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Article ; Online: Recapitulating the Key Advances in the Diagnosis and Prognosis of High-Grade Gliomas: Second Half of 2021 Update.

Frosina, Guido

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: High-grade gliomas (World Health Organization grades III and IV) are the most frequent and fatal brain tumors, with median overall survivals of 24-72 and 14-16 months, respectively. We reviewed the progress in the diagnosis and prognosis of high-grade ... ...

Abstract	High-grade gliomas (World Health Organization grades III and IV) are the most frequent and fatal brain tumors, with median overall survivals of 24-72 and 14-16 months, respectively. We reviewed the progress in the diagnosis and prognosis of high-grade gliomas published in the second half of 2021. A literature search was performed in PubMed using the general terms "radio* and gliom*" and a time limit from 1 July 2021 to 31 December 2021. Important advances were provided in both imaging and non-imaging diagnoses of these hard-to-treat cancers. Our prognostic capacity also increased during the second half of 2021. This review article demonstrates slow, but steady improvements, both scientifically and technically, which express an increased chance that patients with high-grade gliomas may be correctly diagnosed without invasive procedures. The prognosis of those patients strictly depends on the final results of that complex diagnostic process, with widely varying survival rates.
MeSH term(s)	Humans ; Glioma/diagnosis ; Glioma/therapy ; Brain Neoplasms/diagnosis ; Brain Neoplasms/therapy ; Neoplasm Grading
Language	English
Publishing date	2023-03-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076375
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Article ; Online: Radiotherapy of high-grade gliomas: dealing with a stalemate.

Frosina, Guido

Critical reviews in oncology/hematology

2023 Volume 190, Page(s) 104110

Abstract: This article discusses the studies on radiotherapy of high-grade gliomas published between January 1, 2022, and June 30, 2022, with special reference to their molecular biology basis. The focus was on advances in radioresistance, radiosensitization and ... ...

Abstract	This article discusses the studies on radiotherapy of high-grade gliomas published between January 1, 2022, and June 30, 2022, with special reference to their molecular biology basis. The focus was on advances in radioresistance, radiosensitization and the toxicity of radiotherapy treatments. In the first half of 2022, several important advances have been made in understanding resistance mechanisms in high-grade gliomas. Furthermore, the development of several radiosensitization procedures for these deadly tumors, including studies with small molecule radiosensitizers, new fractionation protocols, and new immunostimulatory agents, has progressed in both the preclinical and clinical settings, reflecting the frantic research effort in the field. However, since 2005 our research efforts fail to produce significant improvements to treatment guidelines for high-grade gliomas. Possible reasons for this stalemate and measures to overcome it are discussed.
MeSH term(s)	Humans ; Radiation Oncology ; Glioma/radiotherapy ; Radiation-Sensitizing Agents ; Dose Fractionation, Radiation
Chemical Substances	Radiation-Sensitizing Agents
Language	English
Publishing date	2023-08-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2023.104110
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Article ; Online: Recapitulating the Key Advances in the Diagnosis and Prognosis of High-Grade Gliomas

Guido Frosina

International Journal of Molecular Sciences, Vol 24, Iss 6375, p

Second Half of 2021 Update

2023 Volume 6375

Abstract: High-grade gliomas (World Health Organization grades III and IV) are the most frequent and fatal brain tumors, with median overall survivals of 24–72 and 14–16 months, respectively. We reviewed the progress in the diagnosis and prognosis of high-grade ... ...

Abstract	High-grade gliomas (World Health Organization grades III and IV) are the most frequent and fatal brain tumors, with median overall survivals of 24–72 and 14–16 months, respectively. We reviewed the progress in the diagnosis and prognosis of high-grade gliomas published in the second half of 2021. A literature search was performed in PubMed using the general terms “radio* and gliom*” and a time limit from 1 July 2021 to 31 December 2021. Important advances were provided in both imaging and non-imaging diagnoses of these hard-to-treat cancers. Our prognostic capacity also increased during the second half of 2021. This review article demonstrates slow, but steady improvements, both scientifically and technically, which express an increased chance that patients with high-grade gliomas may be correctly diagnosed without invasive procedures. The prognosis of those patients strictly depends on the final results of that complex diagnostic process, with widely varying survival rates.
Keywords	CNS ; diagnosis ; glioma ; MRI ; neuroradiology ; non-imaging diagnosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Most recent update of preclinical and clinical data on radioresistance and radiosensitivity of high-grade gliomas-a radiation oncologist's perspective.

