Publications by authors named "Antonino Romeo"

69 Publications

Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies.

Biomolecules 2021 08 12;11(8). Epub 2021 Aug 12.

Radiotherapy Unit, IRCCS Istituto Romagnolo Per lo Studio dei Tumori "Dino Amadori"-IRST, 47014 Meldola, Italy.

In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1-65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8-13.2) and 14.3 (95% CI 12.0-18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6-33.0), and the R0 resection rate was 13.7% (95% CI 5.8-21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19-9 were associated with improved OS and PFS. Concerning OS, log(CA19-9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02-1.42), = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46-4.96); for PS 2, HR was 4.18 (95% CI 0.90-19.46); = 0.003. Low CA19-9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52-0.97), = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11081200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393939PMC
August 2021

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report.

World J Clin Cases 2021 Jul;9(20):5540-5546

Radiotherapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola 47014, Italy.

Background: Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer (NSCLC). We describe the case of a patient with locally advanced node-positive NSCLC (LA-NSCLC) treated in a phase II prospective protocol with chemotherapy, accelerated hypofractionated radiotherapy (AHRT) and surgery in the pre-immunotherapy era.

Case Summary: A 69-year-old male, ex-smoker (20 PY), with a Karnofsky performance status of 90, was diagnosed with locally advanced squamous cell lung carcinoma. He was staged by total body computed tomography (CT) scanning, and integrated F-fluorodeoxyglucose positron emission tomography/CT scan [cT4 cN3 cM0, stage IIIC according to TNM (tumor-node-metastasis) 8 edition] and received AHRT between chemotherapy cycles, in accordance with the study protocol (EudractCT registration 2008-006525-14). At the end of the study the patient underwent surgery, which was not part of the protocol, and showed a complete pathological response.

Conclusion: This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement. Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications. We hypothesize that this radiotherapeutic approach, with its proven efficacy, could be delivered as a short course reducing treatment costs, increasing patient compliance and reducing toxicity. We are currently investigating the possibility of combining hypofractionation, chemotherapy and immunotherapy for patients with LA-NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v9.i20.5540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281427PMC
July 2021

The role of radiotherapy in adult soft tissues sarcoma of the extremities.

Eur J Orthop Surg Traumatol 2021 May 6. Epub 2021 May 6.

Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Local management of adult soft tissue sarcoma of the extremities has evolved over the past decades. Until the 1970s, radical surgery (amputations) was the standard therapeutic procedure resulting in significant physical and psychological morbidity for the patients. In the present era, limb sparing surgery combined with radiotherapy represents the current standard of care for high grade and > 5 cm STSs. This approach guarantees high local control rate and function preservation. The aim of this paper is to summarize the current evidence for RT in STSs of the extremities. Outcomes, technical details (techniques, timing, dose, volumes of treatment) and the emerging role of RT in the management of oligometastatic disease will be analysed. Finally, results of the recent clinical trials testing new scenarios in RT of STSs will be described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00590-021-02990-6DOI Listing
May 2021

Italian cohort of Lafora disease: Clinical features, disease evolution, and genotype-phenotype correlations.

J Neurol Sci 2021 May 20;424:117409. Epub 2021 Mar 20.

Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy.

Background: Lafora disease (LD) is characterized by progressive myoclonus, refractory epilepsy, and cognitive deterioration. This complex neurodegenerative condition is caused by pathogenic variants in EPM2A/EPM2B genes, encoding two essential glycogen metabolism enzymes known as laforin and malin. Long-term follow-up data are lacking. We describe the clinical features and genetic findings of a cohort of 26 Italian patients with a long clinical follow-up.

Methods: Patients with EPM2A/EPM2B pathogenic variants were identified by direct gene sequencing or gene panels with targeted re-sequencing. Disease progression, motor functions, and mental performance were assessed by a simplified disability scale. Spontaneous/action myoclonus severity was scored by the Magaudda Scale.

Results: Age range was 12.2-46.2 years (mean:25.53 ± 9.14). Age at disease onset ranged from 10 to 22 years (mean:14.04 ± 2.62). The mean follow-up period was 11.48 ± 7.8 years. Twelve out of the 26 (46%) patients preserved walking ability and 13 (50%) maintained speech. A slower disease progression with preserved ambulation and speech after ≥4 years of follow-up was observed in 1 (11%) out of the 9 (35%) EPM2A patients and in 6 (35%) out of the 17 (65%) EPM2B patients. Follow-up was >10 years in 7 (41.2%) EPM2B individuals, including two harbouring the homozygous p.(D146N) pathogenic variant.

Conclusions: This study supports an overall worse disease outcome with severe deterioration of ambulation and speech in patients carrying EPM2A mutations. However, the delayed onset of disabling symptoms observed in the EPM2B subjects harbouring the p.(D146N) pathogenic variant suggests that the underlying causative variant may still influence LD severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2021.117409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166462PMC
May 2021

Flare phenomenon in prostate cancer: recent evidence on new drugs and next generation imaging.

Ther Adv Med Oncol 2021 24;13:1758835920987654. Epub 2021 Feb 24.

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori "Dino Amadori" (IRST), IRCCS, Meldola, Emilia-Romagna, Italy.

