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Article ; Online: In Defense of Neuroendocrine Tumor Trials.

Strosberg, Jonathan / Al-Toubah, Taymeyah / Cives, Mauro

JAMA oncology

2023 Volume 9, Issue 10, Page(s) 1463–1464

Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Journal Article
ISSN	2374-2445
ISSN (online)	2374-2445
DOI	10.1001/jamaoncol.2023.3392
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Article ; Online: Assessment of bone turnover markers and DXA parameters to predict bone metastasis progression during zoledronate treatment: a single-center experience.

D'Oronzo, Stella / Cives, Mauro / Lauricella, Eleonora / Stucci, Stefania / Centonza, Antonella / Gentile, Marica / Ostuni, Carmela / Porta, Camillo

Clinical and experimental medicine

2024 Volume 24, Issue 1, Page(s) 7

Abstract: Bone metastases (BM) are a serious cancer complication, potentially causing substantial morbidity. Among the clinical issues related to BM, there is the lack of specific tools for early diagnosis and prognosis. We explored whether combining bone turnover ...

Abstract	Bone metastases (BM) are a serious cancer complication, potentially causing substantial morbidity. Among the clinical issues related to BM, there is the lack of specific tools for early diagnosis and prognosis. We explored whether combining bone turnover markers (BTM) with dual-energy X-ray absorptiometry (DXA) assessment could identify early BM progression and risk of skeletal-related events (SREs) during zoledronate treatment. Before the initiation of zoledronate (T0) and after six months of treatment (T1), serum levels of five BTM were measured, and patients (N = 47) underwent DXA evaluation. Standard radiological imaging was performed to assess bone tumor response to medical anti-cancer treatment. High tumor burden in bone correlated with higher serum CTX (p = 0.007) and NTX (p = 0.005) at baseline. Low concentrations of OPG at T0 predicted BM progression with a sensitivity and specificity of 63% and 77%, respectively, when a cutoff of 5.2 pmol/l was used; such a predictive meaning was stronger in patients with lytic BM (sensitivity: 88%, specificity: 80%; p = 0.0006). As for the risk of SREs, we observed an association between low baseline OC (p = 0.04) and OPG (p = 0.08) and the onset of any-time SREs, whereas an increase in OPG over time was associated with reduced risk of on-study events (p = 0.03). Moreover, a statistically significant correlation emerged between low baseline lumbar T-score and femur BMD and on-study SREs (p < 0.001 in both instances). These findings suggest that addition of DXA to BTM dosage could help stratifying the risk of SREs at the time of BM diagnosis but does not enhance our capability of detecting bone progression, during zoledronate treatment.
MeSH term(s)	Humans ; Zoledronic Acid/therapeutic use ; Absorptiometry, Photon ; Bone Neoplasms/diagnostic imaging ; Bone Neoplasms/drug therapy ; Prognosis ; Bone Remodeling/physiology
Chemical Substances	Zoledronic Acid (6XC1PAD3KF)
Language	English
Publishing date	2024-01-19
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-023-01280-1
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Article ; Online: An update on Merkel cell carcinoma.

Sergi, Maria Chiara / Lauricella, Eleonora / Porta, Camillo / Tucci, Marco / Cives, Mauro

Biochimica et biophysica acta. Reviews on cancer

2023 Volume 1878, Issue 3, Page(s) 188880

Abstract: Merkel cell carcinoma (MCC) is a rare cancer of the skin characterized by a neuroendocrine phenotype and an aggressive clinical behavior. It frequently originates in sun-exposed body areas, and its incidence has steadily increased in the last three ... ...

