491 results on '"Angelo Paolo Dei Tos"'
Search Results
102. Direct Costs of Care for Adults with Soft Tissue Sarcomas: A Population-Based Study
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Mocellin, Massimo Rugge, Alessandra Buja, Saveria Tropea, Giovanni Girardi, Luigi Cosenza Franzese, Claudia Cozzolino, Manuel Zorzi, Antonella Vecchiato, Paolo Del Fiore, Antonella Brunello, Alessandra Rosalba Brazzale, Vincenzo Baldo, Angelo Paolo dei Tos, Carlo Riccardo Rossi, and Simone
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soft tissue sarcoma ,cost of illness ,economic impact ,real-world data - Abstract
The clinical treatment of soft tissue sarcoma (STS) has evolved substantially over the last decade. This population-based cohort study based on real-world data included all incidental STS recorded by the Veneto Cancer Registry in 2017. Data on hospital admissions, emergency department and outpatient visits, drug prescriptions, and use of medical devices within two years from STS diagnosis were obtained from administrative databases. The average per-patient real-world costs over this two-year period, in total and by single expenditure item, were calculated and stratified by stage of disease at diagnosis, tumor histology and tumor site. The mean total cost per patient amounted to EUR 16,793. A higher TNM stage at diagnosis was associated with higher healthcare costs, as follows: compared with stage I, the average total cost per patient was 1.32, 2.18 and 3.36 times greater for stages II, III and IV, respectively. Hospital stays generated the greatest costs (averaging EUR 7950 per patient), followed by outpatient visits (mean EUR 3947 per patient) and drug prescriptions (mean EUR 3664 per patient). Given the paucity of population-based studies, the present results can serve as a reference for further cost-effectiveness analyses on care strategies for patients with STS.
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- 2022
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103. Thrombopoietin receptor agonists increase splenic regulatory T-cell numbers in immune thrombocytopenia
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Marco Pizzi, Fabrizio Vianello, Gianni Binotto, Nicola Vianelli, Giuseppe Carli, Giuseppe Auteri, Ilaria Nichele, Marta Sbaraglia, Simone Zoletto, Federico Scarmozzino, Rita Bresciani, Fabio d'Amore, Alberto Friziero, Vincenza Guzzardo, Irene Bertozzi, Barbara Famengo, Emanuele S. G. d'Amore, Elena Sabattini, and Angelo Paolo Dei Tos
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Purpura, Thrombocytopenic, Idiopathic ,Recombinant Fusion Proteins ,TPO receptor agonist ,immune microenvironment ,Hematology ,Receptors, Fc ,immune thrombocytopenia ,splenectomy ,T-Lymphocytes, Regulatory ,Thrombocytopenia ,Thrombopoietin ,Humans ,Receptors, Thrombopoietin ,Spleen - Abstract
Thrombopoietin receptor agonists (TPO-RA) are a valid therapy for immune thrombocytopenia (ITP), due to megakaryocyte stimulation and (poorly characterised) immune-modulatory effects. The spleen is pivotal in the pathogenesis of ITP, yet little is known on its immune microenvironment and on effects of TPO-RA on this organ. To address these topics, we analysed 35 spleens removed for primary refractory ITP. Pre-splenectomy TPO-RA administration correlated with increased splenic regulatory T cells (Tregs), type 2 T-helper cells and histiocyte density and with reduced red pulp sinusoids. Surgical outcome was not associated with TPO-RA administration, other pre-splenectomy therapies and/or Treg density. In conclusion, TPO-RA affect the splenic microenvironment, but this has no impact on splenectomy outcome.
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- 2022
104. Altitude Effect on Cutaneous Melanoma Epidemiology in the Veneto Region (Northern Italy): A Pilot Study
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Mocellin, Paolo Del Fiore, Irene Russo, Alessandro Dal Monico, Jacopo Tartaglia, Beatrice Ferrazzi, Marcodomenico Mazza, Francesco Cavallin, Saveria Tropea, Alessandra Buja, Rocco Cappellesso, Lorenzo Nicolè, Vanna Chiarion-Sileni, Chiara Menin, Antonella Vecchiato, Angelo Paolo Dei Tos, Mauro Alaibac, and Simone
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cutaneous melanoma ,altitude ,coast-plain-hill gradient - Abstract
The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of UVR reaching the Earth’s surface. Our study aimed to explore the relationship between melanoma and altitude in an area with mixed geographic morphology, such as the Veneto region (Italy). We included 2752 melanoma patients who were referred to our centers between 1998 and 2014. Demographics, histological and clinical data, and survival information were extracted from a prospectively maintained local database. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while limb and trunk melanoma were more common in patients living in plain and coastal areas. Breslow thickness, ulceration and mitotic rate impaired with increased altitude. However, the geographical area of origin was not associated with overall or disease-free survival. The geographical area of origin of melanoma patients and the “coast-plain-hill gradient” could help to estimate the influence of different sun exposure and to explain the importance of vitamin D levels in skin-cancer control.
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- 2022
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105. Synaptophysin expression in mutated advanced colorectal cancers identifies a new subgroup of tumours with worse prognosis
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Giovanni Centonze, Marco Volante, Angelo Paolo Dei Tos, Alessandra Boccaccino, Giuseppe Aprile, Massimo Milione, Lorenzo Calvetti, Lorenza Rimassa, Giovanna De Maglio, Emanuela Dell'Aquila, Daniele Santini, Giulia Maddalena, Chiara Cremolini, Sara Lonardi, Vittorina Zagonel, Lisa Salvatore, Massimo Di Maio, Paola Biason, Fotios Loupakis, Chiara Borga, Matteo Fassan, Valeria Smiroldo, Marta Schirripa, Federica Morano, Clizia Zichi, Nicoletta Pella, Roberta Salmaso, Filippo Pietrantonio, Elisa Sperti, F. Cortiula, and Francesca Bergamo
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,Colorectal cancer ,Not Otherwise Specified ,medicine.disease ,Neuroendocrine differentiation ,Confidence interval ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Synaptophysin ,biology.protein ,Medicine ,Adenocarcinoma ,Immunohistochemistry ,business ,Pathological - Abstract
Background Neuroendocrine differentiation has been extensively associated with worse prognosis and to mechanisms of therapy resistance in several epithelial cancers. A high prevalence of neuroendocrine differentiation was recently described in V600EBRAF-mutated (BRAFmt) metastatic colorectal cancers (mCRCs) but no data are available about its prognostic impact in this setting. Methods We assessed synaptophysin immunohistochemical expression in a multi-institutional series of 159 BRAFmt mCRCs with matched clinical and pathological information. Tumours were dichotomized as synaptophysin high and low. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier and log-rank tests. Results Thirty-five tumours (22.0%) showed any level of positivity for synaptophysin, and 18 (11.3%) were characterized by positivity in at least 20% of tumour cells. Four cases resulted 100% synaptophysin positive. The histotype of synaptophysin-positive tumours (i.e. ≥20%) was not otherwise specified in 11 cases (61.1%) and mucinous adenocarcinoma in 4 cases (22.2%). Four cases were DNA mismatch repair deficient (22.2%) and 7 (38.9%) were characterized by a high number of tumour-infiltrating lymphocytes. At multivariate analysis, high synaptophysin expression was a negative independent prognostic factor for both PFS (HR = 2.00, 95% confidence interval [CI] 1.21–3.33, p = 0.006) and OS (HR = 2.27, 95% CI 1.35–3.85, p = 0.001). Conclusions Among BRAFmt mCRCs, synaptophysin-positive tumours are characterized by worse PFS and OS. Further studies should investigate the molecular mechanisms involved in the acquisition of the neuroendocrine phenotype to identify novel-targeted treatment strategies.
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- 2021
106. Impact of DNA mismatch repair proteins deficiency on number and ratio of lymph nodal metastases in colorectal adenocarcinoma
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Federica Zannier, Valentina Angerilli, Gaya Spolverato, Stefano Brignola, Daniele Sandonà, Mariangela Balistreri, Marianna Sabbadin, Sara Lonardi, Francesca Bergamo, Claudia Mescoli, Marco Scarpa, Quoc Riccardo Bao, Angelo Paolo Dei Tos, Salvatore Pucciarelli, Emanuele L.D. Urso, and Matteo Fassan
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lymph node metastasis ,Colorectal adenocarcinoma, lymph node metastasis ,Lymph node ratio ,MMR ,Cell Biology ,Colorectal adenocarcinoma ,Pathology and Forensic Medicine - Published
- 2023
107. Correlation of the immune tumor microenvironment (I-TME) with gene expression profiles as prognostic and predictive factors in patients (pts) with metastatic renal carcinoma (mRCC) treated with immunotherapy (Meet-URO 18 I-TME study)
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Fabio Catalano, Veronica Murianni, Sara Elena Rebuzzi, Francesca Galuppini, Sebastiano Buti, Matteo Brunelli, Marco Maruzzo, Angelo Paolo Dei Tos, Umberto Basso, Giuseppe Lugi Banna, Alessio Signori, Marta Sbaraglia, Alessandra Damassi, Malvina Cremante, Silvia Puglisi, Annalice Gandini, Marta Rebuzzi, Alessandra Mosca, Giuseppe Fornarini, and Pasquale Rescigno
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Cancer Research ,Oncology - Abstract
TPS753 Background: Several studies suggested that response to immunotherapy may be influenced by many factors, including peripheral blood biomarkers, the composition of I-TME and different molecular expression pathways. In mRCC patients, immunotherapy has become part of clinical practice, but the identification of patients most likely to respond to checkpoint inhibitors is still an unmet clinical need. Moreover, there are no validated and clinically applicable gene expression panels as prognostic and/or predictive response biomarkers. To date, three major groups of immune-related gene expression were identified in mRCC: the angiogenesis pathway, the T-effector pathway and the mixed pathway (doi: 10.1038/s41598-020-58804-y). Each group of gene expression seems to be responsible for a different type of immune response in the I-TME. However, a significant association with treatment response to immunotherapy has not yet been demonstrated. Methods: The Meet-URO 18 is a multicentric retrospective translational study aimed at identifying distinctive molecular patterns of the I-TME with a prognostic and predictive role in mRCC (primary objective). Pretreated mRCC patients receiving ≥2nd line nivolumab have been divided according to clinical benefit in responders (PFS ≥ 12 months) versus non-responders (PFS ≤ 3 months). Secondary objectives include the correlation between primary tumor and metastases to identify a potential inter-tumor heterogeneity and the correlation with survival and response outcomes. Histological samples of primary tumors and/or metastases have been collected for the transcriptomic analyses together with clinical data of patients from medical records. The transcriptomic characterization of the I-TME of the primary tumor and/or metastases will be performed using the analytical platform "nCounter" of NanoString®, which analyzes the expression of 71 genes involved in angiogenesis, immunomodulation mediated by T-effector response, mechanisms of tumor invasion and mechanisms of calcium channel flows. The gene-panel include a group of 66 genes previously demonstrated to be related in the immune-response in mRCC (doi: 10.1038/s41598-020-58804-y) and 5 housekeeping genes (RPS13, PPIA, RPL27, RP2, B-ACT).
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- 2023
108. A systematic literature review of diagnostic and treatment approaches of retroperitoneal lipoma
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Ilda Hoxhaj, Luigi Dall'Olmo, Antonella Brunello, Benedetta Chiusole, Marta Sbaraglia, Angelo Paolo Dei Tos, Roberto Stramare, Simone Mocellin, and Marco Rastrelli
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Oncology ,Surgery ,General Medicine - Published
- 2023
109. Primary malignant ossifying fibromyxoid tumour of the bone. A clinicopathologic and molecular report of two cases
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Angelo Paolo Dei Tos, Marco Gambarotti, Alberto Righi, Marta Sbaraglia, Elena Bellan, Lucia Zanatta, and Luisa Toffolatti
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Polycomb-Group Proteins ,Bone Neoplasms ,Soft Tissue Neoplasms ,TFE3 ,soft tissue tumours ,Pathology and Forensic Medicine ,Lesion ,Biomarkers, Tumor ,Humans ,Medicine ,PHF1 ,In Situ Hybridization, Fluorescence ,Aged ,Gene Rearrangement ,rare tumours ,business.industry ,High-Throughput Nucleotide Sequencing ,Soft tissue ,DNA, Neoplasm ,OFMT ,bone tumours ,medicine.disease ,Immunohistochemistry ,Vertebra ,DNA-Binding Proteins ,Primary bone ,medicine.anatomical_structure ,Fusion transcript ,Fibroma, Ossifying ,Osteosarcoma ,Female ,Original Article ,Neoplasm Recurrence, Local ,medicine.symptom ,business ,Transcription Factors - Abstract
Summary Objective To report the exceptional occurrence of ossifying fibromyxoid tumour (OFMT) as a primary bone lesion. OFMT is a rare soft tissue tumour of uncertain differentiation and variable malignant potential, that occurs in adults with a slight male predominance. It is typically located in the subcutis or in the skeletal muscles of the extremities, followed by trunk or head and neck. Methods Two cases of OFMT proven to arise from bone are presented. The first is a 65-year old female with a history of rib “osteosarcoma”, presenting with an inferior lobe left lung mass. The second is a man with a lytic lesion of the 5th cervical vertebra that recurred shortly after resection. Following H&E and immunohistochemical examination, tumour samples were analysed by NGS and by break-apart FISH to detect rearrangement of the PHF1 and TFE3 genes. Results PHF1 gene-rearrangement was identified by FISH on both the primary and the metastatic lesion of first patient. NGS identified a PHF1(intron1) and EPC1 (exon 10) fusion transcript later confirmed by positive PHF1 rearrangement on FISH in the second case. Conclusions The demonstration of PHF1 gene rearrangements represents a fundamental ancillary diagnostic test when presented with challenging examples of OFMT.