Over the years, an increasing proportion of metastatic prostate cancer patients has been found to experience an initial bone flare phenomenon under both standard therapies (androgen deprivation therapy, chemotherapy, radiotherapy, abiraterone, enzalutamide) and novel agents (immunotherapy, bone-targeting radioisotopes). The underlying biological mechanisms of the flare phenomenon are still elusive and need further clarification, particularly in relation to different types of treatment and their treatment response assessment. Flare phenomenon is often underestimated and, in some cases, can negatively affect clinical outcome. In cases with suspected bone flare, the treatment should be continued for a minimum of 12 more weeks before further decisions about efficacy can be taken. Physicians and patients should be aware of this effect to avoid unwarranted anxiety and inadequate early discontinuation of treatment. This review aims at highlighting new evidence on flare phenomenon arising after the introduction of new drugs extending across the biochemical, radiographic and clinical spectrum of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1758835920987654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907710PMC
February 2021

TP53 drives abscopal effect by secretion of senescence-associated molecular signals in non-small cell lung cancer.

J Exp Clin Cancer Res 2021 Mar 5;40(1):89. Epub 2021 Mar 5.

Department of Medical Physics, IRCCS University Hospital of Bologna, via Massarenti 9, 40138, Bologna, Italy.

Background: Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms.

Methods: We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay.

Results: We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization.

Conclusions: In our models, we demonstrate that high radiation dose in wtp53 tumors induce the onset of SASP and secretion of CD63+ EVs loaded with DNA:RNA hybrids and LINE-1 retrotransposons that convey senescence messages out of the irradiation field triggering abscopal effect in NIR tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-021-01883-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934399PMC
March 2021

High-pressure oxygen rewires glucose metabolism of patient-derived glioblastoma cells and fuels inflammasome response.

Cancer Lett 2021 05 27;506:152-166. Epub 2021 Feb 27.

Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. Electronic address:

Human glioblastoma (GBM) is one of the most feared primary malignant brain tumors. We investigated the effect of hyperbaric oxygen (HBO) on GBM patient-derived cells and on microglia cell biology (CHME-5). HBO administered to GBM cells inhibited cell proliferation, downregulated hypoxia-inducible factor 1 α (HIF-1α) expression, and induced glucose metabolism reprogramming (glucose rewiring). It also affected the ability of a cell to perpetuate its lineage, give rise to differentiated cells and interact with its environment to maintain a balance between quiescence, proliferation and regeneration (stemness features). Such an effect may be ascribable to an increase in intracellular ROS levels and to the triggering of inflammasome signaling by HBO itself through caspase1 activation. Moreover, the results obtained from the combination of HBO and radiotherapy (RT) clearly showed a radiosensitising effect of HBO on GBM cells grown in both 2D and 3D, and a radioprotective effect of HBO in CHME-5. In addition, the exposure of M0 microglia cells to exhausted medium or extracellular vesicles (EVs) of HBO-treated GBM cells upregulated the expression of pro-inflammatory cytokines IL1β, IL6 and STAT1, whilst also downregulating the anti-inflammatory cytokine PPARγ. Collectively, these data provide a scientific rationale for the use of HBO in combination with RT for the treatment of patients with GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2021.02.019DOI Listing
May 2021

Neoadjuvant treatment (FOLFOX4 plus hypofractionated tomotherapy) for patients with locally advanced rectal cancer: a multicenter phase II trial.

Ther Adv Med Oncol 2020 8;12:1758835920977139. Epub 2020 Dec 8.

Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Aims: This study aims to evaluate the safety and efficacy of a new neoadjuvant regimen (FOLFOX4 plus hypofractionated tomotherapy) in patients with locally advanced rectal cancer.

Methods: Patients with stage II-III rectal cancer were treated with the pre-operative chemoradiotherapy regimen comprising FOLFOX4 (two cycles), TomoTherapy (25 Gy in five consecutive fractions, one fraction per day in 5 days on the clinical target volume at the isodose of 95% of the total dose), FOLFOX4 (two cycles), followed by surgery with total mesorectal excision and adjuvant chemotherapy with FOLFOX4 (eight cycles). The primary endpoint was pathological complete response (pCR).

Results: Fifty-two patients were enrolled and 50 patients were evaluable. A total of 46 (92%) patients completed chemoradiotherapy according to the study protocol and 49 patients underwent surgery. Overall, 12 patients achieved a pCR (24.5%, 95% CI 12.5-36.5). The most common grade 3 or more adverse events were neutropenia and alteration of the alvus. Adverse reactions due to radiotherapy, mainly grade 1-2 dermatitis, tenesmus, urinary dysfunction and pain, were tolerable and fully reversible. The most important surgical complications included infection, anastomotic leakage and fistula, all resolved with conservative treatment.

Conclusion: FOLFOX and hypofractionated TomoTherapy is effective and safe in patients with locally advanced rectal cancer. Long-term efficacy needs to be further evaluated.

Trial Registration: ClinicalTrials.gov identifier: NCT02000050 (registration date: 26 November 2013) https://clinicaltrials.gov/ct2/show/NCT02000050.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1758835920977139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727058PMC
December 2020

Basal Ganglia Dysmorphism in Patients With Aicardi Syndrome.

