Search Results (143)

Objective: In this study, we aimed to evaluate high-resolution computed tomography (HRCT) features of granulomatous–lymphocytic interstitial lung disease (GLILD) in patients with Common Variable Immunodeficiency (CVID), and to describe a novel imaging feature—termed the “Kebab sign”—as a potential radiologic marker of GLILD. Materials and Methods: We retrospectively reviewed HRCT scans of 15 patients with GLILD diagnosed between 2005 and 2025 at a single institution (seven biopsy-confirmed, eight probable diagnoses based on multidisciplinary consensus). CT patterns were assessed for predominant morphology (nodular, reticular, alveolar, fibrotic), distribution (axial and cranio-caudal), and presence of extra-parenchymal findings. Nodules were characterized by size, density, morphology, and the presence of air bronchograms. The “Kebab sign” was defined as nodules aligned along bronchial structures with associated peribronchial thickening. Results: All patients demonstrated a diffuse nodular pattern, with non-calcified macronodules in 100% and micronodules in 60% of cases. Air bronchograms were present in 87% of macronodules. A peri-bronchovascular distribution with lower lung predominance was observed in the majority of cases. The “Kebab sign” was identified in 87% of patients. Splenomegaly and hilar/mediastinal lymphadenopathy were observed in 75%. In 20% of patients, fibrosing features were also present, particularly in older individuals. Conclusions: HRCT findings of GLILD typically include peri-bronchovascular nodules with lower lobe predominance, typically associated with splenomegaly and mediastinal lymphadenopathy. The newly described “Kebab sign,” reflecting nodular alignment along thickened bronchial structures, may represent a useful imaging clue to support the diagnosis of GLILD. Full article

Background/Objectives: Interstitial lung disease (ILD) is the main thoracic manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. High-resolution computed tomography (HRCT) of the chest is considered the gold standard imaging method for detecting and accurately characterizing ILD. This study aims to perform longitudinal visual and quantitative analyses of HRCT scans of patients with ILD secondary to CTD (ILD-CTD) and to correlate these findings with clinical outcomes (functional decline and death) in order to identify tomographic prognostic markers. Methods: This retrospective and longitudinal study included 195 patients with CTD who underwent HRCT at baseline and after two follow-ups. Data collected included initial disease extent and subjective impression of progression, as well as quantitative parameters such as lung volume and mean lung density. Forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) values were also recorded, along with information on patient outcome. Results: Quantitative and visual assessments demonstrated moderate agreement in estimating ILD extent. Variations in lung volume, ground-glass index, pulmonary vascular volume-to-lung volume ratio, and disease extent correlated with subjective perception of disease progression. Lung volume reduction and increased disease extent were associated with FVC decrease at follow-up 1, whereas an increased fibrosis index correlated with reduced FVC at follow-up 2. No quantitative parameter was associated with mortality risk. Conclusions: The results support the potential benefit of using quantitative CT analysis as a complementary tool to pulmonary function tests and visual analysis in the longitudinal evaluation of ILD-CTD. Full article

Background/Objectives: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is linked to substantial morbidity and mortality. While nintedanib (NTB) slows lung function decline in progressive pulmonary fibrosis (PPF), real-world data—particularly regarding radiographic outcomes—remain limited. We aimed to evaluate the real-world effectiveness and tolerability of antifibrotic therapy—predominantly NTB—on radiographic and functional outcomes in a Hungarian CTD-ILD cohort. Methods: We conducted a retrospective observational cohort study including 72 patients with progressive CTD-ILD who initiated antifibrotic therapy at two Hungarian tertiary centers between January 2021 and June 2025. The primary endpoint was the proportion of patients without significant radiographic progression at 6–12 months, based on blinded assessment of paired high-resolution computed tomography (HRCT) scans by two thoracic radiologists. Secondary endpoints included changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) at 6 and 12 months, safety and tolerability, and correlations between lung function and disease-related factors. Results: The cohort comprised systemic sclerosis–ILD (n = 25), rheumatoid arthritis–ILD (n = 23), and other CTD-ILD (n = 24). Radiographic stability was observed in 65.8–78.9% of patients, with improvement most commonly seen in ground-glass opacities, while traction bronchiectasis remained largely unchanged. Radiographic disease extent showed the strongest inverse correlation with baseline FVC and DLCO (p < 0.05). Significant improvements in FVC and DLCO were observed at 6 and 12 months (p < 0.001). Antifibrotic therapy was well tolerated, including in combination with immunosuppressive treatment. Conclusions: These real-world data support the effectiveness and safety of NTB in PPF–CTD-ILD and highlight radiologic disease burden as a key determinant of functional impairment. Full article

