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Article: The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives.

Bracigliano, Alessandra / Marretta, Antonella Lucia / Guerrera, Luigi Pio / Simioli, Roberto / Clemente, Ottavia / Granata, Vincenza / Minopoli, Anita / Della Vittoria Scarpati, Giuseppina / Picozzi, Fernanda / Cannella, Lucia / Pizzolorusso, Antonio / Di Gennaro, Francesca / Tafuto, Roberto / Sarno, Maria Rosaria / Cavalcanti, Ernesta / Ribera, Dario / Tafuto, Salvatore

Pharmaceuticals (Basel, Switzerland)

2024 Volume 17, Issue 3

Abstract: Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable ... ...

Abstract	Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable somatic alterations in at least one of the known susceptibility genes can be detected. Therefore, about 3/4 of all PPGL patients can be assigned to one of the three molecular clusters that have been identified in the last years with difference in the underlying pathogenetic mechanisms, biochemical phenotype, metastatic potential, and prognosis. While surgery represents the mainstay of treatment for localized PPGLs, several therapeutic options are available in advanced and/or metastatic setting. However, only few of them hinge upon prospective data and a cluster-oriented approach has not yet been established. In order to render management even more personalized and improve the prognosis of this molecularly complex disease, it is undoubtable that genetic testing for germline mutations as well as genome profiling for somatic mutations, where available, must be improved and become standard practice. This review summarizes the current evidence regarding diagnosis and treatment of PPGLs, supporting the need of a more cluster-specific approach in clinical practice.
Language	English
Publishing date	2024-03-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph17030354
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Article: Response to Peptide Receptor Radionuclide Therapy in Pheocromocytomas and Paragangliomas: A Systematic Review and Meta-Analysis.

Marretta, Antonella Lucia / Ottaiano, Alessandro / Iervolino, Domenico / Bracigliano, Alessandra / Clemente, Ottavia / Di Gennaro, Francesca / Tafuto, Roberto / Santorsola, Mariachiara / Lastoria, Secondo / Tafuto, Salvatore

Journal of clinical medicine

2023 Volume 12, Issue 4

Abstract: Introduction: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established.: ... ...

Abstract	Introduction: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established. Background: A search of peer-reviewed and English articles reporting on 177Lu-DOTATATE and 90Y-DOTATOC efficacy was performed through Medline and Scopus. A subsequent meta-analysis was performed to evaluate the pooled effect size on disease control rate (DCR) with PRRT. Secondary endpoints were description of patients' genetic characteristics, hematologic toxicity, and time-to-outcome. The pooled effect was estimated with both a mixed-effects model and a random-effects model. Results: Twelve studies met the criteria for this meta-analysis: ten with 177Lu- and two with 90Y-PRRTs (213 patients). The largest one included 46 patients. Median ages ranged from 32.5 to 60.4 years. When reported, mutations of SDHB were the most frequent genetic alterations. The pooled DCRs were 0.83 (95% CI: 0.75-0.88) and 0.76 (95% CI: 0.56-0.89) for 177Lu- and 90Y-PRRT, respectively. The pooled DCR for PRRT was 0.81 (95% CI: 0.74-0.87). Conclusions: We report an updated and solid estimate of DCR achieved with 177Lu- and 90Y-PRRT in PCCs and PGLs, showing that these therapies can be considered in the multidisciplinary treatment of PCCs and PGLs as alternatives to I-131 MIBG and chemotherapy.
Language	English
Publishing date	2023-02-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12041494
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Article ; Online: The Impact of O6-Methylguanine-DNA Methyltransferase (

Cannella, Lucia / Della Monica, Rosa / Marretta, Antonella Lucia / Iervolino, Domenico / Vincenzi, Bruno / De Chiara, Anna Rosaria / Clemente, Ottavia / Buonaiuto, Michela / Barretta, Maria Luisa / Di Mauro, Annabella / Di Marzo, Massimiliano / Guida, Michele / Badalamenti, Giuseppe / Chiariotti, Lorenzo / Tafuto, Salvatore

Cells

2023 Volume 12, Issue 12

Abstract: Dacarbazine is an important drug in the therapeutic landscape of leiomyosarcoma (LMS). Alkylating agents are subjected to resistance mechanisms based on anti-apoptotic pathways and repair mechanisms, including the DNA repair enzyme O6-methylguanine-DNA ... ...

