Research

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13 pages, 1225 KiB

Open AccessArticle

Role of 11C Methionine Positron Emission Tomography (11CMETPET) for Surgery and Radiation Therapy Planning in Newly Diagnosed Glioblastoma Patients Enrolled into a Phase II Clinical Study

by Federico Pessina, Pierina Navarria, Elena Clerici, Luisa Bellu, Andrea Franzini, Davide Milani, Matteo Simonelli, Pasquale Persico, Letterio S. Politi, Alessandra Casarotti, Bethania Fernandes, Simone Olei, Martina Sollini, Arturo Chiti and Marta Scorsetti

J. Clin. Med. 2021, 10(11), 2313; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10112313 - 25 May 2021

Cited by 7 | Viewed by 1915

Abstract

(1) Background: We investigated the role of [11C]-methionine PET in a cohort of newly diagnosed glioblastoma multiforme (GBM) patients to evaluate whether it could modify the extent of surgical resection and improve radiation therapy volume delineation. (2) Methods: Newly diagnosed GBM patients, ages [...] Read more.

(1) Background: We investigated the role of [11C]-methionine PET in a cohort of newly diagnosed glioblastoma multiforme (GBM) patients to evaluate whether it could modify the extent of surgical resection and improve radiation therapy volume delineation. (2) Methods: Newly diagnosed GBM patients, ages 18–70, with a Karnofsky performance scale (KPS) ≥ 70 with available MRI and [11C]-methionine PET were included. Patients were treated with different amounts of surgical resection followed by radio-chemotherapy. The role of [11C]-methionine PET in surgical and RT planning was analyzed. A threshold of SUVmax was searched. (3) Results: From August 2013 to April 2016, 93 patients were treated and included in this analysis. Residual tumor volume was detected in 63 cases on MRI and in 78 on [11C]-methionine PET, including 15 receiving gross total resection. The location of uptake was mainly observed in FLAIR abnormalities. [11C]-methionine uptake changed RT volume in 11% of patients. The presence of [11C]-methionine uptake in patients receiving GTR proved to influence survival (p = 0.029). The threshold of the SUVmax conditioning outcome was five. (4) Conclusions: [11C]-methionine PET allowed to detect areas at higher risk of recurrence located in FLAIR abnormalities in patients affected by GBM. A challenging issue is represented by integrating morphological and functional imaging to better define the extent of surgical resection to perform. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

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17 pages, 8844 KiB

Open AccessArticle

Prior Neurosurgery Decreases fMRI Estimates of Language Laterality in Patients with Gliomas within Anterior Language Sites

by Monika M. Połczyńska, Bryan Ding, Bianca H. Dang and Lucia Cavanagh

J. Clin. Med. 2021, 10(7), 1491; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10071491 - 03 Apr 2021

Cited by 1 | Viewed by 2277

Abstract

The impact of previous surgery on the assessment of language dominance with preoperative fMRI remains inconclusive in patients with recurrent brain tumors. Samples in this retrospective study included 17 patients with prior brain surgery and 21 patients without prior surgery (38 patients total; [...] Read more.

The impact of previous surgery on the assessment of language dominance with preoperative fMRI remains inconclusive in patients with recurrent brain tumors. Samples in this retrospective study included 17 patients with prior brain surgery and 21 patients without prior surgery (38 patients total; mean age 43.2, SD = 11.9; 18 females; seven left-handed). All the patients were left language dominant, as determined clinically. The two samples were matched on 10 known confounds, including, for example, tumor laterality and location (all tumors affected Brodmann areas 44/45/47). We calculated fMRI language dominance with laterality indices using a whole-brain and region of interest approach (ROI; Broca’s and Wernicke’s area). Patients with prior surgery had decreased fMRI language dominance (p = 0.03) with more activity in the right hemisphere (p = 0.03) than patients without surgery. Patients with prior brain surgery did not display less language activity in the left hemisphere than patients without surgery. These results were replicated using an ROI approach in the affected Broca’s area. Further, we observed no differences between our samples in the unaffected Wernicke’s area. In sum, prior brain surgery affecting Broca’s area could be a confounding factor that needs to be considered when evaluating fMRI language dominance. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

