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1. Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma

Author

Gregucci, Fabiana, Di Guglielmo, Fiorella Cristina, Surgo, Alessia, Carbonara, Roberta, Laera, Letizia, Ciliberti, Maria Paola, Gentile, Maria Annunziata, Calbi, Roberto, Caliandro, Morena, Sasso, Nicola, Davi’, Valerio, Bonaparte, Ilaria, Fanelli, Vincenzo, Giraldi, David, Tortora, Romina, Internò, Valeria, Giuliani, Francesco, Surico, Giammarco, Signorelli, Francesco, Lombardi, Giuseppe, and Fiorentino, Alba

Published
2024
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3. Extreme hypofractionated stereotactic radiotherapy for elderly prostate cancer patients: side effects preliminary analysis of a phase II trial

Author

Gregucci, Fabiana, Carbonara, Roberta, Surgo, Alessia, Ciliberti, Maria Paola, Curci, Domenico, Ciocia, Annarita, Branà, Luciana, Ludovico, Giuseppe Mario, Scarcia, Marcello, Portoghese, Filippo, Caliandro, Morena, Ludovico, Elena, Paulicelli, Eleonora, Di Guglielmo, Fiorella Cristina, Bonaparte, Ilaria, and Fiorentino, Alba

Published
2023
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4. Improving Quality Assurance in a Radiation Oncology Using ARIA Visual Care Path

Author

Bonaparte, Ilaria, primary, Fragnoli, Federica, additional, Gregucci, Fabiana, additional, Carbonara, Roberta, additional, Di Guglielmo, Fiorella Cristina, additional, Surgo, Alessia, additional, Davì, Valerio, additional, Caliandro, Morena, additional, Sanfrancesco, Giuseppe, additional, De Pascali, Christian, additional, Aga, Alberto, additional, Indellicati, Chiara, additional, Parabita, Rosalinda, additional, Cuscito, Rosilda, additional, Cardetta, Pietro, additional, Laricchia, Maurizio, additional, Antonicelli, Michele, additional, Ciocia, Annarita, additional, Curci, Domenico, additional, Guida, Pietro, additional, Ciliberti, Maria Paola, additional, and Fiorentino, Alba, additional

Published
2024
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9. LINAC-Based STereotactic Arrhythmia Radioablation (STAR) for Paroxysmal Atrial Fibrillation in Elderly: a prospective phase II trial

Author

Di Monaco, Antonio, primary, Gregucci, Fabiana, additional, Bonaparte, Ilaria, additional, Romanazzi, Imma, additional, Troisi, Federica, additional, Surgo, Alessia, additional, Vitulano, Nicola, additional, Quadrini, Federico, additional, Valenti, Noemi, additional, Carbonara, Roberta, additional, Di Guglielmo, Fiorella Cristina, additional, Ludovico, Elena, additional, Calbi, Roberto, additional, Guida, Pietro, additional, Ciliberti, Maria Paola, additional, Fiorentino, Alba, additional, and Grimaldi, Massimo, additional

Published
2023
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10. Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma

Author

Gregucci, Fabiana, primary, Di Guglielmo, Fiorella Cristina, additional, Surgo, Alessia, additional, Carbonara, Roberta, additional, Laera, Letizia, additional, Ciliberti, Maria Paola, additional, Gentile, Maria Annunziata, additional, Calbi, Roberto, additional, Caliandro, Morena, additional, Sasso, Nicola, additional, Davi’, Valerio, additional, Bonaparte, Ilaria, additional, Fanelli, Vincenzo, additional, Giraldi, David, additional, Tortora, Romina, additional, Internò, Valeria, additional, Giuliani, Francesco, additional, Surico, Giammarco, additional, Signorelli, Francesco, additional, Lombardi, Giuseppe, additional, and Fiorentino, Alba, additional

Published
2023
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15. Linear accelerator–based stereotactic arrhythmia radioablation for paroxysmal atrial fibrillation in elderly: a prospective phase II trial.