Background/Objectives: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major contributor to morbidity and mortality in RA, yet early recognition remains challenging in routine care. The study aimed to identify clinical factors associated with hrCT-confirmed RA-ILD using a CT-verified case–control design. Methods: A single-center retrospective case–control study was designed to include RA patients who underwent chest hrCT in routine care. Cases were patients with ILD on index hrCT (n = 79) and controls were RA patients with hrCT negative for ILD (n = 59). Data were manually abstracted from clinical interview, laboratory testing, RA activity and structural assessment, respiratory examination, pulmonary function tests (PFT), chest radiography, and hrCT. Predictors were extracted from the 12 months preceding the index scan. Univariate comparisons used nonparametric tests or χ², as appropriate. Prespecified multivariable logistic regression estimated adjusted odds ratios (aORs). Sensitivity analyses included restriction to patients with available pre-index PFT, addition of respiratory examination variables, and a matched conditional logistic regression analysis. Results: In the primary multivariable model, male sex was independently associated with RA-ILD (aOR 5.31, 95% CI 1.91–14.75), and COPD/asthma was also associated (aOR 2.82, 1.05–7.56). Adding dyspnea and Velcro crackles improved discrimination (AUC 0.797 to 0.850); Velcro crackles were independently associated with RA-ILD (aOR 5.11, 1.32–19.73). Findings were directionally similar in sensitivity analyses, though precision decreased in matched models. Conclusions: In this CT-imaged real-world RA cohort, male sex, COPD/asthma, and Velcro crackles were associated with hrCT-confirmed RA-ILD; these findings should be interpreted as preliminary, as they apply to patients selected for imaging and should not be extrapolated to unselected RA populations without validation in larger, multi-center and/or prospective cohorts with systematic ascertainment. Full article

Background: Radiotherapy (RT) combined with androgen deprivation therapy (ADT) is a standard treatment for non-metastatic high-risk (HR) prostate cancer (PC). However, the benefit of elective nodal irradiation (ENI) in clinically node-negative (cN0) patients, although suggested, remains controversial, particularly in the elderly. We report the outcomes of elderly HR PC patients treated with prostate-only RT (PORT) and ADT in a “real-word” setting. Methods: Between 2016 and 2022, 43 consecutive elderly patients (median age 76 years) with HR- or very HR-PC according to NCCN criteria version 1.2026 (cN0, cT3-cT4 and/or ISUP Grade Group 4–5 and/or PSA serum levels at diagnosis ≥ 20 ng/mL) were treated at our institution. All patients were staged with abdominal MRI or CT and bone scan; nineteen patients (44.2%) also underwent 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. All patients received PORT (predominantly moderate hypofractionation, 67.5–70 Gy in 25–28 fractions) and ADT (median duration 24 months). To ensure consistency, all oncological endpoints—Biochemical Failure-Free Survival (BFFS; Phoenix criteria), Disease-Free Survival (DFS), Metastasis-Free Survival (MFS), Prostate Cancer-Specific Survival (PCSS), and Overall Survival (OS)—were calculated from a unified time-zero (initiation of first oncological treatment). DFS was defined as a composite endpoint including biochemical failure, radiological recurrence, or initiation of salvage therapy. Results: at a median follow-up of 60 months, no patient reached the Phoenix threshold, resulting in a 100% 5- and 7-year BFFS. However, 4 patients (9.3%) experienced radiological recurrence detected via PET/CT before reaching the nadir + 2 threshold, yielding an estimated 5-year and 7-year DFS of 94.7% and 71.8%, respectively. The 5- and 7-year MFS was of 97.6% and 88.7%, respectively. Seven deaths occurred, all non-PC related, resulting in a 5-year OS of 86.7% and a Prostate Cancer-Specific Survival of 100%. Gastrointestinal toxicity was notably low (no acute or late G3-G4 events). Conclusions: Our findings suggest that PORT, when combined with long-term ADT and modern staging, provides excellent disease control and a favorable safety profile in elderly HR PC patients. Given the high rate of competing mortality in this population, treatment de-escalation via PORT appears to be a clinically reasonable strategy. These results are hypothesis-generating and warrant validation in prospective randomized trials. Full article