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- 2020
110. Activity of sirolimus in patients with progressive epithelioid hemangioendothelioma: A case‐series analysis within the Italian Rare Cancer Network
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Francesca Greco, Carlo Morosi, Anna Maria Frezza, Antonella Brunello, Elena Palassini, Salvatore Lo Vullo, Paolo G. Casali, Luigi Mariani, Silvia Stacchiotti, Bruno Vincenzi, Angelo Paolo Dei Tos, Giacomo Giulio Baldi, Marta Sbaraglia, Gianpaolo Dagrada, Paola Collini, and Noemi Simeone
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Male ,epitheliod hamangioendothelioma ,Cancer Research ,sarcoma ,medicine.medical_treatment ,Kaplan-Meier Estimate ,chemotherapy ,Gastroenterology ,Metastasis ,0302 clinical medicine ,Interquartile range ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,030212 general & internal medicine ,Child ,integumentary system ,Intracellular Signaling Peptides and Proteins ,Middle Aged ,Prognosis ,epithelioid hemangioendothelioma ,Editorial ,Italy ,Oncology ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Disease Progression ,Hemangioendothelioma, Epithelioid ,Female ,Sarcoma ,medicine.symptom ,medicine.drug ,Adult ,medicine.medical_specialty ,03 medical and health sciences ,Internal medicine ,medicine ,metastasis ,Humans ,Epithelioid hemangioendothelioma ,Aged ,Sirolimus ,Chemotherapy ,business.industry ,Editorials ,medicine.disease ,Irregular menstruation ,prognosis ,serosal effusion ,sirolimus ,Transcriptional Coactivator with PDZ-Binding Motif Proteins ,business ,EHE - Abstract
Background The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. Methods From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. Results All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. Conclusions The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.
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- 2020
111. Detection of <scp>HPV16</scp> /18 <scp>E6</scp> Oncoproteins in Head and Neck Squamous Cell Carcinoma Using a Protein Immunochromatographic Assay
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Paolo Boscolo-Rizzo, Anna Menegaldo, Lea Schroeder, Stefania Rigo, Margherita Tofanelli, Angelo Paolo Dei Tos, Elisa Dal Cin, Dana Holzinger, Monica Mantovani, Monia Niero, Michael Pawlita, Daniele Borsetto, Angela Guerriero, Giancarlo Tirelli, Jerry Polesel, Maria Cristina Da Mosto, Tim Waterboer, Annarosa Del Mistro, Marco Stellin, Menegaldo, Anna, Schroeder, Lea, Holzinger, Dana, Tirelli, Giancarlo, DAL CIN, Elisa, Tofanelli, Margherita, Rigo, Stefania, Mantovani, Monica, Stellin, Marco, Del Mistro, Annarosa, Dei Tos, Angelo P., Guerriero, Angela, Niero, Monia, Borsetto, Daniele, Da Mosto, Maria C., Polesel, Jerry, Pawlita, Michael, Waterboer, Tim, and BOSCOLO RIZZO, Paolo
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,E6 oncoprotein ,Oropharyngeal squamous cell carcinoma ,carcinoma of unknown primary ,human papillomavirus ,neck metastasis ,Lateral flow test ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Clinical significance ,Human papillomavirus ,human papillomaviru ,Aged ,Immunoassay ,Human papillomavirus 16 ,Human papillomavirus 18 ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Papillomavirus Infections ,A protein ,Oncogene Proteins, Viral ,Middle Aged ,medicine.disease ,Head and neck squamous-cell carcinoma ,Primary tumor ,DNA-Binding Proteins ,Repressor Proteins ,Cross-Sectional Studies ,030104 developmental biology ,Otorhinolaryngology ,Head and Neck Neoplasms ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Unknown primary ,Feasibility Studies ,Neoplasms, Unknown Primary ,Female ,Reagent Kits, Diagnostic ,neck metastasi ,business - Abstract
Objectives/hypothesis The accurate diagnostic assessment of clinically relevant human papillomavirus (HPV) infections in patients with head and neck squamous cell carcinoma represents an urgent unmet medical need. The aim of this study was to determine feasibility, accuracy, and clinical significance of HPV16/18 E6 oncoprotein detection on cytological specimens from oropharyngeal squamous cell carcinoma (OPSCC) and neck lymph node metastasis of SCC from unknown primary tumor (CUP) via a protein immunochromatographic assay. Study design Cross-sectional study. Methods Cytological specimens from primary tumor and neck metastases were collected from 34 patients with OPSCC or CUP and applied to a lateral flow format test that detects HPV16 and HPV18 E6 oncoproteins. E6 oncoprotein positivity or negativity in these specimens was compared to the specimens' "HPV-driven" reference status, defined by presence of HPV-DNA in combination with p16INK4a overexpression and/or HPV E6 seropositivity. Results Eighteen of 29 OPSCC (62%) and three of five CUP (60%) were HPV-driven according to our reference method. The E6 oncoprotein lateral flow test had a sensitivity of 94% (95% CI: 70%-100%) and a specificity of 100% (95% CI: 66%-100%) on primary tumor, and a sensitivity of 88% (95% CI: 64%-99%) and a specificity of 100% (95% CI: 74%-100%) on neck metastases. Test agreement between the E6 lateral flow test and the clinical reference method, HPV-DNA plus p16INK4a was excellent, both for primary lesion and neck metastases. Conclusions We found the detection of HPV16/18 E6 oncoproteins to be a feasible, highly reliable, and low-invasive method to assess "HPV-driven" status in OPSCC and CUP. Level of evidence II Laryngoscope, 131:1042-1048, 2021.
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- 2020
112. Gastric metastases of breast cancer: Histopathological and molecular characterization of a single Institution case series
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Giovanni Zarrilli, Valentina Angerilli, Rocco Cappellesso, Francesca Galuppini, Gianmaria Pennelli, Fabio Farinati, Lorenzo Nicolè, Edoardo Savarino, Stefano Realdon, Gaia Griguolo, Michele Bottosso, Maria Vittoria Dieci, Valentina Guarneri, Angelo Paolo Dei Tos, Marcello Lo Mele, and Matteo Fassan
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Keratin-7 ,Stomach ,Breast Neoplasms ,Estrogens ,Cell Biology ,Breast cancer ,Diagnosis ,Gastric metastasis ,Immunohistochemistry ,Molecular classification ,Female ,Humans ,Retrospective Studies ,Pathology and Forensic Medicine - Abstract
The metastatic spread of breast carcinoma to the stomach is a rare event and often represents a diagnostic challenge. In the present study, 23 cases of gastric metastases from breast cancer were retrospectively identified dating back until 2007. Primitive histotype, localization, gross appearance, microscopic architecture were analyzed. Cytokeratins 7 and 20, sex hormones, HER2 and Ki67 expression was evaluated. According to the results, the series was characterized by an enrichment of lobular primitive histotype (43.7%). In most cases gastric metastases were described as parietal nodules, polypoid masses or ulcerated lesions, mainly involving the antro-angular region. In a relatively high rate (10.5%) of cases, endoscopic examinations resulted negative for macroscopic lesions. More than half of the cases (52.2%) microscopically resembled primitive poorly cohesive gastric cancer. Because gross and histological findings can be deceiving, immunohistochemistry may be essential for the diagnosis of gastric metastases from breast cancer. Accordingly with the results of our analysis and literature review, an immunohistochemical panel composed of cytokeratins 7 and 20, Estrogen and Progesteron Receptors would drastically improve diagnostic accuracy. Interaction among the clinician, endoscopist and the pathologist is also essential to provide the patient the best therapeutic option.
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- 2022
113. Periosteal chondrosarcoma: A case series in a referral center with survivorship analysis
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Marina Pacheco, Lucia Barra, Marco Gambarotti, Giovanna Magagnoli, Marta Sbaraglia, Sofia Asioli, Stefania Cocchi, Elisa Carretta, Tommaso Frisoni, Stefania Benini, Angelo Paolo Dei Tos, Alberto Righi, Pacheco, Marina, Barra, Lucia, Gambarotti, Marco, Magagnoli, Giovanna, Sbaraglia, Marta, Asioli, Sofia, Cocchi, Stefania, Carretta, Elisa, Frisoni, Tommaso, Benini, Stefania, Dei Tos, Angelo Paolo, and Righi, Alberto
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Adult ,Male ,IDH ,Periosteal ,Periosteal Chondrosarcoma IDH Prognosis ,Chondrosarcoma ,Bone Neoplasms ,General Medicine ,Survivorship ,Prognosis ,Oncology ,Humans ,Surgery ,Female ,Neoplasm Recurrence, Local ,Referral and Consultation ,Retrospective Studies - Abstract
Background: Periosteal chondrosarcomas are among the rarest types of chondrosarcomas dealt with in few small series of cases. In this study, we aimed to present our experience with this chondrosarcoma, seek for prognostic factors for OS and DFS and survey the status of IDH1 and IDH2. Results: 55 periosteal chondrosarcomas were retrospectively identified. Median age was 37 years, there was a male predominance (62%). The great majority of cases involved the metaphysis of long bones of the extremities. The median size of the tumors was 7.5 cm. Thirty patients underwent to subtotal surgical resection, 22 to tangential resection and the remaining 3 to amputation. The margins, reported in 54 cases, were wide/radical in 38 patients (70.4%), marginal in 9 (16.7%) and intralesional in 7 (12.9%). Histologically, 23 (42%) were grade 1; 27 (49%), grade 2; 3 (5%), grade 3 and 2 (4%) were dedifferentiated. A third of cases in which mutational analysis was feasible harbored heterozygous mutations in codon 132 of IDH1. Fifty-four cases were included for follow-up (median, 137 months). Four patients had local recurrences and six patients developed metastasis to the lungs. All patients that developed metastasis died of disease, two died of unrelated causes and 46 were alive without disease. OS and DFS was not found to be statistically associated with clinical and pathological parameters considered. Conclusions: periosteal chondrosarcomas exhibit a low-grade behavior that can be adequately treated with marginal excisions. Clinical and morphologic parameters do not seem to predict their outcome
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- 2022
114. Inflammatory Myofibroblastic Tumour: State of the Art
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Louis, Gros, Angelo Paolo, Dei Tos, Robin L, Jones, and Antonia, Digklia
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inflammatory myofibroblastic tumour ,ALK ,epithelioid inflammatory myofibroblastic sarcoma tyrosine kinase inhibitors - Abstract
An inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of myofibroblastic and fibroblastic spindle cells accompanied by inflammatory cells, including lymphocytes and eosinophils. It is an ultra-rare tumor, the optimal management of which remains to be defined. Surgery is the treatment of choice for localized tumors. The treatment of advanced disease is not precisely defined. Chemotherapy regimens result in an overall response rate of approximately 50% based on retrospective data. The latest pathophysiological data highlight the role played by tyrosine kinase fusion genes in IMT proliferation. Anaplast lymphoma kinase (ALK) oncogenic activation mechanisms have been characterized in approximately 80% of IMTs. In this context, data regarding targeted therapies are most important. The aims of this article are to review the latest published data on the use of systematic therapy, particularly the use of molecular targeted therapy, and to publish an additional case of an IMT with Ran-binding protein 2 (RANPB2)-ALK fusion showing a long response to a tyrosine kinase inhibitor.