Author

Monaco, Antonio Di, Gregucci, Fabiana, Bonaparte, Ilaria, Romanazzi, Imma, Troisi, Federica, Surgo, Alessia, Vitulano, Nicola, Quadrini, Federico, Valenti, Noemi, Carbonara, Roberta, Guglielmo, Fiorella Cristina Di, Ludovico, Elena, Calbi, Roberto, Guida, Pietro, Ciliberti, Maria Paola, Fiorentino, Alba, and Grimaldi, Massimo

Abstract

Aims Stereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. Methods and results Inclusion criteria were age >70 years, symptomatic AF, antiarrhythmic drugs failure, or intolerance. All patients underwent to 4D cardiac computed tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). Stereotactic arrhythmia radioablation was performed with a total dose of 25 Gy (single fraction) delivered in 3 min. Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and one patient was excluded due to unfavourable oesophagus position. With a median follow-up (FU) of 16 months (range 12–23), no acute toxicity more than Grade 3 was reported. Five patients had a Grade 1 oesophagitis 24 h after STAR; eight patients had an asymptomatic Grade 1 pericardial effusion, and one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac implantable cardioverter-defibrillator implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrolment vs. 75 ± 15 at 12 months FU; P < 0.001). Conclusion The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy. Trial registration ClinicalTrials.gov: NCT04575662 [ABSTRACT FROM AUTHOR]

Published
2023
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16. Phase II Trial of LINAC-Based STereotactic Arrhythmia Radioablation (STAR) for Paroxysmal Atrial Fibrillation in Elderly: Planning and Dosimetric Point of View

Author

Bonaparte, Ilaria, primary, Gregucci, Fabiana, additional, Di Monaco, Antonio, additional, Troisi, Federica, additional, Surgo, Alessia, additional, Ludovico, Elena, additional, Carbonara, Roberta, additional, Paulicelli, Eleonora, additional, Sanfrancesco, Giuseppe, additional, De Pascali, Christian, additional, Vitulano, Nicola, additional, Quadrini, Federico, additional, Ciliberti, Maria Paola, additional, Romanazzi, Imma, additional, Di Guglielmo, Fiorella Cristina, additional, Cusumano, Davide, additional, Calbi, Roberto, additional, Grimaldi, Massimo, additional, and Fiorentino, Alba, additional

Published
2023
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17. Impact of preoperative chemoradiation with higher dose intensity modulated radiotherapy on pathological complete response for locally advanced rectal cancer: a systematic review

Author

Carbonara, Roberta, primary, Surgo, Alessia, additional, Ciliberti, Maria Paola, additional, Gregucci, Fabiana, additional, Bonaparte, Ilaria, additional, Nicosia, Luca, additional, Meldolesi, Elisa, additional, Caliandro, Morena, additional, Ferraro, Valentina, additional, Inchingolo, Riccardo, additional, Memeo, Riccardo, additional, Ludovico, Elena, additional, Calbi, Roberto, additional, Lavalle, Mariadea, additional, Gambacorta, Maria Antonietta, additional, Alongi, Filippo, additional, and Fiorentino, Alba, additional

Published
2022
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18. Radiosurgery and Stereotactic Brain Radiotherapy with Systemic Therapy in Recurrent High-Grade Gliomas: Is It Feasible? Therapeutic Strategies in Recurrent High-Grade Gliomas

Author

Gregucci, Fabiana, primary, Surgo, Alessia, additional, Carbonara, Roberta, additional, Laera, Letizia, additional, Ciliberti, Maria Paola, additional, Gentile, Maria Annunziata, additional, Caliandro, Morena, additional, Sasso, Nicola, additional, Bonaparte, Ilaria, additional, Fanelli, Vincenzo, additional, Tortora, Romina, additional, Paulicelli, Eleonora, additional, Surico, Giammarco, additional, Lombardi, Giuseppe, additional, Signorelli, Francesco, additional, and Fiorentino, Alba, additional

Published
2022
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19. Adding Concomitant Chemotherapy to Postoperative Radiotherapy in Oral Cavity Carcinoma with Minor Risk Factors: Systematic Review of the Literature and Meta-Analysis

Author

Di Rito, Alessia, primary, Fiorica, Francesco, additional, Carbonara, Roberta, additional, Di Pressa, Francesca, additional, Bertolini, Federica, additional, Mannavola, Francesco, additional, Lohr, Frank, additional, Sardaro, Angela, additional, and D’Angelo, Elisa, additional

