Publications by authors named "Angela Ferrari"

98 Publications

Survival and Recurrence in Vitreoretinal Lymphoma Simulating Uveitis at Presentation: The Possible Role of Combined Chemotherapy.

Ocul Immunol Inflamm 2021 Aug 11:1-9. Epub 2021 Aug 11.

Ocular Immunology Unit, Azienda USL-IRCCS, Reggio Emilia, Italy.

To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL). Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group. Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P = .03) and death (r = 0.56, P = .009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04- 0.85]) in the entire cohort. Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL.
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http://dx.doi.org/10.1080/09273948.2021.1962916DOI Listing
August 2021

Primary anaplastic large T-cell lymphoma of the psoas muscle.

Pol J Pathol 2021 ;72(1):89-96

Department of General and Specialistic Surgery "P. Stefanini", Hepato-Biliary Surgery and Organ Transplantation Unit, University of Rome "La Sapienza", Rome, Italy.

Lymphomas presenting and mimicking soft-tissue masses are important to recognize, to avoid unnecessary treatment delays or extensive surgery. We describe a case of primary anaplastic large cell lymphoma (ALCL) arising from a deep skeletal muscle in a middle-aged male. He presented with a two-month history of swelling of his right thigh and mild fever, which led to a diagnosis of abscess formation. Antibiotics were prescribed for two weeks, with little improvement of symptoms. Subsequently, an exploratory surgery, with excision of the mass, demonstrated a ALCL of the psoas muscle, ALK-1 positive.
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http://dx.doi.org/10.5114/pjp.2021.106448DOI Listing
June 2021

Correction to: Actinic keratoses: when and how to treat a single lesion.

G Ital Dermatol Venereol 2020 Dec;155(6):808

Oncologic and Preventative Dermatology, San Gallicano Dermatological Institute, IFO, Rome, Italy, The originally published version of this article is available online at https://www.doi.org/10.23736/S0392-0488.18.06082-0.

This corrects the article DOI: 10.23736/S0392-0488.18.06082-0.
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http://dx.doi.org/10.23736/S0392-0488.21.06996-0DOI Listing
December 2020

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi.

J Clin Oncol 2021 04 12;39(11):1214-1222. Epub 2021 Feb 12.

Division of Hematology, Ospedale di Circolo e Fondazione Macchi-ASST Sette Laghi, University of Insubria, Varese, Italy.

Purpose: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL).

Methods: We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050).

Results: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases.

Conclusion: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.
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http://dx.doi.org/10.1200/JCO.20.02465DOI Listing
April 2021

A Single Center Retrospective Review of Patients from Central Italy Tested for Melanoma Predisposition Genes.

Int J Mol Sci 2020 Dec 11;21(24). Epub 2020 Dec 11.

Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, 00100 Rome, Italy.

Background: Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. CMM pathogenesis involves genetic and environmental factors. Recent studies have led to the identification of new genes involved in CMM susceptibility: beyond CDKN2A and CDK4, BAP1, POT1, and MITF were recently identified as potential high-risk melanoma susceptibility genes.

Objective: This study is aimed to evaluate the genetic predisposition to CMM in patients from central Italy.

Methods: From 1998 to 2017, genetic testing was performed in 888 cases with multiple primary melanoma and/or familial melanoma. Genetic analyses included the sequencing CDKN2A, CDK4, BAP1, POT1, and MITF in 202 cases, and of only CDKN2A and CDK4 codon 24 in 686 patients. By the evaluation of the personal and familial history, patients were divided in two clinical categories: "low significance" and "high significance" cases.

Results: 128 patients (72% belonging to the "high significance" category, 28% belonging to the "low significance" category) were found to carry a DNA change defined as pathogenic, likely pathogenic, variant of unknown significance (VUS)-favoring pathogenic or VUS.

Conclusions: It is important to verify the genetic predisposition in CMM patients for an early diagnosis of further melanomas and/or other tumors associated with the characterized genotype.
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http://dx.doi.org/10.3390/ijms21249432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763813PMC
December 2020

Trace elements in toenails in a population living near a modern municipal solid waste incinerator in Modena (Italy).

