Neuroendocrine Tumor

The NETseq ensemble classifier identified PRRT-naïve GEP-NETs with high accuracy (≥92%) and demonstrated a potential role in early treatment response monitoring in the PRRT setting. This blood-based, non-invasive, multi-analyte molecular method could be developed as a valuable adjunct to conventional methods in the detection and treatment response assessment in NET patients.

Primary treatment strategies predominantly involve surgical intervention coupled with etoposide-cisplatin combination chemotherapy. In cases of recurrence, second-line chemotherapeutic agents including paclitaxel, irinotecan, and doxorubicin are commonly employed alongside localized radiotherapy. While specific genetic mutations remain elusive, emerging evidence suggests potential therapeutic effect involving mTOR inhibitors, PD-1 monoclonal antibodies, and antiangiogenic agents based on isolated case reports. The exploration of representative set of mutations will help for precise targeted therapies and remains a focal point of our ongoing research efforts.

Histology confirmed the diagnosis of poorly differentiated small cell malignancy with positive immunohistochemistry for chromogranin A and synaptophysin. In light of the diagnosis of small cell neuroendocrine carcinoma of the oesophagus with locaregional extension, stage IV, palliative treatment with chemotherapy, radiotherapy and percutaneous endoscopic gastronomy was proposed, with a survival of only 6 months.

Viability analysis following treatment with pevonedistat and SZL-P1-41 in SCLC cell lines and human SCLC-organoid models indicates that RepID expression determines the sensitivity to CRL-targeting anti-cancer drugs. These findings suggest that RepID represents a novel biomarker for NET and SCLC, and insights from RepID research in these cancers could lead to innovative therapeutic strategies.

Volumetric parameters of pretreatment 68[Ga]Ga-DOTA-TATE PET/CT may be useful in prediction of the response to SSA (used in monotherapy as a first-line therapy) in patients with NET.

The recently reported results of the ADIUVO study, although preliminary, discuss the necessity of postoperative therapy with mitotane in patients with low-grade adrenocortical carcinomas (ACCs) after complete resection...Among those, groups (i) and (ii) are more commonly detected in high-grade ACCs but it is also true that specific therapeutic targets based on the molecular characteristics of tumors have remained limited. In addition, possible effects of glucocorticoid excess in functional ACCs on the tumor microenvironment have also been examined, and the utility of immune checkpoint inhibitors is being explored at this juncture.

Our study demonstrates that utilizing broad TGP in examining patients with various functioning NETs, facilitates the identification of new germinal variants in genes that may contribute to the diseases. The verification of revealed findings requires research in vaster sample.

Ovarian NET localizations without teratomous components have a molecular profile analogous to midgut NET metastases. For these patients, a thorough review of imaging should be performed to identify a possible undetected midgut NET and a corresponding follow-up strategy may be recommended.

Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.

No abstract available

As mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.

In present study, we find that hypoxia promoted the methylation degree of CBR4 promoter region thus downgraded the expression of CBR4, which promoted GEP-NETs progression and increased the sensitivity of GEP-NETs cells to everolimus. Further, CBR4 interacted with fatty acid synthase (FASN), displaying a down-regulation of FASN by activating the ubiquitin proteasome pathway and suppressed mTOR signaling. Overall, our results uncovers the CBR4/FASN/mTOR axis as a mechanism for tumor development and inspires us a new molecular guide for the therapeutic strategies for GEP-NETs treatment.

Our findings support NED as independent predictor of OS in EAC after neoadjuvant chemoradiation. While a subset of tumours with NED expressed serotonin, this did not provide additional prognostic information.

In addition, a PDX model with acquired resistance to osimertinib was induced, and the overactivation of RAS mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) signaling pathway caused by the dual-specificity phosphatase 6 (DUSP6) M62I mutation was found to play a key role in the development of osimertinib resistance. Trametinib, a specific inhibitor of the MAPK-ERK pathway significantly slowed down the tumor growth in osimertinib-resistant PDX models, providing an alternative treatment in patients after osimertinib failure.

A new generation of α-particle-emitting radionuclides is being developed, with the advantages of very high energy and a short path length. We survey the most recent developments in this field, summarising the result of currently performed studies in this potentially ground-breaking novel form of therapy for NETs.

Potential high-risk factors in order to treat effectively and prevent these toxicities in NET patients are presented including the management strategy. This review also discusses novel insights, perspectives, and recent advancements in predicting, preventing, and managing toxicity associated with PRRT, while offering prospective future research directions to minimize clinical toxicity and maximize the therapeutic benefits of PRRT as a treatment strategy for NET patients.