Published
2022
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21. Impact of preoperative chemoradiation with higher dose intensity modulated radiotherapy on pathological complete response for locally advanced rectal cancer: a systematic review

Author

Carbonara, Roberta, Surgo, Alessia, Ciliberti, Maria Paola, Gregucci, Fabiana, Bonaparte, Ilaria, Nicosia, Luca, Meldolesi, Elisa, Caliandro, Morena, Ferraro, Valentina, Inchingolo, Riccardo, Memeo, Riccardo, Ludovico, Elena, Calbi, Roberto, Lavalle, Mariadea, Gambacorta, Maria Antonietta, Alongi, Filippo, Fiorentino, Alba, Gambacorta, Maria Antonietta (ORCID:0000-0001-5455-8737), Carbonara, Roberta, Surgo, Alessia, Ciliberti, Maria Paola, Gregucci, Fabiana, Bonaparte, Ilaria, Nicosia, Luca, Meldolesi, Elisa, Caliandro, Morena, Ferraro, Valentina, Inchingolo, Riccardo, Memeo, Riccardo, Ludovico, Elena, Calbi, Roberto, Lavalle, Mariadea, Gambacorta, Maria Antonietta, Alongi, Filippo, Fiorentino, Alba, and Gambacorta, Maria Antonietta (ORCID:0000-0001-5455-8737)

Abstract

Introduction Neoadjuvant chemoradiation (CRT) followed by total mesorectal excision is the current standard-of-care for locally advanced UICC II-III stage rectal cancer (LARC). A pathological complete response (pCR) correlates with survival. Improvements of pCR, including dose escalation, should be explored. The aim of this explorative analysis is to assess the impact on pCR of intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB). Areas Covered A literature search via PICO (Population, Intervention, Comparison, Outcome) in MEDLINE/PubMed and EMBASE and a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Metanalysis) methodology were performed. Studies that reported pCR rate in patients with LARC in clinical stage T2N+M0 or cT3/4 N0/+M0 treated with preoperative CRT with SIB-IMRT/VMAT (Volumetric Modulated Arc Therapy) were included. Sixty-two studies were identified, but only eight clinical trials with a total of 311 patients were included . Median follow-up was 16-61 months. pCR reached the value of 38%. Good survival outcomes were observed with a mild toxicity profile. Expert Opinion Radiotherapy dose intensification in LARC showed a slight increase of pCR compared to historical studies. Prospective evaluations are necessary to define which patients would benefit most.

Published
2022

24. 624: ARIA Visual Care Path for safety and quality assurance in a radiation oncology department

Author

Fragnoli, Federica, Bonaparte, Ilaria, Cuscito, Rosilda, Indellicati, Chiara, Di Guglielmo, Fiorella Cristina, Sanfrancesco, Giuseppe, De Pascali, Christian, Aga, Alberto, Carbonara, Roberta, Surgo, Alessia, Davì, Valerio, Caliandro, Morena, Cardetta, Pietro, Laricchia, Maurizio, Parabita, Rosalinda, Guida, Piero, Ciliberti, Maria Paola, and Fiorentino, Alba

Published
2024
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27. Paroxysmal Atrial Fibrillation in Elderly: Worldwide Preliminary Data of LINAC-Based Stereotactic Arrhythmia Radioablation Prospective Phase II Trial

Author

Di Monaco, Antonio, primary, Gregucci, Fabiana, additional, Bonaparte, Ilaria, additional, Troisi, Federica, additional, Surgo, Alessia, additional, Di Molfetta, Domenico, additional, Vitulano, Nicola, additional, Quadrini, Federico, additional, Carbonara, Roberta, additional, Martinelli, Gaetano, additional, Guida, Pietro, additional, Ciliberti, Maria Paola, additional, Fiorentino, Alba, additional, and Grimaldi, Massimo, additional

Published
2022
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28. Brain Linac-Based Radiation Therapy: “Test Drive” of New Immobilization Solution and Surface Guided Radiation Therapy

