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Texture analysis (TA) can provide quantitative features from medical imaging that can be correlated to clinical endpoints. The challenges relevant to robustness of radiomics features have been analyzed by many researchers, as it seems to be influenced by acquisition and reconstruction protocols. Delta-texture analysis (D-TA), conversely, consist in the analysis of TA feature variations at different acquisition times, usually before and after a therapy. Aim of this study was to investigate the influence of different CT scanners and acquisition parameters in the robustness of TA and D-TA. We scanned a commercial phantom (CIRS model 467, Gammex, Middleton, WI, USA), that is used for the calibration of electron density, two times by varying the disposition of plugs, using three different scanners. After the segmentation, we extracted TA features with LifeX and calculated TA features and D-TA features, defined as the variation of each TA parameters extracted from the same position by varying the plugs with the formula (Y–X)/X. The robustness of TA and D-TA features were then tested with intraclass coefficient correlation (ICC) analysis. The reliability of TA parameters across different scans, with different acquisition parameters and ROI positions has shown poor reliability in 12/37 and moderate reliability in the remaining 25/37, with no parameters showing good reliability. The reliability of D-TA, conversely, showed poor reliability in 10/37 parameters, moderate reliability in 10/37 parameters, and good reliability in 17/37 parameters. The comparison between TA and D-TA ICCs showed a significant difference for the whole group of parameters (p:0.004) and for the subclasses of GLCM parameters (p:0.033), whereas for the other subclasses of matrices (GLRLM, NGLDM, GLZLM, Histogram), the difference was not significant. D-TA features seem to be more robust than TA features. These findings reinforce the potentiality for using D-TA features for early assessment of treatment response and for developing tailored therapies. More work is needed in a clinical setting to confirm the results of the present study.

The evaluation of the efficacy of different therapies is of paramount importance for the patients and the clinicians in oncology, and it is usually possible by performing imaging investigations that are interpreted, taking in consideration different response evaluation criteria. In the last decade, texture analysis (TA) has been developed in order to help the radiologist to quantify and identify parameters related to tumor heterogeneity, which cannot be appreciated by the naked eye, that can be correlated with different endpoints, including cancer prognosis. The aim of this work is to analyze the impact of texture in the prediction of response and in prognosis stratification in oncology, taking into consideration different pathologies (lung cancer, breast cancer, gastric cancer, hepatic cancer, rectal cancer). Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of radiomics approaches related to cancer prognosis in different fields of diseases.

