Cancers

16 pages, 389 KiB

Open AccessReview

The Role of Radiotherapy, Chemotherapy, and Targeted Therapies in Adult Intramedullary Spinal Cord Tumors

by Ines Esparragosa Vazquez and François Ducray

Cancers 2024, 16(16), 2781; https://doi.org/10.3390/cancers16162781 (registering DOI) - 6 Aug 2024

Intramedullary primary spinal cord tumors are rare in adults and their classification has recently evolved. Their treatment most frequently relies on maximal safe surgical resection. Herein, we review, in light of the WHO 2021 classification of central nervous system tumors, the knowledge regarding [...] Read more.

Intramedullary primary spinal cord tumors are rare in adults and their classification has recently evolved. Their treatment most frequently relies on maximal safe surgical resection. Herein, we review, in light of the WHO 2021 classification of central nervous system tumors, the knowledge regarding the role of radiotherapy and systemic treatments in spinal ependymomas, spinal astrocytomas (pilocytic astrocytoma, diffuse astrocytoma, spinal glioblastoma IDH wildtype, diffuse midline glioma H3-K27M altered, and high-grade astrocytoma with piloid features), neuro-glial tumors (ganglioglioma and diffuse leptomeningeal glioneuronal tumor), and hemangioblastomas. In spinal ependymomas, radiotherapy is recommended for incompletely resected grade 2 tumors, grade 3 tumors, and recurrent tumors not amenable to re-surgery. Chemotherapy is used in recurrent cases. In spinal astrocytomas, radiotherapy is recommended for incompletely resected grade 2 astrocytomas and grade 3 or 4 tumors as well as recurrent tumors. Chemotherapy is indicated for newly diagnosed high-grade astrocytomas and recurrent cases. In hemangioblastomas not amenable to surgery, radiotherapy is an effective alternative option. Targeted therapies are playing an increasingly important role in the management of some intramedullary primary spinal cord tumor subtypes. BRAF and/or MEK inhibitors have demonstrated efficacy in pilocytic astrocytomas and glioneuronal tumors, belzutifan in von Hippel–Lindau-related hemangioblastomas, and promising results have been reported with ONC201 in diffuse midline glioma H3-K27M altered. Full article

(This article belongs to the Special Issue State of the Art and New Approaches to Spinal Cord Tumors)

20 pages, 638 KiB

Open AccessReview

Breaking Boundaries: Immunotherapy for Myeloid Malignancies

by Tatyana Gavrilova, Eduard Schulz and Alain Mina

Cancers 2024, 16(16), 2780; https://doi.org/10.3390/cancers16162780 (registering DOI) - 6 Aug 2024

Abstract

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment [...] Read more.

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of immunotherapy for myeloid malignancies, addresses its challenges, and provides insights into future directions in the field. Full article

(This article belongs to the Special Issue Immunotherapy in the Management of Hematologic Malignancy)

14 pages, 696 KiB

Open AccessReview

Early-Stage Non-Small Cell Lung Cancer: New Challenges with Immune Checkpoint Blockers and Targeted Therapies

by Pernelle Lavaud, Martina Bortolot, Lodovica Zullo, David O’Reilly, Jarushka Naidoo, Giannis Mountzios, Olaf Mercier, Lizza E. L. Hendriks and Jordi Remon

Cancers 2024, 16(16), 2779; https://doi.org/10.3390/cancers16162779 (registering DOI) - 6 Aug 2024

Abstract

The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes [...] Read more.

The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected EGFR- and ALK-positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboring EGFR mutations. Numerous trials are still ongoing to investigate neoadjuvant/perioperative TKIs in several oncogene-driven NSCLC. In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC. Despite these advances, many challenges remain regarding the use of TKIs and ICBs in this setting, including the optimal duration of adjuvant TKI or induction ICB therapy, the role of minimal residual disease to identify patients at high-risk of disease relapse and to guide adjuvant treatment decisions, and the role of adjuvant chemotherapy in resected oncogene-driven NSCLC. Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC. Full article

(This article belongs to the Special Issue New Advances in Lung Cancer: Diagnosis, Pathophysiology and Emerging Treatments. A Selection of Papers from the 4th Joint Meeting on Lung Cancer of the FHU OncoAge (Nice, France) and the MD Anderson Cancer Center (Houston, TX, USA))