Abstract	Merkel cell carcinoma (MCC) is a rare cancer of the skin characterized by a neuroendocrine phenotype and an aggressive clinical behavior. It frequently originates in sun-exposed body areas, and its incidence has steadily increased in the last three decades. Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) radiation exposure are the main causative agents of MCC, and distinct molecular features have been documented in virus-positive and virus-negative malignancies. Surgery remains the cornerstone of treatment for localized tumors, but even when integrated with adjuvant radiotherapy is able to definitively cure only a fraction of MCC patients. While characterized by a high objective response rate, chemotherapy is associated with a short-lasting benefit of approximately 3 months. On the other hand, immune checkpoint inhibitors including avelumab and pembrolizumab have demonstrated durable antitumor activity in patients with stage IV MCC, and investigations on their use in the neoadjuvant or adjuvant setting are currently underway. Addressing the needs of those patients who do not persistently benefit from immunotherapy is currently one of the most compelling unmet needs in the field, and multiple clinical trials of new tyrosine kinase inhibitors (TKIs), peptide receptor radionuclide therapy (PRRT), therapeutic vaccines, immunocytokines as well as innovative forms of adoptive cellular immunotherapies are under clinical scrutiny at present.
MeSH term(s)	Humans ; Carcinoma, Merkel Cell/drug therapy ; Carcinoma, Merkel Cell/pathology ; Skin Neoplasms/drug therapy ; Immunotherapy/adverse effects ; Immunotherapy, Adoptive/adverse effects ; Combined Modality Therapy
Language	English
Publishing date	2023-03-11
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2918802-7
ISSN	1879-2561 ; 0304-419X
ISSN (online)	1879-2561
ISSN	0304-419X
DOI	10.1016/j.bbcan.2023.188880
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Article ; Online: Gastroenteropancreatic Neuroendocrine Tumors.

Cives, Mauro / Strosberg, Jonathan R

CA: a cancer journal for clinicians

2018 Volume 68, Issue 6, Page(s) 471–487

Abstract: Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in ... ...

Abstract	Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably. Somatostatin analogs have demonstrated both antisecretory and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177 dotatate (
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Cytoreduction Surgical Procedures/methods ; Humans ; Incidence ; Intestinal Neoplasms/diagnosis ; Intestinal Neoplasms/epidemiology ; Intestinal Neoplasms/etiology ; Intestinal Neoplasms/therapy ; Medical Oncology/methods ; Medical Oncology/standards ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/epidemiology ; Neuroendocrine Tumors/etiology ; Neuroendocrine Tumors/therapy ; Octreotide/administration & dosage ; Octreotide/analogs & derivatives ; Organometallic Compounds/administration & dosage ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/epidemiology ; Pancreatic Neoplasms/etiology ; Pancreatic Neoplasms/therapy ; Patient Selection ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/epidemiology ; Stomach Neoplasms/etiology ; Stomach Neoplasms/therapy ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor ; Organometallic Compounds ; (177lutetium-DOTA(O)Tyr3)octreotate (AE221IM3BB) ; Octreotide (RWM8CCW8GP)
Language	English
Publishing date	2018-10-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603553-x
ISSN	1542-4863 ; 0007-9235
ISSN (online)	1542-4863
ISSN	0007-9235
DOI	10.3322/caac.21493
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Article ; Online: Novel immunotherapy strategies for treatment of neuroendocrine neoplasms.

Al-Toubah, Taymeyah / Cives, Mauro / Strosberg, Jonathan

Translational gastroenterology and hepatology

2020 Volume 5, Page(s) 54

Abstract: Neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are a heterogeneous family of neoplasms. Well-differentiated tumors are often slow growing and characterized by low tumor mutational burden. Poorly differentiated NECs are aggressive, with ...

Abstract	Neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are a heterogeneous family of neoplasms. Well-differentiated tumors are often slow growing and characterized by low tumor mutational burden. Poorly differentiated NECs are aggressive, with an increased mutational burden and higher propensity to express PD-L1. While the therapeutic landscape for neuroendocrine neoplasms (NENs) has evolved substantially over the past decade, immunotherapy has been unexplored in NENs until recently. Checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 agents, bi-specific tumor-targeting antibodies, and chimeric antigen receptor (CAR) T-cell therapy are examples of treatments that have demonstrated efficacy in other cancers and have recently been investigated in NENs. This review examines the immune landscape of NENs in detail, summarizes recent clinical study results, and discusses potential future directions for immunotherapy.
Language	English
Publishing date	2020-10-05
Publishing country	China
Document type	Journal Article ; Review
ISSN	2415-1289
ISSN (online)	2415-1289
DOI	10.21037/tgh.2019.12.18
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Article: Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors.

Cives, Mauro / Pelle', Eleonora / Strosberg, Jonathan

Journal of clinical medicine

2020 Volume 9, Issue 11

Abstract: Treatment options for neuroendocrine tumors (NETs) and carcinomas (NECs) are expanding. Early-phase studies have shown preliminary evidence of the antitumor activity of alpha-emitting peptide receptor radionuclide therapy (PRRT), and novel radiopeptides ... ...

