotta Lucifero, Alice / Luzzi, Sabino

Expert review of anticancer therapy

2022 Volume 22, Issue 9, Page(s) 957–980

Abstract: Introduction: The selection of a tailored and successful strategy for high-grade gliomas (HGGs) treatment is still a concern. The abundance of aberrant mutations within the heterogenic genetic landscape of glioblastoma strongly influences cell expansion, ...

Abstract	Introduction: The selection of a tailored and successful strategy for high-grade gliomas (HGGs) treatment is still a concern. The abundance of aberrant mutations within the heterogenic genetic landscape of glioblastoma strongly influences cell expansion, proliferation, and therapeutic resistance. Identification of immune evasion pathways opens the way to novel immune-based strategies. This review intends to explore the emerging immunotherapies for HGGs. The immunosuppressive mechanisms related to the tumor microenvironment and future perspectives to overcome glioma immunity barriers are also debated. Areas covered: An extensive literature review was performed on the PubMed/Medline and ClinicalTrials.gov databases. Only highly relevant articles in English and published in the last 20 years were selected. Data about immunotherapies coming from preclinical and clinical trials were summarized. Expert opinion: The overall level of evidence about the efficacy and safety of immunotherapies for HGGs is noteworthy. Monoclonal antibodies have been approved as second-line treatment, while peptide vaccines, viral gene strategies, and adoptive technologies proved to boost a vivid antitumor immunization. Malignant brain tumor-treating fields are ever-changing in the upcoming years. Constant refinements and development of new routes of drug administration will permit to design of novel immune-based treatment algorithms thus improving the overall survival.
MeSH term(s)	Brain Neoplasms/genetics ; Brain Neoplasms/therapy ; Glioblastoma/therapy ; Glioma/genetics ; Glioma/therapy ; Humans ; Immunotherapy ; Tumor Microenvironment
Language	English
Publishing date	2022-08-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2112544-2
ISSN	1744-8328 ; 1473-7140
ISSN (online)	1744-8328
ISSN	1473-7140
DOI	10.1080/14737140.2022.2110072
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Article: Immune Landscape in PTEN-Related Glioma Microenvironment: A Bioinformatic Analysis.

Giotta Lucifero, Alice / Luzzi, Sabino

Brain sciences

2022 Volume 12, Issue 4

Abstract: Introduction: PTEN gene mutations are frequently found in the genetic landscape of high-grade gliomas since they influence cell proliferation, proangiogenetic pathways, and antitumoral immune response. The present bioinformatics analysis explores the ... ...

Abstract	Introduction: PTEN gene mutations are frequently found in the genetic landscape of high-grade gliomas since they influence cell proliferation, proangiogenetic pathways, and antitumoral immune response. The present bioinformatics analysis explores the PTEN gene expression profile in HGGs as a prognostic factor for survival, especially focusing on the related immune microenvironment. The effects of PTEN mutation on the susceptibility to conventional chemotherapy were also investigated. Methods: Clinical and genetic data of GBMs and normal tissue samples were acquired from The Cancer Genome Atlas (TCGA)-GBM and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan−Meier survival curves were applied to estimate the overall survival (OS) and disease-free survival (DFS). The Genomics of Drug Sensitivity in Cancer platform was chosen to assess the response of PTEN-mutated GBMs to temozolomide (TMZ). p < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and PTEN status was assessed through Spearman’s correlation analysis. Results: PTEN was found mutated in 22.2% of the 617 TCGA-GBMs patients, with a higher log2-transcriptome per million reads compared to the GTEx group (255 samples). Survival curves revealed a worse OS and DFS, albeit not significant, for the high-PTEN profile GBMs. Spearman’s analysis of immune cells demonstrated a strong positive correlation between the PTEN status and infiltration of Treg (ρ = 0.179) and M2 macrophages (ρ = 0.303). The half-maximal inhibitor concentration of TMZ was proven to be lower for PTEN-mutated GBMs compared with PTEN wild-types. Conclusions: PTEN gene mutations prevail in GBMs and are strongly related to poor prognosis and least survival. The infiltrating immune lymphocytes Treg and M2 macrophages populate the glioma microenvironment and control the mechanisms of tumor progression, immune escape, and sensitivity to standard chemotherapy. Broader studies are required to confirm these findings and turn them into new therapeutic perspectives.
Language	English
Publishing date	2022-04-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci12040501
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Article: Brain AVMs-Related microRNAs: Machine Learning Algorithm for Expression Profiles of Target Genes.

Giotta Lucifero, Alice / Luzzi, Sabino

Brain sciences

2022 Volume 12, Issue 12

Abstract: Introduction: microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous ... ...

Abstract	Introduction: microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs. Methods: A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions. Results: four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression. Conclusion: miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.
Language	English
Publishing date	2022-11-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci12121628
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Article: Editorial: Update on Multidisciplinary Management of Surgical Neurovascular Pathologies.

Luzzi, Sabino / Spina, Alfio / Giotta Lucifero, Alice

Frontiers in surgery

2022 Volume 9, Page(s) 923493

Language	English
Publishing date	2022-06-07
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2773823-1
ISSN	2296-875X
ISSN	2296-875X
DOI	10.3389/fsurg.2022.923493
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Article ; Online: Surgical management of thoracolumbar junction fractures: An evidence-based algorithm.