Neurology 2021 03 4;96(9):e1319-e1333. Epub 2020 Dec 4.

From the Department of Brain and Behavioural Neurosciences (S.M., A.P., M. Formica, S.O.) and Department of Public Health Experimental and Forensic Medicine, Biostatistic and Clinical Epidemiology Unit (P. Borrelli), University of Pavia; Pediatric Neurology Unit (S.M., M. Mastrangelo, P.V.), V. Buzzi Children's Hospital, Milan; Department of Neuroradiology (A.P.), Child Neurology and Psychiatry Unit (R.B., V.D.G., S.O.), and Department of Internal Medicine and Therapeutics, Member of the ERN EpiCARE, University of Pavia and Clinical Trial Center (E.P.), IRCCS Mondino Foundation Pavia; Neuroimaging Lab (F.A.) and Neuropsychiatry and Neurorehabilitation Unit (R.R.), Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco; Child Neuropsychiatric Unit (P.A., L.G.), Civilian Hospital, Brescia; Scientific Institute (P. Bonanni, A.D., E.O.), IRCCS E. Medea, Epilepsy and Clinical Neurophysiology Unit, Conegliano, Treviso; UOC Child Neuropsychiatry (B.D.B., F.D.), Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Italy; Département de Neurologie Pédiatrique (N.D.), Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Belgium; AdPueriVitam (O.D.), Antony; Service d'Explorations Fonctionnelles (S.G.), Centre de Médecine du Sommeil, l'Hôpital Àntoine Béclère, AP-HP, Clamart; Pediatrics Departement (S.G.), André-Grégoire Hospital, Centre Hospitalier Inter Communal, Montreuil, France; Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department (R.G., M. Montomoli, M.C.) and Radiology (M. Mortilla), A. Meyer Children's Hospital, Member of the ERN EpiCARE, University of Florence; IRCCS Stella Maris Foundation (R.G.), Pisa; Child Neuropsychiatry Unit, Epilepsy Center (F.L.B., A.V.), San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan; Child Neurology, NESMOS Department (P.P.), Faculty of Medicine & Psychology, Sant'Andrea Hospital, Sapienza University, Rome; Department of Neuroradiology (L.P.), Pediatric Neuroradiology Section, ASST Spedali Civili, Brescia; Pediatric Neuroradiology Unit (M.S.), IRCCS Istituto Giannina Gaslini, Genova; Neurology Unit, Department of Neuroscience, Member of the ERN EpiCARE (F.V.), Oncological Neuroradiology Unit, Department of Imaging, IRCCS (G.C.), and Department of Neuroscience and Neurorehabilitation (A.F.), Bambino Gesù Children's Hospital, Rome, Italy; Institut Imagine (N.B.-B.), Université Paris Descartes-Sorbonne Paris Cités; Pediatric Neurology (N.B.-B., I.D.), Necker Enfants Malades Hospital, Member of the ERN EpiCARE, Assistance Publique-Hôpitaux de Paris; INSERM UMR-1163 (N.B.-B., A. Arzimanoglou), Embryology and Genetics of Congenital Malformations, France; UOC Neurochirurgia (A. Accogli, V.C.), Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa (F.Z.), and Laboratory of Neurogenetics and Neuroscience, IRCCS (F.Z.), Istituto Giannina Gaslini, Genoa, Italy; Neurochirurgie Pédiatrique (M.B.), Hôpital NEM, Paris, France; Centre Médico-Chirurgical des Eaux-Vives (V.C.-V.), Swiss Medical Network, Genève, Switzerland; Neuroradiology Unit (L.C.) and Developmental Neurology Unit (S.D.), Foundation IRCCS C. Besta Neurological Institute, Milan; Service de Génétique (M.D.-F.), AMH2, CHU Reims, UFR de Médecine, Reims, France; Epilepsy Centre-Clinic of Nervous System Diseases (G.d.), Riuniti Hospital, Foggia, Italy; MediClubGeorgia Co Ltd (N.E.), Tbilisi, Georgia; Epilepsy Center (N.E.), Medical Center, Faculty of Medicine, University of Freiburg, Germany; Child and Adolescence Neurology and Psychiatry Unit (E. Fazzi), ASST Civil Hospital, Department of Clinical and Experimental Sciences, University of Brescia; Child Neurology Department (E. Fiorini), Verona, Italy; Service de Genetique Clinique (M. Fradin, P.L., C.Q.), CLAD-Ouest, Hospital Sud, Rennes, France; Child Neurology Unit, Pediatric Department (C.F., C.S.), Azienda USL-IRCCS di Reggio Emilia; Department of Pediatric Neuroscience (T.G., R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Department of Epilepsy Genetics and Personalized Treatment (K.M.J., R.S.M.), The Danish Epilepsy Centre, Dianalund; Institute for Regional Health Services (K.M.J., R.S.M.), University of Southern Denmark, Odense; Unit of Pediatric Neurology and Pediatric Neurorehabilitation (S.L.), Woman-Mother-Child Department, Lausanne University Hospital CHUV, Switzerland; Unit of Neuroradiology (D.M.), Fondazione CNR/Regione Toscana G. Monasterio, Pisa; Pediatric Neurology Unit and Epilepsy Center (E.R., A.R.), Fatebenefratelli Hospital, Milan, Italy; KJF Klinik Josefinum GmbH (C.U.), Klinik für Kinder und Jugendliche, Neuropädiatrie, Augsburg, Germany; Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology (A. Arzimanoglou), University Hospitals of Lyon, Coordinator of the ERN EpiCARE, France; and Pediatric Epilepsy Unit, Child Neurology Department (P.V.), Hospital San Juan de Dios, Member of the ERN EpiCARE and Universitat de Barcelona, Spain.