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13 pages, 1527 KiB

Open AccessArticle

A Novel Language Paradigm for Intraoperative Language Mapping: Feasibility and Evaluation

by Katharina Rosengarth, Delin Pai, Frank Dodoo-Schittko, Katharina Hense, Teele Tamm, Christian Ott, Ralf Lürding, Elisabeth Bumes, Mark W Greenlee, Karl Michael Schebesch, Nils Ole Schmidt and Christian Doenitz

J. Clin. Med. 2021, 10(4), 655; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10040655 - 08 Feb 2021

Cited by 1 | Viewed by 2346

Abstract

(1) Background—Mapping language using direct cortical stimulation (DCS) during an awake craniotomy is difficult without using more than one language paradigm that particularly follows the demand of DCS by not exceeding the assessment time of 4 s to prevent intraoperative complications. We designed [...] Read more.

(1) Background—Mapping language using direct cortical stimulation (DCS) during an awake craniotomy is difficult without using more than one language paradigm that particularly follows the demand of DCS by not exceeding the assessment time of 4 s to prevent intraoperative complications. We designed an intraoperative language paradigm by combining classical picture naming and verb generation, which safely engaged highly relevant language functions. (2) Methods—An evaluation study investigated whether a single trial of the language task could be performed in less than 4 s in 30 healthy subjects and whether the suggested language paradigm sufficiently pictured the cortical language network using functional magnetic resonance imaging (fMRI) in 12 healthy subjects. In a feasibility study, 24 brain tumor patients conducted the language task during an awake craniotomy. The patients’ neuropsychological outcomes were monitored before and after surgery. (3) Results—The fMRI results in healthy subjects showed activations in a language-associated network around the (left) sylvian fissure. Single language trials could be performed within 4 s. Intraoperatively, all tumor patients showed DCS-induced language errors while conducting the novel language task. Postoperatively, mild neuropsychological impairments appeared compared to the presurgical assessment. (4) Conclusions—These data support the use of a novel language paradigm that safely monitors highly relevant language functions intraoperatively, which can consequently minimize negative postoperative neuropsychological outcomes. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

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Review

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20 pages, 2082 KiB

Open AccessReview

In Silico Mathematical Modelling for Glioblastoma: A Critical Review and a Patient-Specific Case

by Jacopo Falco, Abramo Agosti, Ignazio G. Vetrano, Alberto Bizzi, Francesco Restelli, Morgan Broggi, Marco Schiariti, Francesco DiMeco, Paolo Ferroli, Pasquale Ciarletta and Francesco Acerbi

J. Clin. Med. 2021, 10(10), 2169; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10102169 - 17 May 2021

Cited by 17 | Viewed by 2582

Abstract

Glioblastoma extensively infiltrates the brain; despite surgery and aggressive therapies, the prognosis is poor. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of glioblastoma evolution in every single patient, with the aim of tailoring therapeutic [...] Read more.

Glioblastoma extensively infiltrates the brain; despite surgery and aggressive therapies, the prognosis is poor. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of glioblastoma evolution in every single patient, with the aim of tailoring therapeutic weapons. In particular, the ultimate goal of biomathematics for cancer is the identification of the most suitable theoretical models and simulation tools, both to describe the biological complexity of carcinogenesis and to predict tumor evolution. In this report, we describe the results of a critical review about different mathematical models in neuro-oncology with their clinical implications. A comprehensive literature search and review for English-language articles concerning mathematical modelling in glioblastoma has been conducted. The review explored the different proposed models, classifying them and indicating the significative advances of each one. Furthermore, we present a specific case of a glioblastoma patient in which our recently proposed innovative mechanical model has been applied. The results of the mathematical models have the potential to provide a relevant benefit for clinicians and, more importantly, they might drive progress towards improving tumor control and patient’s prognosis. Further prospective comparative trials, however, are still necessary to prove the impact of mathematical neuro-oncology in clinical practice. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

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25 pages, 3587 KiB

Open AccessReview

Confocal Laser Microscopy in Neurosurgery: State of the Art of Actual Clinical Applications

by Francesco Restelli, Bianca Pollo, Ignazio Gaspare Vetrano, Samuele Cabras, Morgan Broggi, Marco Schiariti, Jacopo Falco, Camilla de Laurentis, Gabriella Raccuia, Paolo Ferroli and Francesco Acerbi

J. Clin. Med. 2021, 10(9), 2035; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10092035 - 10 May 2021

Cited by 9 | Viewed by 4161

Abstract

Achievement of complete resections is of utmost importance in brain tumor surgery, due to the established correlation among extent of resection and postoperative survival. Various tools have recently been included in current clinical practice aiming to more complete resections, such as neuronavigation and [...] Read more.