Abstract	Treatment options for neuroendocrine tumors (NETs) and carcinomas (NECs) are expanding. Early-phase studies have shown preliminary evidence of the antitumor activity of alpha-emitting peptide receptor radionuclide therapy (PRRT), and novel radiopeptides incorporating somatostatin receptor antagonists (rather than agonists) have been developed. Several tyrosine kinase inhibitors (TKIs) with antiangiogenic potential have been evaluated in patients with NETs, including lenvatinib, axitinib, cabozantinib and pazopanib. Recently, two phase 3 clinical trials have demonstrated the efficacy and safety of surufatinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, fibroblast growth factor receptor (FGFR)-1 and colony stimulating factor-1 receptor (CSF-1R), in patients with pancreatic and extra-pancreatic NETs. Multiple clinical trials of combination immunotherapy have been recently completed, but interpretation of the results is hampered by small samples sizes and discordant outcomes. This review summarizes recent data on emerging treatments for neuroendocrine neoplasms.
Language	English
Publishing date	2020-11-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm9113655
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Article: Angiogenesis in NENs, with a focus on gastroenteropancreatic NENs: from biology to current and future therapeutic implications.

Lauricella, Eleonora / Mandriani, Barbara / Cavallo, Federica / Pezzicoli, Gaetano / Chaoul, Nada / Porta, Camillo / Cives, Mauro

Frontiers in oncology

2022 Volume 12, Page(s) 957068

Abstract: Neuroendocrine neoplasms (NENs) are highly vascularized malignancies arising from cells of the diffuse neuroendocrine system. An intricated cross-talk exists between NEN cells and the tumor microenvironment, and three main molecular circuits (VEGF/VEGFR ... ...

Abstract	Neuroendocrine neoplasms (NENs) are highly vascularized malignancies arising from cells of the diffuse neuroendocrine system. An intricated cross-talk exists between NEN cells and the tumor microenvironment, and three main molecular circuits (VEGF/VEGFR pathway, FGF-dependent signaling and PDGF/PDGFR axis) have been shown to regulate angiogenesis in these neoplasms. Multiple randomized trials have investigated antiangiogenic agents over the past two decades, and sunitinib is currently approved for the treatment of advanced, progressive, G1/G2 pancreatic NENs. In recent years, two phase III clinical trials have demonstrated the efficacy and safety of surufatinib, a multi-tyrosine kinase angioimmune inhibitor, in patients with well-differentiated pancreatic and extrapancreatic NENs, and two studies of this agent are currently underway in Europe and US. The HIF-2α inhibitor belzutifan has recently received regulatory approval for the treatment of tumors arising in the context of Von-Hippel Lindau syndrome including pancreatic NENs, and a study of this drug in patients with sporadic tumors is presently ongoing. Combinations of antiangiogenic agents with chemotherapeutics and targeted drugs have been tested, with accumulating toxicities being a matter of concern. The potential of antiangiogenic agents in fine-tuning the immune microenvironment of NENs to enhance the activity of immune checkpoint inhibitors has been only partially elucidated, and further research should be carried out at this regard. Here, we review the current understanding of the biology of angiogenesis in NENs and provide a summary of the latest clinical investigations on antiangiogenic drugs in this malignancy.
Language	English
Publishing date	2022-08-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.957068
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Article ; Online: The impact of COVID-19 on the management of neuroendocrine tumors (NETS): An international NET CONNECT survey of NET patients and healthcare professionals treating net patients.

Cives, Mauro / Hernando, Jorge / Lamarca, Angela / Bouvier, Catherine / Caplin, Martyn / Pavel, Marianne

Journal of neuroendocrinology

2022 Volume 34, Issue 10, Page(s) e13196

Abstract: The COVID-19 outbreak has added complexity in the management of patients with neuroendocrine tumors (NETs). Little information is currently available regarding the real impact of the pandemic in current practice. The present study aimed to capture ... ...

