Alessandro Bozzao - Academia.edu (original) (raw)

Papers by Alessandro Bozzao

Cancers

Stereotactic radiosurgery (SRS) has transformed the management of brain metastases by achieving l... more Stereotactic radiosurgery (SRS) has transformed the management of brain metastases by achieving local tumor control, reducing toxicity, and minimizing the need for whole-brain radiation therapy (WBRT). This review specifically investigates radiation-induced changes in patients treated for metastasis, highlighting the crucial role of magnetic resonance imaging (MRI) in the evaluation of treatment response, both at very early and late stages. The primary objective of the review is to evaluate the most effective imaging techniques for assessing radiation-induced changes and distinguishing them from tumor growth. The limitations of conventional imaging methods, which rely on size measurements, dimensional criteria, and contrast enhancement patterns, are critically evaluated. In addition, it has been investigated the potential of advanced imaging modalities to offer a more precise and comprehensive evaluation of treatment response. Finally, an overview of the relevant literature concerni...

Acta Psychiatrica Scandinavica, Dec 1, 2012

substrates of cognitive and clinical dimensions in first episode schizophrenia. Objective: To exp... more substrates of cognitive and clinical dimensions in first episode schizophrenia. Objective: To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES). Method: Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively. Results: Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts. Conclusion: These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome.

Journal for ImmunoTherapy of Cancer, Dec 1, 2021

Purpose Immunotherapy has shown activity in patients with brain metastases (BM) and leptomeningea... more Purpose Immunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS. Patients and methods One hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity. Results Sixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatmentrelated imaging changes suggestive of radiation-induced brain necrosis (p=0.02). Conclusions Postoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival.

Tomography

The 2021 WHO (World Health Organization) classification of brain tumors incorporated the rapid ad... more The 2021 WHO (World Health Organization) classification of brain tumors incorporated the rapid advances in the molecular, genetic, and pathogenesis understanding of brain tumor pathogenesis, behavior, and treatment response. It revolutionized brain tumor classification by placing great emphasis on molecular types and completely splitting adult-type and pediatric-type diffuse gliomas. Brainstem gliomas (BSGs) are the leading primary tumors of the brainstem, although they are quite uncommon in adults compared with the pediatric population, representing less than 2% of adult gliomas. Surgery is not always the treatment of choice since resection is rarely feasible and does not improve overall survival, and biopsies are not generally performed since the location is treacherous. Therefore, MRI (Magnetic Resonance Imaging) without and with gadolinium administration represents the optimal noninvasive radiological technique to suggest brainstem gliomas diagnosis, plan a multidisciplinary tre...

Frontiers in Psychiatry, Jan 4, 2023

Correlations between cortical gyrification and schizophrenia symptoms with and without comorbid h... more Correlations between cortical gyrification and schizophrenia symptoms with and without comorbid hostility symptoms.

Pharmaceutics

Contrast media are widely diffused in biomedical imaging, due to their relevance in the diagnosis... more Contrast media are widely diffused in biomedical imaging, due to their relevance in the diagnosis of numerous disorders. However, the risk of adverse reactions, the concern of potential damage to sensitive organs, and the recently described brain deposition of gadolinium salts, limit the use of contrast media in clinical practice. In recent years, the application of artificial intelligence (AI) techniques to biomedical imaging has led to the development of ‘virtual’ and ‘augmented’ contrasts. The idea behind these applications is to generate synthetic post-contrast images through AI computational modeling starting from the information available on other images acquired during the same scan. In these AI models, non-contrast images (virtual contrast) or low-dose post-contrast images (augmented contrast) are used as input data to generate synthetic post-contrast images, which are often undistinguishable from the native ones. In this review, we discuss the most recent advances of AI app...

Frontiers in Human Neuroscience

When the language-dominant hemisphere is damaged by a focal lesion, the brain may reorganize the ... more When the language-dominant hemisphere is damaged by a focal lesion, the brain may reorganize the language network through functional and structural changes known as adaptive plasticity. Adaptive plasticity is documented for triggers including ischemic, tumoral, and epileptic focal lesions, with effects in clinical practice. Many questions remain regarding language plasticity. Different lesions may induce different patterns of reorganization depending on pathologic features, location in the brain, and timing of onset. Neuroimaging provides insights into language plasticity due to its non-invasiveness, ability to image the whole brain, and large-scale implementation. This review provides an overview of language plasticity on MRI with insights for patient care. First, we describe the structural and functional language network as depicted by neuroimaging. Second, we explore language reorganization triggered by stroke, brain tumors, and epileptic lesions and analyze applications in clini...