Chemosphere 2021 Jan 10;263:128292. Epub 2020 Sep 10.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Campi, 287, 41125, Modena, Italy. Electronic address:

Background And Objectives: A cross-sectional biomonitoring study was performed in Modena (Italy) to assess trace element levels in toenails in a population living near a municipal solid waste incinerator (SWI), and investigate potential differences in their concentrations according to SWI emission exposure and other environmental and behavioral factors.

Methods: During the winter 2013/14 eligible subjects, aged 18-69 yrs, living within 4 km from SWI, were randomly selected from the population register. Toxic and essential element concentrations (As, Cd, Cr, Cu, Mn, Ni, Pb, Se, Zn) were analyzed in 489 toenail samples. Individual exposure to SWI emissions was estimated by using, as a tracer, fall-out maps of emitted particulate matter. Information on anthropometric parameters, lifestyles, diet, and road traffic, residential and work exposures were collected by questionnaires and objective measurements. Multivariate logistic regression analyses were carried out, separately for females and males.

Results: Excluding As, toxic elements were found, usually at low levels, in many samples, while essential elements, especially Cu and Zn, showed higher levels. Overall, no clear relationships between element levels and SWI exposure were observed, whereas associations with other environmental and lifestyle factors were found, including local food consumption, smoking and occupation.

Conclusions: The low pollutant concentrations measured in SWI emissions could explain the absence of clear patterns in toenail levels across SWI exposure levels. The associations observed with other factors suggest that, at least in this specific population, other environmental exposures and personal behaviors could act as more important predictors of trace element uptake.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128292DOI Listing
January 2021

Gene expression profile unveils diverse biological effect of serum vitamin D in Hodgkin's and diffuse large B-cell lymphoma.

Hematol Oncol 2021 Apr 13;39(2):205-214. Epub 2020 Dec 13.

Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

The primary function of 25(OH)Vitamin D (VitD) is to control calcium; however, recent evidence associated serum VitD deficiency to high aggressiveness and worse outcome in different type of malignancies including lymphomas, and the reasons of such effect are to be defined. In this study, we investigated the association of VitD blood levels with gene expression in a retrospective cohort of 181 lymphomas (104 diffuse large B-cell lymphomas [DLBCLs] and 77 classical Hodgkin's lymphomas [cHLs]) of whom 116 with available gene expression profiles (52 DLBCLs and 64 cHLs, respectively). In DLBCL, VitD deficiency did not cause significant alteration in gene expression suggesting different mechanisms of action including a possible systemic effect or an effect on pharmacokinetics. By contrast, in cHLs, VitD deficiency induced profound changes in the transcriptional program leading to the NF-κB-mediated activation of stress-protective and pro-survival pathways. Coherently, VitD signaling defined by vitamin D Receptor (VDR) expression analysis, resulted highly activated in cHLs but not in DLBCLs. Even if preliminary, these data represent the first evidence of a direct role of VitD in the biology of cHL and suggest a multimodality and disease-specific activity of this vitamin in lymphomas.
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http://dx.doi.org/10.1002/hon.2827DOI Listing
April 2021

Actinic keratoses: when and how to treat a single lesion.

G Ital Dermatol Venereol 2020 Aug;155(4):527-528

Oncologic and Preventative Dermatology, San Gallicano Dermatological Institute, IFO, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.06082-0DOI Listing
August 2020

Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies.

Am J Hematol 2020 12 9;95(12):1473-1478. Epub 2020 Sep 9.

Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.6 years, 57% have been treated. As initial therapy 79% of patients received chemo-immunotherapy, 13% a chemo-free induction and 8% chemotherapy only. At relapse or progression, 6% underwent an autologous stem cell transplantation. Overall, 19% of patients received ibrutinib during the course of the disease. According to IPSSWM, 63% were classified as low risk, 27% as intermediate risk and 10% as high risk. Five-year OS was shorter in high-risk as compared with low or intermediate risk patients (92.9% vs 100% P = .002). According to revised IPSSWM, 92% were classified as very low or low risk and 8% as intermediate risk, with a shorter 5-year OS in the latter group (87.5% vs 100%, P = .028). The OS of young WM patients was not significantly reduced as compared with age-matched, sex-matched and calendar year-matched general population. Early diagnosis, absence of high-risk features in symptomatic patients and high efficacy of modern treatments are the main determinants of the excellent outcome of young WM patients.
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http://dx.doi.org/10.1002/ajh.25961DOI Listing
December 2020

Comment on "Rescheduling of clinical activities and teleconsulting for public dermatology. Two prompt answers to COVID-19 emergency".