Objective: Aiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed.

Methods: Only patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed.

Results: Patients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56% of our patients. Statistical analysis revealed correlations between MRI, EEG at onset, and clinical outcome. On brain imaging, 100% of the patients displayed corpus callosum malformations, 98% cortical dysplasia and nodular heterotopias, and 96.36% intracranial cysts (with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63% of cases) should also be considered a common feature in AIC, our study highlighted the presence (in 76.36%) of basal ganglia dysmorphisms (never previously reported).

Conclusion: The AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome.

Classification Of Evidence: This study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000011237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055324PMC
March 2021

Ga-PSMA-11 PET/CT-Guided Stereotactic Body Radiation Therapy Retreatment in Prostate Cancer Patients with PSA Failure after Salvage Radiotherapy.

Biomedicines 2020 Nov 25;8(12). Epub 2020 Nov 25.

Department of Radiotherapy, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.

(1) Purpose: To investigate the role of Ga-PSMA-11 PET/CT in guiding retreatment stereotactic body radiation therapy (SBRT) in prostate cancer (PCa) patients in biochemical recurrence (BCR) after salvage radiotherapy (S-RT). (2) Methods: We retrospectively evaluated PCa patients previously treated with S-RT on the prostate bed and with proven serum prostate antigen (PSA) failure after S-RT. In all patients (pts), Ga-PSMA-11 PET/CT was positive in the prostate bed only and guided retreatment SBRT. All retreatments were performed by applying the same radiotherapy protocol (median dose of 18 Gy/3 fractions; IQR 18-21 Gy). The median follow-up was 27 months (range 4-35 months). (3) Results: 38 consecutive patients were considered in this analysis. The overall median PSA level before RT was 1.10 ng/mL (IQR 0.82-2.59). PSA decreased at 3 and 6 months after treatment, with a median value of 0.60 ng/mL (IQR 0.31-0.96; < 0.001) and 0.51 ng/mL (IQR 0.29-1.17; < 0.001), respectively. Overall, biochemical recurrence-free survival (b-RFS) was 15.0 months (95% CI 13-23). Grade-1 toxicity was reported in 31.6% of patients (12/38). (4) Conclusion: These results confirm that Ga-PSMA-11-PET/CT is able to identify the site of recurrence in patients who have failed S-RT, thus supporting the use of metastases-directed radiotherapy as a safe and effective treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines8120536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761444PMC
November 2020

Targeted Alpha Therapy in mCRPC (Metastatic Castration-Resistant Prostate Cancer) Patients: Predictive Dosimetry and Toxicity Modeling of Ac-PSMA (Prostate-Specific Membrane Antigen).

Front Oncol 2020 5;10:531660. Epub 2020 Nov 5.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Radioligand therapy is a type of internal radiotherapy combining a short-range radioisotope labeled to a carrier with a high affinity for a specific receptor expressed on tumor cells. Targeted alpha therapy (TAT) combines a high-linear energy transfer (LET) emitter (Ac) with a prostate-specific membrane antigen (PSMA) carrier, specifically binding tumor cells in patients with metastatic castration-resistant prostate cancer. Although the antitumor activity of Ac-PSMA is well-documented, this treatment is nowadays only used as salvage therapy because the high incidence of xerostomia limits the therapeutic window. Thus, methods to reduce salivary toxicity and models able to describe xerostomia incidence are needed. We recently studied the efficacy of salivary gland protectors administered in combination with Lu-PSMA therapy. Starting from these data, we performed a predictive dosimetric evaluation of Ac-PSMA to assess the impact of salivary gland protectors in TAT. Ac-PSMA predictive dosimetry was performed in 13 patients treated with Lu-PSMA. Sequential whole-body planar images were acquired 0.5-1, 16-24, 36-48, and 120 h post-injection. Lu time-activity curves were corrected for Ac physical decay and assumed in equilibrium for all daughters. The OLINDA/EXM spherical model was used for dose estimation of the parotid and submandibular glands. The dose for each daughter was calculated and summed for the total dose estimation. The biologically effective dose formalism was extended to high-LET emitters. For the total biologically effective dose formalism extended to high-LET emitters, including the contribution of all daughter isotopes, the brachytherapy formalism for a mixture of radionuclides was implemented. Equivalent doses in 2 Gy/fraction (EQD2) were then calculated and compared with the normal tissue complication probability model derived from external beam radiotherapy for grade ≥2 xerostomia induction. Median predictive doses were 0.86 Bd/MBq for parotid glands and 1.05 Bd/MBq for submandibular glands, with a 53% reduction compared with previously published data. The results show that the radiobiological model implemented is conservative, as it overestimates the complication rate with respect to the clinical data. Our data shows the possibility of reducing salivary gland uptake in TAT with the coadministration of organ protectors, but these results should be confirmed for TAT with Ac-PSMA by carrying out prospective trials with defined toxicity endpoints and dosimetry procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.531660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674768PMC
November 2020

Investigating the Benefit of Combined Androgen Modulation and Hypofractionation in Prostate Cancer.