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27 pages, 3697 KiB

Open AccessArticle

Preclinical Efficacy of VTX-0811: A Humanized First-in-Class PSGL-1 mAb Targeting TAMs to Suppress Tumor Growth

by Tatiana Novobrantseva, Denise Manfra, Jessica Ritter, Maja Razlog, Brian O’Nuallain, Mohammad Zafari, Dominika Nowakowska, Sara Basinski, Ryan T. Phennicie, Phuong A. Nguyen, Michael A. Brehm, Stephen Sazinsky and Igor Feldman

Cancers 2024, 16(16), 2778; https://doi.org/10.3390/cancers16162778 (registering DOI) - 6 Aug 2024

Abstract

Omnipresent suppressive myeloid populations in the tumor microenvironment limit the efficacy of T-cell-directed immunotherapies, become more inhibitory after administration of T-cell checkpoint inhibitors, and are overall associated with worse survival of cancer patients. In early clinical trials, positive outcomes have been demonstrated for [...] Read more.

Omnipresent suppressive myeloid populations in the tumor microenvironment limit the efficacy of T-cell-directed immunotherapies, become more inhibitory after administration of T-cell checkpoint inhibitors, and are overall associated with worse survival of cancer patients. In early clinical trials, positive outcomes have been demonstrated for therapies aimed at repolarizing suppressive myeloid populations in the tumor microenvironment. We have previously described the key role of P-selectin glycoprotein ligand-1 (PSGL-1) in maintaining an inhibitory state of tumor-associated macrophages (TAMs), most of which express high levels of PSGL-1. Here we describe a novel, first-in-class humanized high-affinity monoclonal antibody VTX-0811 that repolarizes human macrophages from an M2-suppressive phenotype towards an M1 inflammatory phenotype, similar to siRNA-mediated knockdown of PSGL-1. VTX-0811 binds to PSGL-1 of human and cynomolgus macaque origins without inhibiting PSGL-1 interaction with P- and L-Selectins or VISTA. In multi-cellular assays and in patient-derived human tumor cultures, VTX-0811 leads to the induction of pro-inflammatory mediators. RNAseq data from VTX-0811 treated ex vivo tumor cultures and M2c macrophages show similar pathways being modulated, indicating that the mechanism of action translates from isolated macrophages to tumors. A chimeric version of VTX-0811, consisting of the parental murine antibody in a human IgG4 backbone, inhibits tumor growth in a humanized mouse model of cancer. VTX-0811 is exceptionally well tolerated in NHP toxicology assessment and is heading into clinical evaluation after successful IND clearance. Full article

(This article belongs to the Special Issue Building on the Success of Checkpoint Inhibitors to Overcome Resistance)

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36 pages, 2854 KiB

Open AccessReview

Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies

by Muntajin Rahman, Khadija Akter, Kazi Rejvee Ahmed, Md. Maharub Hossain Fahim, Nahida Aktary, Moon Nyeo Park, Sang-Won Shin and Bonglee Kim

Cancers 2024, 16(16), 2777; https://doi.org/10.3390/cancers16162777 (registering DOI) - 6 Aug 2024

Abstract

Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, [...] Read more.

Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, androgen receptor blockers, radiation therapy, immune therapy, and PARP inhibitors, often come with substantial side effects and limited efficacy. Natural compounds, particularly those derived from herbal medicine, have garnered increasing interest as adjunctive therapeutic agents against CRPC. This review explores the role of AR-V7 in CRPC and highlights the promising benefits of natural compounds as complementary treatments to conventional drugs in reducing CRPC and overcoming therapeutic resistance. We delve into the mechanisms of action underlying the anti-CRPC effects of natural compounds, showcasing their potential to enhance therapeutic outcomes while mitigating the side effects associated with conventional therapies. The exploration of natural compounds offers promising avenues for developing novel treatment strategies that enhance therapeutic outcomes and reduce the adverse effects of conventional CRPC therapies. These compounds provide a safer, more effective approach to managing CRPC, representing a significant advancement in improving patient care. Full article

(This article belongs to the Special Issue Natural Compounds in Cancers)

