Neuroendocrine Neoplasm

This is a multicenter, randomized, open-label, phase III study comparing standard of care use of somatostatin analogues (SSAs) to standard of care observation in patients with neuroendocrine neoplasms following treatment with Peptide Receptor Radionuclide Therapy (PRRT) (ethanol-stabilized Lu-177 dotatate).

This study gathers health information for the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.

This study will enroll patients with central lab confirmed NCAM (CD56 IHC) positive metastatic neuroendocrine neoplasms that have progressed after standard of care treatment. CTX-471 to be administered as an intravenous (IV) infusion at either 0.3 mg/kg or 0.6 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The study will be conducted in two stages. In Stage 1, 18 patients will be accrued for each dose level. If there are less than 2 objective responses in these 18 patients at either dose level, the dose level will be stopped. Otherwise, an additional 22 patients will be accrued in Stage 2 with 11 patients for each dose level.

This is a phase I study to assess the safety and efficacy of \[225Ac\]Ac-DOTATATE in patients with inoperable, locally advanced or metastatic, progressive, Well-Differentiatedwell differentiated, somatostatin receptor positive gastroenteropancreatic neuroendocrine neoplasms with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT).

This is a multicentre, controlled, observational prospective study on new biomarkers, as immune profiling, angiogenetic markers and circRNA from TEPs in the diagnosis and in the evaluation of treatment response in pulmonary and gastro-entero-pancreatic NENs.

This is a phase II, single arm, open-label, multicenter study to evaluate the efficacy and safety of Sintilimab combined with IBI310 and Surufatinib for the treatment of high-grade advanced-neuroendocrine neoplasm

According to current guidelines, patients have to withhalt long-acting somatostatin analogues (LA-SSA) for 4-6 weeks prior to every 177Lutetium-DOTATATE administration. The primary objective of the study is to investigate the effect of LA-SSA on the absorbed dose in tumor lesions during PRRT.

For GEP mixed neuroendocrine (NE) non-neuroendocrine neoplasms (MiNENs) a key issue affecting prognosis is sometimes the difficulty in obtaining a timely diagnosis, as the NE component is often localized in deeper anatomical locations and/or becomes prevalent over time. The tissue material of biopsies may be not enough to define the NE component when this is particularly small and this could impact on therapeutic decision. Furthermore GEP NENs need to be characterized for potentially druggable biomarkers and liquid biopsy has clear advantage to the solid one to this aim. Here, we will exploit epigenetic differences characterizing NE tumors to build a DNA methylation-based liquid biopsy assay able to detect circulating tumor DNA of NE derivation, to enable the non-invasive diagnosis and monitoring of GEP-MiNENs.

In this study, we want to randomize patients with neuroendocrine neoplasms (NENs) who are eligible for peptide receptor radionuclide therapy (PRRT), to either standard PRRT consisting of 4 treatments with 7.4 GBq Lu-177-DOTATOC (standard arm) or 4 treatments with individualized doses of Lu-177-DOTATOC (dosimetry arm). In the dosimetry arm, the first dose depends on the patients' kidney function and thereafter the absorbed dose to the kidneys at the previous treatment. A max of 20GBq will be administered at the first treatment and 25GBq at treatment 2-4. We aim to reach an accumulated kidney dose of 24Gy. After the first treatment all patients will go through three SPECT/CT scans 24 hours, 4 days, and 7 days, after treatment to calculate absorbed kidney dose. The patients in the standard dose treatment arm will have one SPECT/CT scan after each of the last three treatments; all performed 24 hours after treatment, used to approximate the kidney dose assuming the clearance of the Lu-177 DOTATOC is the same after all treatments. The patients in the dosimetry based treatment arm will go through three SPECT/CT scans after all four treatments for dosimetry calculation. Bone marrow dosimetry is calculated after all treatments in the dosimetry based treatment arm and after the first treatment in the standard treatment arm. For bone marrow dosimetry, blood samples are drawn right before administration of Lu-177 DOTATOC (time 0) and 3 minutes, 45 minutes, 2 hours, 4 hours, 7-8 hours, 24 hours, 4 days, and 7 days after administration of Lu-177 DOTATOC. Standard blood samples are routinely drawn every 2nd week after every treatment in all included patients and analysed regarding liver, kidney and bone marrow function. Kidney clearance is evaluated with Tc-DTPA clearance at baseline. Blood and urinary samples will be collected at baseline and 3 months after the last treatment for kidney fibrosis analyses. At baseline, blood and urine samples are collected for a biobank. All included patients fill in validated quality of life questionaires at all treatments. To evaluate the effect of the treatment, all patients will be evaluated with standard CT scans prior to treatment and 3 and 9 months after the 4th treatment. Ga-68 DOTATOC PET will be performed at baseline and 6 and 12 months after the last treatment.