Abstract	Dacarbazine is an important drug in the therapeutic landscape of leiomyosarcoma (LMS). Alkylating agents are subjected to resistance mechanisms based on anti-apoptotic pathways and repair mechanisms, including the DNA repair enzyme O6-methylguanine-DNA methyltransferase (
MeSH term(s)	Humans ; Antineoplastic Agents, Alkylating/pharmacology ; Antineoplastic Agents, Alkylating/therapeutic use ; Brain Neoplasms/pathology ; Dacarbazine/therapeutic use ; DNA ; DNA Methylation/genetics ; DNA Modification Methylases/genetics ; DNA Modification Methylases/therapeutic use ; DNA Repair Enzymes/genetics ; Leiomyosarcoma/drug therapy ; Leiomyosarcoma/genetics ; Methyltransferases/genetics ; Retrospective Studies ; Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Tumor Suppressor Proteins/genetics ; Middle Aged
Chemical Substances	Antineoplastic Agents, Alkylating ; Dacarbazine (7GR28W0FJI) ; DNA (9007-49-2) ; DNA Modification Methylases (EC 2.1.1.-) ; DNA Repair Enzymes (EC 6.5.1.-) ; Methyltransferases (EC 2.1.1.-) ; MGMT protein, human (EC 2.1.1.63) ; O-(6)-methylguanine (9B710FV2AE) ; Temozolomide (YF1K15M17Y) ; Tumor Suppressor Proteins
Language	English
Publishing date	2023-06-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12121635
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Article ; Online: The Complex Management of the Breast Angiosarcoma: A Retrospective Study.

Cannella, Lucia / Perri, Francesco / Clemente, Ottavia / von Arx, Claudia / Pizzolorusso, Antonio / Di Bonito, Maurizio / Bracigliano, Alessandra / Di Marzo, Massimiliano / Della Vittoria Scarpati, Giuseppina / De Chiara, Annarosaria / Tafuto, Salvatore

Oncology

2022 Volume 101, Issue 4, Page(s) 234–239

Abstract: Background/aim: Breast angiosarcoma is a rare and aggressive disease with a poor prognosis. Two subtypes have been identified: primary angiosarcoma (PBA) and secondary breast angiosarcoma (SBA). In this retrospective analysis, we describe and compare ... ...

Abstract	Background/aim: Breast angiosarcoma is a rare and aggressive disease with a poor prognosis. Two subtypes have been identified: primary angiosarcoma (PBA) and secondary breast angiosarcoma (SBA). In this retrospective analysis, we describe and compare our institute experience with the data existing in the literature. Materials and methods: We included in our analysis 29 patients who received a diagnosis of PBA or SBA between 2006 and 2019. Results: All patients received surgery as frontline treatment, but only 6 patients underwent to adjuvant treatment. Neoadjuvant chemotherapy was administered 2 patients. The preferred chemotherapeutic regimen was taxanes with or without gemcitabine and associated with anthracyclines. A lower median RFS and OS were reported in patients with PBA compared to those with SBA, but the difference observed was not statistically significant. Patients with PBA had a lower median age at the diagnosis (38 vs. 75). Conclusion: In our analysis, we have shown a lower median RFS and OS in patients with PBA compared with those with SBA, and a significantly younger age at diagnosis in patients affected by PBA.
MeSH term(s)	Humans ; Female ; Hemangiosarcoma/drug therapy ; Retrospective Studies ; Breast Neoplasms/drug therapy ; Breast Neoplasms/surgery ; Antibiotics, Antineoplastic
Chemical Substances	Antibiotics, Antineoplastic
Language	English
Publishing date	2022-12-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	250101-6
ISSN	1423-0232 ; 0030-2414
ISSN (online)	1423-0232
ISSN	0030-2414
DOI	10.1159/000525146
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Article: Selinexor and the Selective Inhibition of Nuclear Export: A New Perspective on the Treatment of Sarcomas and Other Solid and Non-Solid Tumors.

Marretta, Antonella Lucia / Di Lorenzo, Giuseppe / Ribera, Dario / Cannella, Lucia / von Arx, Claudia / Bracigliano, Alessandra / Clemente, Ottavia / Tafuto, Roberto / Pizzolorusso, Antonio / Tafuto, Salvatore

Pharmaceutics

2021 Volume 13, Issue 9

Abstract: Nucleocytoplasmic transport has been found dysregulated in many types of cancer and is often described as a poor prognostic factor. Specifically, Exportin-1 (XPO1) has been found overexpressed in many tumors and has become an attractive target in ... ...

Abstract	Nucleocytoplasmic transport has been found dysregulated in many types of cancer and is often described as a poor prognostic factor. Specifically, Exportin-1 (XPO1) has been found overexpressed in many tumors and has become an attractive target in molecular oncology and therapeutics development. The selective inhibitor of nuclear export, Selinexor, is one of the most scientifically interesting drugs that targets XPO1 in clinical development. In this review, we summarized the most relevant preclinical and clinical results achieved for non-solid tumors, sarcomas, and other kind of solid tumors.
Language	English
Publishing date	2021-09-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13091522
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Article ; Online: Aberrant Expression of Long Non Coding RNA HOTAIR and De-Regulation of the Paralogous 13 HOX Genes Are Strongly Associated with Aggressive Behavior of Gastro-Entero-Pancreatic Neuroendocrine Tumors.