Int J Mol Sci 2020 Nov 10;21(22). Epub 2020 Nov 10.

Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.

Hypofractionation is currently considered a valid alternative to conventional radiotherapy for the treatment of patients with organ-confined prostate cancer. Recent data have demonstrated that extreme hypofractionation, which involves the use of a high radiation dose per delivered fraction and concomitant reduction of sessions, is a safe and effective treatment, even though its radiobiological rationale is still lacking. The present work aims to investigate the biological basis sustaining this approach and to evaluate the potential of a hypofractionated regimen in combination with androgen deprivation therapy, one of the major standards of care for prostate cancer. Findings show that androgen receptor (AR) modulation, by use of androgens and antiandrogens, has a significant impact on cell survival, especially in hypoxic conditions (4% O). Subsequent experiments have revealed that AR activity as a transcription factor is involved in the onset of malignant senescence-associated secretory phenotype (SASP) and activation of DNA repair cascade. In particular, we found that AR stimulation in hypoxic conditions promotes the enhanced transcription of gene, the cornerstone kinase of the DNA damage repair genes. Together, these data provide new potential insights to justify the use of androgen deprivation therapy, in particular with second-generation anti-androgens such as enzalutamide, in combination with radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21228447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698244PMC
November 2020

Re-irradiation of recurrent glioblastoma using helical TomoTherapy with simultaneous integrated boost: preliminary considerations of treatment efficacy.

Sci Rep 2020 11 9;10(1):19321. Epub 2020 Nov 9.

Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014, Meldola, Italy.

Although there is still no standard treatment for recurrent glioblastoma multiforme (rGBM), re-irradiation could be a therapeutic option. We retrospectively evaluated the efficacy and safety of re-irradiation using helical TomoTherapy (HT) with a simultaneous integrated boost (SIB) technique in patients with rGBM. 24 patients with rGBM underwent HT-SIB. A total dose of 20 Gy was prescribed to the Flair (fluid-attenuated inversion recovery) planning tumor volume (PTV) and 25 Gy to the PTV-boost (T1 MRI contrast enhanced area) in 5 daily fractions to the isodose of 67% (maximum dose within the PTV-boost was 37.5 Gy). Toxicity was evaluated by converting the 3D-dose distribution to the equivalent dose in 2 Gy fractions on a voxel-by-voxel basis. Median follow-up after re-irradiation was 27.8 months (range 1.6-88.5 months). Median progression-free survival (PFS) was 4 months (95% CI 2.0-7.9 months), while 6-month PFS was 41.7% (95% CI 22.2-60.1 months). Median overall survival following re-irradiation was 10.7 months (95% CI 7.4-16.1 months). There were no cases of re-operation due to early or late toxicity. Our preliminary results suggest that helical TomoTherapy with the proposed SIB technique is a safe and feasible treatment option for patients with rGBM, including those large disease volumes, reducing toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-75671-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653937PMC
November 2020

The challenge of sustainability in healthcare systems: cost of radiotherapy in the last month of life in an Italian cancer center.

Support Care Cancer 2021 May 28;29(5):2735-2742. Epub 2020 Sep 28.

Healthcare Administration, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, Meldola, FC, 47014, Italy.

Purpose: Cost evaluation is becoming mandatory to support healthcare sustainability and optimize the decision-making process. This topic is a challenge, especially for complex and rapidly evolving treatment modalities such as radiotherapy (RT). The aim of the present study was to investigate the cost of RT in the last month of life of patients in an Italian cancer center.

Methods: This was a retrospective study on a cancer population (N= 160) who underwent RT or only an RT planning simulation in an end of life (EOL) setting. The cost of RT procedures performed on patients was collected according to treatment status, care setting, and RT technique used. Costs were valued according to the sum of reimbursements relating to all procedures performed and assessed from the perspective of the National Health System.

Results: The total cost of RT in the last month of life was €244,774, with an average cost per patient of €1530. Around 7.7% and 30.3% of the total cost was associated with patients who never started RT or who discontinued RT, respectively, while the remaining 62.0% referred to patients who completed treatment. Costs associated with outpatient and inpatient settings represented 54.3% and 38.6% of the total cost, respectively. The higher average cost per patient for the never-started and discontinued groups was correlated with patients who had a poor ECOG Performance Status.

Conclusion: Improved prognostic accuracy and a better integration between radiotherapy and palliative care units could be a key to a better use of resources and to a reduction in the cost of EOL RT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-020-05718-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981311PMC
May 2021

Aicardi Syndrome: Key Fetal MRI Features and Prenatal Differential Diagnosis.

Neuropediatrics 2020 08 3;51(4):276-285. Epub 2020 Jul 3.

Department of Pediatric Radiology and Neuroradiology, Children's Hospital V. Buzzi, Milan, Italy.