Frosina, Guido

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al

2022 Volume 199, Issue 1, Page(s) 1–21

Abstract: Purpose: This review article discusses the studies concerning advances in radiotherapy of high-grade gliomas published in the second half of 2021.: Methods: A literature search was performed in PubMed using the terms ("gliom* and radio*") and time ... ...

Abstract	Purpose: This review article discusses the studies concerning advances in radiotherapy of high-grade gliomas published in the second half of 2021. Methods: A literature search was performed in PubMed using the terms ("gliom* and radio") and time limits 1 July 2021-31 December 2021. The articles were then manually selected for relevance to the analyzed topics. Results:* Considerable progress has been made in the preclinical field on the mechanisms of radioresistance and radiosensitization of high-grade gliomas (HGG). However, fewer early-phase (I/II) clinical trials have been performed and, of the latter, even fewer have produced results that justify moving to phase III. In the 6‑month period under consideration, no studies were published that would lead to a change in clinical practice and the overall survival (OS) of patients remained similar to that of 2005, the year in which it increased significantly for the last time thanks to introduction of the alkylating agent temozolomide. Conclusion: After 17 years of stalemate in improving the OS of patients with HGG, an in-depth analysis of the causes should be carried out in order to identify whether the research efforts conducted so far, including in the radiotherapeutic field, have been the most effective or require improvement. In our opinion, in addition to the therapeutic difficulties related to the biology of HGG tumors (e.g., high infiltrating capacity, multiple resistance mechanisms, blood-brain barrier), some public research policy choices may also play a role, especially in consideration of the limited interest of the pharmaceutical industry in the field of rare cancers.
MeSH term(s)	Humans ; Brain Neoplasms/radiotherapy ; Brain Neoplasms/pathology ; Glioma/pathology ; Radiation Oncologists ; Radiation Tolerance ; Temozolomide/therapeutic use ; Clinical Trials as Topic
Chemical Substances	Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2022-11-29
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	84983-2
ISSN	1439-099X ; 0179-7158 ; 0039-2073
ISSN (online)	1439-099X
ISSN	0179-7158 ; 0039-2073
DOI	10.1007/s00066-022-02020-2
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Article ; Online: Improving control of high-grade glioma by ultra-hyper-fractionated radiotherapy.

Frosina, Guido

Journal of neuroscience research

2022 Volume 100, Issue 4, Page(s) 933–946

Abstract: Ionizing radiation is a mainstay of high-grade glioma therapy. The current standard radiotherapeutic schedule involves a total 60 Gy split in 2.0 Gy fractions delivered on weekdays for six weeks. Thereafter, almost invariably the tumor relapses and ... ...

Abstract	Ionizing radiation is a mainstay of high-grade glioma therapy. The current standard radiotherapeutic schedule involves a total 60 Gy split in 2.0 Gy fractions delivered on weekdays for six weeks. Thereafter, almost invariably the tumor relapses and progresses. In vitro studies have demonstrated that the therapeutic effectiveness of ionizing radiation towards high-grade glioma cells is greatly increased by splitting the total dose in fractions ten times smaller [0.1-0.5 Gy instead of standard 2.0 Gy-ultra-hyper-fractionated radiotherapy (ultra-hyper-FRT)]. Recently, it became possible to consistently translate this therapeutic effect to the animal setting, by using glioma-initiating cell-driven faithful animal modeling. A re-analysis of the literature reporting radiotherapeutic clinical trials also suggests that the lower the average fraction size, the higher is the achievable overall survival of patients. However, average fraction sizes ≤ 0.5 Gy have never been thoroughly investigated in the clinics. We propose to study in the clinical setting the therapeutic effect of an ultra-hyper-FRT schedule promptly extending the conventional radiation component of the current guidelines ("Stupp") therapeutic protocol.
MeSH term(s)	Animals ; Brain Neoplasms/pathology ; Brain Neoplasms/radiotherapy ; Dose Fractionation, Radiation ; Glioma/pathology ; Glioma/radiotherapy ; Humans ; Neoplasm Recurrence, Local
Language	English
Publishing date	2022-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.25030
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Article ; Online: Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies.