Background and objectives: Early biomarkers that can reliably predict treatment outcomes during CDK4/6 inhibitor therapy remain an unmet clinical need in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (MBC). Metabolic changes on ^18F-FDG PET/CT may precede radiologic response and provide insight into tumor biology and early treatment resistance. Methods: This two-center retrospective study included 203 patients with HR+/HER2− MBC who received first-line CDK4/6 inhibitors (ribociclib or palbociclib) plus endocrine therapy between 2018 and 2024. Baseline and interim ^18F-FDG PET/CT scans performed after 2–4 cycles were evaluated. Early metabolic response was defined as a ≥30% reduction in SUVmax on the most metabolically active lesion, consistent with PERCIST 1.0. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and multivariable Cox models. ROC analysis assessed the discriminative performance of ΔSUVmax for predicting disease progression. Results: Among 203 patients, 153 (75.4%) achieved a ≥30% SUVmax reduction. Responders had significantly longer PFS (median 44.4 vs. 4.8 months; p < 0.001) and OS (median not reached vs. 32.0 months; p < 0.001). Metabolic response remained independently associated with improved PFS (HR 0.24; 95% CI 0.15–0.37; p < 0.001) and OS (HR 0.37; 95% CI 0.20–0.67; p = 0.001) after adjustment for tumor grade, endocrine resistance, and visceral disease involvement. Non-responders demonstrated more aggressive baseline features, including higher rates of liver (34.0% vs. 15.0%) and brain metastasis (10.0% vs. 1.3%), as well as lower progesterone receptor expression (median 30% vs. 60%). Conclusions: Early metabolic response assessed by SUV-max on interim ^18F-FDG PET/CT is independently associated with substantially improved PFS and OS in HR+/HER2− MBC receiving treatment with CDK4/6 inhibitors. Although the predictive accuracy of ΔSUVmax alone was modest, the strong survival gradient suggests meaningful prognostic value. Prospective studies with standardized imaging time points and comprehensive metabolic metrics are warranted to define the role of PET-guided treatment adaptation: Full article

Purpose: To explore the correlation between radiologic patterns on high-resolution computed tomography (HRCT) and circulating biomarkers of inflammation and endothelial activation in patients with COVID-19 pneumonia, with the aim of identifying imaging-biomarker phenotypes that may offer insights for clinical stratification. Materials and Methods: This prospective single-center study included 84 consecutive patients hospitalized with PCR-confirmed SARS-CoV-2 infection and respiratory failure. All underwent baseline HRCT, along with parallel biohumoral profiling, including inflammatory (IL-1Ra, IL-6, IL-10) and endothelial (Angiopoietin-2, sVCAM-1, sE-Selectin) biomarkers. HRCT scans were reviewed for parenchymal and vascular abnormalities (vascular tree-in-bud [TIB], vascular enlargement pattern [VEP]). Semi-quantitative scores were assigned for parenchymal (PS) and vascular (VS) involvement. Results: Patients with higher PS had significantly prolonged hospital stay (35 vs. 17 days; p = 0.014), increased ICU admission rates (68.8% vs. 21.4%; p = 0.003), and elevated serum levels of IL-1Ra, IL-6, and IL-10 (p < 0.05). At multivariable analysis, PS remained independently associated with ICU admission after adjustment for age, inflammatory burden, and comorbidities (p = 0.014). A high VS was associated with significantly increased Angiopoietin-2 levels (p = 0.036), although it did not directly correlate with ICU admission or mortality. A significant positive correlation was observed between PS and VS (r =0.392; p < 0.001). Conclusions: in this study, HRCT-based parenchymal and vascular patterns appear significantly correlated with biological processes occurring in severe COVID-19 pneumonia. These observations, although preliminary, may offer a conceptual basis for future studies exploring radiologic and biomarker-based stratification in severe respiratory infections. Full article