Objective: This study was aimed to investigate the prenatal findings in Aicardi syndrome (AIC) by intrauterine magnetic resonance imaging (iuMRI) suggesting possible diagnostic criteria and differential diagnosis.

Methods: The iuMRI features of nine AIC confirmed cases were described and then compared with those of postnatal MRI. Furthermore, all iuMRI cases with both corpus callosum (CC) agenesis-dysgenesis and cortical malformation (AIC mimickers) were retrospectively reviewed and compared with iuMRI AIC cases, in order to identify possible neuroradiological predictors of AIC syndrome. For this purpose, Chi-square statistic and binary logistic regression analysis were performed.

Results: In all AIC cases, iuMRI was able to detect CC agenesis-dysgenesis and cortical development anomalies. Postnatal MRI revealed some additional findings mainly including further cystic lesions and in two cases small coloboma. A statistically significant difference between AIC and AIC mimicker were found regarding sex, nodular heterotopias, posterior fossa abnormalities, coloboma, and cortical gyration abnormalities. The most predictive variables in the logistic regression model were cortical gyration abnormalities, coloboma, and sex.

Conclusion: The iuMRI findings may suggest prenatal diagnosis of AIC syndrome with significant impact on parental counseling. Among possible differential diagnoses, tubulinopathies emerged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1710528DOI Listing
August 2020

Automatic genetic planning for volumetric modulated arc therapy: A large multi-centre validation for prostate cancer.

Radiother Oncol 2020 07 21;148:126-132. Epub 2020 Apr 21.

Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Purpose: The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual).

Methods: Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning.

Results: For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p < 0.05); rectum D and D were reduced by 8.1% and 17.9%, bladder D and D by 5.9% and 10.3%. According to clinicians, 69% of the acceptable AutoGPS plans were superior to the corresponding Manual plan. In case of preferred Manual plans (31%), perceived advantages compared to autoGPS were minor. QA measurements demonstrated that autoGPS plans were deliverable. A quick configuration adjustment in the centre with unacceptable plans rendered 100% of plans acceptable.

Conclusion: A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2020.04.020DOI Listing
July 2020

Erratum: Passardi, A. et al Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study. 2019, , 663.

Cancers (Basel) 2020 Jan 10;12(1). Epub 2020 Jan 10.

Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli n. 40, 47014 Meldola, Italy.

The authors wish to make the following corrections to this paper [...].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12010178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016811PMC
January 2020

The challenge of prognostication in palliative radiotherapy: the way forward is shared decision-making.

Support Care Cancer 2020 04 22;28(4):1545-1546. Epub 2019 Nov 22.

Palliative Care Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, Meldola, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-019-05157-6DOI Listing
April 2020

Clinical evidence of abscopal effect in cutaneous squamous cell carcinoma treated with diffusing alpha emitters radiation therapy: a case report.

J Contemp Brachytherapy 2019 Oct 30;11(5):449-457. Epub 2019 Oct 30.

Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy.

Purpose: Alpha particle treatments could enhance the probability of an immune response, which can lead to abscopal effects (AE). We report a case of a patient affected by multiple cutaneous squamous cell carcinoma (cSCC). After the treatment with diffusing alpha emitters radiation therapy (DaRT) of one lesion, an AE was observed on at least two distant ones.

Material And Methods: We investigated a case of a 65-year-old female patient with multiple synchronous lesions of the skin of lower limbs confirmed by a biopsy. Patient was enrolled in a clinical trial N.CTP-SCC-00 (NCT03015883), with the objective to assess effectiveness of DaRT technique. DaRT is based on the insertion of locally Ra-loaded seeds in a clinical target volume (CTV). Treatment plan with positron emission tomography/computed tomography (PET/CT) was used to entirely cover the CTV. Follow-up and biopsy evaluations were employed to outline the patient outcome.

Results: We performed seeds implantation according to the Paris system. At 28 day, an evident lesion shrinkage with a persistent minimal area of hyperkeratosis was noted. 76 days after implantation, a complete remission of the treated lesion was observed and an evident reduction of the area with two more distant lesion, which could be associated to an immune-mediated response. One year after the treatment, a complete remission of treated lesion was observed as well as spontaneous regression of untreated distant ones.

Conclusions: In this study, we reported evidences of an AE in cSCC stimulated by radiation and possibly mediated by immune system. In the next DaRT treatments, our intent is to monitor T-lymphocytes variations in peripheral blood in order to demonstrate indirect activation of the immune system mediated by radiation also in patients with solitary lesions, in which, by definition, an AE cannot be observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5114/jcb.2019.88138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854861PMC
October 2019

Plasma Androgen Receptor in Prostate Cancer.

Cancers (Basel) 2019 Nov 4;11(11). Epub 2019 Nov 4.

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.