European Neuropsychopharmacology, 2021

Poster: "ECR 2017 / C-2554 / Comparison of non invasive imaging and catheter-based angiograp... more Poster: "ECR 2017 / C-2554 / Comparison of non invasive imaging and catheter-based angiography in dural arteriovenular fistula" by: "A. Di Napoli, L. Pasquini, G. Trasimeni, A. Romano, A. Bozzao; Rome/IT"

Physica Medica, 2021

Radiomic models have been shown to outperform clinical data for outcome prediction in glioblastom... more Radiomic models have been shown to outperform clinical data for outcome prediction in glioblastoma (GBM). However, clinical implementation is limited by lack of parameters standardization. We aimed to compare nine machine learning classifiers, with different optimization parameters, to predict overall survival (OS), isocitrate dehydrogenase (IDH) mutation, O-6methylguanine-DNA-methyltransferase (MGMT) promoter methylation, epidermal growth factor receptor (EGFR) VII amplification and Ki-67 expression in GBM patients, based on radiomic features from conventional and advanced MR. 156 adult patients with pathologic diagnosis of GBM were included. Three tumoral regions were analyzed: contrast-enhancing tumor, necrosis and nonenhancing tumor, selected by manual segmentation. Radiomic features were extracted with a custom version of Pyradiomics, and selected through Boruta algorithm. A Grid Search algorithm was applied when computing 4 times K-fold cross validation (K=10) to get the highest mean and lowest spread of accuracy. Once optimal parameters were identified, model performances were assessed in terms of Area Under The Curve-Receiver Operating Characteristics (AUC-ROC). Metaheuristic and ensemble classifiers showed the best performance across tasks. xGB obtained maximum accuracy for OS Machine Learning predictions for GBM 2 (74.5%), AB for IDH mutation (88%), MGMT methylation (71,7%), Ki-67 expression (86,6%), and EGFR amplification (81,6%). Best performing features shed light on possible correlations between MR and tumor histology. 1. Introduction In recent years, artificial intelligence (AI) applications in biomedical imaging have grown exponentially. The conversion of radiologic images in mineable data and their analysis with AI techniques to support medical decisions is defined 'radiomics' (1). Biomedical images intrinsic parameters can reflect tissue structure, molecular data and patient outcome, providing important information for patient care through quantitative image analyses (1,2). GBM is considered the most frequent and lethal primary malignant tumor for adults, with an estimated incidence rate of 3.19 per 100,000 persons in the United States, and a median age of 64 years (3). Despite combined radio-chemotherapy, the OS of patients with GBM is dismally poor (4). Genetic alterations such as IDH mutation, MGMT promoter methylation, EGFR VII amplification may influence patient outcome, with effects on survival, progression, and treatment response (4,5). Radiomic-based predictive models have been shown to outperform clinical models based on patient age, Karnofsky performance scale, type of surgical resection, genetic alterations, for outcome prediction (6,7), with 36% improvement for progression free survival (PFS) and 37% for OS prediction (6). Recent studies in patients affected by GBM displayed several high-performance radiomic models for predicting OS, PFS, molecular subtypes of GBM, as well as genetic alterations critical for the clinical practice (8-11). Despite these promising results, clinical implementation is extremely limited due to wide variations of model performances (12,13), and controversial findings. For example, a recent study on 152 patients with GBM concluded that Magnetic Resonance (MR) imaging features were not adequate for providing reliable and clinically meaningful predictions through machine learning (ML) classification models (14). Variability in model performance may depend on parameters optimization. Radiomic workflows comprehend multiple steps requiring parameter choice: tumor segmentation on radiologic images, feature extraction and selection, training, testing and validation of the AI model, performance evaluation (15,16). The lack of radiomic parameters standardization might limit results generalizability across studies. A possible solution for this limitation is to compare multiple ML algorithms in the same population for different tasks. In fact, the classification method was shown to be the dominant source of performance variation in radiomic analyses (17). Comparative radiomic studies have been rarely performed in the literature, with suboptimal results. Parmar et al. examined fourteen feature selection methods and twelve classification methods for predicting OS from pretreatment computed tomography images of 464 lung cancer patients, showing the best performance for a random forest classifier (AUC 0.65) (17). Another study compared eight ML algorithms for predicting OS from conventional MR images of 163 patients with GBM. The highest performance was achieved by an ensemble learning model, with poor results in terms of overall accuracy (57.8%) (18). The aim of our study was to compare nine ML classifiers to predict OS, IDH mutation, MGMT promoter methylation, EGFR VII amplification and Ki-67 expression in the same population of patients affected by GBM, based on features extracted from conventional and advanced MR images. We tested different optimization parameters and reported classification results to provide a comprehensive view on model performance for relevant tasks in the clinical practice.