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- 2022
115. A Global CollaboRAtive Study of CIC-Rearranged, BCOR::CCNB3-Rearranged and Other Ultra-Rare Unclassified Undifferentiated Round Cell Sarcomas (GRACefUl)
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Emanuela Palmerini, Marco Gambarotti, Antoine Italiano, Michael Nathenson, Ravin Ratan, Palma Dileo, Salvatore Provenzano, Robin Lewis Jones, Steven G. DuBois, Javier Martin-Broto, Enrique de Alava, Giacomo Giulio Baldi, Giovanni Grignani, Virginia Ferraresi, Antonella Brunello, Luca Paoluzzi, Rossella Bertulli, Nadia Hindi, Michael Montemurro, Christian Rothermundt, Stefania Cocchi, Carmen Salguero-Arand, Davide Maria Donati, Juan Diaz Martin, Amr Abdelhamid Ahmed, Alessandro Mazzocca, Elisa Carretta, Marilena Cesari, Michela Pierini, Alberto Righi, Marta Sbaraglia, Laginestra Maria Antonella, Katia Scotlandi, Angelo Paolo Dei Tos, Toni Ibrahim, Silvia Stacchiotti, and Bruno Vincenzi
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
116. Clinical implications of alpha, beta, and gamma HPV infection in juvenile onset recurrent respiratory papillomatosis
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Massimo Tommasino, Paolo Boscolo-Rizzo, Sandrine McKay-Chopin, Cesare Cutrone, Marta Sbaraglia, Jerry Polesel, Marianna Sari, Tarik Gheit, Piero Nicolai, Angelo Paolo Dei Tos, Martina Bertinazzi, Bertinazzi, M., Gheit, T., Polesel, J., McKay-Chopin, S., Cutrone, C., Sari, M., Sbaraglia, M., Tos, A. P. D., Piero, Nicolai, Tommasino, M., and BOSCOLO RIZZO, Paolo
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Human papillomavirus ,medicine.medical_specialty ,Adolescent ,Genotype ,Alpha (ethology) ,Disease ,Laryngology ,Young Adult ,Internal medicine ,medicine ,Humans ,Child ,Beta (finance) ,Respiratory Tract Infections ,Children ,Juvenile respiratory papillomatosis ,Co-infections ,business.industry ,Papillomavirus Infections ,HPV infection ,Infant ,Retrospective cohort study ,General Medicine ,medicine.disease ,Prognosis ,Co-infection ,Human papillomaviru ,Otorhinolaryngology ,Child, Preschool ,Neurosurgery ,Recurrent Respiratory Papillomatosis ,business ,Juvenile respiratory papillomatosi - Abstract
Purpose The aim of our study was to evaluate the prevalence of different HPV genera—alpha, beta and gamma—in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease. Methods This retrospective observational study included consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporisation of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay. Results Twenty patients with JoRRP, aged 0.3–11 years, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta—HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay’s score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006). Conclusion Despite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease.
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- 2022
117. Chondroblastoma-like osteosarcoma: a clinicopathologic and molecular study of a rare osteosarcoma variant
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Raffaele Gaeta, Alberto Righi, Marco Gambarotti, Paolo Aretini, Francesca Lessi, Chiara Maria Mazzanti, Irene Mancini, Pamela Pinzani, Beatrice Belgio, Marta Sbaraglia, Angelo Paolo Dei Tos, and Alessandro Franchi
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Adult ,Male ,Histology ,H3F3B K36M mutation ,chondroblastoma-like osteosarcoma ,diagnosis ,Bone Neoplasms ,General Medicine ,Immunohistochemistry ,Antibodies ,Pathology and Forensic Medicine ,whole exome sequencing ,Histones ,osteosarcoma ,Humans ,Female ,chondroblastoma - Abstract
Chondroblastoma-like osteosarcoma (CBLOS) is a rare and poorly understood variant of OS. We examined the clinicopathological, immunohistochemical and molecular features of six CBLOSs to highlight the differences with conventional high-grade OS (CHGOS) and CB, including CB with aggressive features.We performed histone 3.3 mutation analysis by gene sequencing and/or immunohistochemistry in all cases, while whole exome sequencing (WES) was performed on two CB-like osteosarcomas and 11 conventional high-grade OS.CBLOSs were predominantly localised at acral sites and involved mainly male subjects with a mean age of 29 years. One patient who had metastases at presentation died of disease, while another patient who developed multiple local recurrences and lung metastases was alive with no evidence of disease (ANED) at 294 months. The remaining patients were ANED after a mean interval of 70.8 months. Histologically, all CBLOS presented aggressive features, including nuclear atypia and infiltrative growth. Immunohistochemistry with H3F3 K36M mutant antibody was negative in all CBLOSs, and none of the five tumours tested by gene sequencing had H3F3B mutations. Conversely, all CBs presented the H3F3B K36M variant and were positive for immunostaining with the H3F3 K36M antibody. Two CBLOSs analysed by WES differed in amount and type of mutation from 11 cases of CHGOS. Moreover, CBLOSs showed lower copy number alteration (CNA) score values than CHGOSs.CBLOS presents a different genetic background and a less aggressive clinical behaviour in comparison with CHGOS. Search of the H3F3B K36M mutation is useful in the differential diagnosis with CB.
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- 2022
118. Tumor-stroma ratio, neoangiogenesis and prognosis in laryngeal carcinoma. A pilot study on preoperative biopsies and matched surgical specimens
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Lara Alessandrini, Marco Ferrari, Stefano Taboni, Marta Sbaraglia, Leonardo Franz, Tommaso Saccardo, Bianca Maria Del Forno, Francesca Agugiaro, Anna Chiara Frigo, Angelo Paolo Dei Tos, and Gino Marioni
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Cancer Research ,Neovascularization, Pathologic ,Carcinoma ,laryngeal carcinoma ,Endoglin ,microvascular density ,Pilot Projects ,Receptors, Cell Surface ,Prognosis ,Immunohistochemistry ,CD105 ,Oncology ,Antigens, CD ,Humans ,tumor-stroma ratio ,CD31 ,biopsy ,Prospective Studies ,Oral Surgery ,Laryngeal Neoplasms ,tumor-stroma ratio, microvascular density, CD105, CD31, laryngeal carcinoma, biopsy - Abstract
The interaction between tumor cells and stroma is critical in tumorigenesis, tumor neo-angiogenesis and cancer progression. The aims of this study were to: (i) evaluate the concordance between tumor-stroma ratio (TSR) and microvascular density (MVD) on paired biopsy and surgical specimens of laryngeal carcinoma (LSCC); (ii) investigate the association of TSR with angiogenesis (CD105- and CD31-assessed MVD); (iii) assess the prognostic role of TSR and MVD evaluated on preoperative biopsies and paired surgical specimens.TSR, CD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 43 consecutive cases.TSR showed good agreement between biopsies and surgical specimens (AC1 statistic: 0.7957). In biopsies, TSR low/stroma-rich cases showed higher CD105-assessed MVD (p = 0.0380). In surgical specimens both median CD105- and CD31-assessed MVD were significantly higher in TSR low/stroma-rich than in TSR high/stroma-poor patients (p = 0.0089 and p = 0.0391). In the univariate Cox's model, TSR predicted disease-free survival (DFS) in both biopsies and surgical specimens (p = 0.0003 and p = 0.0002). DFS was associated with CD105- and CD31-assessed MVD in biopsies (p 0.0001 for both) and surgical specimens (p 0.0001 for both). Considering biopsies, the multivariate analysis found both TSR (p = 0.0032; HR = 6.112, 95%CI: 1.833-20.378) and CD105-assessed MVD (p = 0.0002; HR = 1.201, 95%CI: 1.090-1.322) as DFS predictor. In paired surgical specimens, both TSR (p = 0.0074; HR = 6.137, 95%CI: 1.626-23.172) and CD105-assessed MVD (p = 0.0005; HR = 1.172 95 %CI 1.071-1.282) retained their significance in multivariate analysis.If confirmed by large prospective studies, TSR and MVD could be proposed as prognostic biomarkers of LSCC for a possible treatment intensification or targeted therapy.
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- 2022
119. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: A Sarculator-based risk stratification analysis of the ISG-STS 1001 randomized trial
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Sandro Pasquali, Emanuela Palmerini, Vittorio Quagliuolo, Javier Martin‐Broto, Antonio Lopez‐Pousa, Giovanni Grignani, Antonella Brunello, Jean‐Yves Blay, Oscar Tendero, Robert Diaz‐Beveridge, Virginia Ferraresi, Iwona Lugowska, Gabriele Infante, Luca Braglia, Domenico Franco Merlo, Valeria Fontana, Emanuela Marchesi, Davide Maria Donati, Elena Palassini, Giuseppe Bianchi, Andrea Marrari, Carlo Morosi, Silvia Stacchiotti, Silvia Bagué, Jean Michel Coindre, Angelo Paolo Dei Tos, Piero Picci, Paolo Bruzzi, Rosalba Miceli, Paolo Giovanni Casali, Alessandro Gronchi, Carla Dani, Chiara Villa, Antonella Messina, Lorella Rusi, Anna Maria Nuzzo, Carmen Nuzzo, Antonino De Paoli, Angela Buonadonna, Alessandro Comandone, Antonella Boglione, Lorenzo Livi, Daniela Greto, Nada Riva, Manuela Monti, Elisabetta Pennacchioli, Tommaso De Pas, Vincenzo Ippolito, Patrico Ledesma, Andres Redondo, Claudia Valverde, Raquel Bratos, Josefina Cruz, Javier Martinez Trufero, Ricardo Cubedo, Isabel Sevilla, Pablo Luna, Rafael Lopez, Pilar Sancho, Olivia Bally, Mehdi Brahmi, Isabelle Ray‐Coquard, Philippe Cassier, Nathalie Marques, Luis Tassy, Pascaline Boudou‐Rouquette, Camille Tlemsani, Jerome Alexandre, Francois Goldwasser, Emmanuelle Bompas, Frederic Rolland, Christophe Perrin, Marie Talarmin, Antoine Italiano, Maud Toulmonde, Mathieu Laramas, Jacques‐Olivier Bay, Pascale Dubray‐Longeras, Piotr Rutkowski, PharmaMar, European Commission, Pasquali, Sandro, Palmerini, Emanuela, Grignani, Giovanni, Brunello, Antonella, Blay, Jean-Yves, Stacchiotti, Silvia, Pasquali S., Palmerini E., Quagliuolo V., Martin-Broto J., Lopez-Pousa A., Grignani G., Brunello A., Blay J.-Y., Tendero O., Diaz-Beveridge R., Ferraresi V., Lugowska I., Infante G., Braglia L., Merlo D.F., Fontana V., Marchesi E., Donati D.M., Palassini E., Bianchi G., Marrari A., Morosi C., Stacchiotti S., Bague S., Coindre J.M., Dei Tos A.P., Picci P., Bruzzi P., Miceli R., Casali P.G., Gronchi A., Dani C., Villa C., Messina A., Rusi L., Nuzzo A.M., Nuzzo C., De Paoli A., Buonadonna A., Comandone A., Boglione A., Livi L., Greto D., Riva N., Monti M., Pennacchioli E., De Pas T., Ippolito V., Ledesma P., Redondo A., Valverde C., Bratos R., Cruz J., Martinez Trufero J., Cubedo R., Sevilla I., Luna P., Lopez R., Sancho P., Bally O., Brahmi M., Ray-Coquard I., Cassier P., Marques N., Tassy L., Boudou-Rouquette P., Tlemsani C., Alexandre J., Goldwasser F., Bompas E., Rolland F., Perrin C., Talarmin M., Italiano A., Toulmonde M., Laramas M., Bay J.-O., Dubray-Longeras P., and Rutkowski P.
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Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,sarcoma ,Anthracycline ,medicine.medical_treatment ,Soft Tissue Neoplasms ,Lower risk ,chemotherapy ,Risk Assessment ,nomogram ,Interquartile range ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Ifosfamide ,Chemotherapy ,business.industry ,Soft tissue sarcoma ,neoadjuvant ,clinical trial ,Nomogram ,medicine.disease ,Neoadjuvant Therapy ,Chemotherapy, Adjuvant ,chemotherapy, clinical trial, neoadjuvant, nomogram, sarcoma ,Sarcoma ,business ,medicine.drug - Abstract
[Background] The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS., [Methods] This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%)., [Results] The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In higher risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105)., [Conclusions] High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS., This was a nonfunded analysis. In the ISG-STS 1001 trial, PharmaMar provided trabectedin for the HG-MRLPS cohort. That trial was partially funded through a European Union grant (EUROSARC FP7 278472).
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- 2022
120. Direct Costs of Care for Adults with Soft Tissue Sarcomas: A Population-Based Study
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Massimo, Rugge, Alessandra, Buja, Saveria, Tropea, Giovanni, Girardi, Luigi Cosenza, Franzese, Claudia, Cozzolino, Manuel, Zorzi, Antonella, Vecchiato, Paolo, Del Fiore, Antonella, Brunello, Alessandra Rosalba, Brazzale, Vincenzo, Baldo, Angelo Paolo, Dei Tos, Carlo Riccardo, Rossi, and Simone, Mocellin
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economic impact ,real-world data ,soft tissue sarcoma ,cost of illness - Abstract
The clinical treatment of soft tissue sarcoma (STS) has evolved substantially over the last decade. This population-based cohort study based on real-world data included all incidental STS recorded by the Veneto Cancer Registry in 2017. Data on hospital admissions, emergency department and outpatient visits, drug prescriptions, and use of medical devices within two years from STS diagnosis were obtained from administrative databases. The average per-patient real-world costs over this two-year period, in total and by single expenditure item, were calculated and stratified by stage of disease at diagnosis, tumor histology and tumor site. The mean total cost per patient amounted to EUR 16,793. A higher TNM stage at diagnosis was associated with higher healthcare costs, as follows: compared with stage I, the average total cost per patient was 1.32, 2.18 and 3.36 times greater for stages II, III and IV, respectively. Hospital stays generated the greatest costs (averaging EUR 7950 per patient), followed by outpatient visits (mean EUR 3947 per patient) and drug prescriptions (mean EUR 3664 per patient). Given the paucity of population-based studies, the present results can serve as a reference for further cost-effectiveness analyses on care strategies for patients with STS.