Abstract	The COVID-19 outbreak has added complexity in the management of patients with neuroendocrine tumors (NETs). Little information is currently available regarding the real impact of the pandemic in current practice. The present study aimed to capture patients' and healthcare professionals' experiences on how the NET management has changed during the pandemic and how it should be modified in a foreseeable post-pandemic environment. Physicians and nurses working in ENETS Centers of Excellence or other hospitals with high volume of NET patients (n = 48), as well as NET patients residing worldwide (n = 353), were asked to respond to two online anonymous surveys addressing different aspects of NET care. Deferred diagnoses, delayed surveillance procedures and postponed elective surgeries were among the main negative consequences of the COVID-19 outbreak according to 40%, 54% and 46% of healthcare professionals (HPs) respectively. Somatostatin analogs were increasingly used as bridging strategy for delaying surgery based on the views of 31% of HPs and were self-injected or delivered by home care services more frequently than before the initiation of the pandemic (53% of patients during the pandemic vs. 44% before the pandemic). Multidisciplinary tumor boards kept their usual schedule according to 58% of HPs, but were held virtually in the 77% of cases. The contact with healthcare professionals was maintained by remote methods more often than in the past (69% of patients), but only 34% of patients (59% among subjects < 41 years) would prefer telemedicine to face-to-face consultations in the future. New health policy measures should guarantee the highest standard of treatment to NET patients, regardless of the trajectory followed by the COVID-19 pandemic in the next months. Pros and cons of telemedicine should be carefully weighted before systematic implementation.
MeSH term(s)	Humans ; COVID-19 ; Pandemics ; SARS-CoV-2 ; Neuroendocrine Tumors/therapy ; Telemedicine/methods
Language	English
Publishing date	2022-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1007517-3
ISSN	1365-2826 ; 0953-8194
ISSN (online)	1365-2826
ISSN	0953-8194
DOI	10.1111/jne.13196
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Article: Adamantinoma-like Ewing sarcoma of the salivary glands: a case report and systematic literature review.

Lauricella, Eleonora / Manicone, Anna / Cavallo, Federica / Dagrada, Gian Paolo / Centonze, Giovanni / Bertulli, Rossella / Quattrone, Pasquale / Porta, Camillo / Cives, Mauro

Therapeutic advances in medical oncology

2023 Volume 15, Page(s) 17588359231165979

Abstract: Adamantinoma-like Ewing sarcoma (ALES) of the salivary glands is an exceedingly rare malignancy defined by the t(11,22) ...

Abstract	Adamantinoma-like Ewing sarcoma (ALES) of the salivary glands is an exceedingly rare malignancy defined by the t(11,22)
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Case Reports
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359231165979
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Article ; Online: Treatment Strategies for Metastatic Neuroendocrine Tumors of the Gastrointestinal Tract.

Cives, Mauro / Strosberg, Jonathan

Current treatment options in oncology

2017 Volume 18, Issue 3, Page(s) 14

Abstract: Opinion statement: The therapeutic landscape of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) has evolved significantly in recent years. Current and emerging treatment options include somatostatin analogs, radiolabeled somatostatin analogs, ... ...

Abstract	Opinion statement: The therapeutic landscape of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) has evolved significantly in recent years. Current and emerging treatment options include somatostatin analogs, radiolabeled somatostatin analogs, the mTOR inhibitor everolimus, and the tyrosine kinase inhibitor sunitinib. Although high-quality data from phase III trials are lacking, cytotoxic agents are commonly used for the treatment of poorly differentiated neuroendocrine carcinomas and well-differentiated NETs originating in the pancreas. Hepatic-directed therapies are recommended for patients with slow-growing, liver-predominant disease but have never been compared to systemic agents. Telotristat ethyl, a novel serotonin synthesis inhibitor, has recently demonstrated efficacy in palliating diarrhea in patients with poorly controlled carcinoid syndrome. In the absence of definite predictive biomarkers, therapeutic decisions in most cases rely on clinical and pathological criteria. However, navigating the current therapeutic algorithm may be challenging, and future trials need to address several important questions: what is the best sequence of treatment? Is there a role for combination therapies in GEP-NETs? Are neoadjuvant, adjuvant, or maintenance strategies safe and effective? Do all NET patients require active treatment? What new molecular targets can be clinically exploited? A tight integration between basic and clinical research is needed to further advance the field of NETs.
MeSH term(s)	Algorithms ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Clinical Decision-Making ; Clinical Trials as Topic ; Combined Modality Therapy ; Gastrointestinal Neoplasms/metabolism ; Gastrointestinal Neoplasms/pathology ; Gastrointestinal Neoplasms/therapy ; Humans ; Intestinal Neoplasms/metabolism ; Intestinal Neoplasms/pathology ; Intestinal Neoplasms/therapy ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors/metabolism ; Neuroendocrine Tumors/pathology ; Neuroendocrine Tumors/therapy ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/therapy ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/pathology ; Stomach Neoplasms/therapy ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057351-0
ISSN	1534-6277 ; 1527-2729
ISSN (online)	1534-6277
ISSN	1527-2729
DOI	10.1007/s11864-017-0461-5
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