Author

Gregucci, Fabiana, primary, Bonaparte, Ilaria, additional, Surgo, Alessia, additional, Caliandro, Morena, additional, Carbonara, Roberta, additional, Ciliberti, Maria Paola, additional, Aga, Alberto, additional, Berloco, Francesco, additional, De Masi, Marina, additional, De Pascali, Christian, additional, Fragnoli, Federica, additional, Indellicati, Chiara, additional, Parabita, Rosalinda, additional, Sanfrancesco, Giuseppe, additional, Branà, Luciana, additional, Ciocia, Annarita, additional, Curci, Domenico, additional, Guida, Pietro, additional, and Fiorentino, Alba, additional

Published
2021
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29. Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide

Author

Gregucci, Fabiana, primary, Surgo, Alessia, additional, Bonaparte, Ilaria, additional, Laera, Letizia, additional, Ciliberti, Maria Paola, additional, Carbonara, Roberta, additional, Gentile, Maria Annunziata, additional, Giraldi, David, additional, Calbi, Roberto, additional, Caliandro, Morena, additional, Sasso, Nicola, additional, D’Oria, Salvatore, additional, Somma, Carlo, additional, Martinelli, Gaetano, additional, Surico, Giammarco, additional, Lombardi, Giuseppe, additional, and Fiorentino, Alba, additional

Published
2021
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30. Radiomic analysis to predict local response in locally advanced pancreatic cancer treated with stereotactic body radiation therapy

Author

Gregucci, Fabiana, primary, Fiorentino, Alba, additional, Mazzola, Rosario, additional, Ricchetti, Francesco, additional, Bonaparte, Ilaria, additional, Surgo, Alessia, additional, Figlia, Vanessa, additional, Carbonara, Roberta, additional, Caliandro, Morena, additional, Ciliberti, Maria Paola, additional, Ruggieri, Ruggero, additional, and Alongi, Filippo, additional

Published
2021
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31. Investigation of Radiation-Induced Toxicity in Head and Neck Cancer Patients through Radiomics and Machine Learning: A Systematic Review

Author

Carbonara, Roberta, Bonomo, Pierluigi, Di Rito, Alessia, Didonna, Vittorio, Gregucci, Fabiana, Ciliberti, Maria Paola, Surgo, Alessia, Bonaparte, Ilaria, Fiorentino, Alba, and Sardaro, Angela

Subjects
Article Subject
Abstract

Background. Radiation-induced toxicity represents a crucial concern in oncological treatments of patients affected by head and neck neoplasms, due to its impact on survivors’ quality of life. Published reports suggested the potential of radiomics combined with machine learning methods in the prediction and assessment of radiation-induced toxicities, supporting a tailored radiation treatment management. In this paper, we present an update of the current knowledge concerning these modern approaches. Materials and Methods. A systematic review according to PICO-PRISMA methodology was conducted in MEDLINE/PubMed and EMBASE databases until June 2019. Studies assessing the use of radiomics combined with machine learning in predicting radiation-induced toxicity in head and neck cancer patients were specifically included. Four authors (two independently and two in concordance) assessed the methodological quality of the included studies using the Radiomic Quality Score (RQS). The overall score for each analyzed study was obtained by the sum of the single RQS items; the average and standard deviation values of the authors’ RQS were calculated and reported. Results. Eight included papers, presenting data on parotid glands, cochlea, masticatory muscles, and white brain matter, were specifically analyzed in this review. Only one study had an average RQS was ≤ 30% (50%), while 3 studies obtained a RQS almost ≤ 25%. Potential variability in the interpretations of specific RQS items could have influenced the inter-rater agreement in specific cases. Conclusions. Published radiomic studies provide encouraging but still limited and preliminary data that require further validation to improve the decision-making processes in preventing and managing radiation-induced toxicities.

Published
2021
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33. Linac‐based STereotactic Arrhythmia Radioablation (STAR) of ventricular tachycardia: Case report and literature review

Author

Fiorentino, Alba, primary, Di Monaco, Antonio, additional, Surgo, Alessia, additional, Vitulano, Nicola, additional, Gregucci, Fabiana, additional, Ludovico, Elena, additional, Carbonara, Roberta, additional, Quadrini, Federico, additional, Rubini, Giuseppe, additional, Bonaparte, Ilaria, additional, and Grimaldi, Massimo, additional

Published
2020
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38. Linac‐based STereotactic Arrhythmia Radioablation (STAR) of ventricular tachycardia: Case report and literature review.