Modern external beam radiotherapy (EBRT) on lung cancer improved dose distribution thanks to advanced dose calculation algorithms, but side effects and relapses can occur in any case onset. Differential diagnosis of relapses and side effects is difficult, and when computed tomography (CT) is uncertain 18-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) can support the diagnosis, even if it can also be difficult to construe. The aim of this retrospective analysis was to evaluate 18F-FDG PET/CT qualitative patterns and semiquantitative parameters, both automatic and preceded by physicians, in interpreting lung lesions in the radiotherapy (RT) lung irradiation field. In total, 94 patients (pts) submitted to EBRT (3 months before) for stage II lung cancer were included (74 men, 20 women, mean age of 68 years old, range of 49–84 years old). CT scans were performed on pts, which showed lung lesions in the RT field. 18F-FDG-PET/CT scans were analyzed qualitatively as negative or positive, and the presence of the lung area with a high 18F-FDG uptake pattern was distinguished as the following: focal/wide, deep/shade, or homogeneous/inhomogeneous. Furthermore, the following semiquantitative parameters were collected: gSUVmax (global standardized uptake value max), MTV (tumor metabolic volume), metabolic spatial distribution (MSD) = proximal SUVmax/distal SUVmax, and intratumoral difference in spatial distribution (IDSD%) = [distal SUVmax/proximal SUVmax] × 100. 18F-FDG PET/CT was related to the pts’ outcome (biopsy and/or clinical–instrumental follow-up): positive for lung relapse, negative if the lesions were phlogistic. The following diagnostic performance parameters of 18F-FDG PET/CT were calculated: sensitivity (Sens), specificity (Spec), diagnostic accuracy (DA), positive predictive value (PPV), and negative predictive value (NPV). Qualitative variables were compared by Chi-squared test, while for semiquantitative parameters Student’s t-test was applied; p < 0.05 was considered statistically significant. Statistics tests were performed with MedCalc V.22.018 ©2024. In 76/94 (80.8%) pts, 18F-FDG uptake was higher compared to the background; in 18/94 (19.2%) no high 18F-FDG uptake areas were detected. Outcome was positive for lung relapse in 49/94 pts, while negative in 45/94, with disease prevalence of 52.13% (95%CI = 41.57–62.54%). In the 18/94 pts without high 18F-FDG uptake, the outcome was negative for lung relapse. In 49/76 pts with higher 18F-FDG uptake, the outcome confirmed the presence of relapse, while in 27/76 the lesion was phlogistic. Results about the Sens, Spec, DA, PPV, and NPV (95%CI) were, respectively: 100% (92.75–100%), 40% (25.7–55.67%), 71.28% (61.02–80.14%), 64.47% (58.84–69.73%), and 100% (81.47–100%). Chi-square test showed significant statistical difference between the positive and negative outcome for patterns focal/wide (p = 0.02) and deep/shade (p < 0.00001). A total of 35/49 (71.4%) pts with lung relapse had a focal lesion and 15/27 (55.6%) with phlogosis had a wide pattern. A total of 34/49 (69.4%) pts with lung relapse had a deep pattern and 25/27 (92.6%) with lung phlogosis had the shade one. Significant difference was observed in evaluating the three patterns (p = 0.00007), with prevalence of “focal/deep/homogeneous” patterns in lung relapse and “wide/shade/inhomogeneous” in phlogosis. gSUVmax, MTV, MSD, and IDSD% were in the following order: in the 76 pts, 5.63 (1.4–24.7), 42.49 (4.94–193), 3.61 (1–5.54), and 70.7% (18–100%); in the 49/76 true positive pts, 6.93 (1.5–24.7), 35.28 (4.94–85.99), 3.30 (1.05–5.54), and (18–95%); in the 27/76 false positive pts, 3.27 (1.4–19.2), 38.37 (4.94–193), 1.57 (1–2.13), and 78.6% (4.7–100%). The difference was statistically significant only for MSD (t = 2.779; p = 0.0069) and IDSD% (t = 2.769; p = 0.0071). 18F-FDG-PET/CT confirms its high sensitivity and NPV in evaluating lung lesions after RT. To improve physician confidence in interpreting lung 18F-FDG uptake without further support, MSD and IDSD% could be considered. Heterogeneity of lung lesions, especially in radiotreated tissue, can be turned from a drawback to a resource and analyzed for differentiating relapses from EBRT side effects. Considering the calculation of semiquantitative parameters that require “human intelligence”, even if slightly more time-consuming, can improve the nuclear physician’s confidence in interpreting 18F-FDG PET/CT images.

Background: Accurate preoperative staging is the cornerstone of therapeutic decision-making in gastric cancer (GC), yet standard modalities often fail to capture the full extent of disease, particularly in diffuse and poorly cohesive histotypes. This review aims to provide a comprehensive update on diagnostic imaging for GC, evaluating the established roles of CT, EUS, and PET/CT alongside the emerging capabilities of Magnetic Resonance Imaging (MRI) and Artificial Intelligence (AI). Methods: A structured narrative review was conducted by searching indexed biomedical databases for studies published between 2015 and 2024. A structured literature search screening process identified 410 relevant studies focusing on T, N, and M staging accuracy, quantitative imaging biomarkers, and radiomics. Results: While Multidetector CT remains the universal first-line modality, its sensitivity declines in infiltrative tumors and low-volume peritoneal carcinomatosis. EUS retains superiority for early (T1-T2) lesions but may offer limited value in advanced stages. Conversely, MRI (leveraging diffusion-weighted imaging (DWI) and multiparametric protocols) indicates superior soft-tissue contrast, potentially outperforming CT in the assessment of serosal invasion, nodal involvement, and occult peritoneal metastases. Furthermore, emerging fibroblast activation protein inhibitor (FAPI) PET tracers show promise in overcoming the limitations of FDG in mucinous and diffuse GC. Finally, radiomics and deep learning models are providing novel quantitative biomarkers for non-invasive risk stratification. Conclusions: Contemporary GC staging requires a tailored, multimodality approach. Evidence supports the increasing integration of MRI and quantitative imaging into clinical workflows to overcome the limitations of conventional techniques and support precision oncology.