Frosina, Guido

International journal of molecular sciences

2021 Volume 22, Issue 16

Abstract: Albeit the effort to develop targeted therapies for patients with high-grade gliomas (WHO grades III and IV) is evidenced by hundreds of current clinical trials, radiation remains one of the few effective therapeutic options for them. This review article ...

Abstract	Albeit the effort to develop targeted therapies for patients with high-grade gliomas (WHO grades III and IV) is evidenced by hundreds of current clinical trials, radiation remains one of the few effective therapeutic options for them. This review article analyzes the updates on the topic "radiotherapy of high-grade gliomas" during the period 1 January 2021-30 June 2021. The high number of articles retrieved in PubMed using the search terms ("gliom* and radio*") and manually selected for relevance indicates the feverish research currently ongoing on the subject. During the last semester, significant advances were provided in both the preclinical and clinical settings concerning the diagnosis and prognosis of high-grade gliomas, their radioresistance, and the inevitable side effects of their treatment with radiation. The novel information concerning tumor radiosensitization was of special interest in terms of therapeutic perspective and was discussed in detail.
MeSH term(s)	Animals ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Brain Neoplasms/radiotherapy ; Glioma/drug therapy ; Glioma/pathology ; Glioma/radiotherapy ; Humans ; Radiation-Sensitizing Agents/pharmacology ; Radiotherapy/methods
Chemical Substances	Radiation-Sensitizing Agents
Language	English
Publishing date	2021-08-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22168942
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Article ; Online: Non-routine Tracers for PET Imaging of High-grade Glioma.

Frosina, Guido

Anticancer research

2016 Volume 36, Issue 7, Page(s) 3253–3260

Abstract: Thorough imaging is crucial for diagnosis and treatment of high-grade gliomas (HGG), lethal brain tumours with median survival ranging 1-5 years after diagnosis. Positron-emission tomography (PET) is acquiring importance in imaging of HGG since it has ... ...

Abstract	Thorough imaging is crucial for diagnosis and treatment of high-grade gliomas (HGG), lethal brain tumours with median survival ranging 1-5 years after diagnosis. Positron-emission tomography (PET) is acquiring importance in imaging of HGG since it has the formidable advantage of providing information on tumour metabolism that may be critical for correct diagnosis and treatment planning. Recently employed PET tracers designed for the non-routine investigation of specific aspects of HGG metabolism, including hypoxia, neoangiogenesis, expression of integrins and stem cell markers, are reviewed herein. A thorough choice from among these non-routine tracers may provide important metabolic information complementing those obtained with more common PET analyses, for the sake of diagnostic, prognostic, treatment planning or research purposes.
MeSH term(s)	Animals ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Glioma/diagnostic imaging ; Glioma/pathology ; Humans ; Neoplasm Grading ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/analysis
Chemical Substances	Radiopharmaceuticals
Language	English
Publishing date	2016-07
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article ; Online: Positron emission tomography of high-grade gliomas.

Frosina, Guido

Journal of neuro-oncology

2016 Volume 127, Issue 3, Page(s) 415–425

Abstract: High-grade gliomas [HGG (WHO grades III-IV)] are almost invariably fatal. Imaging of HGG is important for orientating diagnosis, prognosis and treatment planning and is crucial for development of novel, more effective therapies. Given the potentially ... ...