The clinical diagnosis and treatment data of 300 cases of cervical neuroendocrine tumors were collected, including age, preoperative biopsy pathology results, postoperative histopathological results, TCT results, and colposcopy biopsy pathology results. At the same time, paraffin tissue specimens (remaining specimens after pathological diagnosis) from 100 cases of cervical neuroendocrine tumors from multiple centers across the country were collected to establish a cervical neuroendocrine tumor data follow-up database. Protein concentration and omics analysis were performed on the data results, to evaluate the molecular characteristics and prognosis of cervical neuroendocrine tumor proteins, and to preliminarily explore its clinical application value.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of lesions derived from cells with the ability to produce hormones that may arise from multiple different organs. Their clinical behavior is quite variable, encompassing both benign lesions and aggressive tumors that invade surrounding and/or distant structures. NENs may also cause serious morbidity due to hormone oversecretion. NENs are among the most frequently inherited human tumors, presenting either isolated or as part of syndromes in which a single patient or family develops multiple tumors. There are also non-inherited changes in the genetic information of the tumor cells that are potential targets for treatment. Both inherited and non-inherited DNA defects can be identified using modern routine genetic tests which, unfortunately, are not widely available in Mexico. This project seeks to uncover the genetic defects causing NENs in a large cohort of Mexican patients, using three different methods for genetic testing. Adult individuals with various types of NENs from two reference hospitals in Mexico City will be invited to participate. After completing informed consent, blood and, if possible, tissue samples will be obtained from all participants. Clinical details, laboratory results, imaging studies, and histopathological data at disease presentation will be retrieved. An initial screening will be performed by analyzing changes in the sequence of multiple genes that have been associated with the occurrence of NENs. In cases with negative screening, a specific method to assess changes in the number of copies of the same genes will also be employed. Finally, sequences of all DNA regions encoding information required to make proteins will be obtained in selected cases. Analyses will be carried out in blood and, if available, also in tumor tissue samples from study participants. Screening of additional family members will be offered. This project will accurately describe the repertoire of specific defects causing NENs in the study population, and will likely uncover and characterize novel genetic associations. The results will contribute for a better understanding of the alterations within and outside known driver genes that shape syndromic presentations, tumor behaviors, and inheritance patterns in individuals with NENs. These data will contribute to improve the information on the molecular bases of NENs, including alterations that can be used as therapeutic targets.

The 2017 World Health Organization (WHO) introduced a new category of high-grade, well-differentiated neuroendocrine neoplasms (NENs) that called neuroendocrine tumors (NETs) G3 in pancreatic NENs classification and, then, in 2019, for all gastro-entero-pancreatic (GEP) tract NENs. The new classification made it possible to separate NETs G3 from high-grade, poorly-differentiated, NENs that are called neuroendocrine carcinomas (NECs). However, in clinical practice, we observed that several clinical, pathological and radiological differences are arising among NET G3 patients, suggesting that a multiparametric definition of NET G3 is needed.

The objective of the study is to create a common and unique platform for the acquisition of biological samples and, subsequently, the possible identification of predictive and prognostic biomarkers for young adults with gastrointestinal and neuroendocrine cancers.The definition "adolescent and young adults (AYA)" covers a broad group of patients ranging from the upper limit of the paediatric competence to the youngest patients usually considered and treated as adults. However, a well-defined and universally accepted age range is still not established. Young adults with cancer have distinct epidemiological, biological, and clinical characteristics, as well as special medical and psychosocial needs that are often unmet. In consideration of their poor representation in clinical studies, as well as the rarer, albeit increasing, frequency at an epidemiological level, knowledge of the risk factors associated with cancers in young adults is very poor. It is therefore of fundamental importance to focus attention on this specific cohort of patients, in order to describe in ever more detail any specific biomolecular aspects, and make full use of the pharmacological resources currently available.