Background: Computed tomography (CT)-derived body composition parameters, including skeletal muscle and fat indices, are prognosticators in oncology. Most studies focus on baseline body-composition parameters; however, changes during treatment may provide better prognostic value. Standardized methods for measuring/reporting these parameters remain limited. Methods: This retrospective study included patients who were treated with immunotherapy for non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma between 2017 and 2024 and had technically adequate baseline and follow-up CT scans. Body composition was analyzed using a novel, fully automated software (CompoCT) for L3 slice selection and segmentation. Body composition indices (e.g., skeletal muscle index [SMI]) were calculated by dividing the cross-sectional area by the patient’s height squared. Results: The cohort included 376 patients (mean [SD] age 66.4 [11.4] years, 67.3% male, 72.6% NSCLC, 14.6% RCC, and 12.8% melanoma). During a median follow-up of 21 months, 220 (58.5%) died. Baseline body composition parameters were not associated with mortality, except for a weak protective effect of higher SMI (HR = 0.98, p = 0.043). In contrast, longitudinal decreases were strongly associated with increased mortality. Relative decreases in SMI (HR, 1.17; 95% CI, 1.07–1.27) or subcutaneous fat index (SFI) (HR, 1.11; 95% CI, 1.07–1.15) significantly increased mortality risk. Multivariate models showed similar concordance (0.65) and identified older age, NSCLC tumor type, and relative decreases in SMI and SFI (per 5% units) as independent predictors of mortality. Conclusions: Longitudinal decreases in skeletal muscle and subcutaneous fat were independent predictors of mortality in immunotherapy-treated patients. Automated CT-based body composition analysis may support treatment decisions during immunotherapy. Full article

Background: Sarcopenia is a recognized adverse prognostic factor in many cancers and can be reliably assessed using computed tomography (CT) scans. Its prognostic value in bladder cancer patients undergoing neoadjuvant chemotherapy remains underexplored. This study aimed to assess sarcopenia’s impact on survival and compare different measurement thresholds. Methods: We conducted a retrospective multicenter study including patients with invasive urothelial carcinoma treated with neoadjuvant chemotherapy followed by cystectomy between 2015 and 2021. Sarcopenia was assessed by measuring the Skeletal Muscle Index on CT scans before chemotherapy (BC) and prior to surgery (BS). The primary endpoint was overall survival. Secondary endpoints included progression-free survival (PFS), pathological complete response (pCR), and treatment-related complications. Results: Seventy-four patients were included, the majority receiving the MVAC regimen (71.7%). Forty percent of patients achieved a pCR, 35% experienced disease recurrence, and the median PFS was 25 months. Sarcopenia was observed in 27% of patients BC and in 39% BS. Sarcopenia was associated with an increased risk of all-cause mortality: BC according to the definition by Martin et al. (HR 3.38; 95% CI [1.25–9.12]; p = 0.016) and Fearon et al. (HR 4.03; 95% CI [1.13–14.3]; p = 0.031); and BS according to Martin et al. (HR 3.7; 95% CI [1.12–12.2]; p = 0.032) and Fearon et al. (HR 6.08; 95% CI [1.48–24.9]; p = 0.012). Sarcopenia was an independent risk factor of shorter PFS. Conclusions: Sarcopenia represent an independent and reproducible prognostic factor for mortality in patients with bladder cancer. The study is the first study to compare threshold values at different time points. Full article

