Introduction In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development.
Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with unique biological characteristics and complications, including thromboembolism. This systematic review evaluates the incidence, types, and clinical outcomes of venous thromboembolic events (VTEs) in NEN patients. Methods: A systematic search of PubMed, Scopus, and Embase was conducted to identify studies on TEs in NENs. Eligible studies included case reports, case series, and retrospective cohort studies reporting VTEs, including deep vein thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT). Data were extracted on tumor site, functionality, differentiation grade, and VTE type. Results: In total, 33 studies were included, comprising 26 case reports, 2 case series, and 5 retrospective cohort studies. VTE prevalence ranged from 7.5% to 33% across studies. The most common VTEs were DVT, PE, and portal vein thrombosis (PVT). A meta-analysis revealed a pooled VTE prevalence of 11.1% (95% CI: 9.07-13.53%). Pancreatic NENs exhibited the highest thrombotic burden, particularly in poorly differentiated and advanced-stage tumors. Functioning tumors, including glucagonomas and ACTH-secreting NENs, were strongly associated with VTEs, potentially related to their systemic effects on coagulation and inflammation. Conclusions: Venous thromboembolism is a significant complication in NEN patients, especially in advanced or poorly differentiated tumors. Early detection and targeted management are critical for improving outcomes. Further investigations are required to clarify the mechanisms underlying thromboembolism in NENs and to develop optimized prophylactic and therapeutic strategies tailored to this patient population.
Non-metastatic neuroendocrine carcinoma of the cervix (NECC) is a rare and aggressive disease. Lacking prospective studies, the optimal multimodal treatment approach has not yet been clearly defined. This study aims to assess the clinical outcomes of patients with non-metastatic NECC treated with surgery and (neo)adjuvant chemotherapy, according to pathologic prognostic factors and multimodal treatments received. We retrospectively examined data from patients with non-metastatic NECC candidate to receive surgery and (neo)adjuvant chemotherapy and discussed at the European Institute of Oncology’s Multidisciplinary Neuroendocrine Tumor Board, between January 2003 and December 2021. Primary endpoints were event-free survival and overall survival. A total of 27 consecutive patients were evaluated, 15 with early stage NECC and 12 with a locally advanced NECC. Eight patients received neoadjuvant and 19 adjuvant platinum-based chemotherapy; 14 received adjuvant pelvic radiotherapy, half with external-beam radiation therapy alone, and half combined with brachytherapy. No patients progressed or relapsed during (neo)adjuvant chemotherapy. The median event-free survival was 21.1 months and the median overall survival was 33.0 months. Pathological FIGO stage ≥ IIB, adjuvant external-beam radiation therapy with or without brachytherapy emerged as significant and independent prognostic factors for event-free survival. Brachytherapy was also prognostic for overall survival. Non-metastatic NECC requires a multimodal approach, mainly weighted on the FIGO stage. The addition of brachytherapy should be considered, especially in patients with locally advanced disease. Because of the scarcity of robust clinical data, treatment strategy should be discussed in multidisciplinary board, taking into account patient.
Neuroendocrine tumors (NETs) are more commonly slow-growing, therefore patients often receive chronic systemic therapies for tumor growth control and preservation of quality of life. Metronomic chemotherapy (mCT) is in line with this goal as it leads to stabilization of tumor growth over time without severe systemic toxicity. This is a retrospective analysis of patients with metastatic NETs receiving metronomic capecitabine (mCAP) or temozolomide (mTEM), at a NET-referral center. The aims of the study were to explore activity and safety of mCT and relationships between some characteristics of the patient population and clinical outcomes. Among a total of 67 patients with metastatic well or moderately differentiated (W/M-D) NETs, mostly gastroenteropancreatic (GEP) and nonfunctioning, 1.2 years (95% CI: 0.8-1.8) median progression-free survival (mPFS), and 3.0 years (95% CI: 2.3-4.9) median overall survival (mOS) were observed. Disease control rate was 85%. Grade 3 adverse events occurred in 15% of patients in mCAP and 13% in mTEM, and were mostly hematological and gastrointestinal. At univariate and multivariate analysis none of the variables analyzed (treatment regimen, sex, age at diagnosis, site of primary tumor and metastases, number of previous mCT lines, baseline tumor status before mCT, Ki67 value) were significantly correlated to OS and PFS. Our retrospective study suggested that mCAP and mTEM can be active and well tolerated in patients with metastatic W/M-D NETs, irrespective of the primary site, site of metastases, line of treatment and baseline tumor status.
A significant number of pregnancy related disorders is associated with protrombotic abnormalities and consequent risk of maternal and fetal complications. Aim of the study was to research thrombophilic markers and comorbidities in a group of women with personal or familial history of these pathologies. We analyzed 207 patients referred to Haemostasis Diseases Unit, looking for ineredithed and acquired thrombophilic markers. We observed 75 coagulation factor mutations (36.2%), 7 deficiencies of natural anticoagulants (3.3%) and 41 antiphosfolipid antibodies positivity (19.9%). The prevalence was higher than that observed in general population, with exception for the obstetric complications group, where others risk factors can play an important role. From history and laboratory exams, we suggested a therapy in 84 women (40%); indication to a prophylaxis in the group of pregnant women was given to 44%, all with successful outcome, while in the other 56% without treatment, only one woman had pregnancy loss (93% positive outcomes). Outcome and the variability in treatments reflect the uncertainty in scientific literature.