The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known to be involved in the pathogenesis and progression of prostate cancer. Recently, highly sensitive next-generation sequencing and PCR-based methods for analyzing androgen receptor gene (AR) copy numbers (CN) and mutations in plasma were established in cell-free DNA (cfDNA) of patients with castration-resistant prostate cancer (CRPC) treated with different drugs. The study of cfDNA holds great promise for improving treatment in CRPC, especially in the advanced stage of the disease. Recent findings showed the significant association of plasma aberrations with clinical outcome in CRPC patients treated with AR-directed therapies, whereas no association was observed in patients treated with taxanes. This suggests the potential for using plasma as a biomarker for selecting treatment, i.e., hormone therapy or chemotherapy, and the possibility of modulating taxane dose. In recent years, plasma status has also been investigated in association with novel agents, such as Lu-PSMA radioligand therapy and PARP inhibitors. This review will focus on testing in plasma that may have clinical utility for treatment selection in advanced prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11111719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896184PMC
November 2019

Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up.

Radiat Oncol 2019 Jun 24;14(1):112. Epub 2019 Jun 24.

Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Background: Concurrent chemotherapy and radiation using conventional fractionation is the standard treatment for inoperable, locally advanced non-small-cell lung cancer (NSCLC). We tested accelerated hypofractionated radiotherapy (AHR) and chemotherapy for the treatment of locally advanced NSCLC.

Methods: Eligible patients with locally advanced NSCLC were treated with induction chemotherapy (cisplatin and docetaxel), followed by AHR using tomotherapy and consolidation chemotherapy. The prescribed doses were 30 Gy/5 daily fractions at the reference isodose (60-70%) to the tumor, and 25 Gy/5 daily fractions to the clinically involved lymph nodes. The primary end-point was response rate (RR); the secondary end-points were acute and late side-effects, local progression-free survival (PFS), metastasis-free survival (MFS) and overall survival (OS). This trial closed before the first planned interim analysis due to poor accrual.

Results: From January 2009 to January 2012, 17 of the 23 enrolled patients were evaluable. Treatment yielded an overall RR of 82%. Median follow-up was 87 months (range: 6-87), local PFS was 19.8 months (95% CI 9.7 - not reached), MFS was 9.7 months (95% CI 5.8-46.0) and OS was 23 months (95% CI 8.4-48.4). 70% of patients experienced acute G4 neutropenia, 24% G4 leukopenia, 24% G3 paresthesia, 4% G3 cardiac arrythmia, 4% underwent death after chemotherapy. Late toxicity was represented by 24% dyspnea G3.

Conclusions: AHR combined with chemotherapy is feasible with no severe side-effects, and it appears highly acceptable by patients.

Trial Registration: This study is registered with the EudractCT registration 2008-006525-14 . Registered on 9 December 2008.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13014-019-1317-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591967PMC
June 2019

Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study.

Cancers (Basel) 2019 May 13;11(5). Epub 2019 May 13.

Radiotherapy Unit, IRST-IRCCS, Via P. Maroncelli n. 40, 47014 Meldola, Italy.

The aim of the study was to evaluate the safety and efficacy of a new chemo-radiotherapy regimen for patients with locally advanced pancreatic cancer (LAPC). Patients were treated as follows: gemcitabine 1000 mg/m on day 1, and oxaliplatin 100 mg/m on day 2, every two weeks (GEMOX regimen) for 4 cycles, 15 days off, hypofractionated radiotherapy (35 Gy in 7 fractions in 9 consecutive days), 15 days off, 4 additional cycles of GEMOX, restaging. From April 2011 to August 2016, a total of 42 patients with non resectable LAPC were enrolled. Median age was 67 years (range 41-75). Radiotherapy was well tolerated and the most frequently encountered adverse events were mild to moderate nausea and vomiting, abdominal pain and fatigue. In total, 9 patients underwent surgical laparotomy (5 radical pancreatic resection 1 thermoablation and 3 explorative laparotomy), 1 patient became operable but refused surgery. The overall resectability rate was 25%, while the R0 resection rate was 12.5%. At a median follow-up of 50 months, the median progression-free survival and overall survival were 9.3 (95% CI 6.2-14.9) and 15.8 (95% CI 8.2-23.4) months, respectively. The results demonstrate the feasibility of a new chemo-radiotherapy regimen as a potential treatment for unresectable LAPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11050663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562444PMC
May 2019

Invited letter to the editor on the editorials on "High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment".

J Thorac Dis 2018 Dec;10(12):E819-E821

Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2018.11.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344698PMC
December 2018

Long-term follow-up in pediatric patients with paroxysmal hypothermia (Shapiro's syndrome).

Eur J Paediatr Neurol 2018 Nov 29;22(6):1081-1086. Epub 2018 Aug 29.

Neurology Unit, S. Anna Hospital, Como, Italy. Electronic address:

Introduction: Shapiro syndrome (SS) is characterized by spontaneous recurrent episodes of hypothermia, hyperhidrosis and corpus callosum (CC) agenesis. Less than 60 cases have been reported to date and the pathogenic mechanism as well as the prognosis of this syndrome are still debated. We describe the clinical features and long-term follow-up of a pediatric cohort of SS patients.

Methods: We collected 13 (10 novel) pediatric cases of SS and report their long-term follow-up and neurological outcome.

Results: All patients experienced recurring hypothermia, with body temperature below 35 °C during the episodes, often accompanied by hyperidrosis. CC agenesis was an inconstant structural feature in the present series (2/13 patients). Seven patients received antiepileptic drugs (AEDs) or other drug therapy for a mean period of 12 months. At long-term follow-up (mean = 61 months, range: 60-96), all individuals were free from episodes of paroxysmal hypothermia independently from previous AED use or other drug therapy.