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- 2022
121. Primary Malignant Peripheral Nerve Sheath Tumors of Bone: A Clinicopathologic Reappraisal of 8 Cases
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Marco Gambarotti, Alberto Righi, Marta Sbaraglia, Stefania Cocchi, Stefania Benini, Giovanna Magagnoli, Tommaso Frisoni, Emanuela Palmerini, Piero Picci, Angelo Paolo Dei Tos, Gambarotti, Marco, Righi, Alberto, Sbaraglia, Marta, Cocchi, Stefania, Benini, Stefania, Magagnoli, Giovanna, Frisoni, Tommaso, Palmerini, Emanuela, Picci, Piero, and Dei Tos, Angelo P.
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MPNST ,bone ,primary bone sarcomas ,spindle cell sarcoma ,Neurofibrosarcoma ,primary bone sarcoma ,Humans ,Sarcoma ,Soft Tissue Neoplasms ,Nerve Sheath Neoplasms ,Pathology and Forensic Medicine - Abstract
Primary spindle cell and pleomorphic sarcomas of bone represent an exceedingly rare group of mesenchymal malignancies that include "soft tissue" histotypes, as malignant peripheral nerve sheath tumour. Outside the head and neck region, only 36 cases of primary malignant peripheral nerve sheath tumour of bone have been described. We retrieved from our archives eight cases of primary malignant peripheral nerve sheath tumour of bone arising outside the head and neck region, describing their clinical, radiological, and morphologic features. Our series, in which all but one patient died of diseases after a median of seven months, confirms that primary malignant peripheral nerve sheath tumours of bone are aggressive tumours. Pathologists should be aware of this rare histotype. More aggressive and active adjuvant treatments should be investigated.
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- 2022
122. CINSARC in high-risk soft tissue sarcoma patients treated with neoadjuvant chemotherapy: Results from the ISG-STS 1001 study
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Anna Maria Frezza, Silvia Stacchiotti, Frederic Chibon, Jean‐Michelle Coindre, Antoine Italiano, Cleofe Romagnosa, Silvia Bagué, Angelo Paolo Dei Tos, Luca Braglia, Emanuela Palmerini, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez Pousa, Giovanni Grignani, Antonella Brunello, Jean‐Yves Blay, Robert Diaz Beveridge, Iwona Lugowska, Tom Lesluyes, Roberta Maestro, Franco Domenico Merlo, Paolo Giovanni Casali, and Alessandro Gronchi
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Cancer Research ,sarcoma ,Settore MED/06 - Oncologia Medica ,Soft Tissue Neoplasms ,CINSARC ,Prognosis ,chemotherapy ,Neoadjuvant Therapy ,outcome ,prognostication ,Oncology ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Neoplasm Recurrence, Local - Abstract
Background The Complexity INdex in SARComas (CINSARC) is a transcriptional signature derived from the expression of 67 genes involved in mitosis control and chromosome integrity. This study aims to assess CINSARC value of in an independent series of high-risk patients with localized soft tissue sarcoma (STS) treated with preoperative chemotherapy within a prospective, randomized, phase III study (ISG-STS 1001). Patients and Methods Patients with available pre-treatment samples, treated with 3 cycles of either standard (ST) preoperative or histotype-tailored (HT) chemotherapy, were scored according to CINSARC (low-risk, C1; high-risk, C2). The 10-year overall survival probability (pr-OS) according to SARCULATOR was calculated, and patients were classified accordingly (low-risk, Sarc-LR, 10-year pr-OS>60%; high-risk, Sarc-HR, 10-year pr-OS
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- 2022
123. Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study
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Sebastian Bauer, Margherita Nannini, Marta Sbaraglia, Mariella Spalato Ceruso, Nadia Hindi, Heikki Joensuu, Peter Reichardt, Antoine Italiano, Angelo Paolo Dei Tos, Jean-Yves Blay, Silvia Gasperoni, Marianna Silletta, Maria Abbondanza Pantaleo, Winan J. van Houdt, Giuseppe Tonini, Piotr Rutkowski, Robin L. Jones, Giovanni Grignani, Spyridon Gennatas, Giuseppe Badalamenti, Hans Gelderblom, Peter Hohenberger, Nikki S. IJzerman, Neeltje Steeghs, Javier Martin-Broto, Tommaso De Pas, Axel Le Cesne, Marta Fiocco, Ingrid M.E. Desar, Paolo G. Casali, Antonella Brunello, Andrea Napolitano, Johanna Falkenhorst, Bruno Vincenzi, Alessandro Gronchi, Elena Fumagalli, Olivier Mir, Vincenzi, Bruno, Napolitano, Andrea, Fiocco, Marta, Mir, Olivier, Rutkowski, Piotr, Blay, Jean-Yve, Reichardt, Peter, Joensuu, Heikki, Fumagalli, Elena, Gennatas, Spyridon, Hindi, Nadia, Nannini, Margherita, Spalato Ceruso, Mariella, Italiano, Antoine, Grignani, Giovanni, Brunello, Antonella, Gasperoni, Silvia, De Pas, Tommaso, Badalamenti, Giuseppe, Pantaleo, Maria A, van Houdt, Winan J, IJzerman, Nikki S, Steeghs, Neeltje, Gelderblom, Han, Desar, Ingrid M E, Falkenhorst, Johanna, Silletta, Marianna, Sbaraglia, Marta, Tonini, Giuseppe, Martin-Broto, Javier, Hohenberger, Peter, Le Cesne, Axel, Jones, Robin L, Dei Tos, Angelo P, Gronchi, Alessandro, Bauer, Sebastian, Casali, Paolo G, University of Helsinki, Research Programs Unit, Department of Oncology, Heikki Joensuu / Principal Investigator, HUS Comprehensive Cancer Center, and Medical Oncology
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STRUCTURAL BASIS ,EXPRESSION ,Oncology ,Cancer Research ,medicine.medical_specialty ,Gastrointestinal Stromal Tumors ,3122 Cancers ,Medizin ,Antineoplastic Agents ,exon 9 ,Adjuvants, Immunologic ,Internal medicine ,medicine ,Humans ,FAILURE ,Retrospective Studies ,RISK ,RECEPTOR ,GiST ,Proportional hazards model ,business.industry ,GASTROINTESTINAL STROMAL TUMORS ,Hazard ratio ,Imatinib ,Retrospective cohort study ,Exons ,Adjuvant treatment ,Confidence interval ,GENOTYPE ,Proto-Oncogene Proteins c-kit ,Chemotherapy, Adjuvant ,Mutation ,Propensity score matching ,Cohort ,Imatinib Mesylate ,Neoplasm Recurrence, Local ,TYROSINE KINASE INHIBITOR ,business ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,medicine.drug ,GIST - Abstract
[Purpose] The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9–mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort., [Experimental Design] Data from 185 patients were retrospectively collected in 23 European GIST reference centers. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Univariate and multivariate unweighted and weighted Cox proportional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival., [Results] Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79–1.94; mRFS: HR, 1.69; 95% CI, 0.92–3.10; IFFS: HR, 1.35; 95% CI, 0.79–2.28]. The variables consistently associated with worse survival outcomes were high mitotic index and nongastric tumor location., [Conclusions] In this retrospective series of patients with KIT exon 9–mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.
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- 2022
124. Multifocal Medulloblastoma in an Adult Patient: Description of a Rare Presentation and Review of the Literature
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Monica Ronzon, Giuseppe Canova, Lucia Zanatta, Angelo Paolo Dei Tos, Luisa Toffolatti, Giuseppe Lombardi, Sabrina Rossi, Caccese Mario, Irene Troncon, Angela Guerriero, Marta Padovan, and Elisabetta Marton
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Pathology ,medicine.medical_specialty ,Adult Medulloblastoma ,Case Report ,Cerebellar tumors ,03 medical and health sciences ,0302 clinical medicine ,medicine ,RB1-214 ,neoplasms ,Anaplasia ,Medulloblastoma ,business.industry ,Histopathological analysis ,General Medicine ,medicine.disease ,nervous system diseases ,stomatognathic diseases ,030220 oncology & carcinogenesis ,Immunohistochemistry ,medicine.symptom ,Presentation (obstetrics) ,business ,030217 neurology & neurosurgery ,Immunostaining - Abstract
Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy.
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- 2020
125. The Activity of Chemotherapy in Inflammatory Myofibroblastic Tumors: A Multicenter, European Retrospective Case Series Analysis
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Michela Casanova, Axel Le Cesne, Olivier Mir, Salvatore Lo Vullo, Jean-Yves Blay, Giovanni Grignani, Maria Abbondanza Pantaleo, A.M. Frezza, Luigi Mariani, Robin L. Jones, Bruno Vincenzi, Alessandro Gronchi, Elena Cojocaru, Angelo Paolo Dei Tos, Mehdi Brahmi, Silvia Stacchiotti, Giacomo Giulio Baldi, Paolo G. Casali, Paola Collini, Carlo Morosi, Tommaso De Pas, Baldi G.G., Brahmi M., Lo Vullo S., Cojocaru E., Mir O., Casanova M., Vincenzi B., De Pas T.M., Grignani G., Pantaleo M.A., Blay J.Y., Jones R.L., Le Cesne A., Frezza A.M., Gronchi A., Collini P., Dei Tos A.P., Morosi C., Mariani L., Casali P.G., and Stacchiotti S.
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Anthracycline ,medicine.medical_treatment ,Vinblastine ,Vinorelbine ,Inflammatory myofibroblastic tumor ,03 medical and health sciences ,0302 clinical medicine ,Sarcoma ,chemotherapy ,doxorubicin ,inflammatory myofibroblastic tumour ,methotrexate ,vinorelbine ,vinblastine ,Interquartile range ,Internal medicine ,medicine ,Chemotherapy ,business.industry ,Sarcomas ,Gemcitabine ,Regimen ,Methotrexate ,030104 developmental biology ,Docetaxel ,Doxorubicin ,030220 oncology & carcinogenesis ,Localized disease ,business ,medicine.drug - Abstract
Background This study aimed to review the activity of cytotoxic chemotherapy in patients with inflammatory myofibroblastic tumors (IMTs) treated at nine European sarcoma reference centers. Materials and Methods Patients of any age, with histologically proven IMT, treated with anthracycline-based methotrexate plus/minus vinorelbine/vinblastine (MTX-V) or other chemotherapeutic regimens between 1996 and 2018 were retrospectively reviewed. Diagnosis was confirmed at the local level by an expert pathologist. Response was retrospectively assessed by local investigators by RECIST v1.1. Progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS) were computed by Kaplan-Meier method. Results Thirty-eight patients were included. Twenty-five patients (8 localized, 17 advanced disease) received an anthracycline-based regimen; 21 were evaluable for response. Overall response rate (ORR) was 10/21 (47.6%). At a 70.8-month median follow-up (FU), median RFS and median OS were not reached (NR) in patients with localized disease; median PFS and median OS were 6.3 (interquartile range [IQR]: 1.9–13.4) and 21.2 (IQR: 7.7–40.7) months in patients with advanced disease. Thirteen patients received MTX-V (4 localized, 9 advanced disease), all evaluable for response. ORR was 7/13 (53.8%). At a 56.6-month median FU, median RFS and median OS were 42.5 (IQR: 12.9–61.2) months and NR (no death events) in patients with localized disease, and NR (IQR: 24.9 to NR) and 83.4 months (IQR: 83.4 to NR) in patients with advanced disease. In the “other-regimens group,” responses were seen in 3/4 patients treated with oral cyclophosphamide and 1/2 with docetaxel/gemcitabine. Conclusion Anthracycline-based and MTX-V regimens are very effective in IMT, with a similar ORR in both groups. MTX-V achieved a prolonged disease control. Responses were also seen with oral cyclophosphamide and docetaxel/gemcitabine, but few patients were treated with these schedules. Implications for Practice Inflammatory myofibroblastic tumor (IMT) is an ultrarare sarcoma with known sensitivity to anaplastic lymphoma kinase (ALK) inhibitors in ALK-fused cases, although ALK inhibitors are not licensed in the disease. The current knowledge on the activity of cytotoxic chemotherapy is limited. This multi-institutional retrospective study on pediatric and adult patients with IMT shows that cytotoxic chemotherapy, and in particular anthracycline-based and methotrexate plus/minus vinorelbine/vinblastine regimens, represents a treatment option and can be considered in IMT patients irrespectively from ALK status. This study provides a benchmark for future studies on new medical therapies.
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- 2020
126. Lipoblastoma-like tumor of the spermatic cord: case report and review of the literature
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Kivilcim Eren Erdogan, Giovanna Magagnoli, Augusto Delle Rose, Stefania Benini, Marta Sbaraglia, Alberto Righi, Angelo Paolo Dei Tos, Maria Rosaria Raspollini, and Marco Gambarotti
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adolescent ,Liposarcoma ,Spermatic cord ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Female patient ,Biomarkers, Tumor ,medicine ,Humans ,Molecular Biology ,Spermatic Cord ,business.industry ,Mesenchymal Tumor ,Lipoblastoma-like tumor ,Cell Biology ,General Medicine ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,medicine.anatomical_structure ,Molecular Diagnostic Techniques ,Male patient ,030220 oncology & carcinogenesis ,Genital Neoplasms, Male ,Lipoblastoma ,business - Abstract
Lipoblastoma-like tumor is a very rare mesenchymal tumor believed to be restricted to female patients and only recently reported in the spermatic cord of a male patient. We describe herein an additional case of lipoblastoma-like tumor occurring in the spermatic cord, describing its histopathological, immunohistochemical, and molecular features.