Int J Dermatol 2020 10 25;59(10):1284. Epub 2020 Jul 25.

Department of Oncological and Preventative Dermatology, San Gallicano Dermatological Institute IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/ijd.15026DOI Listing
October 2020

COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus.

Leukemia 2020 09 9;34(9):2354-2363. Epub 2020 Jul 9.

Struttura Semplice Dipartimentale di Ematologia, Presidio Ospedaliero Santa Chiara, Trento, Italy.

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
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http://dx.doi.org/10.1038/s41375-020-0959-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347048PMC
September 2020

Vesicular-bullous prurigo pigmentosa in a young Italian man.

Ital J Dermatol Venerol 2021 Feb 15;156(1):109-110. Epub 2020 Jun 15.

IRCCS San Gallicano Dermatological Institute, Rome, Italy -

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http://dx.doi.org/10.23736/S0392-0488.20.06572-4DOI Listing
February 2021

Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma.

Hematol Oncol 2020 Oct 17;38(4):439-445. Epub 2020 Jun 17.

Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy.

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%. As OS at 5 years of the 520 patients is 67%, it is clearly evident that R-IPI tends to overestimate the proportion of patients with poor prognosis. Accordingly, in an attempt to improve the discriminating power of R-IPI, we evaluated and compared three different scores by combining the neutrophil lymphocyte ratio (NLR) and absolute monocyte count (AMC) with the following values: (a) IPI score 3-5, (b) age > 60 years and performance status, (c) age  ≥ 65 years and LDH > ULN. The three indexes studied, had a similar 5 years OS for the high-risk group (46%-52%), but the proportion of patients classified as poor-risk were 37%, 20%, and 32%, respectively, which are lower than 44% identified with R-IPI. Thus, while R-IPI overestimates the number of high-risk patients, after applying our models, it is possible to recognize patients who are truly at high-risk. Of the three scores, the most accurate appears to be that based on NLR, AMC, LDH > ULN and age ≥ 65 years, which identifies 32% of high-risk patients, correlating well with what is seen in clinical practice.
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http://dx.doi.org/10.1002/hon.2757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687198PMC
October 2020

Perineural granulomas without neurological manifestations: The great mimicker strikes again.

J Cutan Pathol 2021 04 8;48(4):602-603. Epub 2020 Sep 8.

Laboratory of Dermatopathology San Gallicano Dermatological Institute IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/cup.13735DOI Listing
April 2021

Clinical management of very small pigmented lesions: Improved clinical outcome through dermoscopy and reflectance confocal microscopy combination.

Skin Res Technol 2020 Sep 24;26(5):718-726. Epub 2020 Mar 24.

Clinical Dermatology, San Gallicano Dermatological Institute-IRCCS, Rome, Italy.

Introduction: Small-sized pigmented lesions (SSPL) <3 mm in diameter are common pitfall in the daily dermatology practice. Dermoscopy alone is hampered by the lack of specific features inversely proportional to the diameter of the lesions and its performance is highly operator-dependent. Reflectance confocal microscopy (RCM) has been demonstrated to be effective in the diagnosis of several difficult lesions where dermoscopy lacks to provide conclusive information.

Materials And Methods: A total of 179 lesions with uncertain or equivocal clinical and dermoscopy appearance were selected. Dermoscopist has been requested to express a diagnostic suspect when possible. Equivocal lesions underwent RCM performed by expert for second-level evaluation before surgical excision for histological diagnosis. Results have been later statistically analysed.

Results: Dermoscopy was not diagnostic in large number of lesions with low concordance histology (39.1%) instead of a much high concordance when combined with RCM (93.9%).

Conclusions: Small-sized pigmented lesions were more likely to be located on the face area. Diagnosis of pigmented BCC was relatively easy on dermoscopy and also in the case of small lesions showing typical signs of BCC. LM and MM have been seen to be particularly difficult to be diagnosed using only dermoscopy. The combination of digital dermoscopy and RCM represents the correct approach of SSPL.
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http://dx.doi.org/10.1111/srt.12863DOI Listing
September 2020

Enlarging melanocytic lesions with peripheral globular pattern: a dermoscopic and confocal microscopy study.

Ital J Dermatol Venerol 2021 Aug 18;156(4):467-472. Epub 2019 Nov 18.