Introduction: Stereotactic radiotherapy (SRT) is increasingly used in oligometastatic non-small-cell lung cancer (NSCLC) and is known to elicit systemic immune effects, although the underlying mechanisms remain not fully understood. Methods: In this prospective pilot study, we evaluated plasma cytokine variations in 19 patients with oligometastatic or oligoprogressive NSCLC undergoing SRT. Peripheral blood samples were collected before treatment (T0) and one month after SRT (T1) and the concentrations of nine cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A and TNF-α) were quantified using a multiplex Luminex assay. Non-parametric tests and Cox regression models were used to investigate associations between cytokine levels, clinical variables, systemic treatments, and survival outcomes. SRT induced significant post-treatment increases in IFN-γ, IL-2, and IL-6, consistent with systemic pro-inflammatory activation and T-cell stimulation. Cytokine dynamics were influenced by patient- and tumor-related factors: female sex was associated with higher IL-2 and TNF-α levels; oncogene-addicted tumors showed lower IL-6 levels; and oligoprogressive disease exhibited attenuated cytokine variations compared with metachronous oligometastatic disease. Tyrosine kinase inhibitors were associated with globally reduced cytokine levels and blunted IL-1/IL-2 changes, whereas patients receiving immune checkpoint inhibitors displayed higher IL-2 and IL-6 concentrations and greater post-SRT increases in IFN-γ. Oncogene-addicted status and IL-12 variation emerged as independent predictors of overall survival and a composite model integrating these variables significantly stratified prognosis. Conclusions: These findings suggest that SRT triggers measurable systemic immune activation in oligometastatic NSCLC, which is further shaped by tumor biology, disease burden, and concomitant systemic therapies. Although limited by the small sample size, this study supports the feasibility and potential utility of cytokine profiling to refine patient selection and guide biomarker-driven combinations of SRT with targeted and immune-based treatments, warranting validation in larger prospective cohorts.

Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25–40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests that older patients may receive less aggressive and suboptimal treatment than younger patients with the same disease status. The aim of this review is to depict and summarize the evidence regarding the different strategies that can be used in the clinical management of elderly HNSCC patients. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of clinical approaches in the context of elderly HNSCC.

In this commentary, using existing clinical trial data and FDA approvals we propose that there is currently a critical need for an appropriate balancing between the financial impact of new cancer drugs and their actual benefit for patients. By adopting “pleural mesothelioma” as our clinical model we summarize the most relevant pertinent and available literature on this topic, and use an analysis of the reliability of the trials submitted for registration and/or recently published as a case in point to raise concerns with respect to appropriate trial design, biomarker based stratification and to highlight the ongoing need for balancing the benefit/cost ratio for both patients and healthcare providers.

Cholangiocarcinoma (CC) accounts for about 3% of the gastrointestinal and 10–25% of all hepatobiliary malignancies. It arises from the epithelium of the bile duct and it can be classified in intrahaepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinoma, depending on the anatomical location. About 50–60% of the cases are PCC. Early detection is very difficult for the lack of symptoms, and most of the patients are not resectable at the time of diagnosis. IRE is a non-thermal ablation technique that determines cellular apoptosis by electrical impulses without involving extracellular matrix like MW or RF ablation (MWA and RFA). The aim of our study is to demonstrate the safety, feasibility and efficacy of this procedure in the treatment of cholangiocarcinoma according to our experience. From 2015 to 2019, fifteen patients with unre-sectable perhilar and intrahepatic colangiocarcinoma (7 female and 8 male, mean age 69.2) were referred to our department to be enrolled in our prospective study that was approved by local Ethical Committee. Eight lesions were defined iCC and seven of them pCC. Six patients had biliary STENT and four external percutaneous transhepatic biliary drainage (PTBD). The IRE procedure was performed to expert radiologist (G.B.) under CT guidance using the Nanoknife IRE device (Angiodynamics, Queensbury, NY). The data before and after treatment were compared using Wilcoxon Rank Test and the survival outcome was evaluated using Kaplan Meyer Test. All procedures performed under CT guidance have been successfully completed. Treated lesions were located seven perhilar and eight intrahepatic sites and showed a mean volume 66.3 (SD 70.9; IC ranged from 5.57 to 267.20 cm3). No major complications were observed. From 30 to 90 days, the mortality rate was around 0%. Progression of the disease in all cases were not observed. Only one patient was reported increase of the Ca19-9 without sign of pancreatitis and bile obstruction. The imaging follow-up showed the local disease control with a decrease of the entire volume of the lesion and a further reduction of the densitometric values. From the comparison between the mean volumes for each group (before and after treatment), the Wilcoxon Rank test demonstrated the statistical significant difference with a p value < 0.01. On the contrary, it is believed that this results encouraging in considering the IRE procedure the safe, feasible and effective method in the treatment of the CC