Author

Fiorentino, Alba, Di Monaco, Antonio, Surgo, Alessia, Vitulano, Nicola, Gregucci, Fabiana, Ludovico, Elena, Carbonara, Roberta, Quadrini, Federico, Rubini, Giuseppe, Bonaparte, Ilaria, and Grimaldi, Massimo

Subjects
VENTRICULAR tachycardia, ARRHYTHMIA, LITERATURE reviews
Abstract

Linac‐based STereotactic Arrhythmia Radioablation (STAR) is a safety and effective approach for selected patients with ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Published
2021
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39. Impressive response and longterm survival in a patient with metastatic extraskeletal myxoid chondrosarcoma treated with radiotherapy and trabectedin: a synergistic activity

Author

Filannino, Ruggero, primary, Nardone, Annalisa, additional, Fucci, Livia, additional, Armenio, Andrea, additional, Luca, Federica De, additional, Figliuolo, Francesco, additional, Macina, Francesco, additional, Ruggieri, Eustachio, additional, Tommasi, Stefania, additional, Traversa, Michele, additional, Orsini, Umberto, additional, Albano, Anna, additional, Carbonara, Roberta, additional, and Guida, Michele, additional

Published
2018
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42. Linac-based stereotactic body radiation therapy in elderly prostate cancer patients.

Author

Carbonara, Roberta, Gregucci, Fabiana, Ciliberti, Maria Paola, Surgo, Alessia, Caliandro, Morena, Ludovico, Giuseppe, Scarcia, Marcello, Paulicelli, Eleonora, Bonaparte, Ilaria, and Fiorentino, Alba

Subjects
*STEREOTACTIC radiotherapy, *RETENTION of urine, *PROSTATE cancer patients, *FRAIL elderly, *VOLUMETRIC-modulated arc therapy, *OLDER patients
Abstract

Aim: An increasing number of literature data recommends SBRT in prostate cancer (PC) patients. A Linac-based SBRT treatment with risk-adjusted prescription dose is usually proposed to elderly patients with PC. An update of data regarding patients treated in 30 months was performed to evaluate the safety and efficacy of SBRT. Methods: Men aged ≥70 years affected by localized PC were treated with Linac-Based SBRT. The entire prostate was irradiated up to a total dose of 35 Gy in 5 fractions. The dose was optimized to isodose line of 90% in low/ favorable intermediate cases and 80% in unfavorable intermediate/high risk cases.A Volumetric Modulated Arc Therapy (VMAT) technique was used for planning and delivery.Treatment was delivered over 1 or 2 weeks based on PTV and pre-treatment urinary symptoms. Some patients also received androgen deprivation therapy (ADT) according to the risk group classification. All patients were supported by corticosteroids. Toxicity and quality of life (QoL) were assessed at baseline, after treatment and during follow-up (FU) using the Common Terminology Criteria for Adverse Events and International Prostatic Symptoms Score (IPSS). PSA values were recorded before treatment and during FU as biochemical response criteria. Results: Between July 2019 and December 2021, 78 patients were treated.Median age was 76 years (range 61- 88); 33 had low risk, 30 favorable/unfavorable intermediate risk and 15 high risk PC. Median pre-treatment PSA was 5 ng/ml (range 0,61-25).ADT was prescribed in 23 (29.5%) patients. In cases in which dose was optimized to isodose 90%, Dmax was 38,9 Gy,whereas when optimizated to isodose 80%, Dmax was 43,8 Gy. Median PTV was 109,6cc (range 75-157,7). Median baseline IPSS was 3(range 0-6). At the end of the treatment, no >G1 acute toxicity was observed. Two-three weeks after SBRT, 13(17%) patients reported G2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention) and 9 patients(12%) presented rectal tenesmus. During FU, only 3 cases of rectal bleeding were observed (related to comorbidities). No relevant deteriorations of QoL were described. At a median FU of 15 months(range 1-27), excellent biochemical disease control was achieved in all cases with a median PSA of 1,5 ng/ml (range 0,01- 7,3). No differences were observed between the two different prescription approaches. Conclusion: Linac-based SBRT for localized PC is feasible and well tolerated, even in elderly and frail patients. Excellent biochemical disease control is associated with high compliance of very elderly patients to treatment.Longer follow-up is needed to confirm late treatment tolerance and efficacy. [ABSTRACT FROM AUTHOR]