Rare Disease Unit, San Gallicano Dermatological Institute, IRCCS, Rome, Italy.

Background: Enlarging melanocytic lesions with peripheral globular pattern (EMLPGP) are a pitfall in dermoscopy. Our aim was to evaluate the meaning of EMLPGP and to assess the use of dermoscopy and reflectance confocal microscopy (RCM) in order to improve the clinical management of this subtype of melanocytic lesions.

Methods: A total of 135 EMLPGP were recruited and, accordingly to the dermoscopy features, were removed; later, an expert dermoscopist reviewed the lesions blinded to histology. Moreover, a subgroup of 63 lesions who underwent also to RCM, were reviewed by an expert confocalist.

Results: Patients had a median age of 41 years old and a female prevalence (61.5%). The main anatomic site was the trunk (86%). Histology of the 135 excised EMLPGP disclosed 116 nevi (86%; P<0.0001) and 19 melanomas (14%). On dermoscopy, statistical significance was detected for small globules that were observed in 106 cases (78.5%; P<0.0001), while globules distribution and color did not impact the diagnosis prediction, as well as age, sex or any other patient profile. Considering the RCM, atypical cytology and irregular architecture were detected in 100% of melanomas (P<0.0001).

Conclusions: Our study shows that EMLPGPs are detectable in every age and can be a pitfall in especially in high risk patients with an over-excision of lesions. The presence of peripheral globules should be evaluated considering the overall dermoscopic features. RCM can contribute significantly in the management of lesions trough the detection of cyto-architectural atypia. Therefore, RCM in combination with dermoscopy can optimize the reduction of harmless lesions.
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http://dx.doi.org/10.23736/S0392-0488.19.06471-XDOI Listing
August 2021

Texture analysis and multiple-instance learning for the classification of malignant lymphomas.

Comput Methods Programs Biomed 2020 Mar 23;185:105153. Epub 2019 Oct 23.

Medical Physics, Azienda USL-IRCCS di Reggio Emilia, Italy. Electronic address:

Background And Objectives: Malignant lymphomas are cancers of the immune system and are characterized by enlarged lymph nodes that typically spread across many different sites. Many different histological subtypes exist, whose diagnosis is typically based on sampling (biopsy) of a single tumor site, whereas total body examinations with computed tomography and positron emission tomography, though not diagnostic, are able to provide a comprehensive picture of the patient. In this work, we exploit a data-driven approach based on multiple-instance learning algorithms and texture analysis features extracted from positron emission tomography, to predict differential diagnosis of the main malignant lymphomas subtypes.

Methods: We exploit a multiple-instance learning setting where support vector machines and random forests are used as classifiers both at the level of single VOIs (instances) and at the level of patients (bags). We present results on two datasets comprising patients that suffer from four different types of malignant lymphomas, namely diffuse large B cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, and mantle cell lymphoma.

Results: Despite the complexity of the task, experimental results show that, with sufficient data samples, some cancer subtypes, such as the Hodgkin's lymphoma, can be identified from texture information: in particular, we achieve a 97.0% of sensitivity (recall) and a 94.1% of predictive positive value (precision) on a dataset that consists in 60 patients.

Conclusions: The presented study indicates that texture analysis features extracted from positron emission tomography, combined with multiple-instance machine learning algorithms, can be discriminating for different malignant lymphomas subtypes.
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http://dx.doi.org/10.1016/j.cmpb.2019.105153DOI Listing
March 2020

Atypical cutaneous lesions in advanced-stage Hodgkin lymphoma: A case report.

World J Clin Cases 2019 Sep;7(17):2513-2518

Hematology, Azienda Unità Sanitaria Locale IRCCS di Reggio Emilia, Reggio Emilia 42123, Italy.

Background: Cutaneous involvement in Hodgkin lymphoma (HL) is a rare finding. Few cases have been reported in literature, most describing paraneoplastic manifestations. Only very few papers have described primary HL skin infiltration, reporting a wide range of clinical presentations that frequently include ulcers; plaques, nodules and papules have also been noticed.

