The Role of Liquid Biopsy in Gastroenteropancreatic Neuroendocrine Neoplasms.

Neuroendocrine neoplasms incidence has been increasing, arising the need for precise and early diagnostic tools. Liquid biopsy (LB) offers a less invasive alternative to tissue biopsy, providing real-time molecular information from circulating tumour components in body fluids. The aim of this review is to analyse the current evidence concerning LB in NENs and its role in clinical practice.

Comparison of Khorana vs. ONKOTEV predictive score to individualize anticoagulant prophylaxis in outpatients with cancer.

Background: Based on the Khorana score, guidelines recommend anticoagulation for primary prophylaxis (PP) in outpatients with cancer with an intermediate-to-high risk of venous thromboembolism (VTE). ONKOTEV score has been prospectively externally validated as novel risk assessment model (RAM) with good discriminatory performances but no direct comparisons with Khorana Score are available.

Methods: Using the ONKOTEV validation dataset (n = 425), we applied generalized decision curve analysis (gDCA) which integrates the principles of evidence-based medicine with treatment effects, model accuracy and patient preferences (weighted as the relative value [RV] of avoiding VTE versus major bleeding [MB]).

Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment.

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy.

Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes.

Textbook outcome as indicator of surgical quality in a single Western center: results from 300 consecutive gastrectomies.

Textbook outcome (TO) has been proposed as a tool to evaluate surgical quality. Textbook oncological outcome (TOO) adds chemotherapeutic compliance to TO. This study was conducted to analyze the TO and TOO of patients with gastric adenocarcinoma who underwent surgery at our center.

Cabozantinib in neuroendocrine tumors: tackling drug activity and resistance mechanisms.

Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models.

Efficacy and safety of systemic chemotherapy for radically resectable esophago-gastric adenocarcinoma in older patients: A systematic review and meta-analysis.

Introduction: A significant proportion of locally-advanced esophago-gastric adenocarcinoma (EGA) is diagnosed in patients ≥70 years old (y.o.) who are commonly underrepresented in clinical trials.

Multimodal treatment for resectable neuroendocrine carcinoma of the cervix.

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.

Role of microsatellite instability and HER2 positivity in locally advanced esophago-gastric cancer patients treated with peri-operative chemotherapy.

Purpose: Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes.

Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE).

The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available.

Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer.

Importance: The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event.

Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series.

Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 to 2020, among patients with histologically confirmed MCC managed at a neuroendocrine neoplasm-referral center, we selected those with an exclusive nodal basin, no distant metastasis, and an unknown primary site defined by cross-sectional and physical examination. A total of 55 out of 310 patients fulfilled the selection criteria.

Addressing the Role of Angiogenesis in Patients with Advanced Pancreatic Neuroendocrine Tumors Treated with Everolimus: A Biological Prospective Analysis of Soluble Biomarkers and Clinical Outcomes.

Background: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment.

Methods: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus.

A randomized phase III study of fractionated docetaxel, oxaliplatin, capecitabine (low-tox) vs epirubicin, oxaliplatin and capecitabine (eox) in patients with locally advanced unresectable or metastatic gastric cancer: the lega trial.

Background: EOX (epirubicin, oxaliplatin, and capecitabine) is one of the standard regimens for metastatic or locally advanced gastric cancer (GC). A new combination based on fractional docetaxel (low-TOX) has been developed in an attempt to increase the efficacy of EOX and reduce the heavy toxicity of classical docetaxel regimens.

Methods: Overall, 169 previously untreated GC patients were randomized between EOX (arm A) and low-TOX (arm B).

Biomarker evaluation in radically resectable locally advanced gastric cancer treated with neoadjuvant chemotherapy: an evidence reappraisal.

Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced resectable gastric cancer but, despite important progresses, relapse-related death remains a major challenge. Therefore, it appears crucial to understand which patients will benefit from peri-operative treatment. Biomarkers such as human epidermal growth factor receptor-2 (HER2), microsatellite instability (MSI), and Epstein-Barr Virus (EBV) have been widely studied; however, they do not yet guide the choice of perioperative treatment in clinical practice.

Does Pathological Stage and Nodal Involvement Influence Long Term Oncological Outcomes after CROSS Regimen for Adenocarcinoma of the Esophagogastric Junction? A Multicenter Retrospective Analysis.

After the results reported by the "Chemoradiotherapy for esophageal Cancer Followed by Surgery Study" (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response.

Evaluation of Biomarkers for the Prediction of Venous Thromboembolism in Ambulatory Cancer Patients.

Background: Venous thromboembolism (VTE) is a common complication of cancer. This study aimed to evaluate immature platelet fraction (IPF), mean platelet volume (MPV), P-selectin, D-dimer, and thrombin generation (TG) as predictive biomarkers for VTE and further the improvement of existing risk assessment models (RAMs).

Methods: A prospective, observational, exploratory study was conducted on ambulatory cancer patients with indication for systemic chemotherapy.

Pharmacodynamics, clinical findings and approval status of current and emerging tyrosine-kinase inhibitors for pancreatic neuroendocrine tumors.

: Pancreatic neuroendocrine tumors (panNETs) represent a rare group of malignancies. For decades, chemotherapy, somatostatin analogs and interferon represented the only systemic therapies; however, over the latest years, new options were registered, including Everolimus, Sunitinib (SUN), and Peptide Receptor Radionuclide Therapy.: This review discusses the role of tyrosine kinase inhibitors (TKIs) in advanced panNETs.

Should platinum-based chemotherapy be preferred for germline BReast CAncer genes (BRCA) 1 and 2-mutated pancreatic ductal adenocarcinoma (PDAC) patients? A systematic review and meta-analysis.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Recent studies have shown that 4-20% of patients with PDAC have a germline BReast CAncer (gBRCA) genes 1 and 2 mutation (m). Because homologous recombination is impaired in patients with gBRCAm, some reports suggested that these tumors may be more sensitive to platinum compounds.

The Italian Rare Pancreatic Exocrine Cancer Initiative.

Introduction: Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices.

Systemic therapies in patients with advanced well-differentiated pancreatic neuroendocrine tumors (PanNETs): When cytoreduction is the aim. A critical review with meta-analysis.

Introduction: Cytoreduction is sometimes an important aim of systemic anti-tumor therapies in well-differentiated pancreatic neuroendocrine tumors (PanNETs). As there is not a gold standard treatment for these tumors in this field, we conducted a literature review in order to identify objective criteria for treatment choice.

Materials And Methods: We critically reviewed and performed a meta-analysis of all published clinical studies of systemic therapies in patients with well-differentiated unresectable PanNETs, selecting only those articles which reported tumor shrinkage (TS) with a waterfall plot (WP).

Systemic Chemotherapy for Advanced Rare Pancreatic Histotype Tumors: A Retrospective Multicenter Analysis.

Objectives: Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients?

Methods: We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival.

Results: Of approximately 4300 exocrine pancreatic cancer patients, 79 advanced cases affected by rare histological types were identified, with pancreatic acinar cell cancer (n = 23), pancreatic adenosquamous cancer (n = 16), and mucinous cystic neoplasm with an associated invasive mucinous cystadenocarcinoma (n = 15) most represented. Survival analyses for each subgroup in relation with the different chemotherapy regimens showed the lack of statistical significance correlations.