Conclusion: Paroxysmal hypothermia, the core symptom of SS, behaved as a age-dependent feature in our cohort, supporting a good long-term prognosis for SS. A prompt diagnosis of SS is crucial to avoid unnecessary diagnostic investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2018.08.004DOI Listing
November 2018

Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients.

Eur J Nucl Med Mol Imaging 2018 11 19;45(12):2035-2044. Epub 2018 Jun 19.

Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014, Meldola, Italy.

Purpose: We studied the usefulness of Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment.

Methods: Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150 ± 50 MBq of Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, Ga-PSMA PET/CT scans were compared with negative F-choline PET/CT scans routinely performed up to 1 month previously.

Results: From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44-92 years) and their median PSApet was 0.83 ng/ml (range 0.003-80.0 ng/ml). Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P < 0.0001). Of 88 patients negative on choline PET/CT scans, 59 (67%) were positive on Ga-PSMA PET/CT.

Conclusion: We confirmed the value of Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-018-4067-3DOI Listing
November 2018

Symptoms of anxiety and depression and family's quality of life in children and adolescents with epilepsy.

Epilepsy Behav 2018 02 4;79:146-153. Epub 2018 Jan 4.

Department of Neuroscience, Istituto di Ricerche Farmacologiche "Mario Negri", IRCCS, Milano, Italy.

Introduction: We studied children and adolescents with epilepsy (CAWE) and their families to evaluate symptoms of anxiety and depression, quality of life (QoL), and their correlations with epilepsy characteristics.

Material And Methods: The study included 326 (52.5% females) 8 to 18years old CAWE. Anxiety and depression were assessed with the "Self-administered psychiatric scales for children and adolescents" (SAFA), and family's QoL with the parents' report "Impact of Epilepsy on QoL" (IEQoL).

Results: The CAWE exhibiting abnormal (T≥70) scores were 8.0% in the anxiety scale, 9.2% in the depression scale, and 4.6% in both scales. Social anxiety was the predominant anxiety symptom, while irritable mood and desperation were the most frequent symptoms of depression. Depressive symptoms were associated with parents' complaint of higher worries about the child's condition and future and lower well-being of the family. Severity and duration of the epilepsy and polypharmacy were independent from abnormal scores of anxiety and depression, but were associated with parents' worries about the child's condition and family's well-being.

Conclusions: Anxiety and depression in CAWE are independent from the characteristics of the disease but are correlated to the lower well-being of the family. A search of these emotional problems is recommended for better care of the patients and their families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2017.11.030DOI Listing
February 2018

STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.

Neurology 2016 Mar 10;86(10):954-62. Epub 2016 Feb 10.

Authors' affiliations are listed at the end of the article.

Objective: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients.

Methods: We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients.

Results: We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features.

Conclusion: De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000002457DOI Listing
March 2016

Eating epilepsy characterised by late-onset epileptic spasms in a case of Cri du chat syndrome.

Seizure 2015 Nov 21;32:49-51. Epub 2015 Sep 21.

Pediatric Neurology Unit and Epilepsy Center, Department of Neuroscience, "Fatebenefratelli e Oftalmico" Hospital, Milano, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2015.09.005DOI Listing
November 2015

Refractory absence seizures: An Italian multicenter retrospective study.

Eur J Paediatr Neurol 2015 Nov 18;19(6):660-4. Epub 2015 Jul 18.

Department of Pediatrics, University of Perugia, Perugia, Italy.

Background: To evaluate evidence and prognosis of refractory cases of absence seizures.

Methods: Subjects with refractory absence seizures were identified retrospectively in 17 Italian epilepsy pediatrics Centers. We analyzed age at onset, family history, presence of myoclonic components, seizure frequency, treatment with antiepileptic drugs (AEDs), interictal electroencephalography (EEG) and neuropsychological assessment. Two subgroups were identified: one with patients with current absence seizures and another with patients that had become seizure free with or without AED treatment. The chi-square test was applied.

Results: A total of 92 subjects with drug-resistant absence seizures were analyzed. 45 subjects still show absence seizures (49%) and the other 47 became seizure free (51%) after a period of drug-resistance. The statistical analysis between these two groups showed no correlation between age of onset, family history and abnormalities at interictal EEG. Statistically significant differences were observed with regard to the number of AEDs used and intellectual disability.

Conclusion: Typical absence epilepsy classifiable as Childhood Absence Epilepsy could not be considered so "benign", as suggested in literature. A longer duration of disease and a higher frequency of seizure seem to be correlated with a higher presence of cognitive impairment. No significant risk factor was observed to allow the faster and better recognition of patients with worse prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2015.07.008DOI Listing
November 2015

Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation.

Brain Dev 2016 Jan 23;38(1):128-31. Epub 2015 Jul 23.

Pediatric Neurology and Muscular Diseases Unit, Laboratory of Neurogenetics, Institute "G. Gaslini", Genoa, Italy.

Background: Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery.

Patient Description: We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A>T]p.[Lys308(∗)]) in the STXBP1 gene that severely affects the protein.

Conclusions: The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2015.07.002DOI Listing
January 2016
-->