Case Summary: We report the case of a 56-year-old man who presented fever, multiple adenomegalies of neck and axilla and thick serpiginous skin lesions involving bilateral pectoral regions. After an initial diagnostic workup for a suspected active infectious disease, a lymph node biopsy was performed, which showed a neoplastic invasion from a mixed cellularity classical HL. The same histological pattern was described in a cutaneous biopsy of the chest lesions. The other staging procedures performed revealed an advanced disease, with unfavourable clinical prognostic features. The patient was prescribed 6 cycles of ABVD chemotherapy scheme (doxorubicin, bleomycin, vinblastine, dacarbazine), a regiment that requires demonstration of metabolic response achievement at the interim PET/CT scan to confirm continuation or to change therapeutic strategy.

Conclusion: Skin involvement in HL is a rare finding and may represent a challenging clinical presentation due to extremely various types of lesions observed.
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http://dx.doi.org/10.12998/wjcc.v7.i17.2513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745318PMC
September 2019

Obinutuzumab and miniCHOP for unfit patients with diffuse large B-cell lymphoma. A phase II study by Fondazione Italiana Linfomi.

J Geriatr Oncol 2020 01 8;11(1):37-40. Epub 2019 Jul 8.

Hematology Unit, Arcispedale S.Maria Nuova, Azienda Unità Sanitaria Locale - IRCCS, Reggio Emilia, Italy; Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, University of Modena and Reggio Emilia, Reggio Emilia, Italy.

Objective: To evaluate activity and safety of obinutuzumab-miniCHOP (Ga101-miniCHOP) combination in older patients with Diffuse Large B-Cell Lymphoma (DLBCL) unfit to receive full dose immunochemotherapy.

Materials And Methods: We conducted a Simon's two-stage phase II multicenter trial to investigate response rate (primary endpoint) and safety of six courses of Ga101-miniCHOP in older patients with DLBCL (≥65 years), prospectively defined as unfit according to a simplified Comprehensive Geriatric Assessment (sCGA).

Results: Overall, 34 patients were enrolled (median age 82 years; range 68-89), with 27 out of the 33 eligible patients completing all six planned courses. Complete Remission (CR) rate was reported in fourteen patients (42%). After a median follow-up of sixteen months, the two-year Progression Free and Overall Survival (PFS and OS) were 49% (95% Confidence Interval (CI), 28 to 67) and 68% (95% CI, 49 to 81), respectively. The most frequent grade 3-4 adverse event was neutropenia in thirteen patients (26%).

Conclusions: Based on the observed CR rate, study accrual was interrupted due to the very low probability of demonstrating the initial study hypothesis that Ga101-miniCHOP could improve results of historical data obtained with R-miniCHOP in this group of patients. Nonetheless, results achieved with the 33 treated patients confirm activity and good tolerability of the Ga101-miniCHOP regimen for older unfit adult patients with DLBCL.
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http://dx.doi.org/10.1016/j.jgo.2019.06.020DOI Listing
January 2020

Early progression as a predictor of survival in marginal zone lymphomas: an analysis from the FIL-NF10 study.

Blood 2019 09 10;134(10):798-801. Epub 2019 Jul 10.

Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome in MZL and identifies a high-risk population. This trial was registered at www.clinicaltrials.gov as #NCT02904577.
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http://dx.doi.org/10.1182/blood.2019001088DOI Listing
September 2019

Outcome of transformed follicular lymphoma worsens according to the timing of transformation and to the number of previous therapies. A retrospective multicenter study on behalf of Fondazione Italiana Linfomi (FIL).

Br J Haematol 2019 05 21;185(4):713-717. Epub 2019 Feb 21.

Haematology, ASST Spedali Civili di Brescia, Brescia, Italy.

Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post-transformation outcome of 176 biopsy-proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five-year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5-year progression-free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre-transformation treatment lines and a short time-to-transformation.
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http://dx.doi.org/10.1111/bjh.15816DOI Listing
May 2019

Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas.

Oncologist 2019 08 14;24(8):e720-e729. Epub 2018 Dec 14.

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Background: International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported.

Subjects, Materials, And Methods: We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort []: = 9) or subsequently (sequential cohort []: = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like).

Results: Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens ( = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in and 37 of 38 in . DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in compared to only one patient in . At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%).

Conclusion: Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity.

Implications For Practice: Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT.
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http://dx.doi.org/10.1634/theoncologist.2018-0331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693710PMC
August 2019

Dietary intake of cadmium, chromium, copper, manganese, selenium and zinc in a Northern Italy community.