Published
2022

46. Synthesis and Toxicopharmacological Evaluation of m-Hydroxymexiletine, the First Metabolite of Mexiletine More Potent Than the Parent Compound on Voltage-Gated Sodium Channels

Author

Catalano, Alessia, primary, Desaphy, Jean-François, additional, Lentini, Giovanni, additional, Carocci, Alessia, additional, Di Mola, Antonia, additional, Bruno, Claudio, additional, Carbonara, Roberta, additional, De Palma, Annalisa, additional, Budriesi, Roberta, additional, Ghelardini, Carla, additional, Perrone, Maria Grazia, additional, Colabufo, Nicola Antonio, additional, Conte Camerino, Diana, additional, and Franchini, Carlo, additional

Published
2012
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48. Paroxysmal atrial fibrillation in elderly: Worldwide preliminary data of LINACbased STereotactic Arrhythmia Radioablation prospective phase II trial .

Author

Gregucci, Fabiana, Monaco, Antonio Di, Bonaparte, Ilaria, Surgo, Alessia, Troisi, Federica, Ludovico, Elena, Vitulano, Nicola, Quadrini, Federico, Carbonara, Roberta, Ciliberti, Maria Paola, Grimaldi, Massimo, and Fiorentino, Alba

Subjects
ATRIAL flutter, ATRIAL fibrillation, CONE beam computed tomography, VOLUMETRIC-modulated arc therapy, ARRHYTHMIA, IMAGE-guided radiation therapy
Abstract

Aim: In elderly, paroxysmal Atrial Fibrillation (AF) is difficult to treat with drugs, or by Catheter ablation, so a non-invasive approach should be favourite. No data are published about the use or radiosurgery for AF, thus in the present analysis the preliminary data of Linac-based STereotectic Arrythmias Radioablation (STAR) for elderly affected by paroxysmal AF were reported. Methods: Inclusion criteria were: age >70 years; symptomatic paroxysmal AF; intolerance or nonresponse to anti-arhythmic therapy (AAT). All patients performed 1-week ECG-Holter monitoring, a complete transthoracic echocardiogram before and after STAR. Patients were immobilized using a vac-lock bag and Computed Tomography (CT, 1mm slice-thickness), in the supine position were performed: CT with/without contrast; 4-Dimension CT. STAR was performed in freebreathing with a PTV prescription total dose (Dp) of 25Gy/1 fraction. Flattening Filter Free (FFF), Volumetric Modulated Arc Therapy (VMAT) plan was generated, normalizing 100% Dp to 95% of the volume, while large intra-target dose heterogeneity D2% (PTV)<150%Dp was accepted. The treatment was optimized and delivered by TrueBeamTM (Varian Medical System). Image-guided radiotherapy with Cone Beam CT and Surface-Guided RadioTherapy with Align-RT were used to reduce setup error and to monitor patients during fraction. The primary endpoint is the 1-month post-STAR safety, as complete STAR delivery and no acute treatment-related adverse events more than G3, assessed according to the Common Terminology Criteria for Adverse Events (version 5.0).Results: From May 2021 to January 2022, 5 patients were treated and followed. AAT was stopped after enrollment. For primary endpoint, no acute treatmentrelated adverse events were registered (>G1). Only 1 patient experienced G1 esophagitis (7 days from STAR), improved by 5 days of medical therapy. The treatment plan was delivered with 3 no coplanar arcs, in all cases. The mean Overall Treatment Time (OTT) was 3minutes. For all treated patients with a mean follow-up of 4 months (patients 1-4), no late side effects were reported, and at 3 months, a rare atrial ectopy was documented without AF recurrences. No patients started AAT after radiotherapy Conclusion: The present collected data are promising, showing the safety of LINAC-based STAR for AF for the first 5 patients worldwide. This new ablation approach could represent a valid non-invasive alternative for elderly who were excluded from catheter ablation. [ABSTRACT FROM AUTHOR]

Published
2022

49. Radiosurgery and stereotactic brain radiotherapy with systemic therapy in recurrent high-grade gliomas: Is it feasible?