Achievement of complete resections is of utmost importance in brain tumor surgery, due to the established correlation among extent of resection and postoperative survival. Various tools have recently been included in current clinical practice aiming to more complete resections, such as neuronavigation and fluorescent-aided techniques, histopathological analysis still remains the gold-standard for diagnosis, with frozen section as the most used, rapid and precise intraoperative histopathological method that permits an intraoperative differential diagnosis. Unfortunately, due to the various limitations linked to this technique, it is still unsatisfactorily for obtaining real-time intraoperative diagnosis. Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data in neurosurgery, due to its established use in other non-neurosurgical fields. Still far to be widely implemented in current neurosurgical clinical practice, this technology was initially studied in preclinical experiences confirming its utility in identifying brain tumors, microvasculature and tumor margins. Hence, ex vivo and in vivo clinical studies evaluated the possibility with this technology of identifying and classifying brain neoplasms, discerning between normal and pathologic tissue, showing very promising results. This systematic review has the main objective of presenting a state-of-the-art summary on actual clinical applications of confocal laser imaging in neurosurgical practice. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

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18 pages, 324 KiB

Open AccessReview

Checkpoint Inhibitors as High-Grade Gliomas Treatment: State of the Art and Future Perspectives

by Pasquale Persico, Elena Lorenzi, Angelo Dipasquale, Federico Pessina, Pierina Navarria, Letterio S. Politi, Armando Santoro and Matteo Simonelli

J. Clin. Med. 2021, 10(7), 1367; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10071367 - 26 Mar 2021

Cited by 17 | Viewed by 3595

Abstract

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Despite significant efforts, no therapies have demonstrated valuable survival benefit beyond the current standard of care. Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape and improved patient survival in [...] Read more.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Despite significant efforts, no therapies have demonstrated valuable survival benefit beyond the current standard of care. Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape and improved patient survival in many advanced malignancies. Unfortunately, these clinical successes have not been replicated in the neuro-oncology field so far. This review summarizes the status of ICI investigation in high-grade gliomas, critically presenting the available data from preclinical models and clinical trials. Moreover, we explore new approaches to increase ICI efficacy, with a particular focus on combinatorial strategies, and the potential biomarkers to identify patients most likely to benefit from immune checkpoint blockade. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

16 pages, 1810 KiB

Open AccessReview

Sonodynamic Therapy for the Treatment of Intracranial Gliomas

by Antonio D’Ammando, Luca Raspagliesi, Matteo Gionso, Andrea Franzini, Edoardo Porto, Francesco Di Meco, Giovanni Durando, Serena Pellegatta and Francesco Prada

J. Clin. Med. 2021, 10(5), 1101; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10051101 - 06 Mar 2021

Cited by 18 | Viewed by 4508

Abstract

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, [...] Read more.

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

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22 pages, 1893 KiB

Open AccessReview

The Neurosurgeon’s Armamentarium for Gliomas: An Update on Intraoperative Technologies to Improve Extent of Resection

by Alexander J. Schupper, Raymund L. Yong and Constantinos G. Hadjipanayis

J. Clin. Med. 2021, 10(2), 236; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020236 - 11 Jan 2021

Cited by 16 | Viewed by 3138

Abstract

Maximal safe resection is the standard of care in the neurosurgical treatment of high-grade gliomas. To aid surgeons in the operating room, adjuvant techniques and technologies centered around improving intraoperative visualization of tumor tissue have been developed. In this review, we will discuss [...] Read more.

Maximal safe resection is the standard of care in the neurosurgical treatment of high-grade gliomas. To aid surgeons in the operating room, adjuvant techniques and technologies centered around improving intraoperative visualization of tumor tissue have been developed. In this review, we will discuss the most advanced technologies, specifically fluorescence-guided surgery, intraoperative imaging, neuromonitoring modalities, and microscopic imaging techniques. The goal of these technologies is to improve detection of tumor tissue beyond what conventional microsurgery has permitted. We describe the various advances, the current state of the literature that have tested the utility of the different adjuvants in clinical practice, and future directions for improving intraoperative technologies. Full article

(This article belongs to the Special Issue Gliomas: Implication for Diagnosis and Treatment)

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