Di Mauro, Annabella / Scognamiglio, Giosuè / Aquino, Gabriella / Cerrone, Margherita / Liguori, Giuseppina / Clemente, Ottavia / Di Bonito, Maurizio / Cantile, Monica / Botti, Gerardo / Tafuto, Salvatore / Tatangelo, Fabiana

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of ... ...

Abstract	Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Homeobox ; Humans ; Intestinal Neoplasms/genetics ; Intestinal Neoplasms/pathology ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; RNA, Long Noncoding/genetics ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Up-Regulation
Chemical Substances	HOTAIR long untranslated RNA, human ; RNA, Long Noncoding
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22137049
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Article ; Online: The psychological impact of COVID-19 pandemic on patients with neuroendocrine tumors: Between resilience and vulnerability.

Lauricella, Eleonora / Cives, Mauro / Bracigliano, Alessandra / Clemente, Ottavia / Felici, Valentina / Lippolis, Rossella / Amoruso, Brunella / Pelle', Eleonora / Mandriani, Barbara / Esposto, Chiara / Forte, Cira / Perri, Francesco / Porta, Camillo / Tafuto, Salvatore

Journal of neuroendocrinology

2021 Volume 33, Issue 10, Page(s) e13041

Abstract: The COVID-19 pandemic has added another layer of complexity to the fears of patients with neuroendocrine tumors (NETs). Little is known regarding the psychological impact of the COVID-19 outbreak on patients with gastroenteropancreatic or ... ...

Abstract	The COVID-19 pandemic has added another layer of complexity to the fears of patients with neuroendocrine tumors (NETs). Little is known regarding the psychological impact of the COVID-19 outbreak on patients with gastroenteropancreatic or bronchopulmonary (BP) NETs. We longitudinally surveyed the mental symptoms and concerns of NET patients during the plateau phase of the first (W1) and second epidemic waves (W2) in Italy. Seven specific constructs (depression, anxiety, stress, health-related quality of life, NET-related quality of life, patient-physician relationship, psychological distress) were investigated using validated screening instruments, including DASS-21, EORTC QLQ-C30, EORTC QLQ GI.NET21, PDRQ9 and IES-R. We enrolled 197 patients (98 males) with a median age of 62 years. The majority of the patients had G1/G2 neoplasms. Some 38% of the patients were on active treatment. At W1, the prevalence of depression, anxiety and stress was 32%, 36% and 26% respectively. The frequency of depression and anxiety increased to 38% and 41% at W2, whereas no modifications were recorded in the frequency of stress. Poor educational status was associated with higher levels of anxiety at both W1 (odds ratio [OR] = 1.33 ± 0.22; p = .07) and W2 (OR = 1.45 ± 0.26; p = .03). Notably, post-traumatic stress symptoms were observed in the 58% of the patients, and both single marital status (OR = 0.16, 95% confidence interval [CI] = 0.06-0.48; p = .0009) and low levels of formal education (OR = 0.47, 95% CI = 0.23-0.99; p = .05) predicted their occurrence. No significant deteriorations of health-related quality of life domains were observed from W1 to W2. High patient care satisfaction was documented despite the changes in health systems resource allocation. NET patients have an increased risk of developing post-traumatic stress symptoms as result of the COVID-19 pandemic. Specific screening measures and psychological interventions should be implemented in NET clinics to prevent, recognize and treat mental distress in this vulnerable population.
Language	English
Publishing date	2021-09-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1007517-3
ISSN	1365-2826 ; 0953-8194
ISSN (online)	1365-2826
ISSN	0953-8194
DOI	10.1111/jne.13041
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Article ; Online: Malignant Sinonasal Tumors: Update on Histological and Clinical Management.

Bracigliano, Alessandra / Tatangelo, Fabiana / Perri, Francesco / Di Lorenzo, Giuseppe / Tafuto, Roberto / Ottaiano, Alessandro / Clemente, Ottavia / Barretta, Maria Luisa / Losito, Nunzia Simona / Santorsola, Mariachiara / Tafuto, Salvatore

Current oncology (Toronto, Ont.)

2021 Volume 28, Issue 4, Page(s) 2420–2438

Abstract: Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define ... ...