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- 2020
127. The natural history of epithelioid sarcoma. A retrospective multicentre case-series within the Italian Sarcoma Group
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Noemi Simeone, Marta Sbaraglia, Annarita Palomba, Sandro Pasquali, Filippo Frenos, Dario Callegaro, Luigi Mariani, Giacomo Giulio Baldi, Marta Barisella, Silvia Stacchiotti, Angelo Paolo Dei Tos, Alessandro Gronchi, Marco Gambarotti, Domenico Andrea Campanacci, Anna Maria Frezza, Paolo G. Casali, and Salvatore Lo Vullo
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Male ,0301 basic medicine ,Proximal type ,Lung Neoplasms ,Neoplasm, Residual ,Soft Tissue Neoplasms ,Kaplan-Meier Estimate ,Gastroenterology ,0302 clinical medicine ,Medicine ,Cumulative incidence ,Nuclear atypia ,Child ,Outcome ,Sarcoma ,General Medicine ,Middle Aged ,Survival Rate ,Natural history ,Italy ,Lower Extremity ,Oncology ,Head and Neck Neoplasms ,Child, Preschool ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,Epithelioid sarcoma ,Groin ,Upper Extremity ,Young Adult ,03 medical and health sciences ,Internal medicine ,Humans ,In patient ,Pathological ,Retrospective Studies ,Series (stratigraphy) ,business.industry ,Infant, Newborn ,Infant ,Distal type ,medicine.disease ,030104 developmental biology ,Surgery ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,Urogenital Neoplasms - Abstract
Introduction This case-series is aimed to describe the natural history of epithelioid sarcoma (ES) and to provide insights into the differential clinical behaviour of its two variants (“classic-type” and “proximal-type”). The value of a subtype-adapted grading system based on pathological features is explored. Methods Data from consecutive, primary, localised, INI1-deleted ES operated at three Italian sarcoma reference centres (1995–2015) were included. Centralised pathological review was performed. Classic-type ES was broken down into “high-grade” and “low-grade”, according to number of mitoses, evidence of necrosis and nuclear atypia. Five- and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were estimated. Results Fifty-two patients were included. 5- and 10-year OS estimates were 70% and 47% in the whole series, 57% and 37% in patients with proximal-type ES, 77% and 54% in patients with classic-type ES (P = 0.02). In classic-type ES, 5- and 10-year OS was higher for low-grade (95% and 72%, respectively) than high-grade tumours (P = 0.002). 5- and 10-year CCI estimates for LR were 21% and 33% in the whole series. 5- and 10-year CCI estimates for DM were 35% and 39% in the whole series, both 28% in classic-type ES, 47% and 59% in proximal-type ES (P = 0.03). Conclusions Suffering from a proximal- or a classic-type is the stronger predictor of outcome in patients with localised ES, with proximal-type ES patients having lower survival due to a higher tendency toward metastatic spreading. However, the “high-grade” classic-type ES was associated with outcomes close to proximal-type ES.
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- 2020
128. Primary Vascular Tumors of Bone
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Marta Sbaraglia, Dino Gibertoni, Roberta Maestro, Costantino Errani, Alberto Righi, Stefania Benini, Marina P Rovira, Angelo Paolo Dei Tos, Marco Gambarotti, and Monica Brenca
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adolescent ,Biopsy ,Bone Neoplasms ,Polymerase Chain Reaction ,Risk Assessment ,Disease-Free Survival ,Pathology and Forensic Medicine ,Hemangioma ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Biomarkers, Tumor ,medicine ,Humans ,Angiosarcoma ,Child ,Pseudomyogenic Hemangioendothelioma ,Epithelioid hemangioendothelioma ,In Situ Hybridization, Fluorescence ,Epithelioid Hemangioma ,Aged ,Aged, 80 and over ,Gene Rearrangement ,Epithelioid Cells ,Cell Differentiation ,Gene rearrangement ,Papillary Intralymphatic Angioendothelioma ,Middle Aged ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,Italy ,Child, Preschool ,030220 oncology & carcinogenesis ,Neoplasms, Vascular Tissue ,Female ,Surgery ,Gene Fusion ,Anatomy ,Epithelioid cell - Abstract
Recent molecular discoveries have refined vascular bone tumor classification. To investigate the clinical relevance of these refinements, we reviewed all cases of primary vascular bone tumors treated at our Institute. On the basis of morphology, cases were assessed immunohistochemically and molecularly. A total of 427 cases of primary vascular tumor of bone with available follow-up and histologic material were retrieved and reclassified according to the most recent diagnostic criteria as follows: 289 hemangiomas, 38 epithelioid hemangiomas, 21 epithelioid hemangioendotheliomas, 2 retiform hemangioendotheliomas, 1 intraosseous papillary intralymphatic angioendothelioma, 24 pseudomyogenic hemangioendotheliomas, and 52 angiosarcomas (of these, 45 were epithelioid angiosarcomas and 7 spindle cell secondary angiosarcoma). Both epithelioid and classic hemangiomas behave as benign tumors with excellent prognosis. The distinction between cellular and conventional type of epithelioid hemangioma was not associated with a different clinical course. Conversely, epithelioid hemangioendothelioma exhibited a more aggressive clinical behavior than hemangioma, with higher rates of multifocality and distant spread. Immunohistochemical positivity for CAMTA1 or TFE3 did not have a prognostic implication. In epithelioid hemangioendothelioma, the presence of morphologic malignant features was associated with reduced disease-free (P=0.064) and overall survival (P=0.055). Pseudomyogenic hemangioendothelioma featured local aggressiveness in 5/24 patients exhibiting a clinical behavior closer to epithelioid hemangioma than epithelioid hemangioendothelioma. Last, 32/45 patients with epithelioid angiosarcoma died of disease with a median survival time of 10 months from diagnosis. In conclusion, the integration of morphologic, immunohistochemical, and molecular features allows a better stratification of primary vascular tumors of bone with significant prognostic and therapeutic implications.
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- 2020
129. Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trialmm
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Jean-Yves Blay, Domenico Franco Merlo, Claudia Valverde, Antonella Brunello, Paola Collini, Salvatore Lorenzo Renne, Cleofé Romagosa, Antonio Lopez-Pousa, Joaquín Dopazo, Silvia Stacchiotti, Piero Picci, Angelo Paolo Dei Tos, Marco Gambarotti, Marta Barisella, Rafael Ramos, Paolo G. Casali, Antonio Gutierrez, Valérie Velasco, J. Martin-Broto, Silvia Bagué, David S. Moura, Nadia Hindi, Vittorio Quagliuolo, Giovanni Grignani, Maria Lopez-Alvarez, Alessandro Gronchi, Jean-Michel Coindre, Daniel Lopez-Lopez, Emanuela Palmerini, Luca Braglia, European Commission, Cancer Research UK, Associazione Italiana per la Ricerca sul Cancro, and Fundación Científica Asociación Española Contra el Cáncer
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Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Translational Research, Biomedical ,stomatognathic system ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Doxorubicin ,Palifosfamide ,Chemotherapy ,Ifosfamide ,Tissue microarray ,business.industry ,Sarcoma ,medicine.disease ,Prognosis ,Nilotinib ,Selumetinib ,Female ,Multidrug Resistance-Associated Proteins ,business ,medicine.drug - Abstract
MRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS. MRP-1 expression was assessed by IHC in tissue microarrays from patients with STS and tested for correlation with disease-free survival (DFS) and overall survival (OS). In vitro studies tested the efficacy of MRP-1 inhibitors (nilotinib, ripretinib, selumetinib, and avapritinib) in sarcoma cell lines. The effect of combinations of the most active MRP-1 inhibitors and chemotherapy was measured on the basis of apoptosis. MRP-1 was evaluable in 231 of 264 cases who entered the study. MRP-1 expression (strong intensity) was independently associated with worse DFS [HR, 1.78; 95% confidence interval (CI), 1.11–2.83; P = 0.016], in the multivariate analysis, with a trend for a worse OS (HR, 1.78; 95% CI, 0.97–3.25; P = 0.062). In vitro studies showed that the addition of MRP-1 inhibitors (nilotinib or avapritinib) to doxorubicin plus palifosfamide, significantly increased cell death in SK-UT-1 and CP0024 cell lines. MRP-1 is an adverse predictive factor in localized high-risk patients with STS treated with neoadjuvant anthracyclines plus ifosfamide followed by surgery. In vitro findings support the clinical assessment of the combination of chemotherapy and MRP-1 inhibitors as a promising strategy to overcome the drug ceiling effect for chemotherapy., The study was partially funded through a European Union grant (EUROSARC FP7 278472). The authors would like to thank Patricio Ledesma Figueroa for Data Management. J. Martin-Broto, D.S. Moura and N. Hindi would like to thank the International Accelerator Award funded by Cancer Research UK [C56167/A29363], Associazione Italiana per la Ricerca sul Cancro [AIRC - 24297] and Fundacion Científica – Asociacion Espanola Contra el Cancer [Foundation AECC - GEACC19007MA]. D.S. Moura was supported by a Sara Borrell grant (CD20/00155) funded by the Instituto de Salud Carlos III. C. Romagosa was supported by a grant from the “Programa d'impuls del talent i de l'ocupabilitat del PERIS 2016–2020.” J-Y. Blay would like to express gratitude for the support from NetSARC (INCA and DGOS) EURACAN (EC 739521) and LYRICAN (INCA-DGOS-INSERM 12563). The ISH1001 study was supported by Eurosarc (FP7–278742).
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- 2021
130. Relevance of bone marrow histology in challenging cases of Acute Myeloid Leukemia
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Angelo Paolo Dei Tos, Luca Dal Santo, Marco Pizzi, Greta Scapinello, Marta Sbaraglia, Stefano Pravato, Annalisa Martines, Francesca Tosato, Gianni Binotto, Debora De Bartolo, and Laura Bonaldi
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Pathology ,medicine.medical_specialty ,Clinical Biochemistry ,acute myeloid leukemia ,Immunophenotyping ,Bone Marrow ,medicine ,Humans ,Pure Erythroid Leukemia ,business.industry ,Biochemistry (medical) ,bone marrow biopsy ,histopathology ,immunophenotype ,pure erythroid leukemia ,Myeloid leukemia ,Histology ,Hematology ,General Medicine ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Myelodysplastic Syndromes ,Histopathology ,Bone marrow ,business - Published
- 2021
131. Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas
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Fabio Farinati, Vittorina Zagonel, Salvatore Pucciarelli, Francesca Bergamo, Marta Sbaraglia, Sabina Murgioni, Monia Niero, Angelo Paolo Dei Tos, Antonio Pellino, Pierluigi Pilati, Floriana Nappo, Fotios Loupakis, Francesco Cavallin, Stefano Merigliano, Erika Riello, Sara Lonardi, Gaya Spolverato, Matteo Fassan, Stefano Realdon, Stefano Brignola, Gianluca Businello, and Maria Guido
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medicine.medical_specialty ,CLDN18.2 ,medicine.drug_class ,Medicine (miscellaneous) ,Monoclonal antibody ,MLH1 ,Gastroenterology ,Article ,Internal medicine ,PMS2 ,Medicine ,Stage (cooking) ,Biomarkers ,Gastric adenocarcinoma ,Immunohistochemistry ,business.industry ,Cancer ,biomarkers ,medicine.disease ,digestive system diseases ,MSH6 ,MSH2 ,immunohistochemistry ,gastric adenocarcinoma ,business - Abstract
The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (n = 280) and GECs (n = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <, 70 (p = 0.0035), positive EBV status (p = 0.002), high stage (III, IV) at diagnosis (p = 0.003), peritoneal involvement (p <, 0.001) and lower incidence of liver metastases (p = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.