Background and Objectives: This study aimed to evaluate the prognostic impact of baseline body composition measurements and changes in muscle and adipose tissue during treatment on overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients treated with nivolumab. Materials and Methods: Eighty-eight metastatic NSCLC patients who were initiated on nivolumab between January 2022 and December 2024 were retrospectively analyzed. Body composition parameters were derived from baseline and 3-month ¹⁸F-FDG PET/CT scans at the L3 level, including psoas muscle index (PMI), skeletal muscle index (SMI), intramuscular adipose content (IMAC), and subcutaneous fat density (SFD). Treatment-related changes in body composition were evaluated, and survival analyses were performed using Kaplan–Meier estimates and Cox regression models. Results: Overall, 34.1% (n = 30) of patients were classified as sarcopenic. Median OS was significantly longer in non-sarcopenic patients (19 months vs. 5 months, p < 0.001). In univariate analysis, older age, higher comorbidity burden, liver metastasis, baseline sarcopenia, and adverse treatment-related changes in muscle and nutritional parameters were found to be associated with OS. In multivariate analysis, only unfavorable changes in skeletal muscle (ΔSMI; HR 3.39, p = 0.003) and subcutaneous fat radiodensity (ΔSFD; HR 2.45, p = 0.02) remained independent adverse prognostic factors. Baseline body composition parameters did not maintain their independence in multivariate models. Conclusions: Our study demonstrates that muscle loss or insufficient gain and unfavorable changes in subcutaneous fat radiodensity during nivolumab treatment more strongly predict overall survival compared to baseline measurements. These findings highlight the clinical importance of monitoring dynamic body composition throughout treatment, rather than static assessments, in NSCLC patients receiving immunotherapy. Full article

Background and Objectives: COVID-19 is an infection caused by the SARS-CoV-2 coronavirus that may develop several complications. Interstitial lung disease (ILD) is the major long-term complication of COVID-19 disease leading to progressive lung fibrosis and reduced respiratory function. The aim of this narrative review is to provide an updated overview of post-COVID-19 ILD by examining research publications and clinical guidelines selected from PubMed, Web of Science, and major respiratory medicine journals from 2020 to 2025. Methods: ILDs are diagnosed by medical history, physiological examination, pulmonary function tests, and chest X-ray or high-resolution computed tomography (HRCT) scan. Lung biopsy, especially cryobiopsy or video-assisted thoracoscopic (VATS) biopsy, can be performed to define histological patterns and confirm the diagnosis. Results: Post-COVID-19 ILD is a chronic condition characterized by long-term respiratory symptoms, radiological findings, and reduced lung function. Fibrotic injury is a consequence of the initial infection and could be influenced by persistent inflammation and dysregulated tissue repair. Risk factors include severe acute illness, advanced age, male sex, and smoking. Clinical course and prognosis of post-COVID-19 ILD is uncertain, as most patients experience gradual improvement or stability, whereas others develop progressive lung function decline. Treatment of post-COVID-19 ILD is not presently defined by guidelines but comprises corticosteroids, antifibrotics (including new drugs such as nerandomilast), supportive oxygen, pulmonary physiotherapy rehabilitation, smoking cessation, and vaccination. Conclusions: ILD represents a significant long-term complication of COVID-19 infection. Further investigations are required to better understand its pathophysiology and clinical management. As research progresses, more effective diagnostic and therapeutic strategies are expected to emerge. Full article

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by repeated exposure to inhaled antigens in susceptible subjects. High-resolution computed tomography (HRCT) of the lungs is the leading diagnostic method for ILDs, but in some cases HRCT findings are not sufficient to distinguish HP and other ILDs, particularly, fibrotic HP (fHP) and usual interstitial pneumonia (UIP). Objective: The aim of this study was to develop HRCT criteria to diagnose fHP in patients with a UIP-like pattern. Methods: In this retrospective study, we analyzed HRCT scans of patients with fHP and a UIP-like pattern who underwent lung biopsy, and patients with idiopathic pulmonary fibrosis (IPF) and a UIP pattern in HRCT. Results: We included 51 patients with confirmed fHP and 24 patients with IPF/UIP in the analysis. IPF/UIP patients were older, were prevalently males, and did not have any systemic autoimmune diseases or risk factors for other ILDs. fHP patients were younger, with an equal number of males and females, and were more likely to be exposed to environmental antigens. HRCT abnormalities in the fHP group predominated in the lower lung areas or were diffuse in axial scans, whereas IPF/UIP patients mostly demonstrated a diffuse craniocaudal distribution and subpleural axial predominance. Centrilobular nodules and mosaic attenuation were present significantly more often in the fHP group; honeycombing, traction bronchiectasis, and emphysema prevailed in IPF/UIP patients. In the logistic regression analysis, patients with fHP and IPF/UIP differed in the presence of centrilobular nodules, honeycombing, and in both craniocaudal and axial distributions of HRCT abnormalities. In the ROC analysis, the combination of centrilobular nodules, honeycombing, and diffuse axial and craniocaudal distributions can predict the diagnosis of fHP (AUC, 0.953 ± 0.022; 95%CI, 0.910–0.995; p < 0.001). Mosaic attenuation and reticulation did not change the probability of fHP. Conclusions: The most significant HRCT features of fHP compared to the UIP pattern were centrilobular nodules, honeycombing, and a diffuse axial and craniocaudal distribution of abnormal findings. Reticulation, mosaic attenuation, and GGO do not increase the probability of fHP. Full article

