Mădălina-Raluca Ostafe

Background and Objectives: Systemic inflammatory biomarkers have emerged as potential prognostic indicators in metastatic colorectal cancer (mCRC). However, the prognostic robustness of inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), and Glasgow Prognostic Score (GPS) remains incompletely characterized. In this study, we aimed to evaluate the prognostic significance of NLR, PLR, CRP, CAR, and GPS for progression-free survival in metastatic colorectal cancer in a cohort of patients from Romania. Materials and Methods: This retrospective observational study included 148 patients diagnosed with mCRC. Inflammatory biomarkers were determined from baseline laboratory parameters. Progression-free survival (PFS) was the primary endpoint. Statistical analyses included correlation testing, Kaplan–Meier survival analysis, Cox proportional hazards regression, Firth penalized Cox regression, restricted cubic spline modeling, time-dependent receiver operating characteristic (ROC) analysis, LASSO penalized regression, multiple imputation, and parsimonious multivariable Cox models adjusted for major clinicopathologic confounders. Results: Median PFS was 21 months (95% CI 19–24). In univariable Cox analyses, elevated NLR (HR 1.98, 95% CI 1.11–3.51, p = 0.020), PLR (HR 1.89, 95% CI 1.25–2.85, p = 0.002), CRP (HR 1.45, 95% CI 1.15–1.83, p = 0.002), and CAR (HR 1.44, 95% CI 1.05–1.98, p = 0.022) were associated with shorter PFS. Restricted cubic spline analysis demonstrated a significant nonlinear association between NLR and PFS (p = 0.0025). After multiple imputation, NLR remained associated with shorter PFS (HR 2.04, 95% CI 1.13–3.68, p = 0.018). However, in a multivariable model adjusted for major clinicopathologic confounders, this association was not retained (HR 1.41, 95% CI 0.81–2.43, p = 0.221) and time-dependent ROC analyses demonstrated its limited discriminatory performance. Conclusions: Although some inflammatory markers were associated with shorter PFS in univariable analyses, the prognostic effect of NLR was attenuated after adjustment and was not consistently confirmed across all analyses.

Background/Objectives: Glioblastoma (GBM) exhibits heterogeneous, nonlinear invasion patterns that challenge conventional modeling and radiomic prediction. Most deep learning approaches describe the morphology but rarely capture the dynamical stability of tumor evolution. We propose an AI framework that approximates a latent attractor landscape of GBM morphodynamics—stable basins in a continuous manifold that are consistent with reproducible morphologic regimes. Methods: Multimodal MRI scans from BraTS 2020 (n = 494) were standardized and embedded with a 3D autoencoder to obtain 128-D latent representations. Unsupervised clustering identified latent basins (“attractors”). A neural ordinary differential equation (neural-ODE) approximated latent dynamics. All dynamics were inferred from cross-sectional population variability rather than longitudinal follow-up, serving as a proof-of-concept approximation of morphologic continuity. Voxel-level perturbation quantified local morphodynamic sensitivity, and proof-of-concept control was explored by adding small inputs to the neural-ODE using both a deterministic controller and a reinforcement learning agent based on soft actor–critic (SAC). Survival analyses (Kaplan–Meier, log-rank, ridge-regularized Cox) assessed associations with outcomes. Results: The learned latent manifold was smooth and clinically organized. Three dominant attractor basins were identified with significant survival stratification (χ² = 31.8, p = 1.3 × 10⁻⁷) in the static model. Dynamic attractor basins derived from neural-ODE endpoints showed modest and non-significant survival differences, confirming that these dynamic labels primarily encode the morphodynamic structure rather than fixed prognostic strata. Dynamic basins inferred from neural-ODE flows were not independently prognostic, indicating that the inferred morphodynamic field captures geometric organization rather than additional clinical risk information. The latent stability index showed a weak but borderline significant negative association with survival (ρ = −0.13 [−0.26, −0.01]; p = 0.0499). In multivariable Cox models, age remained the dominant covariate (HR = 1.30 [1.16–1.45]; p = 5 × 10⁻⁶), with overall C-indices of 0.61–0.64. Voxel-level sensitivity maps highlighted enhancing rims and peri-necrotic interfaces as influential regions. In simulation, deterministic control redirected trajectories toward lower-risk basins (≈57% success; ≈96% terminal distance reduction), while a soft actor–critic (SAC) agent produced smoother trajectories and modest additional reductions in terminal distance, albeit without matching the deterministic controller’s success rate. The learned attractor classes were internally consistent and clinically distinct. Conclusions: Learning a latent attractor landscape links generative AI, dynamical systems theory, and clinical outcomes in GBM. Although limited by the cross-sectional nature of BraTS and modest prognostic gains beyond age, these results provide a mechanistic, controllable framework for tumor morphology in which inferred dynamic attractor-like flows describe latent organization rather than a clinically predictive temporal model, motivating prospective radiogenomic validation and adaptive therapy studies.