J Trace Elem Med Biol 2018 Dec 8;50:508-517. Epub 2018 Mar 8.

CREAGEN, Environmental, Genetic and Nutritional Epidemiology Research Center, Section of Public Health - Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 287 Via Campi, 41125 Modena, Italy; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. Electronic address:

This study provides the dietary intakes of six trace elements (cadmium, chromium, copper, manganese, selenium and zinc), generally characterized by both nutritional and toxicological features depending on their exposure. Being diet the most relevant source of exposure to trace elements in non-professionally exposed subjects, we measured content of these trace elements in foods composing the typical Italian diet using inductively coupled plasma-mass spectrometry, and assessing dietary habits using a validated semi-quantitative food frequency questionnaire we eventually estimated dietary daily intake of trace elements in a Northern Italian community. In the 890 analyzed food samples, the main contributors to cadmium intake are cereals, vegetables and sweets, while cereals, beverages and vegetable are to primary source of manganese. The primary contributors for copper are cereals, fresh fruits and vegetables, while for chromium are beverages, cereals and meat. The main source of selenium intake are cereals and meat, followed by fish, seafood and milk and dairy products, while of zinc intake are meat, cereals, milk and dairy products. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 5.00 (3.17-7.65), 56.70 (36.08-86.70) and 66.53 (40.04-101.32) μg/day for cadmium, chromium and selenium, and corresponding figures are 0.98 (0.61-1.49), 2.34 (1.46-3.52) and 8.50 (5.21-12.48) mg/day for copper, manganese and zinc. The estimated intakes are generally within the average intake reported in other European populations, and in such cases well above the daily dietary intakes recommended by national international agencies, avoiding the risk of excess or deficiency. The present estimated intake data can be used to examine a specific trace element of interest and would afford enhanced health protection from those trace elements characterized by both nutritional and toxicological effects.
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http://dx.doi.org/10.1016/j.jtemb.2018.03.001DOI Listing
December 2018

Daylight photodynamic therapy: experience in the treatment of actinic keratosis in the San Gallicano Institute (Rome) and a review of literature.

G Ital Dermatol Venereol 2020 Jun 24;155(3):312-319. Epub 2018 Jan 24.

San Gallicano Dermatological Institute IRCCS, Rome, Italy.

Background: Actinic keratosis (AK) is a photo-induced skin lesion. It has been considered by several authors as in-situ squamous cell carcinoma (SCC), that can evolve to invasive SCC (iSCC). Given the malignant potential and because it is impossible predict which AK will evolve in iSCC, it is necessary to treat each lesion. Multiple therapeutic approaches have been described to treat AKs. In addition to the topical drugs, photodynamic therapy (PDT) has become an established therapeutic modality for grade I and II of AKs of face and scalp. Recently the daylight photo-dynamic therapy (DL-PDT) has found extensive use in the care of the AK and in the field cancerization.

Methods: The study included 101 patients, 90 males and 11 females, mean age 71, phototype I-II, with multiple AK I and II of the face and the scalp, treated with DL-PDT. Patients were clinically evaluated for 3 months. The aim of this study was to show our experience in Daylight Photodynamic Therapy, to confirm the validity in term of efficacy and safety of DL-PDT for I and II AK of face and scalp and to underline the patient's higher satisfaction for this type of treatment and his availability to be retreated with the DL-PDT.

Results: The efficacy was complete in 16 patients (15.8%), in 71 patients (70.3%) was much improved or improved and only in 14 (13.9%) subjects were minimal, while nobody had worsened or changed. The majority of patients (84.2%) patients were satisfied of the efficacy as well of the cosmetic results, only 15 (14.9%) were low satisfied and one patient was not satisfied.

Conclusions: This study confirms that the DL-PDT is a good alternative to c-PDT for the treatment of grade I and II AK of the face and scalp and in Rome, as in Southern Europe, it is possible to perform the DL-PDT in almost every month of year.
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http://dx.doi.org/10.23736/S0392-0488.18.05880-7DOI Listing
June 2020

Long-Term Results of the FOLL05 Trial Comparing R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Symptomatic Follicular Lymphoma.

J Clin Oncol 2018 03 2;36(7):689-696. Epub 2017 Nov 2.