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20 pages, 15912 KiB

Open AccessArticle

Liver X Receptors Enhance Epithelial to Mesenchymal Transition in Metastatic Prostate Cancer Cells

by Erwan Bouchareb, Sarah Dallel, Angélique De Haze, Christelle Damon-Soubeyrand, Yoan Renaud, Elissa Baabdaty, Marine Vialat, Julien Fabre, Pierre Pouchin, Cyrille De Joussineau, Françoise Degoul, Swapnil Sanmukh, Juliette Gendronneau, Phelipe Sanchez, Céline Gonthier-Gueret, Amalia Trousson, Laurent Morel, Jean Marc Lobaccaro, Ayhan Kocer and Silvère Baron

Cancers 2024, 16(16), 2776; https://doi.org/10.3390/cancers16162776 (registering DOI) - 6 Aug 2024

Abstract

Prostate cancer (PCa) is one of the most common cancers in men. Metastasis is the leading cause of death in prostate cancer patients. One of the crucial processes involved in metastatic spread is the “epithelial–mesenchymal transition” (EMT), which allows cells to acquire the [...] Read more.

Prostate cancer (PCa) is one of the most common cancers in men. Metastasis is the leading cause of death in prostate cancer patients. One of the crucial processes involved in metastatic spread is the “epithelial–mesenchymal transition” (EMT), which allows cells to acquire the ability to invade distant organs. Liver X Receptors (LXRs) are nuclear receptors that have been demonstrated to regulate EMT in various cancers, including hepatic cancer. Our study reveals that the LXR pathway can control pro-invasive cell capacities through EMT in prostate cancer, employing ex vivo and in vivo approaches. We characterized the EMT status of the commonly used LNCaP, DU145, and PC3 prostate cancer cell lines through molecular and immunohistochemistry experiments. The impact of LXR activation on EMT function was also assessed by analyzing the migration and invasion of these cell lines in the absence or presence of an LXR agonist. Using in vivo experiments involving NSG-immunodeficient mice xenografted with PC3-GFP cells, we were able to study metastatic spread and the effect of LXRs on this process. LXR activation led to an increase in the accumulation of Vimentin and Amphiregulin in PC3. Furthermore, the migration of PC3 cells significantly increased in the presence of the LXR agonist, correlating with an upregulation of EMT. Interestingly, LXR activation significantly increased metastatic spread in an NSG mouse model. Overall, this work identifies a promoting effect of LXRs on EMT in the PC3 model of advanced prostate cancer. Full article

(This article belongs to the Collection Prostate Cancer—from Molecular Mechanisms to Clinical Care)

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26 pages, 2616 KiB

Open AccessReview

The Anticancer Activity of Monosaccharides: Perspectives and Outlooks

by Niamh McCallum and Mohammad Najlah

Cancers 2024, 16(16), 2775; https://doi.org/10.3390/cancers16162775 (registering DOI) - 6 Aug 2024

Abstract

A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake [...] Read more.

A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake and consumption of glucose. The Warburg effect may be exploited in the treatment of cancer; certain epimers and derivatives of glucose can enter cancer cells and inhibit glycolytic enzymes, stunting metabolism and causing cell death. These include common dietary monosaccharides (ᴅ-mannose, ᴅ-galactose, ᴅ-glucosamine, ʟ-fucose), as well as some rare monosaccharides (xylitol, ᴅ-allose, ʟ-sorbose, ʟ-rhamnose). This article reviews the literature on these sugars in in vitro and in vivo models of cancer, discussing their mechanisms of cytotoxicity. In addition to this, the anticancer potential of some synthetically modified monosaccharides, such as 2-deoxy-ᴅ-glucose and its acetylated and halogenated derivatives, is reviewed. Further, this article reviews how certain monosaccharides can be used in combination with anticancer drugs to potentiate conventional chemotherapies and to help overcome chemoresistance. Finally, the limitations of administering two separate agents, a sugar and a chemotherapeutic drug, are discussed. The potential of the glycoconjugation of classical or repurposed chemotherapy drugs as a solution to these limitations is reviewed. Full article

(This article belongs to the Special Issue Feature Review for Cancer Therapy)

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11 pages, 615 KiB

Open AccessArticle

Navigating Brain Metastases: Unveiling the Potential of 3-Tesla Intraoperative Magnetic Resonance Imaging

by Ghaith Altawalbeh, Maria Goldberg, Michel Gustavo Mondragón-Soto, Chiara Negwer, Arthur Wagner, Jens Gempt, Bernhard Meyer and Amir Kaywan Aftahy

Cancers 2024, 16(16), 2774; https://doi.org/10.3390/cancers16162774 (registering DOI) - 6 Aug 2024

Abstract

Intraoperative magnetic resonance imaging (iMRI) has witnessed significant growth in the field of neurosurgery, particularly in glioma surgery, enhancing image-guided neuronavigation and optimizing the extent of resection (EOR). Despite its extensive use in the treatment of gliomas, its utility in brain metastases (BMs) [...] Read more.

