White paper on best practices for translational research in neuroendocrine neoplasms.

Basic and translational investigations play a crucial role in advancing our understanding of neuroendocrine neoplasms (NENs). In this white paper by the Basic and Translational Research Group of the European Neuroendocrine Tumor Society, we discuss the qualities and drawbacks of current disease models and propose good practices for integrating state-of-the-art technologies including bulk and single-cell genomics, transcriptomics, and proteomics in contemporary NEN research. We also provide insights on how to properly handle tissue samples (particularly when starting material is limited) and discuss technical hints of relevance when planning liquid biopsy or tumor immunology studies.

Smoking Adversely Affects Survival of Metastatic Lung Carcinoid Patients: Analysis of a Large International Audit and Prognostic Models for Metastasis-Free Survival and Overall Survival.

Introduction: Among neuroendocrine lung cancers, lung carcinoids (LCs, further divided into typical [TC] and atypical [AC]) are rare, representing only the 2% of all bronchopulmonary malignancies, and lack prognostic classification and stratification.

Methods: We audited 2 international cohorts of patients with a confirmed diagnosis of LC for prognostic analysis. We used data from the Christie Hospital (Manchester, UK, N = 282) and validated our findings using the cohort of Vall d'Hebron Hospital patients (Barcelona, Spain, N = 80).

A CT-based deep learning-driven tool for automatic liver tumor detection and delineation in patients with cancer.

Liver tumors, whether primary or metastatic, significantly impact the outcomes of patients with cancer. Accurate identification and quantification are crucial for effective patient management, including precise diagnosis, prognosis, and therapy evaluation. We present SALSA (system for automatic liver tumor segmentation and detection), a fully automated tool for liver tumor detection and delineation.

Genomics Review of Selective RET Inhibitors Sensitivity in Thyroid Cancer Clinical Trials.

RET gene is a driver of thyroid cancer (TC) tumorigenesis. The incidence of TC has increased worldwide in the last few decades, both in medullary and follicular-derived subtypes. Several drugs, including multikinase and selective inhibitors, have been explored.

Maintenance therapy after first-line platinum-based chemotherapy in gastroenteropancreatic neuroendocrine carcinomas: A literature review.

Neuroendocrine carcinomas are rare and aggressive malignancies, often diagnosed at advanced stages, leading to poor prognosis. Platinum-based chemotherapy is the standard first-line treatment for advanced neuroendocrine carcinomas; however after achieving response no consensus exists on maintenance therapies and the results are inconsistent. This review examines the role of maintenance therapy following response to first-line chemotherapy in gastroenteropancreatic neuroendocrine carcinomas.

DPPA3-HIF1α axis controls colorectal cancer chemoresistance by imposing a slow cell-cycle phenotype.

Tumor relapse is linked to rapid chemoresistance and represents a bottleneck for cancer therapy success. Engagement of a reduced proliferation state is a non-mutational mechanism exploited by cancer cells to bypass therapy-induced cell death. Through combining functional pulse-chase experiments in engineered cells and transcriptomic analyses, we identify DPPA3 as a master regulator of slow-cycling and chemoresistant phenotype in colorectal cancer (CRC).

Radiomics and outcome prediction to antiangiogenic treatment in advanced gastroenteropancreatic neuroendocrine tumours: findings from the phase II TALENT trial.

Background: More accurate predictive biomarkers in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are needed. This study aims to investigate radiomics-based tumour phenotypes as a surrogate biomarker of the tumour vasculature and response prediction to antiangiogenic targeted agents in patients with GEP-NETs.

Methods: In this retrospective study, a radiomics signature was developed in patients with GEP-NETs and liver metastases receiving lenvatinib.

Sex differences on multikinase inhibitors toxicity in patients with advanced gastroenteropancreatic neuroendocrine tumours.

Purpose: There is an increasing interest in the role of sex and gender in cancer patients. The impact of sex differences in oncological systemic therapies is still unknown, and there is a lack of evidence specially in uncommon neoplasms like neuroendocrine tumours (NET). In the present study, we combine the differential toxicities by sex in five published clinical trials with multikinase inhibitors (MKI) in gastroenteropancreatic (GEP) NET.

Impact of the COVID-19 pandemic in the early-onset colorectal cancer.

The COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery.

What is the status of immunotherapy in thyroid neoplasms?

Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in thyroid neoplasms. Programmed death-ligand 1 (PD-L1) staining by immunohistochemistry has shown higher expression in anaplastic thyroid cancer (ATC) compared to other subtypes.

What Is the Status of Immunotherapy in Neuroendocrine Neoplasms?

Purpose Of Review: Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in neuroendocrine neoplasms (NENs) of gastro-entero-pancreatic origin.

Recent Findings: PD-L1 staining by immunohistochemistry has shown heterogeneous results across different studies in both well-differentiated neuroendocrine tumors (NETs) and poorly-differentiated neuroendocrine carcinomas (NECs).

Aggressive Pituitary Macroadenoma Treated With Capecitabine and Temozolomide Chemotherapy Combination in a Patient With Nelson's Syndrome: A Case Report.

Nelson's syndrome is considered a severe side effect that can occur after a total bilateral adrenalectomy in patients with Cushing's disease. It usually presents with clinical manifestations of an enlarging pituitary tumor including visual and cranial nerve alterations, and if not treated, can cause death through local brain compression or invasion. The first therapeutic option is surgery but in extreme cases of inaccessible or resistant aggressive pituitary tumors; the off-label use of chemotherapy with capecitabine and temozolomide can be considered.

Brain Metastases in HER2-Positive Breast Cancer: Current and Novel Treatment Strategies.

Development of brain metastases can occur in up to 30-50% of patients with breast cancer, representing a significant impact on an individual patient in terms of survival and quality of life. Patients with HER2-positive breast cancer have an increased risk of developing brain metastases; however, screening for brain metastases is not currently recommended due to the lack of robust evidence to support survival benefit. In recent years, several novel anti-HER2 agents have led to significant improvements in the outcomes of HER2-positive metastatic breast cancer.

Current Perspectives and Novel Strategies of -Mutant Melanoma.

Melanoma is the deadliest cutaneous cancer. Activating mutations in are found in 20% of melanomas. -mutant melanoma is more aggressive and, therefore, has poorer outcomes, compared to non--mutant melanoma.

Treatment outcomes of advanced digestive well-differentiated grade 3 NETs.

There is no standardized treatment for grade 3 neuroendocrine tumors (G3 NETs). We aimed to describe the treatments received in patients with advanced G3 NETs and compare their efficacy. Patients with advanced digestive G3 NETs treated between 2010 and 2018 in seven expert centers were retrospectively studied.

Drug Development in Neuroendocrine Tumors: What Is on the Horizon?

Neuroendocrine neoplasms (NENs) constitute a heterogenous group of malignancies. Translational research into NEN cell biology is the cornerstone for drug development strategies in this field. Somatostatin receptor type 2 (SSTR2) expression is the hallmark of well-differentiated neuroendocrine tumors (NETs).