HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: MEN1-related pancreatic NETs: identification of unmet clinical needs and future directives

Abstract

<jats:p>The PanNET Working Group of the 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) convened in Houston, TX, USA, 27–29 March 2019 to discuss key unmet clinical needs related to PanNET in the context of MEN1, with a special focus on non-functioning (nf)-PanNETs. The participants represented a broad range of medical scientists as well as representatives from patient organizations, pharmaceutical industry and research societies. In a case-based approach, participants addressed early detection, surveillance, prognostic factors and management of localized and advanced disease. For each topic, after a review of current evidence, key unmet clinical needs and future research directives to make meaningful progress for MEN1 patients with nf-PanNETs were identified. International multi-institutional collaboration is needed for adequately sized studies and validation of findings in independent datasets. Collaboration between basic, translational and clinical scientists is paramount to establishing a translational science approach. In addition, bringing clinicians, scientists and patients together improves the prioritization of research goals, assures a patient-centered approach and maximizes patient involvement. It was concluded that collaboration, research infrastructure, methodologic and reporting rigor are essential to any translational science effort. The highest priority for nf-PanNETs in MEN1 syndrome are (1) the development of a data and biospecimen collection architecture that is uniform across all MEN1 centers, (2) unified strategies for diagnosis and follow-up of incident and prevalent nf-PanNETs, (3) non-invasive detection of individual nf-PanNETs that have an increased risk of metastasis, (4) chemoprevention clinical trials driven by basic research studies and (5) therapeutic targets for advanced disease based on biologically plausible mechanisms.</jats:p>

Parathyroid Carcinoma All-In-One, a Rare Life-Threatening Case With Multiple Systemic Manifestations: Case Report and Review of the Literature

“…This inhibitory effect, potentially useful in improving the quality of life in patients affected by recurrent PC, may occur both through a direct action on osteoclasts and osteoblasts and an indirect action via several cellular pathways ( 26 ). For these reasons, TKIs, such as cabozantinib ( 27 ), sorafenib ( 28 ), and vandetanib ( 29 ), were given in a few case studies reported in the last few years, and in some selected cases the drug choice was also guided by patient-specific mutation analysis ( 29 ). In one patient with PC in HPT-JT syndrome with lung metastatic disease, the use of sorafenib brought normocalcemia and radiographic stability of neck and lung tumors.…”

Preclinical drug studies in MEN1-related neuroendocrine neoplasms (MEN1-NENs)

“…The existing therapeutic options for the various NENs have not been formally evaluated in MEN1 patients, being extrapolated from non-MEN1 NENs patients (Pieterman et al 2020). There is scarcity of evidence reporting on these anti-tumour therapies specifically in MEN1-NENs patients.…”

Plasma Polyamines as an Additional to Imaging Biomarker in MEN1 Patients With Duodenopancreatic Neuroendocrine Tumors

“…Screening should be performed every 1 to 3 years in patients without dpNETs and more frequently in patients with symptoms related to hormonal secretion or evident tumors ( 1 , 2 ). This approach, besides the inconvenience and requirement for continuous patient adherence, entails exposure to the risks of gadolinium deposits in several tissues and EUS-related complications ( 3 ). Currently existing serum biomarkers do not have the necessary negative predictive value to replace imaging as a mean of detecting patients at risk for progression or metastatic disease, making imperative the search for new biomarker classes ( 2 , 3 ).…”

“…The findings of the present study are of particular interest as they may help identify MEN1 patients with dpNET who are at a higher risk for a more aggressive course irrespective of tumor size. Currently, the most widely used parameters to identify such patients are tumor size (≥ 2 cm), functionality, growth rate, and grade, but not all high-risk patients will develop metastases, and metastases may also occur in low-risk patients with lesions smaller than 2 cm ( 3 , 8 ). Additional biomarkers for predicting disease progression are currently missing, whereas evolving biomarkers such as the NETest have not been studied extensively in this patient group ( 3 ).…”

“…Currently, the most widely used parameters to identify such patients are tumor size (≥ 2 cm), functionality, growth rate, and grade, but not all high-risk patients will develop metastases, and metastases may also occur in low-risk patients with lesions smaller than 2 cm ( 3 , 8 ). Additional biomarkers for predicting disease progression are currently missing, whereas evolving biomarkers such as the NETest have not been studied extensively in this patient group ( 3 ). Although polyamine levels were particularly elevated in gastrinomas, their levels were still able to differentiate metastatic cases without gastrinomas from controls, suggesting that polyamines are not affected by the functional status of the tumors.…”