Author

Surgo, Alessia, Gregucci, Fabiana, Carbonara, Roberta, Laera, Letizia, Ciliberti, Maria Paola, Caliandro, Morena, Bonaparte, Ilaria, and Fiorentino, Alba

Subjects
STEREOTACTIC radiosurgery, STEREOTACTIC radiotherapy, GLIOMAS, THERAPEUTICS, MAGNETIC resonance imaging, CHEMORADIOTHERAPY
Abstract

Purpose: For recurrent high-grade gliomas (HGG) no standard therapeutic approach has been reported thus surgery, chemotherapy and reirradiation (re-RT) may all be proposed. The aim of the present study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. Material/methods: We included retrospectively all patients with histological diagnosis of HGG that, in the study period, suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT. Median dose was 24 Gy (range 18-36 Gy) and median number of fractions was 5 (range 1-6). Outcome was evaluated by clinical neurological examination and brain MRI performed 1 month after re-RT and then every 2-3 months. Results: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median time between primary/adjuvant RT and disease recurrence was 8 months (range 2-27). In 6 cases (20%) reoperation was performed and, in most cases, (84%), a second line of systemic therapy was administrated. Median OS after recurrence was 12.1 months (95%CI 7.1-23.5). Six-month and 1-year OS were, respectively, 81% (95%CI 57-93%) and 51% (95%CI 26-72%). Median PFS after recurrence was 11.2 months (95%CI 6.2-23.1). Six-month and 1-year PFS were, respectively, 70% (95%CI 48-84%) and 32% (95%CI 13.12-52.8%). Regarding SRS/FSRT, no acute or late neurological side effects grade ≥ 2 were reported. No case of radionecrosis was detected. Conclusion: Re-RT with SRT/FSRT in association with second line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. However, validation of these results by prospective studies is needed. [ABSTRACT FROM AUTHOR]

Published
2022

50. Molecular Dissection of Lubeluzole Use–Dependent Block of Voltage-Gated Sodium Channels Discloses New Therapeutic Potentials

Author

Desaphy, Jean-François, Carbonara, Roberta, Costanza, Teresa, Lentini, Giovanni, Cavalluzzi, Maria Maddalena, Bruno, Claudio, Franchini, Carlo, and Camerino, Diana Conte

Abstract

Lubeluzole, which acts on various targets in vitro, including voltage-gated sodium channels, was initially proposed as a neuroprotectant. The lubeluzole structure contains a benzothiazole moiety [N-methyl-1,3-benzothiazole-2-amine (R-like)] related to riluzole and a phenoxy-propranol-amine moiety [(RS)-1-(3,4-difluorophenoxy)-3-(piperidin-1-yl)propan-2-ol (A-core)] recalling propranolol. Both riluzole and propranolol are efficient sodium channel blockers. We studied in detail the effects of lubeluzole (racemic mixture and single isomers), the aforementioned lubeluzole moieties, and riluzole on sodium channels to increase our knowledge of drug-channel molecular interactions. Compounds were tested on hNav1.4 sodium channels, and on F1586C or Y1593C mutants functionally expressed in human embryonic kidney 293 cells, using the patch-clamp technique. Lubeluzole blocked sodium channels with a remarkable effectiveness. No stereoselectivity was found. Compared with mexiletine, the dissociation constant for inactivated channels was ∼600 times lower (∼11 nM), conferring to lubeluzole a huge use-dependence of great therapeutic value. The F1586C mutation only partially impaired the use-dependent block, suggesting that additional amino acids are critically involved in high-affinity binding. Lubeluzole moieties were modest sodium channel blockers. Riluzole blocked sodium channels efficiently but lacked use dependence, similar to R-like. F1586C fully abolished A-core use dependence, suggesting that A-core binds to the local anesthetic receptor. Thus, lubeluzole likely binds to the local anesthetic receptor through its phenoxy-propranol-amine moiety, with consequent use-dependent behavior. Nevertheless, compared with other known sodium channel blockers, lubeluzole adds a third pharmacophoric point through its benzothiazole moiety, which greatly enhances high-affinity binding and use-dependent block. If sufficient isoform specificity can be attained, the huge use-dependent block may help in the development of new sodium channel inhibitors to provide pharmacotherapy for membrane excitability disorders, such as myotonia, epilepsy, or chronic pain.

Published
2013
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