Frontiers in Oncology, 2021

Radiomic models outperform clinical data for outcome prediction in high-grade gliomas (HGG). Howe... more Radiomic models outperform clinical data for outcome prediction in high-grade gliomas (HGG). However, lack of parameter standardization limits clinical applications. Many machine learning (ML) radiomic models employ single classifiers rather than ensemble learning, which is known to boost performance, and comparative analyses are lacking in the literature. We aimed to compare ML classifiers to predict clinically relevant tasks for HGG: overall survival (OS), isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, epidermal growth factor receptor vIII (EGFR) amplification, and Ki-67 expression, based on radiomic features from conventional and advanced magnetic resonance imaging (MRI). Our objective was to identify the best algorithm for each task. One hundred fifty-six adult patients with pathologic diagnosis of HGG were included. Three tumoral regions were manually segmented: contrast-enhancing tumor, necrosis, and non-enhancing ...

Multiple Sclerosis Journal, 2021

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the centr... more Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS), clinically defined by an acute polyfocal neurological syndrome usually with monophasic course. ADEM often occurs after infections, but 5%–10% of cases are preceded by vaccinations. Several cases of ADEM have been described after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas no case has been reported after adenovirus-vectored or mRNA COVID-19 vaccine administration. Here we describe a case of ADEM presenting 2 weeks after receiving the first dose of ChAdOx1 nCoV-19 vaccine. Patient clinical/magnetic resonance imaging (MRI) status spontaneously improved and rapidly resolved with corticosteroids. A 4-month follow-up showed complete recovery and no relapses.

Journal of Neuroimaging, 2021

Background and PurposeGlioblastoma (GBM) is an aggressive primary CNS neoplasm with poor overall ... more Background and PurposeGlioblastoma (GBM) is an aggressive primary CNS neoplasm with poor overall survival (OS) despite standard of care. On MRI, GBM is usually characterized by an enhancing portion (CET) (surgery target) and a nonenhancing surrounding (NET). Extent of resection is a long debated issue in GBM, with recent evidence suggesting that both CET and NET should be resected in <65 years old patients, regardless of other risk factors (i.e., molecular biomarkers). Our aim was to test a radiomic model for patient survival stratification in <65 years old patients, by analyzing MRI features of NET, to aid tumor resection.MethodsSixty‐eight <65 years old GBM patients, with extensive CET resection, were selected. Resection was evaluated by manually segmenting CET on volumetric T1‐weighted MRI pre and postsurgery (within 72 h). All patients underwent the same treatment protocol including chemoradiation. NET radiomic features were extracted with a custom version of Pyradiomic...

Neuro-Oncology, 2020

Background The evolution of radiation necrosis (RN) varies depending on the combination of radion... more Background The evolution of radiation necrosis (RN) varies depending on the combination of radionecrotic tissue and active tumor cells. In this study, we characterized the long-term metabolic evolution of RN by sequential PET/CT imaging with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (F-DOPA) in patients with brain metastases following stereotactic radiosurgery (SRS). Methods Thirty consecutive patients with 34 suspected radionecrotic brain metastases following SRS repeated F-DOPA PET/CT every 6 months or yearly in addition to standard MRI monitoring. Diagnoses of local progression (LP) or RN were confirmed histologically or by clinical follow-up. Semi-quantitative parameters of F-DOPA uptake were extracted at different time points, and their diagnostic performances were compared with those of corresponding contrast-enhanced MRI. Results Ninety-nine F-DOPA PET scans were acquired over a median period of 18 (range: 12–66) months. Median follow-up from the baseline F-DOPA PET/CT was...