Intraoperative magnetic resonance imaging (iMRI) has witnessed significant growth in the field of neurosurgery, particularly in glioma surgery, enhancing image-guided neuronavigation and optimizing the extent of resection (EOR). Despite its extensive use in the treatment of gliomas, its utility in brain metastases (BMs) remains unexplored. This study examined the effect of iMRI on BM resection. This retrospective study was conducted at the neurosurgical center of the University Hospital of the Technical University of Munich and involved 25 patients with BM who underwent resection using 3-Tesla iMRI between 2018 and 2022. Volumetric measurements of the resected contrast-enhancing metastases were performed using preoperative, intraoperative, and postoperative MRI images. The Karnofsky Performance Score (KPS) and neurological status of the patients were assessed pre- and postoperatively. Local recurrence and in-brain progression were reported in patients who underwent follow-up MRI at 3 and 6 months postoperatively. In this cohort (n = 25, mean age 63.6 years), non-small-cell lung cancer (NSCLC) was the most common origin (28%). The mean surgical duration was 219.9 min, and that of iMRI was 61.7 min. Indications for iMRI were primarily associated with preoperative imaging, suggesting an unclear entity that is often suspicious for glioma. Gross total resection (GTR) was achieved in 21 patients (84%). Continued resection was pursued after iMRI in six cases (24%), resulting in an improved EOR of 100% in five cases and 97.6% in one case. Neurological status postoperatively remained stable in 60%, improved in 24%, and worsened in 16% of patients. No wound healing or postoperative complications were observed. Among the thirteen patients who underwent follow-up MRI 3 months postoperatively, one patient showed local recurrence at the site of resection, and seven patients showed in-brain progression. Of the eight patients who underwent a 6-month follow-up MRI, two showed local recurrence, while three exhibited in-brain progression. The observed favorable profiles of GTR, coupled with the notable absence of wound-healing problems and acute postoperative complications, affirm the safety and feasibility of incorporating iMRI into the neurosurgical workflow for resecting BM with specific indications. The real-time imaging capabilities of iMRI offer unparalleled precision, aiding meticulous tumor delineation and informed decision-making, ultimately contributing to improved patient outcomes. Although our experience suggests the potential benefits of iMRI as a safe tool for enhancing EOR, we acknowledge the need for larger prospective clinical trials. Comprehensive investigations on a broader scale are imperative to further elucidate the specific indications for iMRI in the context of BMs and to study its impact on survival. Rigorous prospective studies will refine our understanding of the clinical scenarios in which iMRI can maximize its impact, guiding neurosurgeons toward more informed and tailored decision-making. Full article

(This article belongs to the Special Issue Brain Metastases: Diagnosis and Treatment)

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23 pages, 863 KiB

Open AccessReview

Surgical Implications for Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma

by Centura R. Anbarasu, Sophia Williams-Perez, Ernest R. Camp and Derek J. Erstad

Cancers 2024, 16(16), 2773; https://doi.org/10.3390/cancers16162773 (registering DOI) - 6 Aug 2024

Abstract

Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are [...] Read more.

Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are frequently obese and medically complex, posing challenges for clinical management. In this review, we discuss NASH-specific challenges and the associated implications, including benefits of minimally invasive operative approaches in obese patients; the value of y90 as a locoregional therapy; and the roles of weight loss and immunotherapy in disease management. The relevant literature was identified through queries of PubMed, Google Scholar, and clinicaltrials.gov. Provider understanding of clinical nuances specific to NASH-HCC can improve treatment strategy and patient outcomes. Full article

(This article belongs to the Special Issue Pathogenesis of Non-alcoholic Steatohepatitis (NASH)-Related Hepatocellular Carcinoma (HCC))