Colorectal cancer (CRC), a prevalent malignancy, is a significant global health concern. The intricate interplay of genetic mutations, inflammatory processes, and environmental factors underscores the complexity of CRC’s etiology. The human gut harbors a diverse microbial community that plays a key role in maintaining homeostasis and influencing various aspects of host physiology. Perturbations in the gut microbiome (GM) composition and function have been implicated in CRC carcinogenesis. This bidirectional relationship involves microbial contributions to inflammation, DNA damage, and immune modulation, shaping the tumor microenvironment (TME). Bacteriophages, viruses that infect bacteria, contribute to the microbiome’s diversity and function by influencing bacterial abundance and composition. These phages can impact host–microbiome interactions, potentially influencing CRC risk. Furthermore, they can be manipulated to transport targeted medication, without being metabolized. Antibiotics exert selective pressures on the gut microbiome, leading to shifts in bacterial populations and potential dysbiosis. Probiotics can modulate the composition and activity of the GM and could be considered adjunctive therapy in the treatment of CRC. Understanding the intricate balance between bacteriophages, antibiotics–probiotics, and the GM is essential for comprehending CRC etiology and progression.

Background: Survival prediction in patients with brain metastases remains a major clinical challenge, where timely and individualized prognostic estimates are critical for guiding treatment strategies and patient counseling. Methods: We propose a novel hybrid deep learning framework that integrates volumetric MRI-derived imaging biomarkers with structured clinical and demographic data to predict overall survival time. Our dataset includes 148 patients from three institutions, featuring expert-annotated segmentations of enhancing tumors, necrosis, and peritumoral edema. Two convolutional neural network backbones—ResNet-50 and EfficientNet-B0—were fused with fully connected layers processing tabular data. Models were trained using mean squared error loss and evaluated through stratified cross-validation and an independent held-out test set. Results: The hybrid model based on EfficientNet-B0 achieved state-of-the-art performance, attaining an R² score of 0.970 and a mean absolute error of 3.05 days on the test set. Permutation feature importance highlighted edema-to-tumor ratio and enhancing tumor volume as the most informative predictors. Grad-CAM visualizations confirmed the model’s attention to anatomically and clinically relevant regions. Performance consistency across validation folds confirmed the framework’s robustness and generalizability. Conclusions: This study demonstrates that multimodal deep learning can deliver accurate, explainable, and clinically actionable survival predictions in brain metastases. The proposed framework offers a promising foundation for integration into real-world oncology workflows to support personalized prognosis and informed therapeutic decision-making.

Background/Objectives: This study explores the application of vision transformers to predict early responses to stereotactic radiosurgery in patients with brain metastases using minimally pre-processed magnetic resonance imaging scans. The objective is to assess the potential of vision transformers as a predictive tool for clinical decision-making, particularly in the context of imbalanced datasets. Methods: We analyzed magnetic resonance imaging scans from 19 brain metastases patients, focusing on axial fluid-attenuated inversion recovery and high-resolution contrast-enhanced T1-weighted sequences. Patients were categorized into responders (complete or partial response) and non-responders (stable or progressive disease). Results: Despite the imbalanced nature of the dataset, our results demonstrate that vision transformers can predict early treatment responses with an overall accuracy of 99%. The model exhibited high precision (99% for progression and 100% for regression) and recall (99% for progression and 100% for regression). The use of the attention mechanism in the vision transformers allowed the model to focus on relevant features in the magnetic resonance imaging images, ensuring an unbiased performance even with the imbalanced data. Confusion matrix analysis further confirmed the model’s reliability, with minimal misclassifications. Additionally, the model achieved a perfect area under the receiver operator characteristic curve (AUC = 1.00), effectively distinguishing between responders and non-responders. Conclusions: These findings highlight the potential of vision transformers, aided by the attention mechanism, as a non-invasive, predictive tool for early response assessment in clinical oncology. The vision transformer (ViT) model employed in this study processes MRIs as sequences of patches, enabling the capture of localized tumor features critical for early response prediction. By leveraging patch-based feature learning, this approach enhances robustness, interpretability, and clinical applicability, addressing key challenges in tumor progression prediction following stereotactic radiosurgery (SRS). The model’s robust performance, despite the dataset imbalance, underscores its ability to provide unbiased predictions. This approach could significantly enhance clinical decision-making and support personalized treatment strategies for brain metastases. Future research should validate these findings in larger, more diverse cohorts and explore the integration of additional data types to further optimize the model’s clinical utility.