European Journal of Nuclear Medicine and Molecular Imaging, 2019

Purpose Diagnosis of spondylodiscitis (SD) may be challenging due to the nonspecific clinical and... more Purpose Diagnosis of spondylodiscitis (SD) may be challenging due to the nonspecific clinical and laboratory findings and the need to perform various diagnostic tests including serologic, imaging, and microbiological examinations. Homogeneous management of SD diagnosis through international, multidisciplinary guidance would improve the sensitivity of diagnosis and lead to better patient outcome. Methods An expert specialist team, comprising nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), neuroradiologists appointed by the European Society of Neuroradiology (ESNR), and infectious diseases specialists appointed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), reviewed the literature from January 2006 to December 2015 and proposed 20 consensus statements in answer to clinical questions regarding SD diagnosis. The statements were graded by level of evidence level according to the 2011 Oxford Centre for Evidence-based Medicine criteria and included in this consensus document for the diagnosis of SD in adults. The consensus statements are the result of literature review according to PICO (P:population/patients, I:intervention/indicator, C:comparator/control, O:outcome) criteria. Evidence-based recommendations on the management of adult patients with SD, with particular attention to radiologic and nuclear medicine diagnosis, were proposed after a systematic review of the literature in the areas of nuclear medicine, radiology, infectious diseases, and microbiology. Results A diagnostic flow chart was developed based on the 20 consensus statements, scored by level of evidence according to the Oxford Centre for Evidence-based Medicine criteria. Conclusions This consensus document was developed with a final diagnostic flow chart for SD diagnosis as an aid for professionals in many fields, especially nuclear medicine physicians, radiologists, and orthopaedic and infectious diseases specialists.

Journal for ImmunoTherapy of Cancer, 2019

Purpose: To investigate the efficacy and safety of concurrent stereotactic radiosurgery (SRS) and... more Purpose: To investigate the efficacy and safety of concurrent stereotactic radiosurgery (SRS) and ipilimumab or nivolumab in patients with untreated melanoma brain metastases. Patients and Methods: Eighty consecutive patients with 326 melanoma brain metastases receiving SRS in combination with ipilimumab or nivolumab were identified from an institutional database and retrospectively evaluated. Patients started systemic treatment with intravenous nivolumab or ipilimumab within one week of receiving SRS. Nivolumab was given at doses of 3 mg/kg every two weeks. Ipilimumab was administered up to four doses of 10 mg/kg, one every 3 weeks, then patients had a maintenance dose of 10 mg/kg every 12 weeks, until disease progression or inacceptable toxicity. Primary endpoint of the study was intracranial progression-free survival (PFS). Secondary endpoints were extracranial PFS, overall survival (OS), and neurological toxicity. Results: Eighty patients were analyzed. Forty-five patients received SRS and ipilimumab, and 35 patients received SRS and nivolumab. With a median follow-up of 15 months, the 6-month and 12-month intracranial PFS rates were 69% (95%CI,54-87%) and 42% (95%CI,24-65%) for patients receiving SRS and nivolumab and 48% (95%CI,34-64%) and 17% (95%CI,5-31%) for those treated with SRS and ipilimumab (p = 0.02), respectively. Extracranial PFS and OS were 37 and 78% in SRS and nivolumab group, respectively, and 17 and 68% in SRS and ipilimumab group, respectively, at 12 months. Subgroup analysis showed significantly better intracranial PFS for patients receiving multi-fraction SRS (3 × 9 Gy) compared to single-fraction SRS (70% versus 46% at 6 months, p = 0.01), especially in combination with nivolumab. Grade 3 treatment-related adverse events occurred in 11 (24%) patients treated with SRS and ipilimumab and 6 (17%) patients who received SRS and nivolumab. Radiation-induced brain necrosis (RN) occurred in 15% of patients. Conclusions: Concurrent SRS and ipilimumab or nivolumab show meaningful intracranial activity in patients with either asymptomatic and symptomatic melanoma brain metastases, although a subset of patients may develop symptomatic RN. The combination of nivolumab with SRS is associated with better intracranial control.

Rivista di Neuroradiologia, 2005

This study aimed to assess anatomical and functional changes disclosed by magnetic resonance imag... more This study aimed to assess anatomical and functional changes disclosed by magnetic resonance imaging in a patient with suspect normal pressure hydrocephalus following surgical third ventriculostomy with placement of a ventriculoperitoneal shunt. The patient was investigated by phase contrast sequences to calculate CSF flow in the Sylvian aqueduct before and after the two surgical procedures. In addition, T1-weighted volumetric MPRAGE images were acquired using voxel-based morphometry to study any changes in size of the ventricular system and CSF in the subarachnoid spaces before and after surgery. CSF flow measurements were closely correlated with the patient's clinical course, increased CSF flow coinciding with worsening symptoms, and a decrease in flow noted after surgery. There were no significant changes in the CSF volumes analyzed. Phase contrast technique proved reliable and effective for the purposes of diagnosis and long-term follow-up in patients with suspect normal pre...

The Neuroradiology Journal, 2001

The Neuroradiology Journal, 1999