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- 2021
132. Prognostic impact of FGFR2/3 alterations in patients with biliary tract cancers receiving systemic chemotherapy: the BITCOIN study
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Mario Rizzato, Stefano Brignola, Giada Munari, Maura Gatti, Vincenzo Dadduzio, Chiara Borga, Francesca Bergamo, Antonio Pellino, Valentina Angerilli, Claudia Mescoli, Maria Guido, Jessica Rearden, Enrico Gringeri, Umberto Cillo, Angelo Paolo Dei Tos, Vittorina Zagonel, Fotios Loupakis, Sara Lonardi, and Matteo Fassan
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Biliary tract cancers ,Biomarkers ,FGFR2 ,NGS ,Proto-Oncogene Proteins B-raf ,Cancer Research ,Prognosis ,Cholangiocarcinoma ,Bile Ducts, Intrahepatic ,Biliary Tract Neoplasms ,Oncology ,Bile Duct Neoplasms ,Humans ,Receptor, Fibroblast Growth Factor, Type 3 ,Receptor, Fibroblast Growth Factor, Type 2 ,Retrospective Studies - Abstract
FGFR2 rearrangements have been identified as a novel therapeutic target of biliary tract cancer (BTC). However, reliable prevalence estimates of this molecular alteration and its prognostic role have not been fully elucidated.A retrospective mono-institutional series of 286 patients affected by locally advanced or metastatic BTC (183 intrahepatic cholangiocarcinomas, 67 extrahepatic cholangiocarcinomas, 36 gallbladder carcinomas) was profiled by means of targeted DNA/RNA next-generation sequencing, immunohistochemistry and fluorescence in situ hybridisation for FGFR2/3, ERBB2, NTRK alterations, IDH1/2 and BRAF mutations and DNA mismatch repair complex proteins alterations/microsatellite instability.FGFR2 rearrangements, amplifications and point mutations were detected in 15 (5.2%), 1 and 3 cases, respectively. FGFR3 alterations were observed in 5 (1.7%) cases. IDH1/2 were mutated in 35/223 cases (15.7%). A total of 9/258 (3.5%) and 6/260 (2.3%) BTCs had ERBB2 and BRAF gene alterations, respectively. Two cases (2/242; 0.8%) had NTRK1 amplifications but no rearrangement was found. A deficit of mismatch repair protein expression was identified in 9/237 cases (3.8%). At multivariate analysis, age, ECOG performance status, number of metastatic sites, tumour stage, FGFR2/3 alterations and IDH1/2 mutations were prognostic factors of overall survival.These data provide a strong proof - challenged with a robust and detailed multivariate model - that FGFR2/3 aberrations (including FGFR2 rearrangements) and IDH1/2 mutations can be prognostic for better survival in patients with BTC . The recognition and the measurement of their prognostic impact could be of primary importance for the correct interpretation of currently available data and in the design of new therapeutic trials.
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- 2021
133. Beware of Histiocytes: Whipple Adenopathy and its Mimics
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Marta Sbaraglia, Luca Dal Santo, Angelo Paolo Dei Tos, Marco Pizzi, Luisa Santoro, Melissa Cecchetto, Alessandra Faedo, and Debora De Bartolo
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Lymphadenopathy ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Rare case ,Medicine ,Humans ,Histiocyte ,business.industry ,Whipple Disease ,Histiocytes ,medicine.disease ,Histiocytosis ,030104 developmental biology ,Infectious disease (medical specialty) ,030220 oncology & carcinogenesis ,Etiology ,Surgery ,Anatomy ,Differential diagnosis ,business ,Hematopathology - Abstract
Histiocytic proliferations are heterogeneous lesions with distinct pathogenic and clinical-pathological features. While many of these conditions are nonspecific immune responses to variable causes, a minority of them is associated with specific etiological factors and unique clinical-pathological pictures. By presenting a rare case of Whipple adenopathy, we address the peculiar histological features of this condition and the differential diagnosis of nodal histiocytosis in general.
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- 2021
134. Alpha, Beta, and Gamma HPV Infection in Juvenile Onset Recurrent Respiratory Papillomatosis
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Cesare Cutrone, Massimo Tommasino, Jerry Polesel, Paolo Boscolo-Rizzo, Angelo Paolo Dei Tos, Marta Sbaraglia, Martina Bertinazzi, Tarik Gheit, Sandrine McKay-Chopin, Piero Nicolai, and Marianna Sari
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Juvenile onset ,business.industry ,Immunology ,HPV infection ,Alpha (ethology) ,Medicine ,Recurrent Respiratory Papillomatosis ,business ,Beta (finance) ,medicine.disease - Abstract
Purpose The aim of our study is to evaluate the prevalence of different HPV genera – alpha, beta and gamma – in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease. Methods This retrospective observational study includes consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporization of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay. Results Twenty patients with JoRRP, aged 0.3–11 years old, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta – HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay’s score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006). Conclusion Despite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease.
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- 2021
135. Clinical, Histological, and Molecular Features of Solitary Fibrous Tumor of Bone: A Single Institution Retrospective Review
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Luca Sangiorgi, Elena Pedrini, Laura Pazzaglia, Alberto Righi, Marta Sbaraglia, Giuseppe Bianchi, Katia Scotlandi, Debora Lana, Isabella Bartolotti, Cristina Ferrari, Angelo Paolo Dei Tos, and Marco Gambarotti
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0301 basic medicine ,Cancer Research ,Solitary fibrous tumor ,Pathology ,medicine.medical_specialty ,Necrosis ,CD34 ,risk stratification ,primary bone tumor ,Article ,03 medical and health sciences ,0302 clinical medicine ,NAB2-STAT6 fusion transcripts ,prognosis ,solitary fibrous tumor ,medicine ,Clinical significance ,Single institution ,RC254-282 ,business.industry ,Soft tissue ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Mitotic Figure ,Immunohistochemistry ,medicine.symptom ,business - Abstract
Simple Summary Solitary fibrous tumors arising from the bone are an extremely rare event and only few cases have been previously described in the literature. It is characterized by a prominent, branched vascularization, with a thin and dilated vascular texture defined as “staghorn” and by the presence of the NAB2-STAT6 gene rearrangement, present in about 90% of cases and considered a pathognomonic feature. In the present study, we described our series of 24 cases of primary solitary fibrous tumor of the bone to find any clinical and molecular prognostic factors and to compare them with those currently used for soft tissue solitary fibrous tumor and to evaluate the risk stratification system proposed by Demicco, in order to understand whether this system was able to correctly predict the risk of local and distant metastatic relapse even in the case of solitary fibrous tumor of the bone. Abstract Primary solitary fibrous tumor (SFT) of the bone is extremely rare, with only few cases reported in the literature. We retrieved all cases of primary SFT of the bone treated at our institution and we assessed the morphology and the immunohistochemical and molecular features to investigate the clinical outcome of primary SFT of the bone and any clinical relevance of clinical and histological criteria of aggressiveness currently adopted for the soft tissues counterpart. Morphologically, 15 cases evidenced high cellularity, cytologic atypia, and foci of necrosis and were associated with more than 4 mitotic figures/10 HPF. Immunohistochemical analysis showed an expression of CD34 and of STAT6 immunopositivity in 95% and in 100% of cases, respectively. The presence of NAB2-STAT6 chimeric transcripts was found in 10 out of 12 cases in which RT-PCR analysis was feasible, whereas TERT promoter mutations analysis was feasible in 16 cases and only a C-to-T substitution in a heterozygous state was found in one DNA sample for the C228T genetic variant. P53 variants were assessed in 12 cases: 11 (91.6%) cases showed a variation, while in one case, no alteration was found. Disease-specific survival was 64% at 5 years and 49% at 10 years. Statistical analysis showed no correlation between survival and all the clinicopathological and molecular parameters evaluated. In conclusion, at difference to SFT of soft tissues, aggressive behavior of primary SFT of the bone seems to be independent from mitotic count or any other clinicopathological and molecular features.
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- 2021
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136. When does a new sarcoma exist?
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Paolo G. Casali, Angelo Paolo Dei Tos, and Alessandro Gronchi
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medicine.medical_specialty ,Editorial ,Oncology ,Surgical oncology ,business.industry ,General surgery ,medicine ,MEDLINE ,Sarcoma ,medicine.disease ,business ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 - Published
- 2020
137. Chordoma: update on disease, epidemiology, biology and medical therapies
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Angelo Paolo Dei Tos, Laura Botta, A.M. Frezza, Silvia Stacchiotti, and Annalisa Trama
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musculoskeletal diseases ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Disease epidemiology ,MEDLINE ,Bone Neoplasms ,Disease ,Bone Sarcoma ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,Chordoma ,Humans ,Medicine ,Protein Kinase Inhibitors ,Epigenesis ,business.industry ,Incidence (epidemiology) ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunotherapy ,business - Abstract
Chordoma is an exceedingly rare subtype of bone sarcoma. This review aims to provide a comprehensive insight into chordoma epidemiology, and an update on the recent advances in disease, biology and medical therapies.The incidence of chordoma is approximately 0.08/100 000 and the 5-year overall age-adjusted relative survival is 72% in the United States and 61% in Europe. Over the last years, significant steps forwards have been done in the comprehension of chordoma complexity, with insights gained into the biology and morphology of this disease. New entities have been described and potentially druggable molecular targets identified. This is becoming all the more relevant today, as new potentially active agents are under development.Chordoma is a complex disease because of its rarity, biological heterogeneity and peculiar clinical behaviour. Despite the progress done, the outcome in this disease remains unsatisfactory and the identification of active systemic treatments remains an urgent, unmet medical need.
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- 2019
138. Interferon-Gamma and Tumor Necrosis Factor-Related Weak Inducer of Apoptosis Expression in Neoangiogenesis in Colorectal Polypoid Lesions
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Nicolò Bassi, Francesco Ferrara, Stefano Benvenuti, Marta Campo Dell'Orto, Marco Massani, Andromachi Kotsafti, Angelo Paolo Dei Tos, Luca Maria Saadeh, Marco Scarpa, Anna Pozza, Luisa Toffolatti, and Cesare Ruffolo
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Adult ,Male ,Vascular Endothelial Growth Factor A ,Colorectal polypoid lesions ,VEGF receptors ,Interferon-gamma ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,TWEAK ,medicine ,Humans ,Interferon gamma ,Inducer ,Prospective Studies ,RNA, Messenger ,Aged ,Aged, 80 and over ,Neovascularization, Pathologic ,biology ,business.industry ,IFNγ ,VEGF ,Cancer ,Cytokine TWEAK ,Middle Aged ,medicine.disease ,Vascular Endothelial Growth Factor Receptor-2 ,Vascular endothelial growth factor ,Reverse transcription polymerase chain reaction ,Logistic Models ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,030211 gastroenterology & hepatology ,Surgery ,Tumor necrosis factor alpha ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
Background: Interferon gamma (IFNγ) and tumor necrosis factor-related weak inducer of apoptosis (TWEAK) molecules seem to have a potential effect on angiogenic factors such as vascular endothelial growth factor (VEGF). The aim of this study was to assess a possible interplay between IFNγ and TWEAK cytokines and VEGF machinery in the different steps of colorectal carcinogenesis. Methods: A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Polypoid lesion tissue samples were collected and frozen. Real-time reverse transcription polymerase chain reaction for IFNγ, TWEAK, and VEGF-A mRNA expression was performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Nonparametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. Results: IFNγ and TWEAK mRNA expression was higher in patients with T2 or more advanced colorectal cancer than in those with adenomas or T1 cancer (p < 0.001 and p = 0.01, respectively). IFNγ and TWEAK mRNA expression levels directly correlated with VEGF-A mRNA expression levels (rho = 0.44, p < 0.001 and rho = 0.29, p = 0.004, respectively). On the contrary, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGF-C protein levels (rho = –0.29, p = 0.04 and rho = –0.31, p = 0.03, respectively). Similarly, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGFR2 protein levels (rho = –0.38, p = 0.033 and rho = –0.40, p = 0.025, respectively). Conclusion: This study showed that in colorectal polypoid lesions, IFNγ and TWEAK expressions are directly correlated to VEGF-A expression but inversely correlated with VEGFR2 levels, suggesting a possible feedback mechanism in the regulation of VEGF-A expression.
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- 2019
139. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: Results of the expanded cohort of myxoid liposarcoma of the randomized clinical trial from the Italian Sarcoma Group (ISG), the Spanish Sarcoma Group (GEIS), the French Sarcoma Group (FSG), and the Polish Sarcoma Group (PSG)
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Alessandro Gronchi, Emanuela Palmerini, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez-Pousa, Giovanni Grignani, Antonella Brunello, Jean-Yves Blay, Robert Diaz Beveridge, Virginia Ferraresi, Iwona Lugowska, Sara Pizzamiglio, Paolo Verderio, Valeria Fontana, Davide Maria Donati, Elena Palassini, Silvia Stacchiotti, Rosalba Miceli, Angelo Paolo Dei Tos, and Paolo Giovanni Casali
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Cancer Research ,Oncology - Abstract
11508 Background: An ISG, GEIS, FSG and PSG randomized trial on 3 cycles of neoadjuvant epirubicine+ifosfamide (EI) versus a histology-tailored (HT) regimen in selected localized high-risk STS showed some superiority of EI in all histologies with the exception of Myxoid Liposarcoma (MLPS) where EI and HT regimens seemed equivalent (J Clin Oncol 2020; 38:2178-86). This MLPS cohort was expanded with the aim to assess the non-inferiority of the HT regimen compared to EI. Methods: This was a multicenter European randomized trial comparing EI versus a HT regimen. Patients (pts) had localized high-risk (grade = 3; size >5 cm; deeply seated) undifferentiated pleomorphic sarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma or MLPS of extremities or trunk wall. Primary end-point was Disease Free Survival (DFS). Secondary end-point was Overall Survival (OS). The MLPS cohort was expanded after the results of the 3rd interim analysis (Lancet Oncol 2017; 18:812-22) in order to reject the hypothesis that HT regimen trabectedin is associated with a HR of relapse = 1.25 with a non-inferiority design. To this aim, a Bayesian monitoring approach was used until the probability that the true HR is higher than 1.25 was greater than 80% or smaller than 5%. Results: From May 2011 to June 2020, 101 pts affected by high-risk MLPS were randomized, 56 to EI and 45 to HT regimen. The median follow-up was 66 months (IQ range 37-89). Median size was 107 mm (IQ range 84-143), 108 mm (IQ range 86-150) in the EI and 106 mm (IQ range75-135) in the HT arm. The DFS and OS probabilities at 60 months were 0.86 and 0.73 (HR:0.60; 95%CI: 0.24-1.46; log rank p = 0.26 for DFS) and 0.88 and 0.90 (HR:1.20; 95%CI:0.37-3.93; log rank p = 0.77 for OS), in the HT and EI arm, respectively. 5-yr observed and Sarculator-predicted OS were 0.89 (95% CI 0.82-0.97) and 0.80 in all patients (p = 0.020), 0.90 (95% CI 0.81-1.00) and 0.79 in the EI arm (p = 0.049) and 0.88 (95% CI 0.77-1.00) and 0.81 in the HT arm (p = 0.204) respectively. Conclusions: In the expanded cohort of MLPS, the HT neoadjuvant therapy trabectedin was not inferior to EI. While survival in both arms was better than predicted by Sarculator, it is left to understand whether this patient population, who had on average a lower Sarculator-predicted risk of death compared with the rest of the trial population, may benefit from a neoadjuvant therapy. Clinical trial information: NCT01710176.