Background Despite the recent progress in the treatment and outcome of Non Small Cell Lung Cancer (NSCLC), immunotherapy has still significant limitations reporting a significant proportion of patients not benefiting from therapy, even in patients with high PD-L1 expression. We have previously demonstrated that the combined inhibition of MEK and PD-L1 in NSCLC patients derived three dimensional cultures exerted significant synergistic effect in terms of immune-dependent cancer cell death. However, subsequent experiments analyzing the expression of Indoleamine 2,3-dioxygenase-1 (Ido-1) gene expression demonstrated that Ido-1 resulted unaffected by the MEK inhibition and even increased after the combined inhibition of MEK and PD-L1 thus representing a potential escape mechanism to this combination. Methods We analyzed transcriptomic profile of NSCLC lung adenocarcinoma cohort of TCGA (The Cancer Genome Atlas), stratifying tumors based on EMT (Epithelial mesenchymal Transition) score; in parallel, we investigated the activation of Ido-1 pathway and modulation of immune cytokines productions both in NSCLC cells lines, in peripheral blood mononuclear cells (PBMCs) and in ex-vivo NSCLC spheroids induced by triple inhibition with an anti-PD-L1 monoclonal antibody, the MEK inhibitor and the Ido-1 inhibitor. Results In NSCLC lung adenocarcinoma patient cohort (from TCGA) Ido-1 gene expression was significantly higher in samples classified as mesenchymal according EMT score. Similarly, on a selected panel of NSCLC cell lines higher expression of MEK and Ido-1 related genes was detected in cells with mesenchymal phenotype according EMT score, thus suggesting a potential correlation of co-activation of these two pathways in the context of EMT, with cancer cells sustaining an immune-suppressive microenvironment. While exerting an antitumor activity, the dual blockade of MEK and PD-L1 enhances the secretion of pro-inflammatory cytokines (IFNγ, TNFα, IL-12 and IL-6) and, consequently, the expression of new immune checkpoints such as Ido-1. The triple inhibition with an anti-PD-L1 monoclonal antibody, the MEK inhibitor and the Ido-1 inhibitor demonstrated significant antiproliferative and proapoptotic activity on ex-vivo NSCLC samples; at the same time the triple combination kept increased the levels of pro-inflammatory cytokines produced by both PBMCs and tumor spheroids in order to sustain the immune response and simultaneously decreased the expression of other checkpoint (such as CTLA-4, Ido-1 and TIM-3) thus promoting an immune-reactive and inflamed micro-environment. Conclusions We show that Ido-1 activation is a possible escape mechanism to immune-mediated cell death induced by combination of PD-L1 and MEK inhibitors: also, we show that triple combination of anti-PD-L1, anti-MEK and anti-Ido-1 drugs may overcome this negative feedback and restore anti-tumor immune response in NSCLC patients’ derived three dimensional cultures.

Background: Radiomics enables the extraction of quantitative imaging biomarkers that can non-invasively capture tumor biology and treatment response. Delta-radiomics, by assessing temporal changes in radiomic features, may improve reproducibility and reveal early therapy-induced alterations. This study investigated whether delta-texture features from contrast-enhanced CT could predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) liver metastases treated with cetuximab rechallenge plus avelumab within the CAVE trial. Methods: This retrospective substudy included 42 patients enrolled in the multicenter CAVE phase II trial with evaluable liver metastases on baseline and first restaging CT. Liver lesions were manually segmented by two readers, and radiomic features were extracted according to IBSI guidelines. Delta-values were calculated as relative changes between baseline and post-treatment scans. Reproducibility (ICC > 0.70), univariate and multivariable analyses, ROC/AUC, bootstrap resampling, cross-validation, and decision curve analysis were performed to evaluate predictive performance and clinical utility. Results: Among reproducible features, delta-GLCM Homogeneity emerged as the most robust predictor. A decrease in homogeneity independently correlated with longer PFS (HR = 0.32, p = 0.003) and OS (HR = 0.41, p = 0.021). The combined clinical–radiomic model achieved good discrimination (AUC 0.94 training, 0.74 validation) and stable performance on internal validation (bootstrap C-index 0.77). Decision curve analysis indicated greater net clinical benefit compared with clinical variables alone. Conclusions: This exploratory study provides preliminary evidence that delta-GLCM Homogeneity may serve as a reproducible imaging biomarker of response and survival in mCRC patients receiving cetuximab plus avelumab rechallenge. If validated in larger, independent cohorts, delta-radiomics could enable early identification of non-responders and support personalized treatment adaptation in immuno-targeted therapy. Given the small sample size, the potential for overfitting should be considered. Future work should prioritize prospective multicenter validation with a pre-registered, locked model and explore multimodal integration (radiogenomics, circulating biomarkers, and AI-driven fusion of imaging with clinical/omic data) to strengthen translational impact. Beyond imaging advances, these findings align with broader trends in personalized oncology, including response-adaptive strategies, multimodal biomarker integration, and AI-enabled decision support.