Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE).

Subsequent Thyroid Carcinomas in Children and Adolescents Registered in the German MET Consortium (1997-2023).

Among childhood cancer survivors, the cumulative incidence rate of differentiated thyroid carcinomas (DTCs) is estimated to be 8-11%. Although the association of DTC with prior radiotherapy is well-studied, the association with chemotherapy remains less understood. Most studies focused on young adults, leaving a knowledge gap on subsequent DTC occurring in childhood and adolescence.

The role of FDG PET assessment in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 inhibitors in the second-line setting.

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have demonstrated a survival benefit in the second-line treatment of patients with hormone receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer. However, identifying prognostic biomarkers remains a challenge. Thus, we aimed to assess the prognostic value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) performed before CDK4/6 inhibitors initiation.

Diagnostic relevance of p53 and Rb status in neuroendocrine tumors G3 from different organs: an immunohistochemical study of 465 high-grade neuroendocrine neoplasms.

The double inactivation of TP53 and RB1 is considered typical of neuroendocrine carcinomas (NECs) but is assumed to be rare in high-grade neuroendocrine tumors (NETs). The immunohistochemical determination of the p53 and Rb status has therefore been proposed as a diagnostic tool. We studied this status in a large series of high-grade neuroendocrine neoplasms, from multiple origins, in order to (a) assess the patterns observed in the different histopathological categories, (b) compare them between the various anatomic sites, and (c) evaluate their possible diagnostic relevance.

Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force.

Assessing the response to systemic therapy in neuroendocrine tumors (NET) is challenging since morphological imaging response is often delayed and not necessarily reflective of clinical benefit. Peptide receptor radionuclide therapy (PRRT) has a complex mechanism of action, further complicating response assessment. In response to these challenges, the European Neuroendocrine Tumor Society (ENETS) Theranostics Task Force conducted a statement-based survey among experts to identify the current landscape and unmet needs in PRRT response assessment.

Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes.

Time toxicity of lutetium 177 in gastroenteropancreatic neuroendocrine tumours.

Objectives: We aim to investigate the time toxicity of patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate in a single institution.

Design: This is a retrospective cohort study.

Methods: All patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate at the Alexander Fleming Institute were included.

Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study.

Background: Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients' outcomes have not been reported so far.

Patients And Methods: In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy.

Screening and surveillance practices for Multiple Endocrine Neoplasia type 1-related Neuroendocrine Tumours in European Neuroendocrine Tumor Society Centers of Excellence (ENETS CoE)-An ENETS MEN1 task force questionnaire study.

Multiple Endocrine Neoplasia type 1 (MEN1) Clinical Practice Guidelines (2012) are predominantly based on expert opinion due to limited available evidence at the time, leaving room for interpretation and variation in practices. Evidence on the natural course of MEN1-related neuroendocrine tumours (NET) and the value of screening programs has increased and new imaging techniques have emerged. The aim of this study is to provide insight in the current practices of screening and surveillance for MEN1-related NETs in ENETS Centers of Excellence (CoEs).

Thyroidectomy without radioiodine in patients with low-risk thyroid cancer: 5 years of follow-up of the prospective randomised ESTIMABL2 trial.

Background: ESTIMABL2, a multicentre randomised phase 3 trial in patients with low-risk differentiated thyroid cancer (ie, pT1am or pT1b, N0 [no evidence of regional nodal involvement] or Nx [involvement of regional lymph nodes that cannot be assessed in the absence of neck dissection]), showed the non-inferiority of a follow-up strategy without radioactive iodine (I) administration compared with a postoperative I administration at 3 years post-randomisation. Here, we report a pre-specified analysis after 5 years of follow-up.

Methods: Patients treated with total thyroidectomy with or without prophylactic neck lymph node dissection, without postoperative suspicious findings on neck ultrasonography, were randomly assigned to the no-radioiodine group or to the radioiodine group (1·1 GBq-30 mCi after recombinant human thyrotropin-stimulating hormone).

Perspective review: lessons from successful clinical trials and real-world studies of systemic therapy for metastatic pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are orphan tumors with the potential to spread to distant organs such as the lymph nodes, the skeleton, the lungs, and the liver. These metastatic tumors exhibit high rates of morbidity and mortality due to their frequently large tumor burden, the progression of the disease, and the excessive secretion of catecholamines that lead to cardiovascular disease and gastrointestinal dysmotility. Several molecular drivers responsible for the development of PPGLs have been described over the last 30 years.

Metanephrine mirage: distinguishing the phaeocopies, a case report and literature review.

Background: We present one of only seven reported cases of a catecholamine-secreting adrenal neuroblastoma in an adult. The case is used as a platform to discuss key biochemical, genomic and imaging considerations that are central to the successful, targeted management of catecholamine-secreting adrenal tumours.

