- Systematic Review
Assessing the Value of Data-Driven Frameworks for Personalized Medicine in Pituitary Tumours: A Critical Overview
- Joan Gil,
- Paula de Pedro-Campos and
- Cristina Carrato
- + 21 authors
Background: Pituitary neuroendocrine tumours (PitNETs) are clinically and biologically heterogeneous neoplasms that remain challenging to diagnose, prognosticate, and treat. Although recent WHO classifications using transcription-factor-based markers have refined pathological categorisation, histopathology alone still fails to predict tumour behaviour or support individualised therapy. Objective: This systematic review aimed to evaluate how machine learning (ML) and knowledge extraction approaches can complement pathology by integrating multi-dimensional omics datasets to generate predictive and clinically meaningful insights in PitNETs. Methods: The review followed the PRISMA 2020 statement for systematic reviews. Searches were conducted in PubMed, Google Scholar, arXiv, and SciSpace up to June 2025 to identify omics studies applying ML or computational data integration in PitNETs. Eligible studies included original research using genomic, transcriptomic, epigenomic, proteomic, or liquid biopsy data. Data extraction covered study design, ML methodology, data accessibility, and clinical annotation. Study quality and validation strategies were also assessed. Results: A total of 726 records were identified. After the reviewing process, 98 studies met inclusion criteria. PitNET research employed unsupervised clustering or regularised regression methods reflecting their suitability for high-dimensional omics datasets and the limited sample sizes. In contrast, deep learning approaches were rarely implemented, primarily due to the scarcity of large, clinically annotated cohorts required to train such models effectively. To support future research and model development, we compiled a comprehensive catalogue of all publicly available PitNET omics resources, facilitating reuse, methodological benchmarking, and integrative analyses. Conclusions: Although omics research in PitNETs is increasing, the lack of standardised, clinically annotated datasets remains a major obstacle to the development and deployment of robust predictive models. Coordinated efforts in data sharing and clinical harmonisation are required to unlock its full potential.
8 January 2026


![PRISMA 2020 flow diagram for systematic reviews. Modified from: Page MJ et al. [18]. This slow diagram exemplifies how the papers were selected through the review process.](https://mdpi-res.com/make/make-08-00016/article_deploy/html/images/make-08-00016-g001-550.jpg)


![Left (A–D) and right (E–H) panels show results on artificial data for the classical and plausible PDE-based naïve Bayes classifier, respectively. Each panel contains four rows: N = 500 sampled points with predicted labels (A,H), class-conditional densities estimated from the training data (B,F), the posterior probability P(C1∣x) computed from the fitted model (C,G), and the test set of N = 5000 points with its predictions (D,H). Because class 1 (dark green) has a smaller variance, its posterior decays in both tails (C), and the MAP rule assigns extreme observations to class 2 in (D); we argue in favor of using the smoothed PDE to estimate the class likelihoods and the concept by [14] to correct assignments in regions of very low likelihood (F) that are not plausible in (G). In addition, the right panel shows that the fine structure of distributions should be accounted for in the class likelihoods (F). Without prior knowledge, applying the left model (C) to the test data produces misclassifications relative to the true boundary (magenta predictions to the left of the green predications in (D)) and is less interpretable in comparison to (H).](https://mdpi-res.com/make/make-08-00013/article_deploy/html/images/make-08-00013-g001-550.jpg)