Background: Computed tomography (CT)-based sarcopenia is a promising predictor of postoperative complications and recovery. However, studies on the longitudinal evolution of skeletal muscle markers are lacking and findings regarding its correlation with survival are still not clear. Methods: We conducted a retrospective single-center cohort study of consecutive patients undergoing curative-intent colon cancer surgery. Skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiation attenuation (SMRA), and intermuscular adipose tissue (IMAT) area and index (IMATI) were measured on a single axial CT slice at the third lumbar vertebral level before surgery and at 6, 12, and 24 months after. Descriptive statistics were used to report the evolution over time of CT-based sarcopenia markers. Their correlation with overall survival was analyzed using Cox’s proportional hazards regression analysis. Results: The final cohort included 102 patients (65.7% males) with a mean age of 66 ± 13 years. Eighty-five (86.7%) patients were alive at 24 months, and forty-five (45.9%) underwent a CT scan at all time points. CT-based sarcopenia markers remained statistically stable over 2 years. Age (HR 1.07, 95% CI 1.00–1.14) and ASA score (HR 2.4, 95% CI 1.00–5.7) were negative independent predictive factors. Patients with larger differences ($\mathrm{\Delta }$) of IMAT area and IMATI at 12 months, HR 0.79 (95% CI 0.67–0.93) and 0.49 (95% CI 0.30–0.80), respectively, had a lower mortality. Conclusions: CT-based markers of skeletal muscle quantity (SMA, SMI) and quality (IMAT area, IMATI) remained statistically stable after curative-intent colon cancer surgery. No preoperative CT-based sarcopenia markers were predictive of overall survival. Larger cohorts are needed to generalize these initial findings. Full article

Background/Objectives: To explore the prognostic potential of gross tumor volume (GTV)-based delta-radiomic features from CT simulation scans in patients with locally advanced unresectable vulvar cancer. Methods: A total of 21 patients (between 2019 and 2024) undergoing definitive radiotherapy were included, with baseline and post-phase I (after 25 fractions) CT simulation scans analyzed. Radiomic features (n = 107) were extracted from GTVs using PyRadiomics, and delta features were calculated as the relative change between scans. A multi-step selection pipeline (univariable Cox screening (p < 0.10), correlation filtering, and Lasso–Cox) was applied for each endpoint: local control (LC), regional control, distant metastasis-free survival, progression-free survival, and overall survival (OS). Model discrimination was assessed via 500-iteration bootstrapped concordance index (C-index), and calibration was plotted at 24 months. Results: Median follow-up was 50.0 months. The 2-year LC and OS rates were 56.2% and 55.9%, respectively. Final multivariable models retained a sole texture Δ feature for LC (HR = 2.62, 95% CI = 1.05–6.52, p = 0.039; C-index = 0.748) and six Δ features for OS (C-index = 0.864). No features were retained for other endpoints. For LC, increased run-length non-uniformity after phase I predicted poorer control. For OS, increased texture/shape complexity predicted worse survival, whereas increased uniformity predicted better survival. Conclusions: CT-based delta-radiomic features, particularly shape and texture metrics, may predict LC and OS in unresectable vulvar cancer. Despite the small sample size, these findings highlight the potential for delta-radiomics as a noninvasive biomarker for risk stratification. Validation in larger cohorts and exploring potential in adaptive radiotherapy are warranted. Full article

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. Full article