In the current context, breast cancer survivors are characterized by an increased life expectancy through the introduction of screening methods but also of the multidisciplinary therapeutic approach. Thus, the appearance and persistence of adverse effects associated with cancer and its treatment, including cognitive dysfunction, can influence the quality of life in these patients. It is imperative to define the ideas that are incorporated in the vast concept of "cognitive dysfunction associated with cancer" or "oncobrain," alongside to describe the processes that lead to it. Therefore, certain physiological, but also pathological, values of the patient's profile influence the appearance and progression of chemobrain. Among the most frequently cited factors in the literature are age, disorders such as anxiety and depression, and educational level. Furthermore, based on the etiology of neurodegenerative diseases, researchers have developed multiple theories about the causes of chemobrain, many of which rely on data from clinical practice. Given the wide range of changes involved, it's crucial to identify the tests that can both subjectively and objectively demonstrate the cognitive dysfunction associated with the various targeted cognitive impairments. These observations will pave the way for progress in the therapy of these adverse effects.

Background/Objectives : This study investigates the utility of vision transformers (ViTs) for predicting early responses to SRS using a minimal pre-processing approach on MRI images. Methods: We analyzed MRI scans from 19 patients with BM, focusing on axial fluid-attenuated inversion recovery (FLAIR) and high-resolution contrast-enhanced T1-weighted (CE T1w) sequences. Patients were classified as responders (complete or partial response) or non-responders (stable or progressive disease). Results: Our findings demonstrate that ViTs can effectively predict treatment responses, achieving an overall accuracy of 97%. The model exhibited high precision (96% for progression and 97% for regression) and strong recall rates (92% for progression and 99% for regression), distinguishing between treatment outcomes reliably. The confusion matrix analysis further supports its reliability, with minimal misclassifications. The model also achieved an almost perfect area under the ROC curve (AUC = 0.99), indicating accurate differentiation between responders and non-responders across various thresholds. Conclusions : These findings highlight the potential of the Vision Transformer model as a non-invasive predictive tool in clinical settings, significantly influencing clinical decision-making processes and enhancing patient management for brain metastases. By improving early response predictions, this model contributes to the development of personalized treatment strategies in oncology. Future research should focus on validating these results in larger, diverse cohorts, integrating additional data types, and refining the model to further enhance its utility in clinical practice.

Oncolytic viruses (OVs) are emerging as potential treatment options for cancer. Natural and genetically engineered viruses exhibit various antitumor mechanisms. OVs act by direct cytolysis, the potentiation of the immune system through antigen release, and the activation of inflammatory responses or indirectly by interference with different types of elements in the tumor microenvironment, modification of energy metabolism in tumor cells, and antiangiogenic action. The action of OVs is pleiotropic, and they show varied interactions with the host and tumor cells. An important impediment in oncolytic virotherapy is the journey of the virus into the tumor cells and the possibility of its binding to different biological and nonbiological vectors. OVs have been demonstrated to eliminate cancer cells that are resistant to standard treatments in many clinical trials for various cancers (melanoma, lung, and hepatic); however, there are several elements of resistance to the action of viruses per se. Therefore, it is necessary to evaluate the combination of OVs with other standard treatment modalities, such as chemotherapy, immunotherapy, targeted therapies, and cellular therapies, to increase the response rate. This review provides a comprehensive update on OVs, their use in oncolytic virotherapy, and the future prospects of this therapy alongside the standard therapies currently used in cancer treatment.