Abstract	High-grade gliomas [HGG (WHO grades III-IV)] are almost invariably fatal. Imaging of HGG is important for orientating diagnosis, prognosis and treatment planning and is crucial for development of novel, more effective therapies. Given the potentially unlimited number of usable tracing molecules and the elevated number of available radionuclides, PET allows gathering multiple informations on HGG including data on tissue metabolism and drug pharmacokinetics. PET studies on the diagnosis, prognosis and treatment of HGG carried out by most frequently used tracers and radionuclides ((11)C and (18)F) and published in 2014 have been reviewed. These studies demonstrate that a thorough choice of tracers may confer elevated diagnostic and prognostic power to PET imaging of HGG. They also suggest that a combination of PET and MRI may give the most complete and reliable imaging information on HGG and that research on hybrid PET/MRI may be paying back in terms of improved diagnosis, prognosis and treatment planning of these deadly tumours.
MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Glioma/diagnostic imaging ; Glioma/pathology ; Humans ; Neoplasm Grading ; Positron-Emission Tomography/methods
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-016-2077-1
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Article ; Online: Advances in drug delivery to high grade gliomas.

Frosina, Guido

Brain pathology (Zurich, Switzerland)

2016 Volume 26, Issue 6, Page(s) 689–700

Abstract: If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor barriers and reach adequate concentrations at the tumor sites. Effective delivery of ... ...

Abstract	If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor barriers and reach adequate concentrations at the tumor sites. Effective delivery of drugs to brain cancer tissues is thus a necessary, albeit not sufficient, condition to effectively target the disease. In order to analyze the current status of research on drug delivery to high grade gliomas (HGG-WHO grades III and IV), the most frequent and aggressive brain cancers, a literature search was conducted in PubMed using the terms: "drug delivery and brain tumor" over the publication year 2015. Currently explored drug delivery techniques for HGG include the convection and permeabilization-enhanced deliveries, drug-releasing depots and Ommaya reservoirs. The efficacy/safety ratio widely varies among these techniques and the success of current efforts to increase this ratio widely varies as well.
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Brain Neoplasms/diagnostic imaging ; Convection ; Drug Delivery Systems/methods ; Glioma/drug therapy ; Humans
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2016-08-24
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12423
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Article ; Online: Nanoparticle-mediated drug delivery to high-grade gliomas.

Frosina, Guido

Nanomedicine : nanotechnology, biology, and medicine

2016 Volume 12, Issue 4, Page(s) 1083–1093

Abstract: High grade gliomas (HGGs) are fatal brain tumors due to their infiltration capacity and the presence of resistant cell populations. Further, the brain is naturally protected from many exogenous molecules by the brain blood barrier (BBB), which limits or ... ...

Abstract	High grade gliomas (HGGs) are fatal brain tumors due to their infiltration capacity and the presence of resistant cell populations. Further, the brain is naturally protected from many exogenous molecules by the brain blood barrier (BBB), which limits or cancels passage of cytotoxic drugs to the tumor sites. In order to cope with the latter problem, nanoparticle (NP)-based carriers are intensively investigated, due to multiple possibilities to drive them across the BBB to the tumor sites and drop cytotoxic molecules there. The current status of research on NP for drug delivery to HGGs has been analyzed. The results indicate gold, lipids and proteins as three main materials featuring NP formulations for HGG treatment. Albeit specific drug targeting to HGG cells may have not been so far significantly improved, NP may help drugs crossing the BBB and enter the brain thus potentially fixing at least one part of the problem. From the clinical editor: High grade gliomas (HGG) are very aggressive tumours and current therapy remains unsatisfactory. The advance in nanomedicine has allowed the development of novel treatment modalities. In this review article, the authors outlined the current status in using nanoparticle (NP)-based carriers for drug delivery to HGG. This should help readers to understand and develop ideas for further drug carrier designs.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Blood-Brain Barrier/drug effects ; Brain/drug effects ; Brain/pathology ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Drug Delivery Systems ; Glioma/drug therapy ; Glioma/pathology ; Humans ; Nanomedicine ; Nanoparticles/administration & dosage ; Neoplasm Grading
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2016-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2015.12.375
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