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- 2022
140. Trabectedin in advanced retroperitoneal well differentiated/dedifferentiated liposarcoma and leiomyosarcoma (TRAVELL): Results of a phase 2 study from Italian sarcoma group (ISG)
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Roberta Sanfilippo, Giovanni Grignani, Chiara Fabbroni, Bruno Vincenzi, Elena Fumagalli, Tommaso Martino De Pas, Alessandro Mazzocca, Toni Ibrahim, Maria A. Pantaleo, Antonella Brunello, Giacomo Giulio Baldi, Antonella Boglione, Sonia Fatigoni, Andrea Marrari, Alfredo Berruti, Monica Giordano, Angelo Paolo Dei Tos, Luciano Carlucci, Eliana Rulli, and Paolo Giovanni Casali
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Cancer Research ,Oncology - Abstract
11575 Background: To further explore the activity of T as second/further line treatment in retroperitoneal leiomyosarcoma (LMS) and well differentiated/dedifferentiated liposarcoma (LPS). The primary endpoint of the study was the growth modulation rate (GMR) defined as the ratio between the time to progression under T (TTP) and during previous chemotherapy treatment (TTP-1). The secondary end-points were objective response rate as per RECIST and PFS. Methods: This was a multicenter, single-arm Phase 2 study, conducted in 20 Italian centers. Patients with locally relapsed or metastatic disease, already treated with one or more previous systemic treatments with anthracyclines and/or ifosfamide, were enrolled. T was administered at a dose of 1.3-1.5 mg/mq with a top dose of 2.6 mg per cycle. T was administered as a 24h continuous infusion until progressive disease, major toxicity, patient’s intolerance or medical decision. As per protocol, patients were considered responders if the GMR was > 1.33, non-responders if < 0.75 and neither if 0.76-1.32. Eighty evaluable patients were needed to detect an odds of trabectedin response ≥ 2.5, corresponding to 71.4% of patients with a GMR > 1.33 (80% power, one-sided alpha 2.5%). Results: From August 2014 to February 2019, 104 patients were registered and 91 were evaluable for the primary endpoint (32 pts with LMS and 59 with LPS). Overall, the median number of cycles received was 6.0 (q1-q3 3.0-12.0), the main reason for treatment discontinuation was disease progression in 72% of patients, followed by medical decision (8%). The median TTP was 6.0 months (6.2 and 6.0 for LMS and LPS), while the median TTP-1 was 7.5 months (8.1 and 6.4 for LMS and LPS). Thirty three patients (52% 95%CI: 36-58, p = 0.674, odds of response = 1.1) had a GMR > 1.33 (LMS: 46%, 95%CI 26-67,odds = 0.85; LPS 56%, 95%CI 40-72, odds = 1.3).Overall, response rate (CR+PR) was 16% (24% for LMS and 12% for LPS). Overall, in LPS we observed 15/47 patients with GMR < 0.5 and 15/47 with GMR > 2. Among LMS patients, 9/26 had a GMR < 0.5 and 10/26 > 2. Between LPS six patients had a GMR > 5. Previous treatment had been based on anthracyclines and/or ifosfamide in 85% of patients (91% in LPS population). Conclusions: While the primary end point of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with T in comparison to previous therapy (GMR < 0.5 or > 2, the latter including some pts with a long TTP with T). Efforts are ongoing to assess the pathologic counterparts of such discrepancies. T seems to be selectively active in poorly understood subgroups, with a pattern of activity distinct from other available agents. Clinical trial information: 2012-005428-14.
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- 2022
141. Prevalence of ultra-rare undifferentiated round cells sarcoma of bone and soft tissue after genomic classification
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Emanuela Palmerini, Alberto Righi, Marta Sbaraglia, Elisa Carretta, Angelo Paolo Dei Tos, GIovanna Magagnoli, Marilena Cesari, Anna Paioli, Alessandra Longhi, Rossella Hakim, Piero Picci, Margherita Maioli, Stefania Cocchi, Katia Scotlandi, Davide Maria Donati, Toni Ibrahim, and Marco Gambarotti
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Cancer Research ,Oncology - Abstract
11559 Background: Over the last decade, the category of undifferentiated round cell sarcomas (URCS), defined by the absence of Ewing sarcoma-associated translocations, has emerged. Aim of this study was to assess prevalence of each entity and outcome after genomic classification. Methods: Ewing sarcoma and other URCS diagnosed between 1920 and 2020 were reviewed. All URCS with available material were analyzed with FISH, RT-qPCR and/or Archer FusionPlex Sarcoma Panel. Demographic and treatment were collected. Survival was analyzed in patients with available follow-up. Results: 1995 cases identified, 20 cases lacked material for further genetic analysis and were excluded. 1975 cases were classified as follows: 1925 Ewing sarcomas (97.47%), 25 CIC-rearranged sarcomas (1.27%), 16 BCOR-CCNB3 rearranged sarcomas (0.81%), 2 EWSR1-NFATC2 sarcoma (0.1%), one each as CIC-LEUTX and FUS-NFATC2 rearranged sarcoma (0.05% each), and 5 as unclassified URCS (0.25%). A different presentation according to tumor type was shown in 43/50 ultra-rare tumors (Table). Forty-one/50 cases had available follow-up: 20/41 patients underwent surgery, 14/41 surgery+radiotherapy, 6 radiotherapy only, and no local treatment for 1 patient. Chemotherapy was administrated to 36/41 patients (Ewing sarcoma drugs in 16/22 CIC-DUX-4 and 8/11 BCOR-CCNB3; osteosarcoma drugs in 2/11 BCOR-CCNB3, and doxorubicin/ifosfamide in 2/22 CIC-DUX4 and 2/5 URCS; not specified in 6 cases). The 3-years overall survival (OS) was 32.7%f for CIC-rearranged sarcomas (75% in localize disease, 7,7% for the advanced disease, p 0.0084), 81.8% for BCOR-CCNB3 sarcomas (87.5% localized, 66.7% advanced; p 0.0734), and 60% for URCS (p 0.057). 1 patient with CIC-LEUTX sarcoma presenting with metastases died 13 months from diagnosis, 1 patient with FUS-NFATC2 and 1 with EWSR1-NFATC2 rearrenged sarcomas were alive without disease at 8 and 5 years from onset. Conclusions: Prevalence of URCS characterized by a combination of morphologic observation ad molecular techniques is provided. The majority of the cases underwent surgery or surgery combined with radiotherapy, and Ewing-like chemotherapy. The survival difference among different entities underscores the need of accurate subclassification of round cell sarcomas. Novel drugs for CIC-DUX-4 sarcomas presenting with metastases are needed. [Table: see text]
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- 2022
142. Evidence for improvements to risk stratification in high-risk gastrointestinal stromal tumor patients
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Sabrina Rossi, Angelo Paolo Dei Tos, Giovanni Morana, Alessandra Greco, Cesare Ruffolo, Marco Massani, and Bruno Pauletti
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Risk stratification ,medicine ,High Risk Gastrointestinal Stromal Tumor ,business - Published
- 2018
143. Osteoblastoma-like osteosarcoma: high-grade or low-grade osteosarcoma?
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Piero Picci, Daniel Vanel, Dino Gibertoni, Angelo Paolo Dei Tos, Michael J. Klein, Marco Gambarotti, Alberto Righi, Gambarotti M., Dei Tos A.P., Vanel D., Picci P., Gibertoni D., Klein M.J., and Righi A.
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Adult ,Male ,musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Histology ,Adolescent ,Bone Neoplasms ,Kaplan-Meier Estimate ,Bone Neoplasm ,Disease-Free Survival ,World health ,Pathology and Forensic Medicine ,Metastasis ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Osteoblastoma ,osteosarcoma ,Humans ,Medicine ,In patient ,osteoblastoma ,Child ,neoplasms ,Grading (tumors) ,grading ,prognosis ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,Low grade osteosarcoma ,030220 oncology & carcinogenesis ,Cohort ,Osteosarcoma ,Female ,Radiology ,Neoplasm Grading ,business ,prognosi ,Human - Abstract
Aims: Osteoblastoma-like osteosarcoma is a rare variant of osteosarcoma (1% of all osteosarcomas), histologically similar to osteoblastoma. In the current World Health Organisation (WHO) classification, osteoblastoma-like osteosarcoma is classified within the group of conventional (high-grade) osteosarcomas. However, several published cases have been actually regarded as low-grade malignant tumours. As strict morphological criteria to distinguish between low- and high-grade lesions are not available, we reviewed our series of osteoblastoma-like osteosarcomas in the attempt to identify clinical and morphological features predictive of aggressiveness. Methods and results: We retrieved 15 cases of osteoblastoma-like osteosarcoma from the files of the Istituto Ortopedico Rizzoli. Patients received various treatments. Five patients developed metastasis and five patients developed local recurrences (all after incomplete surgery). Eleven patients were alive without disease, while four patients died of their disease. Statistical analysis revealed a statistically significant (P=0.048) lower disease-free survival in patients with areas of conventional (high-grade) osteosarcoma. Conclusions: With the important limitation of a small cohort of patients, the presence of areas of conventional (high-grade) osteosarcoma is the only parameter to predict the aggressiveness of osteoblastoma-like osteosarcoma.
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- 2018
144. mTOR pathway and somatostatin receptors expression intratumor-heterogeneity in ileal NETs
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Eugenio De Carlo, Giada Munari, Claudio Pasquali, Vittorina Zagonel, Matteo Fassan, Chiara Martini, Carlo Alberto Dal Pozzo, Francesca Bergamo, Roberto Vettor, Chiara Borga, Angelo Paolo Dei Tos, Anna Caterina Milanetto, Sabina Murgioni, Gianmaria Pennelli, Vincenza Guzzardo, Elisabetta Trevellin, and Umberto Cillo
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0301 basic medicine ,Gene isoform ,Cancer Research ,Endocrinology, Diabetes and Metabolism ,Neuroendocrine tumors ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Medicine ,PTEN ,Humans ,Receptors, Somatostatin ,PI3K/AKT/mTOR pathway ,biology ,Somatostatin receptor ,business.industry ,TOR Serine-Threonine Kinases ,Liver Neoplasms ,Ribosomal Protein S6 Kinases, 70-kDa ,medicine.disease ,MicroRNAs ,Neuroendocrine Tumors ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Immunohistochemistry ,business ,NODAL - Abstract
The knowledge of the molecular landscape of ileal neuroendocrine tumors (NETs) is affected by the lack of systematic studies investigating intra-tumoral heterogeneity. In this study, intra-tumoral heterogeneity was investigated in 27 primary ileal G1-NETs and their matched nodal and liver metastases in order to assess the tumor grading, the expression status of two somatostatin receptor isoforms (i.e. SSTR2A and SSTR5) and mTOR signaling dysregulation (ph-mTOR, ph-p70S6K, ph-4EBP1, PTEN and miR-21). Among the 27 G1 primary tumors, 4 shifted to G2 in the matched liver metastasis. Although mTOR activation was pretty consistent between primary and secondary malignancies, mTOR effectors (ph-p70S6K and ph-4EBP1) were overexpressed in matched liver metastases, whereas PTEN expression profile changed in only two cases. MiR-21 was significantly up-regulated in the metastatic setting. Although SSTRs expression was present in most of the primary tumors and matched metastasis, we found SSTR5 expression to be significantly increased in liver metastases. Notably, SSTRs expression was heterogeneous within the same lesions in most of the lesions. Overall, despite primary and metastatic ileal NETs show a similar molecular landscape, tumor grading and mTOR signaling pathway may diverge in the metastatic setting, thus affecting prognosis and treatment.