Thus, c-MYC overexpression results in different but related tumor types depending on the targeted cell. The GEMMs represent valuable tools for testing immunotherapies and targeted therapies for these diseases.

These tumors were histologically identified as LCNEC and were accompanied by both neuroendocrine and non-neuroendocrine precursor lesions. Using immunofluorescence, a derivation from resident neuroendocrine cells in the gastric corpus was demonstrated, suggesting that at least a portion of LCNEC may originate directly from neuroendocrine cells.

NGS, with its capacity for comprehensive genomic analysis, excels in detecting diverse genetic alterations, offering superior resolution compared to CMA. This study supports the use of the PGDx elio tissue complete panel as a compelling alternative to CMA, showcasing its accuracy in assessing the HRD phenotype. The observed high concordance rate further enhances its value in the clinical diagnostic setting.

P=N/A, N=214, Recruiting, Changhai Hospital, The Navy Military Medical University; Changhai Hospital, The Navy Military Medical University

P=N/A, N=20, Not yet recruiting, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi

P4, N=882, Not yet recruiting, Beijing Tiantan Hospital

The earlier diagnosis of MTC significantly improves survival and prompts better management of MEN2A. In this editorial, we will discuss the significance of molecular diagnostic approaches in detecting RET oncogene mutations in MEN2A.

P2, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

Our findings showed that KIF1A promotes NE differentiation to NEPC by regulating the OGT-mediated O-GlcNAcylation. Targeting O-GlcNAcylation may impede the development of NEPC for a group of PCa patients with elevated KIF1A expression.

The development of multi-kinase inhibitors cabonzantinib and vandetanib, and RET-targeted inhibitors selpercatinib, has completely changed the therapeutic arsenal for advanced disease, but their prescription is reserved to progressive disease with high tumor volume or to symptomatic disease inaccessible to local treatment in expert centers from the ENDOCAN-TUTHYREF network. Active surveillance is the alternative of choice for slowly progressing disease.

There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC.

The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body 68Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up. https://www.

P1, N=18, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

sPitNETs fall into three relevant cytogenetic groups: highly aneuploid tumors characterized by known prognostically favorable features and low aneuploidy tumors including specific subtype with chromosome 11 loss.

Genetic analysis detected pathogenic variants in TP53 and SMAD4, rarely found in pancreatoblastomas. This juxtaposition of large cell neuroendocrine carcinoma and pancreatoblastoma suggests a potential evolution from well-differentiated neuroendocrine tumors to poorly-differentiated carcinomas within pancreatoblastomas.

This study provides an important new model for the study of NEPC, reveals the ability of ASCL1+ NEPC cells to also assume a NEUROD1+ state, and demonstrates the changes to tumor cell phenotypes following ASCL1 loss. See related article by Rodarte et al., p. 3522.

P2, N=55, Active, not recruiting, Dwight Owen | Trial primary completion date: Jul 2024 --> Dec 2024

P=N/A, N=230, Completed, Fudan University | Not yet recruiting --> Completed | N=112 --> 230 | Trial completion date: Dec 2027 --> Aug 2024 | Trial primary completion date: Dec 2025 --> May 2024

P2, N=43, Recruiting, Andrew J. Armstrong, MD | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Dec 2024 --> Dec 2025

There is a correlation between CAF-PDPN and tumoral/stromal PD-L1 expression, and positive status for either CAF-PDPN or stromal PD-L1 expression could be an independent favorable prognostic factor in surgically resected HGNEC patients.

The prototype molecular theranostic is the 68Ga/177Lu DOTATATE pair that targets somatostatin receptor subtype 2 in neuroendocrine tumors...Despite challenges and limitations, molecular theranostics is a powerful tool in the precision medicine landscape. Molecular theranostics is a vehicle for improved outcomes in cancer patients with a future-facing portfolio of opportunities.

Furthermore, ROC curve analysis highlighted the diagnostic significance of the positive expression of the immunohistochemical markers CLU, SSTR2, and RB in identifying NET G3. To guide more suitable treatment strategies, it is essential to develop and apply valuable and more targeted immunohistochemical and molecular pathological markers for a comprehensive analysis.

The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

However, there is no published case of mucinous adenocarcinoma with 68Ga-DOTATATE uptake. We present a unique case of metastatic mucinous adenocarcinoma of unknown origin on 68Ga-DOTATATE PET/CT.

Upon reevaluation, the primary resected specimen was found to include approximately 10% of neuroendocrine tumor components. This case suggests that different FDG uptake between primary and metastatic cancer may necessitate differential diagnosis.

P=N/A, N=360, Recruiting, Cedars-Sinai Medical Center | Trial primary completion date: Jun 2025 --> Jan 2026