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14 pages, 2294 KiB

Open AccessArticle

The Pivotal Role of the Key Angiogenic Factors in the Development of Endometrioid Pathologies of the Uterus and Ovary

by Gabriela Sabolová, Ivana Špaková, Peter Artimovič, Peter Bohuš, Miroslava Rabajdová and Mária Mareková

Cancers 2024, 16(16), 2772; https://doi.org/10.3390/cancers16162772 (registering DOI) - 6 Aug 2024

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Abstract

A characteristic feature of uterine pathologies is a specific change in cell metabolism, which predominantly manifests as a shift in the need for nutrients, thereby directing cells to engage in different angiogenic marker activities. Angiogenesis is one of the main signals supporting the [...] Read more.

A characteristic feature of uterine pathologies is a specific change in cell metabolism, which predominantly manifests as a shift in the need for nutrients, thereby directing cells to engage in different angiogenic marker activities. Angiogenesis is one of the main signals supporting the survival and development of cells and tissues not only under physiological conditions. Therefore, it is necessary that we understand pathological hyperactivation in all uterine diseases, from endometriosis through ovarian endometrioid adenocarcinoma to malignant transformed cells of the uterine epithelium and body. This work presents the gene expression results of selected angiogenesis targets (VEGF-A, TGF-β1, ANG1/2, and HIF-1α), cell migration, and cell–cell interaction determined in vitro. Our results suggest that angiogenesis varies in the tested pathological conditions (ectopic endometriosis—12Z; ovarian endometrioid adenocarcinoma—A2780; tumors—SK-UT-1 and RL-95-2) compared to physiological angiogenesis (HME1). The differential expression of angiogenic factors may contribute (or is a contributing factor) to the observed differences to acknowledge an inherent variability in angiogenesis among cell lines. Determining the genomic phenomena responsible for processes associated with inadequate angiogenesis in the pelvic region could help us to develop individual treatment strategies and explain resistance to treatment. Full article

(This article belongs to the Special Issue Genetics of Endometrial Cancer: Latest Insights and Innovations in Research)

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11 pages, 1875 KiB

Open AccessArticle

Combined Fluorescence-Guided Surgery with 5-Aminolevulinic Acid and Fluorescein in Glioblastoma: Technical Description and Report of 100 Cases

by Alessandro Pesaresi, Pietro La Cava, Marta Bonada, Pietro Zeppa, Antonio Melcarne, Fabio Cofano, Pietro Fiaschi, Diego Garbossa and Andrea Bianconi

Cancers 2024, 16(16), 2771; https://doi.org/10.3390/cancers16162771 (registering DOI) - 6 Aug 2024

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Abstract

Background: Fluorescence-guided resection (FGR) of glioblastomas has been previously explored with the use of 5-amivelulinic acid (5-ALA) and sodium fluoresceine (SF), allowing us to maximize the extent of resection (EoR). In this study, we highlight the most relevant concerns regarding this technique and [...] Read more.

Background: Fluorescence-guided resection (FGR) of glioblastomas has been previously explored with the use of 5-amivelulinic acid (5-ALA) and sodium fluoresceine (SF), allowing us to maximize the extent of resection (EoR). In this study, we highlight the most relevant concerns regarding this technique and present the methods and results from the experience of our center. Methods: A case series of 100 patients operated on in AOU Città della Salute e della Scienza in Turin with a histological diagnosis of glioblastoma (grade IV, according to WHO 2021) was retrospectively analyzed. Both 5-ALA and SF were administered and intraoperatively assessed with an optical microscope. Results: 5-ALA is the only approved drug for FGR in glioblastoma, reporting an increased EoR. Nevertheless, SF can be positively used in addition to 5-ALA to reduce the risk of false positives without increasing the rate of adverse effects. In our experience, SF was used to guide the initial phase of resection while 5-ALA was used to visualize tumor spots within the surgical cavity. In 96% of cases, gross total resection was achieved, with supra-maximal resection in 11% of cases. Conclusions: Combined FGR using 5-ALA and SF seems to be a promising method of increasing the extent of resection and to improving the prognosis in glioblastoma patients. Full article

(This article belongs to the Special Issue Intraoperative Visualization Techniques and Advanced Imaging in Brain Tumors)

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Cancers, Volume 16, Issue 16 (August-2 2024) – 11 articles

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