Case Presentation: A 63-year-old male was urgently reviewed at a tertiary hospital endocrinology outpatient clinic for a 12 cm right-sided adrenal incidentaloma.

Bioinspired orthogonal-shaped protein-biometal nanocrystals enable oral protein absorption.

With the growing number of marketed biological drugs, the development of technological strategies for their oral systemic absorption, becomes increasingly important. The harsh gastrointestinal environment and low permeability of the intestinal epithelium, represent a huge challenge for their systemic delivery. Herein, bioinspired in the physiological insulin-Zn interaction, the design of orthogonal-shaped protein-biometal hybrid nanocrystals, further enveloped by a bilayer of functional biomaterials, is reported.

Ectopic adrenocorticotrophic hormone syndrome in a 10-year-old girl with a thymic neuroendocrine tumor: a case report.

Background: Thymic neuroendocrine tumor as a cause of Cushing syndrome is extremely rare in children.

Case Presentation: We report a case of a 10-year-old girl who presented with typical symptoms and signs of hypercortisolemia, including bone fractures, growth retardation, and kidney stones. The patient was managed with oral ketoconazole, during which she experienced adrenal insufficiency, possibly due to either cyclic adrenocorticotropic hormone (ACTH) secretion or concurrent COVID-19 infection.

EANM expert opinion: How can lessons from radiobiology be applied to the design of clinical trials? Part I: back to the basics of absorbed dose-response and threshold absorbed doses.

Purpose: This study by the EANM radiobiology working group aims to analyze the efficacy and toxicity of targeted radionuclide therapy (TRT) using radiopharmaceuticals approved by the EMA and FDA for neuroendocrine tumors and prostate cancer. It seeks to understand the correlation between physical parameters such as absorbed dose and TRT outcomes, alongside other biological factors.

Methods: We reviewed clinical studies on TRT, focusing on the relationship between physical parameters and treatment outcomes, and applying basic radiobiological principles to radiopharmaceutical therapy to identify key factors affecting therapeutic success.

KIF1A promotes neuroendocrine differentiation in prostate cancer by regulating the OGT-mediated O-GlcNAcylation.

Neuroendocrine prostate cancer (NEPC) arises from prostate adenocarcinoma after endocrine treatment failure and implies lethality and limited therapeutic options. Deciphering the molecular mechanisms underlying transdifferentiation from adenocarcinoma to NEPC may provide valuable therapeutic strategies. We performed a pan-cancer differential mRNA abundance analysis and identified that Kinesin-like protein (KIF1A) was highly expressed in NEPC.

Imaging PD-L1 in the brain-Journey from the lab to the clinic.

Background: Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated with immunosuppressive and aggressive phenotypes in GBM. Presently, there is no standardized protocol for assessing PD-L1 expression levels to select patients and monitor their response to ICPI therapy.

Role of [F]FDG PET/CT in the management of follicular cell-derived thyroid carcinoma.

Follicular cell-derived thyroid carcinomas constitute the majority of thyroid malignancies. This heterogeneous group of tumours includes well differentiated, poorly differentiated, and undifferentiated forms, which have distinct pathological features, clinical behaviour, and prognosis. Positron emission tomography with 2-[F]fluoro-2-deoxy-D-glucose combined with computed tomography ([F]FDG PET/CT) is an imaging modality used in routine clinical practice for oncological patients.

CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response.

CDK4/6 inhibitors are standard of care in the treatment of metastatic breast cancer. Treatment regimen consists of a combination with endocrine therapy, since their therapeutic efficacy as monotherapy in most clinical trials was rather limited. Thus, understanding the molecular mechanisms that underlie response to therapy might allow for the development of an improved therapy design.

Neuroendocrine neoplasms of head and neck, genitourinary and gynaecological systems, unknown primaries, parathyroid carcinomas and intrathyroid thymic neoplasms: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

• This Clinical Practice Guideline provides key recommendations for managing rare endocrine tumours. • Neuroendocrine neoplasms of different origins, parathyroid carcinoma and intrathyroid thymic neoplasms are included. • The guideline covers clinical imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.

Intraoperative evaluation of tumor margins using a TROP2 near-infrared imaging probe to enable human breast-conserving surgery.

Intraoperative surgical margin assessment remains a challenge during breast-conserving surgery. Here, we report a combined strategy of immuno-positron emission tomography (PET) for preoperative detection of breast cancer and guided assessment of margins in breast-conserving surgery through second near-infrared (NIR-II) fluorescence imaging of trophoblastic cell surface antigen 2 (TROP2). We demonstrated that the intensity of PET signals in the tumors was nearly five times higher than in normal breast tissue with a zirconium-89 tracer conjugated to sacituzumab govitecan (SG) in a mouse spontaneous breast cancer model, enabling the identification of tumors.