Giotta Lucifero, Alice / Bruno, Nunzio / Luzzi, Sabino

World neurosurgery: X

2023 Volume 17, Page(s) 100151

Abstract: Background: The management of thoracolumbar junction (TLJ) fractures, involving the restoring anatomical stability and biomechanics properties, still remains a challenge for neurosurgeons.Despite the high frequency of these injuries, specific treatment ... ...

Abstract	Background: The management of thoracolumbar junction (TLJ) fractures, involving the restoring anatomical stability and biomechanics properties, still remains a challenge for neurosurgeons.Despite the high frequency of these injuries, specific treatment guidelines, set on biomechanical properties, have not yet been assumed. The present study is meant to propose an evidence-based treatment algorithm. The primary aim for the protocol validation was the assessment of postoperative neurological recovery. The secondary objectives concerned the evaluation of residual deformity and rate of hardware failure. Technical nuances of surgical approaches and drawbacks were further discussed. Methods: Clinical and biomechanical data of patients harboring a single TLJ fracture, surgically managed between 2015 and 2020, were collected. Patients' cohorts were ranked into 4 groups according to Magerl's Type, McCormack Score, Vaccaro PLC point, Canal encroachment, and Farcy Sagittal Index. The outcome measures were the early/late Benzel-Larson Grade and postoperative kyphosis degree to estimate neurological status and residual deformity, respectively. Results: 32 patients were retrieved, 7, 9, 8, and 8 included within group 1, 2, 3, and 4, respectively. Overall neurological outcomes significantly improved for all patients at every follow-up stage (p < 0.0001). Surgeries gained a complete restoration of post-traumatic kyphosis in the entire cohort (p < 0.0001), except for group 4 which experienced a later worsening of residual deformity. Conclusions: The choice of the most appropriate surgical approach for TLJ fractures is dictated by morphological and biomechanical characteristics of fracture and the grade of neurological involvement. The proposed surgical management protocol was reliable and effective, although further validations are needed.
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article
ISSN	2590-1397
ISSN (online)	2590-1397
DOI	10.1016/j.wnsx.2022.100151
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Article ; Online: Impact of augmented reality fiber tractography on the extent of resection and functional outcome of primary motor area tumors.

Luzzi, Sabino / Simoncelli, Anna / Galzio, Renato

Neurosurgical focus

2023 Volume 56, Issue 1, Page(s) E3

Abstract: Objective: This study aimed to evaluate the impact of augmented reality intraoperative fiber tractography (AR-iFT) on extent of resection (EOR), motor functional outcome, and survival of patients with primary motor area (M1) intra-axial malignant tumors. ...

Abstract	Objective: This study aimed to evaluate the impact of augmented reality intraoperative fiber tractography (AR-iFT) on extent of resection (EOR), motor functional outcome, and survival of patients with primary motor area (M1) intra-axial malignant tumors. Methods: Data obtained from patients who underwent AR-iFT for M1 primary tumors were retrospectively analyzed and compared with those from a control group who underwent unaugmented reality intraoperative fiber tractography (unAR-iFT). A full asleep procedure with electrical stimulation mapping and fluorescein guidance was performed in both groups. The Neurological Assessment in Neuro-Oncology (NANO), Medical Research Council (MRC), and House-Brackmann grading systems were used for neurological, motor, and facial nerve assessment, respectively. Three-month postoperative NANO and MRC scores were used as outcome measures of the safety of the technique, whereas EOR and survival curves were related to its cytoreductive efficacy. In this study, p < 0.05 indicated statistical significance. Results: This study included 34 and 31 patients in the AR-iFT and unAR-iFT groups, respectively. The intraoperative seizure rate, 3-month postoperative NANO score, and 1-week and 1-month MRC scores were significantly (p < 0.05) different and in favor of the AR-iFT group. However, no difference was observed in the rate of complications. Glioma had incidence rates of 58.9% and 51.7% in the study and control groups, respectively, with no statistical difference. Metastasis had a slightly higher incidence rate in the control group, without statistical significance, and the gross-total resection and near-total resection rates and progression-free survival (PFS) rate were higher in the study group. Overall survival was not affected by the technique. Conclusions: AR-iFT proved to be feasible, effective, and safe during surgery for M1 tumors and positively affected the EOR, intraoperative seizure rate, motor outcome, and PFS. Integration with electrical stimulation mapping is critical to achieve constant anatomo-functional intraoperative feedback. The accuracy of AR-iFT is intrinsically limited by diffusion tensor-based techniques, parallax error, and fiber tract crowding. Further studies are warranted to definitively validate the benefits of augmented reality navigation in this surgical scenario.
MeSH term(s)	Humans ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/surgery ; Brain Neoplasms/pathology ; Retrospective Studies ; Augmented Reality ; Motor Cortex/diagnostic imaging ; Motor Cortex/surgery ; Neuronavigation/methods ; Seizures/surgery
Language	English
Publishing date	2023-12-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2026589-X
ISSN	1092-0684 ; 1092-0684
ISSN (online)	1092-0684
ISSN	1092-0684
DOI	10.3171/2023.10.FOCUS23477
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