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- 2021
145. Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities
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Otto Visser, Alessandro Gronchi, Axel Le Cesne, Shreyaskumar Patel, Jean-Yves Blay, Annalisa Trama, Mrinal M. Gounder, Rick L. Haas, Andrew J. Wagner, Hans Gelderblom, Young-Joo Won, María Dolores López, Olivier Mir, Tomohiro Matsuda, Rafael Marcos-Gragera, Akira Kawai, Sylvie Bonvalot, Winette T. A. van der Graaf, Paolo G. Casali, Damon R. Reed, Christopher D.M. Fletcher, Robin L. Jones, Margaret von Mehren, Anna Maria Frezza, Piotr Rutkowski, Dario Callegaro, Suzanne George, Roberta Maestro, Jiwon Lim, Andrea Hayes-Jardon, Breelyn A. Wilky, Ru Ru Chun ju Chiang, Jayesh Desai, David G. Kirsch, Peter Hohenberger, Roberta Sanfilippo, Kevin B. Jones, David Thomas, Silvia Stacchiotti, Chandrajit P. Raut, Javier Martin Broto, Eugene S. Kleinerman, Dirk C. Strauss, Winan J. van Houdt, Abha A. Gupta, Mikael Eriksson, Judith V.M.G. Bovée, Angelo Paolo Dei Tos, Elizabeth H. Baldini, Albiruni Ryan Abdul Razak, George D. Demetri, Inga-Marie Schaefer, Bernd Kasper, Kirsten Sundby Hall, Marta Sbaraglia, Elisabeth G. Demicco, and William D. Tap
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Oncology ,Cancer Research ,medicine.medical_specialty ,sarcoma ,Consensus ,ultra-rare ,ultra‐rare ,Soft Tissue Neoplasms ,Disease ,registry ,Bone Sarcoma ,World health ,Article ,drug development ,incidence ,rarity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,business.industry ,Soft tissue sarcoma ,Incidence (epidemiology) ,Incidence ,Cancer ,Sarcoma ,medicine.disease ,Connective Tissue ,030220 oncology & carcinogenesis ,Epidemiologic data ,business - Abstract
Background Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. Methods The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. Results It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. Conclusions Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.
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- 2021
146. Selinexor versus doxorubicin in dedifferentiated liposarcoma PDXs: evidence of greater activity and apoptotic response dependent on p53 nuclear accumulation and survivin down‐regulation
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Sandro Pasquali, Monica Tortoreto, Calogero Lauricella, Gianpaolo Dagrada, Alessandro Gronchi, Roberta Sanfilippo, Silvia Stacchiotti, Marta Barisella, Chiara Colombo, Stefano Percio, Valentina Zuco, Mrinal M. Gounder, Paolo G. Casali, Rihan El Bezawy, Silvia Brich, Nadia Zaffaroni, and Angelo Paolo Dei Tos
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Male ,0301 basic medicine ,Cancer Research ,Survivin ,Down-Regulation ,Mice, Nude ,Selinexor ,Apoptosis ,lcsh:RC254-282 ,Dedifferentiated liposarcoma ,Doxorubicin ,PDX ,Primary cell culture ,XPO1 ,Mice ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,HMGA2 ,Downregulation and upregulation ,medicine ,Animals ,Humans ,STAT3 ,Nuclear export signal ,Cell Nucleus ,Antibiotics, Antineoplastic ,biology ,Chemistry ,Research ,Liposarcoma ,Cell Dedifferentiation ,Triazoles ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Xenograft Model Antitumor Assays ,Hydrazines ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Mdm2 ,Tumor Suppressor Protein p53 ,medicine.drug - Abstract
Background Dedifferentiated liposarcoma (DDLPS), a tumor that lacks effective treatment strategies and is associated with poor outcomes, expresses amplified MDM2 in the presence of wild-type p53. MDM2 ubiquitination of p53 facilitates its XPO1-mediated nuclear export, thus limiting p53 tumor suppressor functions. Consequently, nuclear export is a rational target in DDLPS. We directly compared the antitumor activity of the first-in class XPO1 inhibitor selinexor and doxorubicin, the standard front-line therapy in sarcomas, in DDLPS patient-derived xenografts (PDXs) and primary cell lines. Methods Drug activity was assessed in three PDXs (and two corresponding cell lines) established from the dedifferentiated component of primary untreated retroperitoneal DDLPS with myogenic (N = 2) and rhabdomyoblastic (N = 1) differentiation from patients who underwent surgery. These models were marked by amplification of MDM2, CDK4 and HMGA2 genes. Results Selinexor was moderately active in the three PDXs but achieved greater tumor response compared to doxorubicin (maximum tumor volume inhibition: 46–80 % vs. 37–60 %). The PDX harboring rhabdomyoblastic dedifferentiation showed the highest sensitivity to both agents. PDX response to selinexor and doxorubicin was not associated with the extent of MDM2 and CDK4 gene amplification. Interestingly, the most chemosensitive PDX model showed the lowest extent of HMGA2 amplification. Selinexor was also more efficient than doxorubicinin in inducing an apoptotic response in PDXs and cell lines. Consistently, an increased nuclear accumulation of p53 was seen in all selinexor-treated models. In addition, a time-dependent decrease of survivin expression, with an almost complete abrogation of the cytoplasmic anti-apoptotic pool of this protein, was observed as a consequence of the decreased acetylation/activation of STAT3 and the increased ubiquitination of nuclear survivin. Conclusions Selinexor showed a moderate antitumor activity in three DDLPS PDXs, which was, however, consistently higher than doxorubicin across all different models regardless the extent of MDM2 amplification and the histological differentiation. The depletion of survivin protein seems to significantly contribute to the induction of apoptosis through which selinexor exerts its antitumor activity.
- Published
- 2021
147. Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin
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Roberta Sanfilippo, Angelo Paolo Dei Tos, Carlo Morosi, Alessandro Gronchi, Paolo G. Casali, Elena Fumagalli, Chiara Fabbroni, Marta Barisella, Giovanni Fucà, Francesca Ligorio, and Paola Collini
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Liposarcoma ,Logistic regression ,chemotherapy ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Grading (tumors) ,Trabectedin ,business.industry ,Soft tissue sarcoma ,Hazard ratio ,grading ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Chemotherapy ,Grading ,Confidence interval ,030104 developmental biology ,liposarcoma ,030220 oncology & carcinogenesis ,soft tissue sarcoma ,Cohort ,trabectedin ,business ,medicine.drug - Abstract
Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94, adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.
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- 2021
148. Molecular profiling of appendiceal serrated lesions, polyps and mucinous neoplasms: a single-centre experience
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Claudia Mescoli, Salvatore Pucciarelli, Marta Sbaraglia, Gaya Spolverato, Antonio Sommariva, Giada Munari, Gianluca Businello, Elena Bellan, Angelo Paolo Dei Tos, Claudio Luchini, Matteo Fassan, Gianmaria Pennelli, Francesca Galuppini, Chiara Borga, Paola Mattiolo, Sara Lonardi, and Fotios Loupakis
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Adenoma ,DNA Mutational Analysis ,Appendiceal neoplasms ,medicine.disease_cause ,Polyps ,Tubular adenoma ,medicine ,PMS2 ,Biomarkers, Tumor ,Humans ,Pseudomyxoma peritonei ,neoplasms ,Aged ,Molecular pathology ,business.industry ,Serrated lesions ,General Medicine ,Biomarkers ,medicine.disease ,Prognosis ,Adenocarcinoma, Mucinous ,digestive system diseases ,MSH6 ,Gene Expression Regulation, Neoplastic ,Oncology ,Hyperplastic Polyp ,Dysplasia ,MSH2 ,Mutation ,KRAS ,business ,Original Article – Cancer Research ,Follow-Up Studies - Abstract
Purpose Non-neuroendocrine neoplasms of the appendix are a phenotypically heterogeneous group of lesions; a comprehensive molecular characterization of these tumors is still lacking. Methods A total of 52 samples taken from 49 patients was evaluated: 18 sessile serrated lesions (SSL; 3 with dysplasia), 2 high-grade tubular adenomas, 1 tubulo-villous adenoma,1 hyperplastic polyp, 18 low-grade appendiceal mucinous neoplasms (LAMN), 3 high-grade appendiceal mucinous neoplasms (HAMN) and 9 mucinous adenocarcinomas. Hotspot mutational profiling of the RNF43, SMAD4, KRAS, NRAS, BRAF and PIK3CA genes was performed. Expression of p53, MLH1, PMS2, MSH2, and MSH6 was evaluated by immunohistochemistry. Results KRAS was the most frequently mutated gene (53.9% of cases), followed by RNF43 (15.4%), and BRAF (13.5%). In particular: KRAS was mutated in 44.4% of adenocarcinomas, 66.7% of HAMNs, 61.1% of LAMNs, 53.3% of SSL without dysplasia and in 66.7% of SSL with dysplasia; RNF43 was mutated in 33.3% of adenocarcinomas, 66.7% of HAMNs, 11.1% of LAMNs and in 6.7% of SSL without dysplasia; BRAF was mutated in 11.1% of adenocarcinomas, 26.7% of SSL without dysplasia and in 5.6% of LAMNs. Only a case of high-grade tubular adenoma showed mismatch repair deficiency, while immunohistochemical expression of p53 was altered in 21.1% of cases. Conclusions The histological phenotypic similarities between appendicular mucinous lesions and serrated colon lesions do not reflect a similar genetic landscape. Mismatch repair deficiency is a rare event during appendiceal mucinous carcinogenesis.
- Published
- 2021
149. Lymph node core needle biopsy in lymphoproliferative disorders - Authors' reply to Al-Abbadi and colleagues
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Luca Dal Santo, Francesco Piazza, Marta Sbaraglia, Clara Bertuzzi, Marco Pizzi, Elena Sabattini, Pier Luigi Zinzani, Claudio Agostinelli, Alberto Friziero, Angelo Paolo Dei Tos, Luisa Santoro, Pizzi M., Agostinelli C., Santoro L., Sbaraglia M., Bertuzzi C., Dal Santo L., Friziero A., Piazza F., Zinzani P.L., Dei Tos A.P., and Sabattini E.
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Core needle ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Biopsy ,Lymph Node ,Lymphoproliferative disorders ,Lymphatic Metastasi ,Hematology ,General Medicine ,medicine.disease ,Lymphoproliferative Disorders ,medicine.anatomical_structure ,medicine ,Biopsy, Large-Core Needle ,business ,Lymph node ,Human - Published
- 2021
150. Detection of Molecular Residual Disease Using Personalized Circulating Tumor DNA Assay in Patients With Colorectal Cancer Undergoing Resection of Metastases
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Shruti Sharma, Meenakshi Malhotra, Giada Munari, Derrick Renner, Cosimo Rasola, Bernhard Zimmermann, Mario Domenico Rizzato, Alexey Aleshin, Allyson Koyen Malashevich, Vittorina Zagonel, Svetlana Shchegrova, Himanshu Sethi, Umberto Cillo, Solomon Moshkevich, S. Lonardi, Fotios Loupakis, Jonathon Sedgwick, Madiha Derouazi, Angelo Paolo Dei Tos, Pierluigi Pilati, Sabina Murgioni, Matteo Fassan, Marta Schirripa, Paul Billings, and Paola Biason
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Stage IV Colorectal Cancer ,Neoplasm, Residual ,Colorectal cancer ,Disease ,Resection ,Circulating Tumor DNA ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Original Reports ,medicine ,Humans ,In patient ,business.industry ,medicine.disease ,Prognosis ,030104 developmental biology ,Circulating tumor DNA ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,business ,Colorectal Neoplasms ,Biomarkers - Abstract
PURPOSE More than 50% of patients with stage IV colorectal cancer (metastatic colorectal cancer [mCRC]) relapse postresection. The efficacy of postoperative systemic treatment is limited in this setting. Thus, these patients would greatly benefit from the use of a reliable prognostic biomarker, such as circulating tumor DNA (ctDNA) to identify minimal or molecular residual disease (MRD). PATIENTS AND METHODS We analyzed a cohort of 112 patients with mCRC who had undergone metastatic resection with curative intent as part of the PREDATOR clinical trial. The study evaluated the prognostic value of ctDNA, correlating MRD status postsurgery with clinical outcomes by using a personalized and tumor-informed ctDNA assay (bespoke multiple PCR, next-generation sequencing assay). Postresection, systemic therapy was given to 39.2% of the patients at the discretion of the treating physician. RESULTS Postsurgical, MRD positivity was observed in 54.4% (61 of 112) of patients, of which 96.7% (59 of 61) progressed at the time of data cutoff (hazard ratio [HR]: 5.8; 95% CI, 3.5 to 9.7; P < .001). MRD-positive status was also associated with an inferior overall survival: HR: 16.0; 95% CI, 3.9 to 68.0; P < .001. At the time of analyses, 96% (49 of 51) of patients were alive in the MRD-negative arm compared with 52.4% (32 of 61) in the MRD-positive arm. Patients who did not receive systemic therapy and were MRD-negative in the combined ctDNA analysis at two time points had an overall survival of 100%. In the multivariate analysis, ctDNA-based MRD status was the most significant prognostic factor associated with disease-free survival (HR: 5.78; 95% CI, 3.34 to 10.0; P < .001). CONCLUSION This study confirms that in mCRC undergoing resection of metastases, postoperative MRD analysis is a strong prognostic biomarker. It holds promises for being implemented in clinical decision making, informing clinical trial design, and further translational research.
- Published
- 2021
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