Stefano Luminari, Angela Ferrari, and Francesco Merli, Azienda Ospedaliera Arcispedale Santa Maria Nuova-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Reggio Emilia; Stefano Luminari, Martina Manni, Alessandra Dondi, Vittoria Tarantino, Luigi Marcheselli, and Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; Annalisa Chiarenza, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, University of Catania, Catania; Chiara Rusconi, Azienda Socio Sanitaria Territoriale (ASST) -Grande Ospedale Metropolitano Niguarda; Andrés J.M. Ferreri, IRCCS San Raffaele Scientific Institute, Milano; Alessandra Tucci, ASST-Spedali Civili di Brescia, Brescia; Umberto Vitolo, Città della Salute e della Scienza University and Hospital, Torino; Sofia Kovalchuk, University of Florence, Florence; Emanuele Angelucci, Ospedale Policlinico San Martino, Genova; Alessandro Pulsoni, Sapienza University of Rome, Rome; Luca Arcaini, Fondazione IRCCS Policlinico San Matteo, Pavia; Francesco Angrilli, Spirito Santo Hospital, Pescara; Gianluca Gaidano, University of Eastern Piedmont, Novara; Caterina Stelitano, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria; Giovanni Bertoldero, Ospedale di Mirano, Mirano; Nicola Cascavilla, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo; Flavia Salvi, Ospedale SS Antonio e Biagio, Alessandria; and Daniele Vallisa, Guglielmo da Saliceto Hospital, Piacenza, Italy.

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy.
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http://dx.doi.org/10.1200/JCO.2017.74.1652DOI Listing
March 2018

Work-related stress and role of personality in a sample of Italian bus drivers.

Work 2017 ;57(3):433-440

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Background: Several studies have shown that professional drivers are at risk of developing work-related stress. Stress may be responsible for a variety of adverse effects and may also be associated with an increased number of accidents.

Objective: Perform an integrated, objective and subjective evaluation of work-related stress in bus drivers, that also considered the role of personality traits.

Methods: Salivary α-amylase and cortisol were measured in 42 bus drivers. Subjective stress evaluation was performed with the Perceived Stress Scale (PSS-10) and Driver Stress Inventory (DSI). To evaluate personality traits, we administered the Eysenck Personality Questionnaire-Revised (EPQ-R) and the Impulsivity Inventory (IVE).

Results: Salivary biomarkers showed no associations with PSS-10 and personality traits. Cortisol levels were positively correlated with fatigue (r = 0.44) at the middle of the work-shift and with aggression (r = 0.51) at the end of a day off. At the end of the work-shift, cortisol levels were negatively correlated with hazard monitoring (r = -0.37) and salivary α-amylase was positively correlated with thrill-seeking (r = 0.36). Neuroticism (β= 0.44) and impulsiveness (β= 0.38) were predictors of perceived stress by multiple regression.

Conclusions: An integrated method, considering both objective and subjective indicators, seems adequate to evaluate work-related stress in professional drivers. Personality traits are relevant in determining perception of stress.
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http://dx.doi.org/10.3233/WOR-172581DOI Listing
April 2018

Lentigo maligna of the face: A quantitative simple method to identify individual patient risk probability on dermoscopy.

Australas J Dermatol 2017 Nov 7;58(4):286-291. Epub 2017 Jun 7.

Department of Oncological and Preventative Dermatological, San Gallicano Dermatological Institute, IRCCS, Rome, Italy.

Background/objectives: The clinical and dermoscopic differential diagnosis of flat pigmented facial lesions represents a great challenge for the clinicians. Our aim was to report a quantitative method based on dermoscopic features to better classify pigmented facial lesions.

Methods: This is a retrospective case-series study that analysed the dermoscopic features of 582 pigmented facial lesions.

Results: The individual patient probability of lentigo maligna (LM) was predicted by a multivariate model, with an accuracy of 0.72. According to the odds ratio at the multivariate analysis, an individual scoring index was assigned to each criterion, and a value of 4.56 was identified as optimal cut-off point. Up to a score of 2.5, the probability that a lesion is an LM is 0. The probability increases from 10 to 50% for a score ranging between 4.5 and 6. It is about 90% for a score of 7.

Conclusion: The optimal cut-off point obtained and the curve that identifies the probability of a patient having a LM could improve the classification and the management strategies of equivocal pigmented facial lesions.
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http://dx.doi.org/10.1111/ajd.12595DOI Listing
November 2017
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