Abstract	Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define pathologic features and possible treatment strategies. From a diagnostic point of view, it is mandatory to have high expertise and perform an immunohistochemical assessment to distinguish between different histotypes. Due to the extreme rarity of these neoplasms, there are no standard and evidence-based therapeutic strategies, lacking prospective and large clinical trials. In fact, most studies are retrospective analyses. Surgery represents the mainstay of treatment of TuNSs for small and localized tumors allowing complete tumor removal. Locally advanced lesions require more demolitive surgery that should be always followed by adjuvant radio- or chemo-radiotherapy. Recurrent/metastatic disease requires palliative chemo- and/or radiotherapy. Many studies emphasize the role of specific genes mutations in the development of TuNSs like mutations in the exons 4-9 of the TP53 gene, in the exon 9 of the PIK3CA gene and in the promoter of the TERT gene. In the near future, this genetic assessment will have new therapeutic implications. Future improvements in the understanding of the etiology, biology, and clinical features of TuNSs are warranted to improve their management.
MeSH term(s)	Humans ; Nasal Cavity ; Paranasal Sinus Neoplasms/etiology ; Paranasal Sinus Neoplasms/genetics ; Paranasal Sinuses ; Prospective Studies ; Retrospective Studies
Language	English
Publishing date	2021-07-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol28040222
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Article ; Online: Is immunotherapy in the future of therapeutic management of sarcomas?

Clemente, Ottavia / Ottaiano, Alessandro / Di Lorenzo, Giuseppe / Bracigliano, Alessandra / Lamia, Sabrina / Cannella, Lucia / Pizzolorusso, Antonio / Di Marzo, Massimiliano / Santorsola, Mariachiara / De Chiara, Annarosaria / Fazioli, Flavio / Tafuto, Salvatore

Journal of translational medicine

2021 Volume 19, Issue 1, Page(s) 173

Abstract: Sarcomas are rare, ubiquitous and heterogeneous tumors usually treated with surgery, chemotherapy, target therapy, and radiotherapy. However, 25-50% of patients experience local relapses and/or distant metastases after chemotherapy with an overall ... ...

Abstract	Sarcomas are rare, ubiquitous and heterogeneous tumors usually treated with surgery, chemotherapy, target therapy, and radiotherapy. However, 25-50% of patients experience local relapses and/or distant metastases after chemotherapy with an overall survival about 12-18 months. Recently, immuno-therapy has revolutionized the cancer treatments with initial indications for non-small cell lung cancer (NSCLC) and melanoma (immune-checkpoint inhibitors).Here, we provide a narrative review on the topic as well as a critical description of the currently available trials on immunotherapy treatments in patients with sarcoma. Given the promising results obtained with anti-PD-1 monoclonal antibodies (pembrolizumab and nivolumab) and CAR-T cells, we strongly believe that these new immunotherapeutic approaches, along with an innovative characterization of tumor genetics, will provide an exciting opportunity to ameliorate the therapeutic management of sarcomas.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung ; Humans ; Immunotherapy ; Lung Neoplasms ; Neoplasm Recurrence, Local ; Sarcoma/therapy
Language	English
Publishing date	2021-04-26
Publishing country	England
Document type	Journal Article ; Review
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-021-02829-y
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Article: Effect of Octreotide Long-Acting Release on Tregs and MDSC Cells in Neuroendocrine Tumour Patients: A Pivotal Prospective Study.

von Arx, Claudia / Rea, Giuseppina / Napolitano, Maria / Ottaiano, Alessandro / Tatangelo, Fabiana / Izzo, Francesco / Petrillo, Antonella / Clemente, Ottavia / Di Sarno, Antonella / Botti, Gerardo / Scala, Stefania / Tafuto, Salvatore

Cancers

2020 Volume 12, Issue 9

Abstract: Octreotide long-acting repeatable (LAR) is largely used to treat functional and/or metastatic neuroendocrine neoplasms (NENs). Its effect in controlling carcinoid syndrome and partially reduce tumour burden is attributable to the ability of octreotide to ...

Abstract	Octreotide long-acting repeatable (LAR) is largely used to treat functional and/or metastatic neuroendocrine neoplasms (NENs). Its effect in controlling carcinoid syndrome and partially reduce tumour burden is attributable to the ability of octreotide to bind somatostatin receptors (SSTRs) on the tumour and metastasis, regulating growth hormone secretion and cell growth. Notably, SSTRs are also expressed, at different levels, on Tregs. Tregs, together with myeloid-derived suppressor cells (MDSCs), are key components in the anti-tumour immunoregulation. This is the first prospective study aimed to explore the impact of Octreotide (OCT) LAR on the immune system, with a particular focus on Tregs and MDSC cells. Here, we show that circulating Tregs are elevated in NENs patients compared to healthy donors and that treatment with OCT LAR significantly decrease the level of total Tregs and of the three functional Tregs populations: nTregs, eTregs and non-Tregs. Furthermore, OCT LAR treatment induces a functional impairment of the remaining circulating Tregs, significantly decreasing the expression of PD1, CTLA4 and ENTPD1. A trend in circulating MDSC cells is reported in patients treated with OCT LAR. The results reported here suggest that the effect of OCT LAR on Tregs could tip the balance of the patients' immune-system towards a durable anti-tumour immunosurveillance with consequent long-term control of the NENs disease.
Language	English
Publishing date	2020-08-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12092422
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