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Open research questions in Neuroendocrine Tumor Research Advances

30 unresolved questions extracted from the limitations and future-work sections of 181 Neuroendocrine Tumor Research Advances papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • There are certain limitations of the current study. Therefore, the expression of INSM-1 across the spectrum of NE tumors of the lung could not be assessed.

    Insulinoma-associated protein-1: A novel marker for diagnosis of small cell carcinoma of the lung · 2026 · DOI

  • This study presents the largest series of neuroendocrine tumors operated on at a single Brazilian center, including epidemiological data, survival, and prognostic factors. Pancreatic surgery remains a procedure with high morbidity, and minimally invasive approaches are gaining more ground. Patients treated surgically showed a high 5-year overall survival rate of 92.1%. The identification of poor prognostic factors plays an important role in oncological follow-up and in better selecting patients for the "Active Surveillance" (AS) strategy and non-standardized surgeries. Important prognostic factors were correlated, such as tumor size greater than 2.0 cm, Ki-67 index, and lymphovascular invasion. In a subgroup analysis of patients with tumors measuring 2.1- 2.5 cm, we found a recurrence and lymph node disease profile comparable to patients eligible for active surveillance. _______________________________________________________________ HIGHLIGHTS Pancreatic neuroendocrine tumors (pNETS) constitute a heterogeneous and rare disease worldwide. SciELO Preprints - This document is a preprint and its current status is available at: https://doi.org/10.1590/0102-672020260000027e1956 This study presents the largest series of pNET operated on at a single Brazilian center. Size is not enough to predict behavior in pNETS. Patients with 2.1-2.5cm tumor present with a pattern of recurrence similar do less than 2.0cm patients which are candidates for active surveillance strategy. _______________________________________________________________ Authors’ contributions Conceptualization: Cortelli DASM, Coimbra FJF Investigation: Cortelli DASM Methodology: Cortelli DASM, Coimbra FJF, Farias IC Data analysis: Cortelli DASM, Coimbra FJF Writing original article: Cortelli DASM, Coimbra FJF, Farias IC, Diniz AL, Ribeiro HSC Literature review: Cortelli DASM, Torres SM, Godoy AL, Gonçalves CA _______________________________________________________________________ The information regarding the investigation, methodology and data analysis of the article is archived under the responsibility of the authors. Editor: Nelson Adami Andreollo _____________________________________________________________________ INTRODUCTION Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous disease, which can exhibit either an indolent or an overtly malignant behavior. The primary treatment for pNETs is surgical. Minimally invasive surgery (laparoscopic and robotic) has been SciELO Preprints - This document is a preprint and its current status is available at: https://doi.org/10.1590/0102-672020260000027e1956 increasingly performed, with superior outcomes in terms of morbidity and length of hospital stay1,12.

    O tamanho por si só não basta: Ki-67 e padrões de invasão identificam tumores neuroendócrinos pancreáticos de alto risco · 2026 · DOI

  • Abstract The role of primary tumor resection (PTR) in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing peptide receptor radionuclide therapy (PRRT) remains uncertain.

    Primary tumor resection prior to peptide receptor radionuclide therapy is associated with improved survival in metastatic gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis · 2026 · DOI

  • Advanced prostate cancer can relapse as neuroendocrine prostate cancer (NEPC), a treatment-resistant, androgen receptor (AR)-independent state whose developmental identity remains unclear.

    Neuroendocrine prostate cancer converges on a fetal pulmonary neuroendocrine-like program · 2026 · DOI

  • An additional strength of this case is the availability of biochemical data obtained both at the initial evaluation and at the time of definitive diagnosis, illustrating the evolution from nondiagnostic findings to unequivocal evidence of endogenous hyperinsulinism. At that stage, the available biochemical and imaging findings were insufficient to establish a diagnosis of insulinoma despite the presence of recurrent, predominantly postprandial hypoglycemic symptoms.

    Occult Insulinoma: A 19-Year Diagnostic Delay in a Patient With Recurrent Hypoglycemia · 2026 · DOI

  • While [¹⁸F]AlF-NOTA-octreotide ([¹⁸F]AlF-OC) has shown comparable or even superior diagnostic performance in controlled clinical studies, realworld evidence remains limited, particularly for underrepresented NEN subtypes.

    Evaluation of [¹⁸F]AlF-NOTA-octreotide PET/CT in routine clinical use: a retrospective analysis in 288 neuroendocrine tumor patients · 2026 · DOI

  • Accord- ingly, in our model, necrosis was insufficient for a robust prognostic classification, if not in conjunction with MC and Ki-67.

    Three-Tier Prognostic Stratification of Lung Carcinoids (NET G1-G2-G3) by Multivariable, Data-Driven Integration of Ki-67 and Mitotic Count · 2026 · DOI

  • While chemoimmunotherapy (chemo-IO) has become the standard of care for SCLC and NSCLC, prospective data regarding its efficacy and safety in LCNEC are limited, and the optimal chemotherapy backbone remains unclear.

    Chemoimmunotherapy for large cell neuroendocrine carcinoma (LCNEC) of the lung: A multi-institutional prospective study (NEJ044). · 2026 · DOI

  • This report is limited by its single-case nature, and the diag- nostic performance of POU2F3/YAP1 immunostaining and 90- GEP in NE-marker–negative high-grade NEC requires validation in larger cohorts. Interpretation of immunohistochemistry and GEP- based lineage assignment may also vary across platforms and laboratories. Comprehensive genomic profiling was not performed. In addition, patient-reported outcomes were collected retrospec- tively without standardized symptom or quality-of-life instruments, limiting the granularity of clinical assessment.

    Case Report: Neuroendocrine-marker–negative high-grade neuroendocrine carcinoma mimicking squamous cell carcinoma: an underrecognized diagnostic pitfall · 2026 · DOI

  • The proposed use of serum IgG4 levels as a predictor of malignant nodules requires validation in larger, multi-center studies to establish clinical applicability.

    Serum IgG4 level for malignancy prediction in indeterminate thyroid nodules among patients with or without autoimmune thyroid disease · 2022 · DOI

  • Optimal surgical management for locally advanced grade 3 pancreatic neuroendocrine tumors and pancreatic neuroendocrine carcinomas remains debated due to their differing biological behaviors and prognoses.

    Liver metastasis from pancreatic neuroendocrine tumor: A case report · 2026 · DOI

  • Further research of dual-agent radio- pharmaceutical–radiosensitizing drug combinations in phase I trials should be operationalized and activated for patients with meta- static NETs.

    A case report of acute carcinoid heart failure during lutetium-177 dotatate–triapine treatment for well-differentiated neuroendocrine tumors · 2026 · DOI

  • Further research on the response to histone deacelytase inhibitors, which restore acetylation, and bromo- domain and extraterminal inhibitors which act by inhibiting bromodomain–acetyl histone binding, is underway.

    An Intriguing Case of Chemical Mimicry: Raised AFP Levels in NUT Carcinoma in Anterior Mediastinum · 2026 · DOI

  • The genomic landscape of GEP-NETs has been scarcely studied in terms of genomic profiling.

    The Role of Genetics in Sporadic GEP-NETs: A Comprehensive Review of the Literature · 2017 · DOI

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30 open questions have been extracted from the limitations and future-work passages of 181 Neuroendocrine Tumor Research Advances papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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